Journal of Clinical Medicine doi: 10.3390/jcm15124826

Authors: Toshiki Oka Mari Sakamoto Sotaro Mori Kaori Ueda Yuko Yamada-Nakanishi Makoto Nakamura

Background/Objectives: The objective was to describe the one-year outcomes of salvage trabeculectomy (TLE) in eyes with persistent elevation of intraocular pressure (IOP) requiring early surgical intervention after failed minimally invasive glaucoma surgery (MIGS). Methods: This retrospective observational study included 38 eyes of 38 consecutive Japanese patients who underwent TLE within 100 days after Trabectome (TOM) or microhook ab interno trabeculotomy (μTLO) because of uncontrolled IOP despite maximally tolerated medical therapy. Surgical success was defined as (1) IOP reduction ≥30% from baseline, (2) 5 < IOP < 18 mmHg, (3) no additional glaucoma surgery, and (4) no loss of light perception. The Kaplan–Meier method was used to estimate the one-year success rate. Changes in IOP, medication use, best-corrected visual acuity (BCVA), and mean deviation (MD) were analyzed using the Wilcoxon matched-pairs signed-rank test and a linear mixed-effects model. Results: The median interval between MIGS and TLE was 41.5 days (interquartile range, 28–70 days). The one-year surgical success rate was 86.8% (Kaplan–Meier estimate). IOP and medication use were significantly reduced after TLE (p < 0.0001) and remained stable throughout the 12-month follow-up. BCVA did not differ significantly between baseline and 12 months after TLE, whereas a small but statistically significant difference in MD was observed. No serious vision-threatening complications were encountered. Conclusions: TLE performed shortly after failed MIGS achieved substantial IOP reduction with acceptable safety over a one-year follow-up period. TLE may be considered as one of the surgical options in cases where sufficient IOP reduction cannot be achieved after failed MIGS, and no effective alternative treatments are available.

Journal of Clinical Medicine doi: 10.3390/jcm15124825

Authors: Chia-Chen Lin Wan-Ni Lin Li-Jen Hsin Ming-Shao Tsai Li-Ang Lee Hsueh-Yu Li

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a systemic disorder associated with insulin resistance and elevated risk of type 2 diabetes. While continuous positive airway pressure (CPAP) is the standard therapy, its long-term metabolic benefits remain inconsistent. The metabolic impact of upper airway surgery is less well defined. Methods: In this retrospective study, 49 patients with polysomnography-confirmed OSA who underwent upper airway surgery were evaluated. Respiratory and metabolic parameters—including apnea–hypopnea index (AHI), fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR)—were assessed preoperatively and at 6 months postoperatively. Associations between changes in AHI (ΔAHI) and insulin resistance (ΔHOMA-IR) were analyzed using correlation and receiver operating characteristic (ROC) analyses. Results: Significant improvements were observed in both respiratory and metabolic parameters. AHI decreased from 46.6 ± 25.8 to 20.7 ± 14.1 events/h (p < 0.001). Fasting plasma glucose, insulin levels, and HOMA-IR were significantly reduced postoperatively (all p < 0.05), while HbA1c showed a downward trend. Reduction in AHI was moderately correlated with improvement in insulin resistance (r = 0.527, p < 0.001). ROC analysis demonstrated modest discriminative ability of ΔAHI for identifying normalization of insulin resistance (AUC = 0.62). Conclusions: Upper airway surgery was associated with significant improvements in insulin resistance and glycemic parameters in patients with OSA. The correlation between airway improvement and metabolic change supports a physiological link between upper airway obstruction and insulin sensitivity. These findings suggest that upper airway surgery may represent a clinically relevant adjunct within multimodal strategies for metabolic risk reduction, particularly in patients unable to tolerate CPAP therapy.

Journal of Clinical Medicine doi: 10.3390/jcm15124824

Authors: Ioanna Mitsia Vasiliki Matziou Maria Polikandrioti Sofia Zyga Victoria Alikari

Background/Objectives: Pain is a common symptom in patients undergoing hemodialysis (HD) and may influence their quality of life. Pain self-efficacy may play an important role in self-management and adherence behaviors. This study aimed to examine the association between pain self-efficacy and adherence to the HD regimen in patients undergoing HD. Methods: In this descriptive and cross-sectional study, 199 patients undergoing HD from a single private hospital (convenience sample) in Athens, Greece, completed the Greek-Simplified Adherence Questionnaire-HD (GR-SMAQ-HD) to assess adherence and the Pain Self-efficacy Questionnaire (PSEQ) to assess pain self-efficacy. Sociodemographic and clinical data were also recorded. Bivariate analyses and multiple linear regression were performed to identify factors associated with adherence. Statistical significance was set at p < 0.05. Results: Patients demonstrated moderate levels of pain self-efficacy (mean PSEQ = 33.96 ± 9.74) and moderate adherence to the HD regimen (mean GR-SMAQ-HD = 4.78 ± 2.54). No significant correlation was found between pain self-efficacy and adherence in bivariate analysis (rho = 0.125, p = 0.221). However, in multivariate analysis, pain self-efficacy was a significant independent predictor of adherence (β = 0.056, p = 0.032). Longer duration of End-Stage Renal Disease (ESRD) (β = −0.158, p < 0.001), higher pill burden (rho = −0.237, p = 0.030) were associated with lower adherence. Marital status was also a significant predictor of adherence (β = 1.631, p = 0.016). The model explained 24% of the variance in adherence (Adjusted R2 = 0.24). Conclusions: Pain self-efficacy may indirectly affect adherence to the HD regimen, although its direct effect is modest. Adherence appears to be negatively influenced by pill burden and ESRD duration, while social support may play an important role.

Journal of Clinical Medicine doi: 10.3390/jcm15124823

Authors: Abdullah Y. Alsuhail Abdullah M Alkandari Ahmed Mohammad Sara Almutawtah Yaqoub AlFoudari Fatmah S. Semairan Fahad Mohammad Abdullah AlOtaibi Omar Almutairi Rashed A. Alasoosi Shahad T. Ahmad Abdullah M. Alharran

Background: Dry Eye Disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and inflammation. Cyclosporine A, an immunomodulator, and Diquafosol sodium, a mucin secretagogue, represent two distinct therapeutic pathways. However, current evidence directly comparing their clinical efficacy is inconsistent. This meta-analysis aimed to compare treatment outcomes and efficacy between 0.05% Cyclosporine A and 3% Diquafosol sodium in patients with moderate-to-severe DED. Methods: In January 2026, we conducted a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials directly comparing 0.05% Cyclosporine A to 3% Diquafosol sodium in adult patients with moderate-to-severe DED. For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1+563. Results: We included six RCTs with a total of 859 patients. No significant differences were found between Cyclosporine A and Diquafosol sodium in Tear Break-Up Time (TBUT) at 4, 8, or 12 weeks. Cyclosporine A showed a suggestive greater improvement in Schirmer test scores at 4 weeks (SMD = 0.35, 95% CI 0.07 to 0.63). A modest benefit in symptom scores favoring Diquafosol sodium was observed at 12 weeks (SMD = 0.23, 95% CI 0.06 to 0.41). Subgroup analysis suggested this symptomatic benefit may be more pronounced in patients with severe disease, although subgroup interaction tests were not statistically significant. There were no significant differences in corneal or conjunctival staining at any time point. The risk of adverse events did not differ significantly between treatments. Conclusions: Early improvement in tear production showed a potential benefit for Cyclosporine A, while longer-term symptomatic relief showed a potential benefit for Diquafosol sodium, with suggestive evidence in severe disease. However, these findings should be interpreted cautiously, given the methodological limitations and inconclusive TSA evidence for several outcomes. Future large-scale, standardized trials with extended follow-up are warranted to confirm these findings.

Journal of Clinical Medicine doi: 10.3390/jcm15124822

Authors: Furkan Konus Faruk Oztekin

Background/Objectives: The aim of this study was to compare the effectiveness of the Reciproc Blue (RB) and MicroMega Remover (MR) systems in removing root canal filling material and to evaluate the effect of passive ultrasonic irrigation (PUI) on remaining filling material (RFM) using micro-computed tomography (micro-CT)-based three-dimensional (3D) analysis. Methods: Forty single-rooted mandibular premolar teeth were included in the study. The root canals were prepared up to size F2 using the ProTaper Gold rotary file system and obturated with the lateral compaction technique. After the initial micro-CT scan, the teeth were randomly divided into four groups: Group RB, Group MR, Group RB + PUI, and Group MR + PUI (n = 10). Following retreatment, a second micro-CT scan was performed. The percentage of RFM was calculated, and statistical analyses were performed using Kruskal–Wallis and Mann–Whitney U tests with Bonferroni correction. A rank-based factorial analysis was additionally performed (p < 0.05). Results: RFM was observed in all groups. No significant difference was found between the RB (7.37%) and MR (7.31%) systems (p > 0.05). However, the groups treated with PUI (RB + PUI and MR + PUI) showed significantly lower RFM values than the groups without PUI (p = 0.001). Factorial analysis revealed no significant effect of file system or file system × PUI interaction, whereas PUI significantly reduced RFM (p < 0.001). Conclusions: The RB and MR systems demonstrated similar effectiveness in removing root canal filling material. Although complete canal cleanliness could not be achieved, under the in vitro conditions of the present study, PUI significantly reduced the amount of micro-CT-measured RFM.

Journal of Clinical Medicine doi: 10.3390/jcm15124821

Authors: Ünal Öztürk Ergül Belge Kurutaş Nuray Üremiş Muhammed Mehdi Üremiş Fatma Nur Özkömeç

Background/Objectives: The G protein-coupled estrogen receptor (GPER) is known to interact with cellular stress responses and DNA damage pathways. Therefore, exposure to ionizing radiation may modulate the biological consequences of single-nucleotide polymorphisms in the GPR30 gene. This study aims to evaluate the association between GPER polymorphisms and radiation sensitivity. Methods: The study included 50 healthcare workers exposed to ionizing radiation and 36 healthy individuals with no known occupational exposure to radiation. Genomic DNA was isolated and PCR products were purified using GeneAll kits. Genomic regions encompassing three GPER single-nucleotide polymorphisms (rs3808350, rs3808351, and rs11544331) were amplified by polymerase chain reaction (PCR), followed by DNA sequencing analysis using the BigDye Cycle Sequencing Kit. In addition, an in silico functional and clinical annotation of rs11544331 was performed using Ensembl VEP, SIFT, PolyPhen-2, AlphaMissense, CADD, UniProt, and ClinVar. Results: Genotypic, dominant, and allelic analyses revealed no significant association between radiation exposure and the rs3808350 or rs3808351 polymorphisms. In contrast, a statistically significant association was observed for rs11544331. The frequency of individuals carrying the CT and TT genotypes (CT + TT) was significantly higher in the ionizing radiation-exposed group compared with the control group (OR = 2.981; 95% CI: 1.106–7.904; p = 0.0241). In allelic analysis, the T allele was more prevalent in the exposed group and was significantly associated with radiation exposure (OR = 2.959; 95% CI: 1.282–6.606; p = 0.0110). In silico analysis confirmed that rs11544331 corresponds to the p.Pro16Leu substitution in GPER1; however, SIFT, PolyPhen-2, AlphaMissense, CADD, and ClinVar consistently indicated a tolerated, benign, likely benign, or low-deleteriousness profile. Conclusions: GPER-mediated stress responses and genetic polymorphisms may play a potential role in determining genetic susceptibility following exposure to ionizing radiation.

Journal of Clinical Medicine doi: 10.3390/jcm15124820

Authors: Yingying Hao Ming Yan Rujing Bai Chenyu Li Chen Qu Zhuxi Yu Wenkui Yu Ning Liu Tao Gao Ying Xu

Background/Objectives: The gut–liver axis is central to sepsis, but assessing mesenteric perfusion remains challenging. Indocyanine green (ICG) clearance reflects hepatic blood flow. Since portal flow is derived from mesenteric circulation and supplies most of the liver, reduced ICG clearance may indicate mesenteric hypoperfusion, which can lead to enteral feeding intolerance (EFI). This study examines whether reduced ICG clearance in septic patients without overt liver injury is associated with EFI. Methods: This study is a secondary analysis of a prospective cohort study (March–May 2024, 20-bed ICU). Septic patients without sepsis-related liver injury or recent abdominal surgery were included. ICG plasma disappearance rate (ICG-PDR) was measured at admission; patients were grouped by ICG-PDR (≤18%/min vs. >18%/min). The primary outcome was EFI within 7 days. Multivariate logistic regression and correlation analyses were performed. Results: Among 77 patients (44 with ICG-PDR > 18%/min, 33 with ≤18%/min), the decreased ICG-PDR group had higher SOFA scores (8.4 ± 4.2 vs. 5.4 ± 3.5, p = 0.001) and higher EFI rates (66.7% vs. 43.1%, p = 0.041). Univariate analysis showed ICG-PDR ≤ 18%/min associated with EFI (OR = 2.632, p = 0.043), but this was attenuated after SOFA adjustment (OR = 2.247, p = 0.171). Reduced ICG-PDR correlated with central venous pressure (CVP) (r = 0.626, p < 0.001) but not with mean arterial pressure (r = −0.175, p = 0.129). Conclusions: In septic patients with preserved hepatocyte function, reduced ICG clearance is associated with EFI, but this relationship is largely explained by disease severity (SOFA). Reduced ICG clearance correlates with CVP; however, ICG-PDR cannot distinguish between portal venous and arterial inflow components. The exact mechanism remains speculative.

Journal of Clinical Medicine doi: 10.3390/jcm15124819

Authors: Ilenia Monaco Mounia Sedrati Insaf Chouarfia Fatima Zahra Samet Bouhaik Valeria Trivelloni Yassine Bencharef Mohammed Fouad Sekkal Dario Bottigliero

Background: Amyloidosis is an infiltrative cardiomyopathy caused by amyloid deposition into the myocardium. In recent years, recognition of this treatable cause of heart failure has increased. There are striking sex differences in the diagnosis, clinical course and outcome of the disease. Notably, women have a worse prognosis than men with similar amounts of cardiac involvement. Methods: This review provides an overview of the current state of knowledge regarding the epidemiology, clinical features, diagnosis and treatment of amyloid heart disease. The differences observed between men and women are discussed, and recent advances in the field are highlighted. Results: Compared to men, women are generally older at diagnosis, appear to have less severe cardiac disease at the time of impairment and are more frequently diagnosed late. The less apparent disease manifestations in women may be responsible for the delay in diagnosis. Moreover, women may be underdiagnosed when sex-neutral diagnostic criteria are used. Conclusions: Addressing diagnostic disparities may require the use of sex-specific diagnostic thresholds, as well as a more expansive use of multimodality imaging. Future clinical trials should aim to enroll a greater number of female participants to inform optimal therapeutic approaches and to define the sex-specific disease phenotype for this increasingly treatable disease.

Journal of Clinical Medicine doi: 10.3390/jcm15124818

Authors: İnci Yılmaz Nakir Melike Nur Özçelik Rumeysa Gülistan Karaduman Esra Zerdali

Background/Objectives: Despite widespread antiretroviral therapy (ART) use, whether the expected transition from AIDS-defining to non-AIDS-defining cancers has occurred in settings with persistent late HIV presentation remains unclear. We examined long-term cancer patterns, determinants, and survival outcomes in a large HIV cohort. Methods: This retrospective, single-center cohort included 1419 people living with HIV followed between 2006 and 2024. Patients who developed malignancy were classified as AIDS-defining cancers (ADC) or non-AIDS-defining cancers (NADC). Immuno-virological parameters were assessed at HIV and cancer diagnosis. Survival was analyzed using Kaplan–Meier methods, and predictors of mortality were evaluated using Cox proportional hazards regression. Determinants of ADC development were assessed using multivariable logistic regression. Temporal changes were evaluated by trend analysis. Results: Sixty-six patients (4.6%) developed malignancy (31 ADC, 35 NADC). Late HIV presentation was common, with 72.7% having CD4+ T-lymphocyte counts < 350 cells/mm3 at cancer diagnosis, particularly among ADC cases. Most ADCs (93.5%) occurred within 24 months of HIV diagnosis. Overall survival did not differ between ADC and NADC groups (log-rank p = 0.14). Although mortality declined after 2015, temporal changes in ADC and NADC proportions did not reach statistical significance (p = 0.14). In Cox regression analysis, viral suppression before death or last follow-up was independently associated with lower mortality risk (HR 0.12; 95% CI 0.05–0.31). Lower CD4+ T-lymphocyte counts were associated with ADC development, and a CD4+ T-lymphocyte threshold of 295 cells/mm3 showed good discriminative performance (AUC = 0.83), although this cutoff should be interpreted cautiously due to the lack of external validation. Conclusions: In this long-term cohort from Türkiye, a clear epidemiological transition from ADC to NADC could not be demonstrated. The cancer spectrum remained strongly influenced by late HIV presentation and advanced immunodeficiency. Sustained viral suppression was independently associated with lower mortality risk, supporting the importance of early HIV diagnosis, timely ART initiation, and sustained virological control.

Journal of Clinical Medicine doi: 10.3390/jcm15124809

Authors: Miguel Robles-García Juan Luis Sánchez González José Luis Sánchez-Sánchez Laura Calderón-Díez Miguel Santos Del Rey Javier Martín-Vallejo

Background/Objectives: Chronic non-specific low back pain is a leading cause of disability. Although therapeutic exercise and manual therapy are commonly recommended, their relative effects are often interpreted using broad therapeutic categories. This network meta-analysis aimed to compare the relative effectiveness of specific therapeutic exercise and manual therapy techniques on post-treatment self-reported disability in adults with chronic non-specific low back pain. Methods: A systematic review and frequentist random-effects network meta-analysis were conducted according to Cochrane recommendations and PRISMA-NMA guidance. The protocol was registered in PROSPERO (CRD42022331411). Randomized controlled trials including adults aged 18–65 years with chronic non-specific low back pain were searched in CENTRAL, PubMed, PEDro, Google Scholar, and SciELO up to 31 March 2026. Disability was assessed using the Roland–Morris Disability Questionnaire or Oswestry Disability Index. Effects were synthesized as standardized mean differences. Risk of bias was assessed with RoB 2, and confidence in network estimates was evaluated using CINeMA. Results: Forty-five studies were included. Compared with control/placebo, the largest favorable estimates were observed for equipment-based Pilates, stabilization with motor control, stabilization exercise, soft tissue manipulation, and Pilates Mat. Equipment-based Pilates showed the largest favorable estimate with moderate-confidence evidence, and soft tissue manipulation also showed moderate-confidence evidence. However, heterogeneity was substantial, and confidence in most favorable exercise estimates was low. Conclusions: Specific exercise and manual therapy techniques may reduce post-treatment disability in adults with chronic non-specific low back pain. Equipment-based Pilates and soft tissue manipulation showed favorable signals supported by moderate-confidence evidence. However, the findings do not support a definitive hierarchy of efficacy or categorical superiority of therapeutic exercise over manual therapy.

Journal of Clinical Medicine doi: 10.3390/jcm15124817

Authors: Jiawei Chen Katelyn Kaye-Ling Lim Hong Yu Jared Chua Jeremy Tze En Lim Nicolaas C. Budhiparama Seng Jin Yeo Ming Han Lincoln Liow

Introduction: Currently, there is an ongoing debate regarding the benefits of kinematic alignment (KA) versus mechanical alignment (MA) in total knee arthroplasty (TKA). Robotic-assisted TKA has been shown to improve implant positioning and precision of the KA technique, enabling successful kinematic alignment. However, its impact on early postoperative and functional outcomes remains unclear. This study aims to examine how imageless, table-mounted, robotic-assisted KA-TKA compares with conventional MA-TKA. Methods: Registry data of all primary TKAs using ATTUNE™ cruciate-retaining implants (January 2021–December 2024) performed by a single, experienced surgeon in a high-volume arthroplasty center were retrospectively reviewed. A total of 64 patients who underwent robotic-assisted KA-TKA were compared to 39 patients who underwent conventional MA-TKA. The mean age was 70.3 ± 7.71 and 69.3 ± 9.47 in the KA-TKA group and the MA-TKA group, respectively, while the male proportion was 32.8% and 30.7%, respectively. Early postoperative outcomes (static/dynamic pain score, ambulation distance, length of stay) and 6-month functional outcomes (range of motion, Knee Society Score, Oxford Knee Score, SF-36, patient expectation/satisfaction scores) were analyzed. Delta changes in outcome scores and proportion of patients attaining a minimum clinically important difference (MCID) were studied. Results: Robotic-assisted KA-TKA displayed benefits in the majority of the early postoperative outcomes, with significant improvements in ambulation distance (23.3 vs. 14.7 m, p = 0.002) compared to conventional MA-TKA. Both groups showed significant improvements in the majority of the functional outcomes at 6 months. Robotic-assisted KA-TKA also shows significant improvements in selected mental health aspects of SF-36, namely vitality (p = 0.001), mental health (p = 0.048), mental component summary (MCS) (p = 0.004), and a larger proportion attaining SF-36 vitality MCID (p = 0.045). Following false discovery rate correction for multiple comparisons, postoperative ambulation distance, SF-36 vitality, and MCS remained statistically significant between groups. No significant differences in KSS, OKS, and satisfaction/expectation fulfillment were noted. Conclusions: Robotic-assisted KA-TKA demonstrated early rehabilitation and select mental health-related quality of life improvements compared to conventional MA-TKA. Further studies are needed to examine its long-term clinical outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124816

Authors: Mert Tohumcuoğlu Tolga Köşeci Alpay Düşgün Abdullah Evren Yetişir Cem Mirili Burak Mete Mahmut Büyükşimşek

Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application.

Journal of Clinical Medicine doi: 10.3390/jcm15124815

Authors: Zeynel Mert Asfuroğlu Bengisu Özçivit Asfuroğlu Elyesa Ergen Emre Öztürk Ender Gümüşoğlu Metin Manouchehr Eskandari

Background and Objectives: Syndactyly is a common congenital hand anomaly that may affect hand appearance, function, and psychosocial well-being. This study aimed to evaluate long-term patient-centered outcomes after congenital syndactyly reconstruction, including aesthetic, functional, and psychosocial domains. Methods: This retrospective study included 53 patients with 90 reconstructed web spaces. Aesthetic outcomes were assessed using the Withey score, functional outcomes using the QuickDASH questionnaire, and psychosocial outcomes using an exploratory patient-centered survey developed by the authors. Results: The median follow-up duration was 10 years. The median outcome scores suggested generally favorable long-term results, with a Withey score of 2, a QuickDASH score of 14, and a psychosocial survey score of 29, all within the favorable range of their respective scales. Poorer aesthetic outcomes were observed in patients with complicated syndactyly, those who underwent surgery between 1 and 5 years of age, and those who underwent multiple surgeries. Female sex was associated with poorer functional and psychosocial scores. Complicated syndactyly was associated with less favorable outcomes across all domains. The psychosocial survey demonstrated high internal consistency and significant correlations with both functional and aesthetic outcomes. Conclusions: Congenital syndactyly reconstruction was associated with generally favorable long-term patient-centered outcomes. Less favorable results were observed particularly in patients with complicated syndactyly, while age- and surgery-related associations should be interpreted cautiously because of the retrospective design. These findings support the importance of individualized counseling and long-term assessment that includes aesthetic, functional, and psychosocial dimensions.

Journal of Clinical Medicine doi: 10.3390/jcm15124811

Authors: Marie Nicoline Ordaz-Kücks Iván Alejandro Arteaga-Martínez Hugo Alfredo Funes-González Fernando Martín Guerra-Infante Roberto Montes-de-Oca-Jiménez Martha Elba Ruiz-Riva-Palacio Javier Morales-Fabian Enrique Rojano-Lastra Heberto Hernández-Miranda José Carlos Aguilar-Carrasco Gabriel Arteaga-Troncoso

Background/Objectives: Ventilator-associated pneumonia (VAP) remains a major complication in patients requiring prolonged mechanical ventilation. The effect of tracheostomy on VAP risk remains controversial, particularly when differences in duration of mechanical ventilation are considered. This study evaluated the association between tracheostomy, VAP occurrence, and clinical outcomes in mechanically ventilated ICU patients. Methods: We conducted a retrospective matched exposed–unexposed cohort study in a tertiary-care ICU in Mexico City. Patients undergoing tracheostomy were compared with an age- and sex-matched subcohort of intubated patients receiving invasive mechanical ventilation for ≥48 h. VAP incidence was assessed using cumulative incidence, incidence density, and multivariable generalized linear models. Results: A total of 218 patients were included (55 tracheostomized and 163 intubated). VAP incidence density was similar between groups (31.5 vs. 30.3 per 1000 ventilator-days; RR 1.04, 95% CI 0.7–1.7), whereas cumulative incidence was higher among tracheostomized patients (61.8% vs. 22.7%; RR 2.7, 95% CI 1.9–3.9). Broad-spectrum antibiotics, mechanical ventilation ≥ 5 days, chronic pulmonary disease, and ICU stay remained associated with VAP occurrence in an exploratory multivariable model. Gram-negative microorganisms predominated, and antimicrobial resistance was more frequent among tracheostomized patients. Conclusions: Tracheostomy was associated with higher cumulative incidence of VAP, but a similar incidence density compared with endotracheal intubation. The crude association between tracheostomy and VAP disappeared after adjustment for confounding factors, suggesting that prolonged mechanical ventilation and ICU exposure are more important determinants of VAP risk than tracheostomy itself.

Journal of Clinical Medicine doi: 10.3390/jcm15124814

Authors: Stephanie M. Mueller Ovya Ganesan Ana M. Pachano-Bravo Harriet Kiwanuka LaYow C. Yu Joanna Woodman Erin Bertagnolli Dennis P. Orgill

Background: Pressure injuries (PIs) are common in patients with limited mobility and may require flap reconstruction for definitive management. However, postoperative complications and PI recurrence frequently occur. Certain flap types may be more prone to poor outcomes. This study evaluated outcomes after flap reconstruction for PIs in a medically complex population. Methods: We performed a retrospective review of patients who underwent flap reconstruction for sacral, ischial, trochanteric, or lateral malleolar PIs by a single surgeon at a tertiary care center between 2015 and 2023. Patient demographics, comorbidities, neurologic status, wound characteristics, flap type, and postoperative outcomes were collected. Outcomes were analyzed at the flap level. Results: Sixty-eight patients underwent 101 flap reconstructions. Most patients were male (68%), and spinal cord injury was present in 71%. Medical comorbidity burden was high, including anemia (61%), malnutrition (42%), preoperative osteomyelitis (44%), stool exposure near the wound (49%), and near-universal urinary incontinence. Postoperative complications were common across flap types, most commonly wound dehiscence and PI recurrence. New PIs developed at non-operative sites in about 14% of reconstructions during recovery. During the eight-year follow-up period, 19 (28%) patients expired and 21% of reconstructions were complicated by recurrence at the operative site. Conclusions: Flap reconstruction remains an important treatment for advanced PIs but is associated with high complication and recurrence rates in patients with substantial comorbidities and limited mobility. These findings support careful patient selection, preoperative optimization, and multidisciplinary postoperative care focused on preventing new PIs.

Journal of Clinical Medicine doi: 10.3390/jcm15124810

Authors: Laura Carbajo Martín Ignacio Párraga-Martínez Luis Matías Beltrán-Romero Máximo Bernabeu Wittel Northern Huelva Health Management Area Research Group Northern Huelva Health Management Area Research Group

Objectives: To evaluate the impact of Point-of-Care Ultrasound (POCUS) performed by family physicians on the management of abdominal pain in the emergency department, assessing its effect on length of stay, performance of complementary diagnostic tests, diagnostic concordance, and patient satisfaction. Methods: Quasi-experimental pilot study with a control group conducted in a hospital emergency department. A total of 222 adult patients with abdominal pain were included and allocated according to the attending professional (with or without ultrasound training). Clinical, care-related, and patient-satisfaction variables (SERVPERF questionnaire) were analyzed. Non-parametric statistical tests were used, and multiple linear regression analyses were performed. Results: The POCUS group showed a shorter length of stay (3.46 vs. 4.41 h; p = 0.022) and a lower number of plain radiographies (16.8% vs. 69.9%; p < 0.001) and CT scans (p = 0.034). Diagnostic concordance was significantly higher in the experimental group (99.2% vs. 75.7%; p < 0.001). Overall satisfaction with received care was also higher in the intervention group (p < 0.001), with significant differences observed across all evaluated dimensions. The multivariate model explained 26.6% of the variability, with patient satisfaction emerging as a positive predictor. Conclusions: POCUS improves the quality of care in emergency departments by reducing length of stay and the use of complementary diagnostic tests while increasing diagnostic accuracy and patient satisfaction. Its implementation can be considered an effective and potentially cost-effective strategy; however, further studies with greater methodological robustness are required to validate the development of standardized composite indexes.

Journal of Clinical Medicine doi: 10.3390/jcm15124813

Authors: Katsuhiko Oda Makoto Takahashi Ryuichi Taketomi Kota Itagaki Takehiro Sato Shintaro Katahira

Medical intervention for ischemic heart disease began approximately 150 years ago with nitrates, and for nearly a century thereafter, little fundamental progress was made. With the advent of the left internal thoracic artery to the left anterior descending artery (LITA-LAD) bypass in the 1960s, treatment entered a new stage; however, its essential significance remained insufficiently recognized for many years. Numerous studies were subsequently conducted to evaluate alternative or parallel treatment strategies, but these investigations also helped bring the durable capacity of LITA-LAD to perfuse ischemic myocardium into sharper focus. Over the past quarter century, the treatment of ischemic heart disease has remained in a state of uncertainty, and its central prognostic foundation has often been obscured, although in recent years this uncertainty has begun to resolve. In this review, we reexamine the historical process by which the significance of LITA-LAD remained incompletely appreciated in parts of the cardiology and cardiac surgical communities. We further outline how the principal basis of the long-term prognostic benefit conferred by LITA-LAD gradually became evident and define the contemporary roles of medical therapy and percutaneous coronary intervention in relation to LITA-LAD-based coronary artery bypass grafting (CABG).

Journal of Clinical Medicine doi: 10.3390/jcm15124812

Authors: Mustafa Ferhat Keten Kadir Biyikli Barkin Kultursay Halit Eminoglu Dogancan Ceneli Nesri Danisman Cagri Kafkas Ismail Balaban

Background: New-onset atrial fibrillation (NOAF) is a common complication after transcatheter aortic valve implantation (TAVI) and is associated with unfavorable clinical outcomes. Sodium–glucose cotransporter-2 (SGLT2) inhibitors may have antiarrhythmic effects, but their association with NOAF after TAVI remains uncertain. This study evaluated the relationship between SGLT2 inhibitor use and NOAF following TAVI. Methods: This retrospective observational study included 573 consecutive patients who underwent transfemoral TAVI between January 2020 and December 2025. Patients with prior atrial fibrillation or atrial flutter were excluded. NOAF was defined as any atrial fibrillation episode lasting ≥30 s during index hospitalization. A doubly robust inverse probability weighted logistic regression model was applied to reduce baseline imbalances and assess the association between SGLT2 inhibitor use and NOAF. Results: Overall, 169 patients received SGLT2 inhibitors, while 404 patients constituted the control group. NOAF occurred less frequently in the SGLT2 inhibitor group than in controls (11% vs. 19%, p = 0.041). In adjusted analysis, SGLT2 inhibitor use was independently associated with lower odds of NOAF (adjusted OR: 0.171, 95% CI: 0.076–0.381, p < 0.001). Older age and diabetes mellitus were associated with increased NOAF risk, whereas higher baseline left ventricular ejection fraction was associated with lower risk. Subgroup analysis indicated a possible interaction by diabetes status (P-interaction = 0.040), although this exploratory finding should be interpreted cautiously. Conclusions: SGLT2 inhibitor use was independently associated with lower odds of NOAF after TAVI. These findings should be interpreted as observational and hypothesis-generating and require confirmation in prospective randomized studies.

Journal of Clinical Medicine doi: 10.3390/jcm15124808

Authors: Alicja Danieluk Tomasz Pilecki Bartosz Rutka Krzysztof Mucha

Cardiovascular disease remains the leading cause of mortality in kidney transplant recipients (KTRs). Arterial hypertension is present in a vast majority of patients after kidney transplantation, constituting the most prevalent cardiovascular comorbidity, and is a significant modifiable risk factor for other cardiovascular complications and graft loss. The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not address blood pressure control strategies in KTRs, and the prior 2021 KDIGO recommendations targeting values below 130/80 mmHg rely primarily on data extrapolated from non-KTR populations. This represents an existing evidence gap in the management of post-transplant hypertension. Dihydropyridine calcium channel blockers and angiotensin receptor blockers remain first-line antihypertensive medications, although most studies assessing their effectiveness in KTRs date back more than 15 years. The current treatment guidelines are based largely on limited and outdated data. Optimal selection and individualization of immunosuppressive therapy and—when feasible—its modification in some KTRs may be important in improving blood pressure control. This includes, for example, a reduction in the calcineurin inhibitor or steroid dose, as well as the use of mTOR inhibitors or belatacept. The lack of large, up-to-date randomized trials in the KTR population underscores the pressing need for further extensive research focused on this patient group.

Journal of Clinical Medicine doi: 10.3390/jcm15124807

Authors: Duygu Tozcu Yilmaz Mehmet Ali Gul Mustafa Capraz Melek Tufek Nihat Aydin

Background/Objectives: Type 2 diabetes may impair anterior segment immune regulation. Because transforming growth factor-β2 maintains ocular immune privilege, while nuclear factor-κB is linked to inflammatory activation, we compared their aqueous humor levels in cataract patients with and without diabetes. Methods: In this prospective cross-sectional study, aqueous humor samples were collected from 90 patients (30 diabetic, 60 non-diabetic) via anterior chamber needle aspiration at the commencement of routine phacoemulsification, prior to viscoelastic injection, without additional intervention. Transforming growth factor-β2 and nuclear factor-κB levels were then measured using enzyme-linked immunosorbent assay (ELISA). Between-group comparisons and ROC curve analyses were performed to evaluate differences in biomarker levels and their discriminative ability in distinguishing diabetic status. Covariate-adjusted analysis (ANCOVA) was additionally performed. Results: Transforming growth factor-β2 levels were significantly lower in the diabetic group (p < 0.001), while nuclear factor-κB levels showed no significant difference (p = 0.285). The between-group difference in transforming growth factor-β2 remained significant after adjustment for cataract grade and hypertension duration (F(1,86) = 17.901, p < 0.001, partial η2 = 0.172; Cohen’s d = 0.94). Transforming growth factor-β2 demonstrated high specificity (100%) but limited sensitivity (45%) for identifying diabetic status at a cut-off of <449.25 ng/L; however, given the small sample size and exploratory nature of the study, this specificity value should be interpreted with caution and requires validation in larger cohorts. Conclusions: Lower aqueous humor TGF-β2 levels in diabetic cataract patients, independent of cataract severity and hypertension duration, suggest that TGF-β2 suppression may represent an earlier molecular event in anterior segment immune dysregulation preceding overt inflammatory activation. While TGF-β2 shows exploratory biomarker potential, validation in larger, prospective, mechanistic studies is required before clinical application.

Journal of Clinical Medicine doi: 10.3390/jcm15124806

Authors: Natalia Katarzyna Mazur-Ejankowska Zuzanna Małgorzata Brzóska Maciej Ejankowski Amelia Sztangierska Kinga Jaguszewska Dariusz Grzegorz Wydra Magdalena Emilia Grzybowska

Introduction: Obstructed HemiVagina and Ipsilateral Renal Anomaly (OHVIRA) syndrome, also known as Herlyn–Werner–Wunderlich syndrome, is a rare congenital Müllerian duct anomaly, characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Symptoms typically appear shortly after menarche and include dysmenorrhea and pelvic pain. The psychological burden associated with fertility and reproductive outcomes in women with OHVIRA syndrome remains poorly investigated. Materials and methods: A 30-year-old primigravida with left renal agenesis and a history of vaginal abscess, dysmenorrhea, and chronic pelvic pain received a delayed OHVIRA syndrome diagnosis. The patient had previously been informed that spontaneous conception and an uncomplicated pregnancy were highly unlikely because of her congenital gynecological condition, resulting in significant fertility-related anxiety and psychological distress. Under careful supervision and counseling, she conceived successfully, and the pregnancy progressed without complications; an elective cesarean section was performed at term. A literature search using the PubMed and Embase databases was conducted between November 2025 to April 2026 to identify studies reporting reproductive outcomes and psychological aspects in patients diagnosed with OHVIRA syndrome and other Müllerian anomalies. Results: Evidence-based counseling contributed to improvement of quality of life and reduction of pregnancy-related anxiety of the reported patient with OHVIRA syndrome. A limited number of studies discuss the mental burden and fertility-related anxiety of patients with OHVIRA syndrome and other Müllerian anomalies. Conclusions: Spontaneous conception and uncomplicated pregnancy are possible for women with OHVIRA syndrome. The psychological burden associated with congenital gynecological conditions remains under-recognized and requires further investigation. Comprehensive counseling and interdisciplinary care are essential to improve reproductive education, mental health support, and pregnancy outcomes in patients with congenital gynecological anomalies.

Journal of Clinical Medicine doi: 10.3390/jcm15124805

Authors: Serdar Derya Ahmet Kutur Mustafa Safa Pepele Funda Kavak Budak

Objective: This study was conducted to examine the relationship between ruminative thinking styles and suicide probability in individuals presenting to the emergency department with suspected alcohol and substance intoxication/use, and to investigate whether these variables differ according to various demographic characteristics. Methods: The sample of this descriptive study consisted of 45 cases presenting to the emergency departments of two hospitals in eastern Turkey. Data were collected using a Sociodemographic Data Form, the Rumination Scale, and the Suicide Probability Scale. Descriptive statistics, Pearson correlation, independent samples t-test, and Linear Regression analysis were used for data analysis. Results: Of the participants, 66.7% were male and 44.4% were in the 18–23 age group. A positive and moderately significant relationship was found between rumination and suicide probability (r = 0.441; p = 0.001). Regression analysis revealed that rumination explained 34% of the variance in the suicide probability. Furthermore, suicide probability scores of those using non-alcohol or multiple substances were significantly higher than those using only alcohol (p = 0.025). Conclusions: Ruminative thinking is a significant associated factor of suicide risk in patients with alcohol and substance use disorders presenting to the emergency department. It is recommended that cognitive assessments of these patients be conducted during clinical processes and that multiple-substance users, in particular, should be closely monitored for suicide risk.

Journal of Clinical Medicine doi: 10.3390/jcm15124804

Authors: Yeon Joo Lee Sung Woo Moon

Background/Objectives: In February 2024, a nationwide medical crisis in South Korea caused a massive withdrawal of resident physicians. We described changes in patient characteristics and early clinical outcomes among emergency department (ED)-admitted inpatients during this disruption. Methods: We retrospectively analyzed 8149 internal medicine admissions via the ED at a tertiary hospital, 6 months pre- and post-crisis. Multivariable logistic regression evaluated early clinical outcomes, adjusting for baseline confounders. Results: Post-crisis, the internal medicine physician workforce decreased by 36%. Total admissions dropped, while patient acuity increased. After adjustment, the post-crisis group exhibited higher odds of Orders for Life-Sustaining Treatment documentation (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.34–1.74), inter-hospital transfers (aOR 1.71, 95% CI 1.49–1.96), and 48 h mortality (aOR 1.81, 95% CI 1.25–2.61). However, adjusted overall in-hospital mortality did not significantly differ (aOR 1.10, 95% CI 0.95–1.27). Conclusions: The crisis led to decreased admissions and higher patient acuity. Despite these shifts, adjusted in-hospital mortality did not significantly differ. This suggests that during severe workforce shortages, acute care was concentrated on a highly selected, high-acuity patient cohort, accompanied by an increased reliance on inter-hospital transfers.

Journal of Clinical Medicine doi: 10.3390/jcm15124803

Authors: Mehmet Mutlu Kidi Harun Muğlu Mustafa Karaağaç Sinan Koca Oguz Kara Ahmet Bilici Ertugrul Bayram

Background: Soft tissue sarcomas (STS) disproportionately affect older adults, yet patients aged ≥65 years remain markedly underrepresented in pivotal trials, limiting evidence on pazopanib in this population. We aimed to characterise the real-world efficacy and safety of pazopanib in elderly patients with advanced STS. Methods: This multicentre retrospective cohort study included consecutive patients aged ≥65 years with locally advanced unresectable or metastatic STS who received pazopanib between July 2010 and June 2022 at four tertiary Turkish oncology centres. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and the safety profile. Results: A total of 109 patients (median age, 70 years; 50.5% female; 48.6% with Eastern Cooperative Oncology Group [ECOG] performance status ≥ 2) were analysed. The objective response rate was 11.0% (95% CI, 5.8–18.4), and the disease control rate was 45.9%. Median PFS was 4.11 months (95% CI, 3.25–4.47), and median OS was 7.85 months (95% CI, 6.91–9.00) over a median follow-up of 17.6 months. PFS showed a borderline difference across age tertiles (log-rank p = 0.078), whereas a marked monotonic OS gradient was observed (9.00, 7.86, and 5.71 months for ages 65–69, 70–74, and ≥75 years, respectively; p < 0.001). In age-stratified multivariable Cox analysis, ECOG ≥ 2 (adjusted hazard ratio [aHR], 1.68; 95% CI, 1.01–2.80; p = 0.045) and female sex (aHR, 1.66; 95% CI, 1.02–2.72; p = 0.043) were independently associated with shorter OS. Grade ≥ 3 treatment-emergent adverse events occurred in 27.5% of patients, most commonly hypertension. Because only the single most clinically prominent treatment-emergent adverse event per patient was recorded, these figures represent a conservative, non-cumulative estimate of toxicity. No treatment-related deaths occurred. Conclusions: Pazopanib retains clinically meaningful activity in unselected patients aged ≥65 years with advanced STS. Performance status, rather than chronological age, is the dominant predictor of overall survival and should guide treatment decisions in this population.

Journal of Clinical Medicine doi: 10.3390/jcm15124802

Authors: Kim Sarah Fritz Paul C. Helm Dominik Tobias Janina Semmler Jannos Siaplaouras Christian Apitz Constanze Pfitzer

Background: Congenital heart defects (CHD) are the most common congenital malformations and often require complex, lifelong pharmacotherapy. In pediatric CHD populations, multidrug regimens targeting cardiac function and comorbidities predispose patients to polypharmacy. At the molecular level, concomitant drug use increases the risk of pharmacokinetic and pharmacodynamic interactions. Methods: This study aimed to characterize medication patterns and assess polypharmacy and potential drug–drug interactions in patients with CHD. A cross-sectional online survey was conducted in collaboration with the German National Register for Congenital Heart Defects (NRCHD) between November and December 2021. Patients aged 6–17 years with CHD were eligible for inclusion. Participants reported their current medications in open-ended questions. Drugs were categorized into pharmacological classes, and common drug combinations were evaluated for potential interactions. Results: Of 894 participants included in the analysis, 372 reported current medication use. Among these, 179 (48.1%) met criteria for polypharmacy (≥2 drugs). Polypharmacy was more frequent in patients with higher disease severity and comorbidity burden. Several drug combinations showed potential for clinically relevant pharmacokinetic and pharmacodynamic interactions, including mechanisms involving renal electrolyte handling, altered protein binding, cytochrome P450-mediated metabolism, and additive pharmacodynamic effects. Conclusions: Children with CHD are exposed to complex multidrug regimens with a considerable interaction risk, underscoring the need for systematic medication review and mechanistically informed pharmacological management in pediatric CHD care.

Journal of Clinical Medicine doi: 10.3390/jcm15124800

Authors: Dina A. Akhmedzyanova Yuliya F. Shumskaya Kristina V. Charaya Yuriy A. Vasilev Anton V. Vladzymyrskyy Yulya A. Alymova Ivan A. Blokhin Roman V. Reshetnikov Irina V. Kuprina Olga V. Taschyan Marta V. Yurazh Marina G. Mnatsakanyan

Background: Telemedicine is increasingly used in inflammatory bowel disease (IBD), but its effects on quality of life (QoL) and psychological outcomes remain unclear. Objectives: This study aimed to evaluate the impact of 6-month telemonitoring on QoL, disease activity, treatment adherence, psychological well-being, patient satisfaction, and healthcare utilization. Methods: This randomized, open-label, single-center study conducted in Russia (July 2023–December 2024) included adults with ulcerative colitis or Crohn’s disease, who were assigned 1:1 to telemonitoring or standard care. The intervention involved monthly remote assessments and access to a web-based platform containing educational information, disease activity assessment, and a chat with a gastroenterologist. The primary outcome was health-related QoL (SIBDQ). Exploratory outcomes included general QoL (WHOQOL-26), psychological well-being (HADS), alexithymia (TAS-26), visceral sensitivity (VSI), treatment adherence (GMAS), patient satisfaction (PSQ-18), achievement of clinical remission, and healthcare utilization. Results: Sixty-eight patients completed the study (32 intervention, 36 control). Telemonitoring was associated with lower anxiety levels (β = −1.76, p = 0.021), reduced visceral sensitivity (β = −5.08, p = 0.039), and higher medication adherence (β = 1.75, p = 0.008). No significant associations were observed for SIBDQ, WHOQOL-26 domains, depressive symptoms, alexithymia, achievement of clinical remission, or patient satisfaction with care (p > 0.05). Patients in the telemonitoring group also required fewer outpatient visits (p < 0.001), with no difference in hospitalizations. Within-group analysis demonstrated improvements in QoL, treatment adherence, visceral sensitivity, and disease activity in the telemonitoring group, but not in the controls. Conclusions: Six-month telemonitoring in IBD was associated with lower anxiety, reduced visceral sensitivity, improved treatment adherence, and fewer outpatient visits. The health-related QoL assessed by the SIBDQ did not differ compared to standard care. No clear clinical disadvantage compared with standard care was detected during the study period.

Journal of Clinical Medicine doi: 10.3390/jcm15124801

Authors: Marcin Jadczak Michał Kaczmarczyk Paweł Rozbicki Dariusz Jurkiewicz Sandra Krzywdzińska

Background: Correct performance of rhinoseptoplasty often requires osteotomy, the effectiveness and safety of which depend on precise knowledge of nasal anatomy, particularly the shape, length, and thickness of the nasal bones. Aim: The aim of this study was to assess the morphometry of the nasal bone and nasal pyramid in adult patients based on three-dimensional computed tomography (CT) using Slicer 3D software. Materials and Methods: A retrospective analysis was performed on data from 87 patients (44 women and 43 men; mean age 50.64 SD ±16.7 years) who underwent head CT between 1 January 2024 and 31 December 2025 because of trauma (to exclude intracranial hemorrhage) or dizziness (to diagnose central causes). Results: The comparative analysis demonstrated statistically significant differences in the dimensions of the nasal bony structures between women and men, with women showing lower values for all assessed parameters. For point 1L, the mean value was 6.29 in women compared with 8.07 in men (p = 0.0056). For point 4L, the values were 2.07 vs. 2.55, respectively (p = 0.009), whereas for point 5L they were 1.52 vs. 1.66 (p = 0.01). A similar relationship was also noted on the right side: for point 1R, the values were 5.95 vs. 8.02 (p = 0.03), and for point 5R they were 1.54 vs. 1.89 (p = 0.03), confirming consistently smaller dimensions of the bony structures in women in the analyzed study group. Conclusions: The obtained results may have important practical significance in planning osteotomy during rhinoseptoplasty procedures, enabling a more precise and safer surgical procedure.

Journal of Clinical Medicine doi: 10.3390/jcm15124799

Authors: Alexandru-Ionut Irimie Sorin-Nicolae Dinescu Marius-Bogdan Novac Ramona-Constantina Vasile Alexandra-Daniela Rotaru-Zavaleanu Mihai-Andrei Ruscu Lucretiu Radu

Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in whom immunosenescence may alter the leukocyte phenotype, remains poorly characterized. Methods. In a single-center retrospective cohort of patients aged ≥65 years admitted to a tertiary ICU with Sepsis-3-defined sepsis (n = 127, 33 deaths), we compared the discrimination of six indices (NLR, PLR, MLR, SII, SIRI, AISI) for 30-day all-cause mortality using AUROC with bootstrap confidence intervals and pairwise DeLong tests. Independent associations were assessed by logistic regression adjusted for APACHE II and age; incremental value over APACHE II was explored using IDI, cNRI, calibration and decision curve analysis, with bootstrap optimism correction. Results. Thirty-day mortality was 26.0%. The monocyte-containing indices (AISI, SIRI, MLR) discriminated better than SII and NLR, and AISI was significantly superior to SII, NLR and PLR on DeLong testing, though not to SIRI, MLR or APACHE II. After adjustment for APACHE II and age, AISI, SIRI and MLR remained independently associated with mortality, whereas SII and PLR did not. Adding AISI to APACHE II improved reclassification and calibration and yielded higher net clinical benefit across clinically relevant thresholds. Conclusions. In this exploratory, single-center analysis, monocyte-containing indices, particularly AISI, were more strongly associated with 30-day mortality in elderly ICU sepsis than SII or NLR. AISI, SIRI and MLR were strongly intercorrelated and near-equivalent, and AISI did not significantly exceed APACHE II in discrimination. These hypothesis-generating findings require prospective external validation before clinical use.

Journal of Clinical Medicine doi: 10.3390/jcm15124797

Authors: Nikolaos Tsetsos

Chronic rhinosinusitis (CRS) constitutes a multicausal inflammatory disease of the nose and paranasal sinuses, often associated with olfactory dysfunction (OD), a symptom that significantly impacts patients’ quality of life. OD in CRS was traditionally thought to be related to mechanical obstruction of the olfactory cleft, but is now considered to be multifactorial, involving conductive, inflammatory, and sensorineural mechanisms as well. Type-2 inflammatory response (high interleukins IL-4, IL-5, IL-13), eosinophilia, and increased IgE are involved in epithelial damage, impaired neurogenesis, and persistent olfactory loss, especially in chronic rhinosinusitis with nasal polyps (CRSwNP). In addition, peripheral chronic inflammation may also play a role in central neural remodeling, which may potentially affect olfactory function. Objective psychophysical testing is necessary to accurately assess olfactory function because self-reports may lack reliability. Management strategies aim at reducing inflammation and restoring sinonasal ventilation. First-line therapy with intranasal corticosteroids and short courses of systemic corticosteroids may be useful for symptomatic relief. Biologic agents directed against type-2 inflammation have demonstrated significant benefits in selected cases. Functional Endoscopic Sinus Surgery (FESS) plays an important role in the treatment of refractory CRS to restore the airflow and to improve the delivery of topical drugs. Olfactory outcomes following surgery, however, are variable and often incomplete, reflecting underlying inflammation and neuroepithelial damage. Disease recurrence, especially in type-2–driven CRS, affects long-term outcomes, underscoring the necessity to incorporate surgery in an individualized, endotype-informed treatment strategy.

Journal of Clinical Medicine doi: 10.3390/jcm15124798

Authors: Manapat Praditaukrit Anucha Thatrimontrichai Praew Chareesri Pattima Pakhathirathien Gunlawadee Maneenil Supaporn Dissaneevate

Background/Objectives: Preterm (<37 weeks) and very preterm (<32 weeks) infants face considerably higher mortality and morbidity rates than full-term infants. We compared clinical outcomes between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) preterm infants. Methods: This retrospective cohort study used a prospectively collected database, obtained from 2014 to 2025. Propensity score matching (PSM), multivariate regression, and subgroup analyses of very preterm infants were performed to minimize confounding. Results: Among the 5890 neonatal admissions, 2331 preterm infants met the inclusion criteria. After PSM, 298 SGA and 298 AGA preterm infants were analyzed. Multivariate analysis showed that SGA preterm infants had significantly higher risks of the composite outcome of mortality or major morbidity (adjusted risk ratio [aRR], 1.89; 95% confidence interval [CI], 1.18–3.02), mortality (aRR, 3.53; 95% CI, 1.57–7.95), and mortality or moderate-to-severe bronchopulmonary dysplasia (aRR, 2.13; 95% CI, 1.30–3.48). In the subgroup analysis after PSM, 190 very preterm infants showed similar results, with SGA infants having increased risks of the composite outcome of mortality or major morbidity (aRR, 1.81; 95% CI, 1.02–3.23), mortality (aRR, 3.23; 95% CI, 1.09–9.62), mortality or moderate-to-severe bronchopulmonary dysplasia (aRR, 2.03; 95% CI, 1.10–3.72), and mortality or treated retinopathy of prematurity (aRR, 2.62; 95% CI, 1.03–6.65). Conclusions: SGA status is associated with a higher risk of mortality and major morbidity in preterm and very preterm infants. In resource-limited settings, the focused management of SGA infants is critical to improving short- and long-term outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124796

Authors: Mario Pinzi Alessandro Cuomo Pietro Carmellini Claudia Libri Maria B. Rescalli Caterina Pierini Alessia Santangelo Benjamin Patrizio Andrea Fagiolini

Background: Treatment-resistant obsessive–compulsive disorder (TR-OCD) remains a major therapeutic challenge. Although current guidelines recommend optimized serotonin reuptake inhibitor (SRI) therapy, clomipramine switching, exposure and response prevention, and antipsychotic augmentation, a substantial proportion of patients continue to experience severe and disabling symptoms. In such cases, clinicians may consider pharmacological intensification strategies beyond guideline-endorsed algorithms. Methods: This study combines a structured narrative synthesis of pharmacological strategies for TR-OCD with a retrospective observational case series from a tertiary OCD referral clinic. Treatment resistance was defined as failure to achieve at least a 35% reduction in Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score after at least two adequate SRI trials, including clomipramine, and optimized exposure and response prevention when available. Five patients treated with pharmacological intensification strategies were included. The primary outcome was percentage change in Y-BOCS score at 12 weeks. Results: The case series illustrates five strategies used in highly refractory OCD: supratherapeutic SSRI dosing, SSRI plus mirtazapine augmentation, dual SSRI therapy, serotonergic intensification in a clozapine-treated patient, and glutamatergic/GABAergic augmentation with topiramate. Baseline Y-BOCS scores ranged from 28 to 32. At 12 weeks, symptom reduction ranged from 23% to 36%. One patient met criteria for response, three showed near-response, and one demonstrated partial improvement. No cases of serotonin toxicity or clinically significant cardiac complications occurred. Conclusions: These cases suggest that carefully monitored pharmacological intensification may be feasible in selected specialist settings, but efficacy and safety require confirmation in prospective controlled studies. Recommendations: Pharmacological intensification should be reserved for highly refractory patients managed in specialist services, implemented with gradual titration, structured serotonin toxicity and electrocardiographic monitoring, and explicit individualized risk–benefit discussion; dual SSRI therapy should be regarded as the most experimental and highest-risk serotonergic option; and prospective controlled studies incorporating standardized functional outcomes are needed to refine patient-selection criteria and clarify which patients may benefit.

Journal of Clinical Medicine doi: 10.3390/jcm15124795

Authors: Yang Yang Zheng Liu Jing Zhang

Background/Objectives: Weight loss achieved through lifestyle interventions has been demonstrated to improve the clinical prognosis of female hyperandrogenism. However, the interplay between such interventions, androgens, and glucose–lipid metabolism remains heterogeneous. This study evaluated the effects of lifestyle-induced weight loss on glucose and lipid metabolism and androgen levels in Chinese women of reproductive age with hyperandrogenism and examined the association between the degree of weight loss and changes in androgen levels, glucose and lipid metabolism, exercise capacity, and dietary patterns. Methods: This observational study, based on real-world clinical settings, collected medical records of women of reproductive age with hyperandrogenism who underwent weight-loss interventions between July 2023 and September 2025. Correlation analysis employed Spearman’s rank correlation coefficient, whilst pre- and post-weight-loss comparisons utilised paired t-tests or Wilcoxon signed-rank tests. Results: After a follow-up of 6 to 7 months, a total of 66 participants achieved a mean weight loss of 5.67 ± 4.27 kg. Statistically significant reductions were observed in testosterone (0.40 ± 0.10 vs. 0.30 ± 0.10 ng/mL, p < 0.001), androstenedione (p < 0.001), and the free androgen index (p < 0.001). Glucose metabolism showed statistically significant improvement, with decreases in HOMA-IR (p = 0.040), fasting glucose (p = 0.001), and fasting/2 h postprandial insulin (p < 0.001). However, lipid profiles showed no statistically significant changes. Multiple linear regression revealed that change in testosterone was independently and inversely associated with change in apolipoprotein A1 (β = −0.496, p = 0.008), while change in dehydroepiandrosterone sulfate was inversely associated with change in fasting insulin (β = −0.357, p = 0.032). A non-linear, inverted U-shaped relationship was found between weight loss magnitude and change in sex hormone-binding globulin, with moderate weight loss (5–10%) yielding the greatest increase (p = 0.044). Marked weight loss (≥10%) was associated with the lowest follow-up fasting insulin levels (p = 0.039). Conclusions: Weight loss achieved through lifestyle interventions is associated with improvements in androgen levels and glucose metabolism, though its impact on lipid metabolism remains limited. The degree of improvement in insulin sensitivity correlates more strongly with the magnitude of weight reduction.

Journal of Clinical Medicine doi: 10.3390/jcm15124794

Authors: Li Tian Xuan Qiu Qiqi Cheng Jun Shen Suqing Wang

Objectives: To determine the prognostic value of the triglyceride-glucose (TyG) index, which serves as a surrogate for insulin resistance, for heart failure rehospitalization and all-cause mortality in older adults with chronic heart failure, and to evaluate its clinical utility in risk stratification and nursing care. Methods: In this single-center retrospective cohort study, 786 patients aged ≥65 years with chronic heart failure hospitalized at a tertiary referral hospital in Central China (January 2022–January 2025) were included and divided into low vs. high TyG index groups based on the median. Baseline data were extracted from medical records. Follow-up ended in December 2025. Associations between TyG index and adverse outcomes were examined using Kaplan–Meier curves, restricted cubic spline (RCS) regression, and multivariable Cox proportional hazards models. Results: The median TyG index was 8.35. In unadjusted analyses, the high-TyG group had significantly greater cumulative risks of heart failure rehospitalization (p < 0.001) and all-cause mortality (p = 0.028). After multivariable adjustment, the TyG index remained independently associated with heart failure rehospitalization (hazard ratio [HR]= 1.63), whereas its association with all-cause mortality was attenuated and no longer significant. Restricted cubic spline analysis revealed a nonlinear dose–response relationship between the TyG index and heart failure rehospitalization, and a linear relationship with all-cause mortality. Conclusions: In elderly patients with chronic heart failure, the TyG index independently predicted heart failure rehospitalization and demonstrated a nonlinear dose–response relationship; its independent association with all-cause mortality was not significant after full adjustment. The index may nonetheless aid in risk stratification and individualized nursing in this population.

Journal of Clinical Medicine doi: 10.3390/jcm15124793

Authors: Nikolaos Stalikas Marios G. Bantidos Efstratios Karagiannidis Athina Nasoufidou Sara Corradetti Anthony Kechichian Christos Kofos Maria Fasoula Matthaios Didagelos Marios Sagris Barbara Fyntanidou Antonios Ziakas Theodoros Karamitsos Georgios Giannopoulos

Background: The triglyceride–glucose (TyG) index has emerged as a simple surrogate marker of insulin resistance and metabolic disruption. In the context of ST-elevation myocardial infarction (STEMI), such disturbances have been associated with adverse cardiovascular outcomes, more complex angiographic profiles, and microvascular complications. However, data on the association between TyG and intracoronary thrombus burden (TB) in STEMI remain limited. Methods: In this prospective observational study, we included consecutive STEMI patients treated with primary percutaneous coronary intervention (pPCI). The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TB was graded according to the modified thrombolysis in myocardial infarction (mTIMI) thrombus classification score after restoration of antegrade flow with a wire or small balloon when the culprit vessel was initially totally occluded. Patients were categorized as low-TB (LTB; mTIMI grades 1–3) and high-TB (HTB; mTIMI grade 4). The primary outcome was HTB; secondary outcomes were distal embolization and no-reflow. Associations between TyG and outcomes were assessed using univariable and multivariable logistic regression, restricted cubic spline analysis, and receiver operating characteristic (ROC) curves to evaluate incremental predictive value. Results: A total of 309 patients were analyzed. The TyG index was significantly higher in the HTB group compared with the LTB group (9.12 ± 0.62 vs. 8.92 ± 0.64, p = 0.004). In a stepwise multivariable model, TyG remained independently associated with HTB (adjusted odds ratio = 1.61; 95% confidence interval: 1.11–2.37; p = 0.014). Adding TyG to a baseline clinical model only numerically improved discrimination for HTB, as reflected by a small increase in ROC area under the curve. Restricted cubic spline analysis demonstrated a monotonic rise in the probability of HTB with higher TyG values. Higher TyG also showed non-significant trends toward increased odds of distal embolization and no-reflow. Conclusions: The TyG index was independently associated with HTB in STEMI patients undergoing pPCI and may serve as an accessible adjunctive marker for incremental risk stratification beyond conventional clinical and angiographic factors.

Journal of Clinical Medicine doi: 10.3390/jcm15124791

Authors: Xifang Zhang Shuang Liu Jing Guo Shuai Yang Tengteng Yao Yuheng Zhang Zhaoyang Wang

Objectives: We aimed to descriptively evaluate the feasibility and clinical utility of TowardPi BO (4K ultra-HD microscope integrated with a 400 kHz swept-source intraoperative optical coherence tomography (SS-iOCT) system) in managing various ophthalmic surgical conditions in a real-world setting. Methods: We analyzed surgical videos and data from 123 consecutive cases that underwent elective surgery with the assistance of this SS-iOCT system at Beijing Tongren Hospital between 2 September 2025 and 10 February 2026. Cases were included when the iOCT provided critical, real-time information that directly influenced surgical decision-making or technique modification. Cases were excluded if iOCT served only routine confirmatory or educational purposes without altering the surgical plan. Results: A total of 72 surgical cases were included, comprising 7 intraocular lens implantations with ciliary sulcus fixation, 19 macular holes, 3 cases of macular hole retinal detachment (MHRD), 4 cases of macular schisis with or without foveal detachment (MSRD), 12 cases of submacular hemorrhage, 20 cases of rhegmatogenous retinal detachment (RRD), and 7 intraocular mass lesions. The 400 kHz SS-iOCT significantly aided in surgical visualization, guided real-time decision-making, and prompted modifications in surgical techniques. Conclusions: To our knowledge, this is the first real-world study to evaluate the application of a 400 kHz SS-iOCT system across a wide spectrum of ophthalmic conditions, including its novel use in intraocular tumors. From routine to complex surgical cases, SS-iOCT enhances surgical precision and facilitates real-time decision-making, ultimately contributing to improved surgical outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124792

Authors: Giuseppe Neri Giuseppe Mazza Helenia Mastrangelo Jessica Ielapi Federico Longhini Vincenzo Bosco Alessandro Russo Francesca Serapide Isabella Aquila Matteo Antonio Sacco Zaninni Caroleo Andrea Bruni Eugenio Garofalo

Background/Objectives: Adult patients supported with extracorporeal membrane oxygenation (ECMO) frequently require invasive diagnostic, therapeutic, surgical, or bedside procedures during ongoing extracorporeal support. These procedures are clinically challenging because ECMO-related anticoagulation, platelet dysfunction, acquired coagulopathy, and circuit-related coagulation activation may increase both bleeding and thrombotic risks. This systematic review evaluated the safety of invasive procedures performed during adult ECMO support, excluding tracheostomy/tracheotomy because this procedure has recently been addressed in a dedicated systematic review. Methods: A systematic search of PubMed/MEDLINE and Scopus was performed. The final bibliographic data collection was completed in April 2026. Studies were eligible if they included adult ECMO or extracorporeal life support patients undergoing invasive procedures during ongoing ECMO support, or with ECMO used as procedural support, and reported at least one procedure-specific safety outcome. Primary outcomes were procedure-related complications, bleeding, major bleeding, and transfusion requirements. Secondary outcomes included thrombotic and circuit-related complications, oxygenator exchange, reintervention, reoperation, procedural failure, ECMO duration, intensive care unit and hospital length of stay, and mortality. Results: The final qualitative synthesis included 46 studies, comprising 26 studies from PubMed/MEDLINE and 20 additional unique studies from Scopus. Included procedures were grouped into six domains: airway, bronchoscopic, and tracheobronchial procedures; thoracic surgery and lung resections; abdominal surgery, gastrointestinal endoscopy, and decompressive laparotomy; lung transplantation and perioperative extracorporeal life support; cardiovascular, vascular, pulmonary embolism-related, and mechanical circulatory support-related procedures; and mixed non-cardiac surgery. Airway and bronchoscopic procedures generally showed high procedural success in selected cohorts, although registry-level tracheal procedure data reported hemorrhagic complications in 26.0% and surgical-site bleeding in 13.0%. Emergency thoracic and abdominal procedures carried the highest bleeding, transfusion, reintervention, and mortality burden. Lung transplantation studies showed that ECMO can be integrated into perioperative pathways, but hemothorax, transfusion, thromboembolism, and anticoagulation strategy remained central safety issues. Conclusions: Invasive procedures during adult ECMO are feasible in selected patients and experienced centers, but procedural safety varies markedly by procedure type, urgency, baseline disease severity, and anticoagulation strategy. A procedure-centered, multidisciplinary approach with individualized anticoagulation management and careful planning is essential.

Journal of Clinical Medicine doi: 10.3390/jcm15124790

Authors: Amir Mahdi Ghafarian Ali Samani Jawad Saad Mohammad Ghafarian Muaaz Wajahath Sarah Foster Seungwon Lim Aliyah Sutton Faddi G. Saleh Velez Denise Battaglini Andrea Loggini

Background: Stroke significantly increases morbidity and mortality in patients receiving extracorporeal membrane oxygenation (ECMO). This study evaluates the prognostic impact of stroke subtypes, acute ischemic stroke (AIS) and hemorrhagic stroke (HS), and neurologic injury severity in a contemporary adult population. Methods: We conducted a retrospective cohort study using the TriNetX federated electronic health record network, including adult patients who underwent ECMO between 1 October 2015 and 31 December 2025. Stroke was defined as a first-instance diagnosis of AIS, HS, or unspecified cerebrovascular event occurring within 24 h of ECMO cannulation during the index hospitalization. Propensity score matching (1:1 nearest neighbor) was performed to balance baseline demographics, comorbidities, anticoagulant use, and ECMO modality between the stroke and non-stroke cohorts. Primary outcomes included all-cause mortality at 30 days, 90 days, and 1 year. Secondary outcomes included cardiac arrest, seizures, palliative care utilization, and hospital readmission. Kaplan–Meier survival analysis and multivariable Cox proportional hazards modeling were performed. Results: Among 18,981 ECMO patients, 1481 (7.8%) developed a stroke within 24 h of ECMO cannulation, including 814 AIS (54.9%), 454 HS (30.6%), and 213 unspecified cerebrovascular events (14.4%). After propensity score matching, stroke was associated with significantly higher all-cause mortality at 30 days (RR 1.16), 90 days (RR 1.18), and 1 year (RR 1.18), all p < 0.05. Stroke was also associated with higher rates of cardiac arrest, seizures, hospital readmission, and palliative care utilization (all p < 0.001). AIS was associated with significantly lower mortality than HS at 30 days, 90 days, and 1 year (all p < 0.0001). In multivariable Cox regression, only HS was independently associated with increased 30-day mortality compared with no stroke. Markers of neurologic injury severity, including cerebral edema, brain compression, and coma, were among the strongest independent predictors of mortality. Conclusions: Stroke occurring early after ECMO cannulation is associated with substantially worse short- and long-term survival, with hemorrhagic subtype and markers of neurologic injury severity driving the strongest prognostic signals. These findings support early stroke recognition and subtype-informed prognostic discussions in ECMO patients.

Journal of Clinical Medicine doi: 10.3390/jcm15124789

Authors: Yong Ahn Han-Byeol Park Sung-Ho Do Sojung Lee

Background: Radiculopathy originating from a previously fused lumbar segment is a clinically relevant but often underrecognized problem. Progressive foraminal stenosis may develop due to postoperative structural changes, leading to mechanical irritation of the exiting nerve root. Transforaminal endoscopic lumbar foraminotomy (TELF) is a minimally invasive option, but its role in this setting is not well defined. Methods: In this retrospective cohort study, we included 36 consecutive patients who underwent TELF for symptomatic foraminal stenosis at a previously fused segment between 2020 and 2023. Clinical outcomes were assessed using the visual analog scale (VAS) for leg pain, Oswestry Disability Index (ODI), and modified MacNab criteria, with follow-up of up to 2 years. Radiographic and intraoperative findings were reviewed to explore the underlying mechanisms. Results: The mean VAS score improved significantly from 8.36 preoperatively to 2.00 at 2 years, and the mean ODI decreased from 70.9% to 16.8%. According to the modified MacNab criteria, 86.1% of the patients achieved excellent or good outcomes. Intraoperative findings revealed fibrotic or hypertrophic foraminal stenosis in 86.1% patients (n = 31), whereas 13.9% of patients (n = 5) showed pedicle screw-related nerve root irritation. Five patients experienced transient postoperative dysesthesia, and no postoperative instability was observed. Conclusions: Radiculopathy at the fused segment is primarily caused by progressive mechanical foraminal compromise after fusion. TELF provides effective symptom relief through direct decompression and may serve as a less invasive alternative to revision fusion in selected patients.

Journal of Clinical Medicine doi: 10.3390/jcm15124788

Authors: Nerea Escandell Marí Marta Sánchez-Ric Marina Velez Sabela Carballal Leticia Moreira

Background: Gastric cancer is a major global health concern. Although sex- and gender-based differences have been described, they are not yet well established, and the available evidence is often inconsistent. This systematic review aims to explore these differences in the incidence, clinicopathological characteristics, risk factors, treatment, and survival of gastric cancer, thereby contributing to healthcare equity. Methods: A systematic search was conducted in the main medical bibliographic databases (PubMed, Embase and Web of Science) in February 2026 following the PRISMA 2020 guidelines. Studies on gastric cancer were selected based on predefined inclusion and exclusion criteria. The results were synthesized qualitatively according to incidence, clinicopathological characteristics, risk factors, treatment outcomes, and survival. Due to the heterogeneity and predominantly observational design of the included studies, no meta-analysis or formal risk-of-bias assessment was conducted. Results: A total of 38 studies, involving more than 500,000 participants, were included. Most reported a higher incidence of gastric cancer in men, with a predominance of intestinal and well-differentiated tumors, while diffuse and poorly differentiated tumors were more common in women. Men showed higher rates of smoking, alcohol consumption, and postoperative complications. Overall survival tended to be higher in women, especially in early stages, although some studies described worse outcomes among young women. Conclusions: This review highlights relevant sex- and gender-related differences in gastric cancer and underscores the need to systematically incorporate these variables into future research to advance towards more personalized medicine. The available evidence was limited by the predominance of retrospective observational studies and heterogeneity across study designs and reported outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124787

Authors: Louise D’Argent Eline Vandenabeele Olivier Hoogmartens Didier Desruelles Nathalie Charlier Marc Sabbe

Background/Objectives: This prospective, randomised controlled trial aimed to evaluate whether using a real-time feedback device during basic life support (BLS) training for laypersons improves chest compression quality immediately after training and at the four-month follow-up. Methods: Participants were randomly assigned to a control group (standard BLS training) or an intervention group (BLS training with a real-time feedback device). All participants completed a standardised 2-h BLS course, followed by a 4-min practical assessment immediately after training and at the four-month follow-up. The primary outcomes were chest compression rate and depth, while the secondary outcomes were correct hand position, full chest recoil and flow fraction. These compression parameters were compared within and between groups at both time points. Results: Data from 101 participants were analysed. Both groups showed significantly decreased mean and adequate compression rates over time, but only the intervention group demonstrated significantly better performance at follow-up. The mean compression depth was approximately 5 cm in both groups; however, the proportion of adequate compression depth was low and did not differ significantly within or between groups. Correct hand position was consistently higher in the intervention group across both assessments. Full chest recoil improved in both groups, whereas flow fraction increased only in the control group. Conclusions: Incorporating real-time feedback devices into layperson BLS training leads to superior performance in selected chest compression parameters, particularly compression rate and hand position. Therefore, real-time feedback devices can be a valuable adjunct to standard BLS training to enhance skill retention over time.

Journal of Clinical Medicine doi: 10.3390/jcm15124786

Authors: Crhistian-Mario Oblitas María Luz Alonso-Alonso Antonio J. Mosqueira Manuel Rodríguez-Yáñez Iria López-Dequidt Francisco Campos Tomás Sobrino José Castillo Pablo Hervella Ramón Iglesias-Rey

Background: Following a stroke, body and brain temperatures are closely linked. Elevated temperature may reflect the severity of brain injury rather than infection. The significance of admission temperature remains unclear, and hypothermia treatment lacks proven efficacy and safety. Administering paracetamol (acetaminophen) above 36.5 °C is considered safe, though its clinical benefit is modest. This study aimed to examine how admission temperature, peak temperature in the first 24 h, and temperature fluctuations affect three-month functional outcomes. Methods: We conducted a retrospective study using data from a prospective stroke registry, including 5883 patients (4830 with ischemic stroke [IS] and 1053 with hemorrhagic stroke [HS]). Temperature at admission, maximum temperature within the first 24 h, and the temperature increase during the first day were assessed. Patients with a temperature ≥ 37.5 °C received 3 g of paracetamol per day until normothermia was achieved. Results: Baseline temperature was not associated with 3-month functional outcomes. In IS patients, an increasing temperature during the first 24 h was associated with a 10-fold higher risk of poor functional outcome (sensitivity 81%, specificity 64%); whereas in HS, the risk increased sevenfold (sensitivity 88%, specificity 53%). The most reliable predictor of therapeutic response was the temperature increase on the first day, with sensitivities of 89% and 83%, and specificities of 84% and 71%, for IS and HS, respectively. Conclusions: An increase in temperature during the first 24 h, rather than a single measurement, is the most reliable temperature-based biomarker for predicting poor functional outcomes and guiding the initiation of antihyperthermic treatment.

Journal of Clinical Medicine doi: 10.3390/jcm15124785

Authors: Yooha Hong Mi-Kyoung Kang Soo-Jin Cho

Background/Objective: Medication overuse headache (MOH) is a disabling secondary headache disorder that arises from an underlying primary headache, most commonly migraine. Although treatment reduces headache frequency and medication overuse, the interictal burden—the impact experienced between headache attacks—remains poorly characterized over the long term. This study evaluated interictal burden and clinical outcomes two years after MOH diagnosis. Methods: This study was derived from a prospective multicenter cohort of patients with MOH, using data from a single center. Of 149 patients enrolled between April 2020 and November 2022, 117 (78.5%) completed the two-year follow-up. Clinical characteristics, medication overuse, monthly headache days, and standardized questionnaires were assessed at baseline and follow-up. Interictal burden was evaluated at two years using the Migraine Interictal Burden Scale (MIBS-4), with scores ≥5 indicating severe burden. Results: At baseline, patients (81.2% female; median age, 45.0 years) reported a median of 16.0 monthly medication days (interquartile range, 13.0–23.0). Medication overuse decreased from 100% at baseline to 24.2% at one year and 17.1% at two years. Among 117 patients with available two-year MIBS-4 data, 25 (21.4%) had severe interictal burden. Compared with those without severe burden, these patients had greater headache-related impact and disability (HIT-6: 68.0 vs. 64.0, p = 0.019; MIDAS: 110.0 vs. 36.0, p = 0.002), higher psychological burden (PHQ-9: 11.0 vs. 8.0, p = 0.032; GAD-7: 7.0 vs. 4.0, p = 0.010), and were more likely to be current smokers (20.0% vs. 4.3%, p = 0.036). Notably, 14.4% of patients with resolved medication overuse still reported severe interictal burden. Conclusions: Two years after MOH diagnosis, severe interictal burden was observed in a substantial proportion of patients and was associated with greater baseline disability and psychological distress. These findings highlight the need for long-term monitoring and management beyond initial medication withdrawal.

Journal of Clinical Medicine doi: 10.3390/jcm15124784

Authors: Gülçin Babaoğlu Ali Çoştu Ülkü Sabuncu Şükriye Dadalı Nevcihan Şahutoğlu Bal Şaziye Şahin Erkan Yavuz Akçaboy

Background/Objectives: Peripheral pulsed radiofrequency (PRF) is a minimally invasive option for trigeminal neuralgia (TN) with a favorable safety profile compared with neurorestorative techniques, but its durability and recurrence patterns remain uncertain. This study evaluated the early effectiveness, durability, recurrence-free survival, and safety of peripheral PRF in refractory classical or idiopathic TN. Methods: This retrospective single-center cohort study assessed procedure-level outcomes of peripheral PRF targeting the ophthalmic, maxillary, and mandibular branches. Pain intensity and clinical status were evaluated using the Numeric Rating Scale (NRS) and Barrow Neurological Institute (BNI) pain score. Early effectiveness was defined as clinically meaningful pain relief sustained for at least 1 month, and sustained effectiveness as NRS ≤ 3 at 6 months. Recurrence-free survival was analyzed using Kaplan–Meier methods. Results: A total of 68 procedures in 57 patients were analyzed. Early effectiveness at 1 month was achieved in 85.3% of procedures. Median NRS decreased from 9 (IQR 8–9) at baseline to 2 (0–4) at 1 month and 0 (0–2) at 3 and 6 months (p < 0.001). In a worst-case analysis, 6-month sustained effectiveness was 72.1%. Recurrence occurred in 61.8% of procedures, with a median recurrence-free survival of 11 months. Among procedures with recurrence, repeat peripheral PRF was performed in 45.2%. Medication requirements decreased in 66.2% of procedures, and no major complications occurred. Conclusions: Peripheral PRF provides rapid and meaningful early pain relief in TN, but durability is limited. These findings support peripheral PRF as a safe, repeatable neuromodulatory intervention within a staged treatment strategy rather than a definitive therapy.

Journal of Clinical Medicine doi: 10.3390/jcm15124783

Authors: Davide Negrini Laura Pighi Simone Mignolli Gian Luca Salvagno Giuseppe Lippi

Background/Objectives: Iron deficiency remains a prevalent condition, needing specific laboratory tests for diagnosis. This study aimed to evaluate whether routine complete blood cell count (CBC) parameters can be used within a machine learning framework to predict low ferritin and low transferrin saturation, used as biochemical markers of altered iron status, potentially supporting more targeted laboratory test utilization. Methods: In this single-center retrospective outpatient study, we analyzed 32,437 records from subjects undergoing both complete blood cell count and iron metabolism testing between 2023 and 2026. Low ferritin and low transferrin saturation were defined using sex-specific thresholds. Low ferritin was present in 14,344 subjects (44.2%), whereas low transferrin saturation was present in 7791 subjects (24.0%). After cleaning data and excluding incomplete records, demographic variables and CBC indices were tested as potential predictors. The dataset was split into training and test sets with stratified sampling. Multiple supervised machine learning models, including logistic regression, decision tree, random forest, XGBoost, support vector machine, k-nearest neighbors, and Naive Bayes, were trained. Hyperparameter tuning and model selection were performed using repeated stratified 10-fold cross-validation, optimizing the area under the curve (AUC). Model performance was assessed by AUC, sensitivity, and specificity, and validated on an independent test set. Results: All models showed predictive capability for low ferritin and low transferrin saturation using CBC parameters alone. Ensemble methods, especially random forest and XGBoost, reached the best performance (AUC values of 0.80–0.87 for ferritin and 0.85–0.96 for transferrin saturation). Sensitivity and specificity were balanced, supporting clinical screening applicability. Results were maintained across validation and confirmed in the test set. Prediction of transferrin saturation showed slightly higher accuracy than ferritin. Feature importance analysis identified mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red blood cell distribution width (RDW) as key predictors. Conclusions: CBC-based machine learning models may help identify subjects with low ferritin or low transferrin saturation, supporting subsequent targeted assessment of iron status.

Journal of Clinical Medicine doi: 10.3390/jcm15124782

Authors: Anson B. Rosenfeldt Elizabeth Claire Weyman Heller Eric Zimmerman Sara Davidson John Gardner Grant Alberts Benjamin Broz Jordan Klein Louie Sutte Emily Hopkins Jay L. Alberts

Background/Objectives: Falls have devastating consequences for older adults. The Functional Ambulation and Stair Test (FAST) was developed to characterize older adult mobility and eventual fall risk. This project aimed to determine the criterion validity of the FAST assessment by comparing the relationship between FAST outcomes and existing gold-standard clinical assessments of mobility and fall risk. A secondary aim was assessing the FAST’s capacity to elicit dual-task effects in older adults. Methods: The FAST is a multi-faceted mobility assessment combining stair navigation, turning and level-ground walking; total time and time spent in each phase are the calculated outcomes. Data from 199 older adults completing the FAST, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Ten Meter Walk Test (10MWT) at comfortable and fast speed were evaluated. Relationships between the FAST and clinical outcomes were evaluated with Spearman’s correlations. The FAST and TUG were assessed under single- and dual-task conditions; linear mixed models evaluated the dual-task effects for overall FAST time and each phase. Results: Spearman’s correlations between the FAST and the BBS, TUG, 10MWT comfortable and 10MWT fast were −0.65, 0.88, −0.79, and −0.83, respectively. Participants experienced an 8.6% and 13.2% dual-task cost in the FAST and TUG, respectively. The greatest dual-task cost during the FAST was in the gait initiation, walking, and wide turn phases. Conclusions: Agreement between the FAST and gold-standard clinical mobility assessments confirms the criterion validity of the FAST. Delineation of mobility phases via the FAST offers insight into specific mobility deficits. Future work is ongoing to evaluate the FAST as a fall risk assessment in older adults.

Journal of Clinical Medicine doi: 10.3390/jcm15124781

Authors: Ibrahim K. Altami Eyad A. Alabdulrahim Osamah M. Alfayez

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes and obesity treatment and may influence reward-related behaviors, including alcohol use. This study aimed to evaluate the effects of GLP-1RAs on alcohol consumption and related outcomes in adults with alcohol use or alcohol use disorder (AUD). Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed and Web of Science were searched from inception to December 2025. Eligible studies included randomized controlled trials (RCTs), secondary analyses of RCTs, and observational studies reporting quantitative alcohol consumption outcomes. Data extraction and risk of bias assessment (RoB 2 and ROBINS-I) were performed independently by two reviewers. Results: Five studies (n = 49,892) were included, comprising three RCT-based analyses and one large cohort study. Semaglutide and dulaglutide were associated with modest reductions in alcohol consumption and craving in several studies, with statistically significant improvements in selected behavioral outcomes. In contrast, exenatide did not demonstrate significant effects in the overall AUD population, with signals limited to subgroups. The cohort study showed small but statistically significant reductions in AUDIT-C scores following GLP-1RA initiation. Objective measures (e.g., PEth, breath alcohol concentration) showed reductions in selected contexts but were reported in a few studies. Conclusions: GLP-1RAs may be associated with modest reductions in alcohol consumption, but evidence remains limited and heterogeneous. Larger, well-designed RCTs are needed to define their role in the management of AUD.

Journal of Clinical Medicine doi: 10.3390/jcm15124780

Authors: Anahita Dua Naseer Ahmad Cyaandi R. Dove Matthew J. Regulski Sara Rose-Sauld Matthew G. Garoufalis

Background/Objectives: Chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) remain a major source of morbidity, healthcare utilization, and limb loss, despite adherence to established standards of care protocols and the widespread availability of advanced wound technologies. Many advanced modalities only target isolated aspects of wound healing and fail to address the complex, interdependent pathophysiology of chronic wounds, particularly tissue hypoxia, edema, impaired microcirculation, and persistent inflammation. Cyclical Pressurized Topical Wound Oxygen (TWO2) therapy is a home-based, multimodal intervention that combines humidified topical oxygen delivery with cyclical non-contact compression to address these core drivers simultaneously. Methods: This review synthesizes mechanistic rationale and evidence from randomized controlled trials, long-term venous ulcer studies, and real-world comparative effectiveness analyses. Emphasis is placed on the large cohort study by Yellin et al., which directly compared TWO2 with other advanced modalities including negative pressure wound therapy (NPWT), skin substitutes, and growth factor therapies. Results: Across these studies, TWO2 therapy is consistently associated with improved healing durability, reduced recurrence, and substantial reductions in hospitalization and amputation rates compared with both standard care and advanced wound therapies. Conclusions: The convergence of randomized and real-world evidence supports TWO2 therapy as a clinically meaningful and mechanism-driven adjunctive treatment option for patients with chronic, high-risk lower-extremity wounds.

Journal of Clinical Medicine doi: 10.3390/jcm15124778

Authors: Claudia Lommatzsch Antoine Capucci Swaantje Grisanti Carsten Heinz Kai Rothaus

Background/Objectives: Optical coherence tomography (OCT) and OCT angiography (OCT-A) provide detailed measurements of retinal structure and vasculature; however, age-related differences in how these parameters correlate with one another remain poorly understood. We hypothesized that vascular–structural integration in the macula is more pronounced in adults than in children. Our aim was to characterize correlation patterns in pediatric and adult populations to inform the development of age-specific clinical interpretation guidelines. Methods: This prospective cross-sectional observational study enrolled 37 healthy children (age 1–17 years) and 28 healthy adults (age 18–65 years). Eyes with ocular or systemic conditions affecting the retina or prior intraocular surgery were excluded. Standardized OCT and OCT-A acquisition protocols provided structural and vascular measures. Univariable correlation analyses applied a stringent threshold (p < 0.001) to identify robust associations. Significant univariable results were entered into multivariable regression models adjusting for age, gender, intraocular pressure, and axial length. A Group-wise Linkage Proportion quantified the percentage of potential significant correlations among eight predefined anatomical parameter groups. Results: Ninety univariable correlations met p < 0.001. Fourteen correlations were shared across age groups, notably foveal avascular zone metrics and vessel density, showing very large negative correlations (r = −0.70 to −0.87). The pediatric cohort displayed 40 unique correlations, primarily linking optic nerve head flow indices to retinal nerve fiber layer thickness. Adults exhibited 36 unique correlations, dominated by macular vascular–thickness coupling concentrated in the parafoveal region. After multivariable adjustment, 52 of 90 associations remained significant. Adult-specific associations lost significance more frequently (58%) than pediatric-specific associations (43%), whereas correlations shared across both groups showed complete stability (100%). The Group-wise Linkage Proportion indicated pronounced macular vascular–structural coupling in adults (48.4%) versus near absence in children (1.2%). Conclusions: Retinal parameter correlation patterns show fundamental differences between pediatric and adult eyes. While optic nerve head-macular thickness relationships remain consistent across ages, adults exhibit mature, localized integration of macular vascular and structural parameters absent in children. These findings suggest that pediatric and adult OCT/OCT-A measurements may benefit from separate reference standards, although prospective validation is required before clinical implementation.

Journal of Clinical Medicine doi: 10.3390/jcm15124779

Authors: Sung-Hoon Jung Sung-Goo Kang Sang-Wook Song Se-Hong Kim Dongjin Nam Junseung Rho

Background: The deep learning-derived retinal cardiovascular risk index (Reti-CVD) is a deep learning-derived retinal biomarker calculated from non-mydriatic fundus photographs for cardiovascular risk assessment. This study examined whether obesity phenotype, particularly central adiposity, modifies the association between Reti-CVD and coronary artery calcium score (CACS) in asymptomatic adults undergoing routine health screening. Methods: We retrospectively analyzed 237 Korean adults who underwent fundus photography for Reti-CVD assessment and cardiac computed tomography for CACS measurement. Abdominal obesity was defined as waist circumference (WC) ≥ 90 cm in men and ≥85 cm in women, and general obesity as body mass index (BMI) ≥ 25 kg/m2. Multivariable linear regression models with sequential adjustment were used to evaluate the association between Reti-CVD and CACS. Effect modification was assessed using interaction terms for Reti-CVD×WC and Reti-CVD×BMI. Discriminatory performance for coronary calcification, defined as CACS > 0, was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Abdominal obesity was present in 78 participants (32.9%), and general obesity in 102 (43.0%). Participants with CACS > 0 had significantly higher Reti-CVD scores than those with CACS = 0 (0.15 ± 0.09 vs. 0.09 ± 0.05; p < 0.001). Reti-CVD remained positively associated with CACS after adjustment for metabolic and lifestyle factors. In fully adjusted models, WC significantly moderated this association (interaction p = 0.0288), whereas BMI did not (interaction p = 0.5381). Overall discrimination for CACS > 0 was moderate (AUC = 0.735) and numerically higher in participants with abdominal obesity than in those with normal WC (0.787 vs. 0.695). Conclusions: Reti-CVD is independently associated with coronary calcification, and WC-based central adiposity modifies this relationship. Incorporating obesity phenotype may improve personalized interpretation of retinal biomarker-based cardiovascular risk assessment.

Journal of Clinical Medicine doi: 10.3390/jcm15124777

Authors: Agnieszka Lach Wiktoria Jędrzejak Patrycja Loba Maria Depczyńska Zuzanna Radziszewska Dobrochna Stachecka Maciej Wilczak Karolina Chmaj-Wierzchowska

Background: Uterine fibroids are among the most common benign tumors affecting women of reproductive age and may substantially impair health-related quality of life (HRQL). Although anxiety and stress are frequently reported by affected women, their contribution to HRQL remains unclear. This study aimed to evaluate the relationships between symptom severity, anxiety, stress, and HRQL in women with uterine fibroids. Methods: A cross-sectional study was conducted among 107 women hospitalized for uterine fibroid treatment. Symptom severity and HRQL were assessed using the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire. Anxiety and information needs were evaluated using the Amsterdam Preoperative Anxiety and Information Scale (APAIS), while subjective anxiety and stress levels were measured with the Visual Analog Scale (VAS). Associations between variables were analyzed using non-parametric tests, Spearman’s correlations, and multiple regression analysis. Results: Clinically significant anxiety was observed in 41.1% of participants. The mean HRQL score was 57.4 ± 22.3 points. In multivariate analysis, symptom severity was the only independent predictor of HRQL (β = −0.67, p < 0.001), explaining approximately 45% of its variance. Anxiety, stress, and sociodemographic factors were not independently associated with overall HRQL. However, higher levels of anxiety and stress were significantly associated with poorer sexual functioning. Women living in rural areas and those with higher body weight reported poorer outcomes in selected quality-of-life domains. Conclusions: Symptom severity is the primary determinant of HRQL in women with uterine fibroids. Although anxiety and stress do not independently predict overall quality of life, they may adversely affect sexual functioning. These findings support a comprehensive management approach that combines symptom-oriented treatment with psychological and educational support.

Journal of Clinical Medicine doi: 10.3390/jcm15124776

Authors: Zeljko Stepanovic Branko Ristic Aleksandar Matic Nikola Prodanovic Jelena Milosevic Ivan Stojadinovic Nikola Andric Tijana Prodanovic Bojan Milenkovic Dragan Knezevic Djordje M. Kolak

Background: The optimal route of tranexamic acid (TXA) administration remains one of the most debated topics in total knee arthroplasty. This study aimed to compare the effects of intravenous (IV), intra-articular (IA), and combined TXA protocols on total blood loss (TBL) and hidden blood loss (HBL), while identifying independent predictors of perioperative bleeding. Methods: In a prospective cohort study of 245 patients undergoing primary TKA, participants were assigned into four groups: IV TXA (15 mg/kg), IA TXA (1 g), combined (IV + IA), and a control group. TBL and HBL were calculated using the Gross formula. A multivariate linear regression model was used to assess independent associations of each protocol. Results: The IV group demonstrated significantly lower TBL (mean 898 mL) and HBL (mean 568 mL) compared with both the control (1329 mL and 894 mL; p = 0.002) and IA groups (1129 mL and 748 mL; p = 0.008). While IA TXA reduced 24 h drain output (p < 0.001), it did not significantly reduce TBL (p = 0.539) or HBL (p = 0.875). No significant differences were found between the IV-only and combined groups (p > 0.05). Multivariate regression identified the IV route as an independent predictor of reduced TBL (B = −383.7, p = 0.001). Conclusion: A single intravenous dose of TXA was associated with lower total and hidden blood loss compared with intra-articular administration. The lack of additional benefit in the combined group suggests a possible plateau effect of systemic administration, which is hypothesis-generating and limited by the study design for blood conservation in TKA. Level of Evidence: Level II, Prospective Cohort Study.

Journal of Clinical Medicine doi: 10.3390/jcm15124775

Authors: Fausto Zamparini Andrea Spinelli Gioia Quadrini Maria Giovanna Gandolfi Carlo Prati

Background: The objective was to synthesize and critically appraise systematic reviews with meta-analysis evaluating the association between irrigation, instrumentation, and obturation procedures and post-operative endodontic pain. Methods: An umbrella review was conducted following PRISMA guidelines. Electronic searches identified systematic reviews published between 2016 and 2025. Eligible studies are systematic reviews that include meta-analyses, published in English and correlating the presence of post-operative pain in 3 different critical stages of root canal treatments, namely irrigation, instrumentation and obturation. Methodological quality was assessed using the AMSTAR 2 tool. Outcomes included pain prevalence and intensity at different time points. Results: Out of 368 records, 25 systematic reviews with meta-analysis met the inclusion criteria: 9 on irrigation, 8 on instrumentation, and 8 on obturation. NaOCl concentrations, irrigant activation, and intracanal cryotherapy were repeatedly reported as being associated with reduced short-term post-operative pain. For instrumentation, most reviews reported lower pain with rotary systems, but two studies found no difference or favored reciprocating kinematics. Apical patency did not appear to increase pain and foraminal enlargement may increase early pain. No clinically consistent differences were observed between bioceramic/calcium silicate-based and resin-based sealers, although calcium silicate sealers seem to support periapical healing. However, the certainty of these findings was limited by heterogeneity, methodological weaknesses, and overlap among primary studies. Methodological limitations were identified across reviews, mainly related to no protocol registration (n = 4), incomplete reporting of excluded studies with justification (n = 11), limited assessment of publication bias, and poor reporting of funding sources for primary studies. Conclusions: Based on current evidence, irrigation, instrumentation, and obturation procedures may influence short-term post-operative pain. However, these findings remain tentative because of heterogeneity, methodological weaknesses, variable review quality, and overlap among primary studies. Further high-quality reviews and clinical trials are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15124774

Authors: Argyro Pachi Ioannis Ilias Athanasios Tselebis

Sleep is not a passive state of rest but a biologically active process essential for cognitive function, immune regulation, emotional homeostasis, and metabolic integrity [...]

Journal of Clinical Medicine doi: 10.3390/jcm15124772

Authors: Vedat Gençer Yavuz Sultan Selim Akgül Burcu Eren Cengiz İsmail Altıntop

Background: Chronic kidney disease (CKD) accelerates biological aging and amplifies the risk of adverse geriatric outcomes. Albuminuria reflects systemic endothelial dysfunction beyond renal damage, yet its specific relationship with falls, fear of falling, and frailty in predialysis CKD patients remains underexplored. Objectives: We aimed to evaluate the association between albuminuria levels (urinary albumin-to-creatinine ratio, ACR) with falls, fear of falling (Falls Efficacy Scale, FES), and frailty (FRAIL scale and Clinical Frailty Scale, CFS) in older adults with CKD. Methods: This cross-sectional study analyzed 295 patients aged ≥60 years attending nephrology and geriatrics clinics at Kayseri City Hospital, Turkey (April–June 2025). ACR was categorized per KDIGO (A1: <30, A2: 30–300, A3: ≥300 mg/g). Inflammatory indices (NLR, SII, CAR) were calculated. Hierarchical multivariable logistic regression and ROC analyses were performed. Results: Fall prevalence showed a clear dose-response across ACR categories: 31.2% (A1), 72.0% (A2), and 93.2% (A3) (p < 0.001). In the fully adjusted model, each unit increase in log-ACR was associated with a 3.84-fold increase in fall odds (OR 3.84, 95% CI 2.74–6.65). Although bivariate ACR-frailty associations were non-significant, fully adjusted models uncovered independent associations across both instruments and thresholds: FRAIL ≥ 3 (OR 1.41, 95% CI 1.05–2.03), FRAIL ≥ 2 (OR 1.49, 95% CI 1.08–2.21), CFS ≥ 5 (OR 1.87, 95% CI 1.38–2.83), and CFS ≥ 4 (OR 1.37, 95% CI 1.02–1.93). ACR showed good discriminative ability for falls (AUC 0.773, optimal cut-off 21.70 mg/g) but poor discrimination for frailty (AUC 0.50–0.54). The ACR–fall association was stronger in patients with GFR < 60 (OR 4.48) than GFR ≥ 60 (OR 2.18). Conclusions: Albuminuria is a strong, independent, and graded predictor of falls in older CKD patients, with a nearly 4-fold increase in risk per log-unit ACR increase after full adjustment. ACR measurement, already routine in CKD monitoring, could help identify older patients at increased fall risk and guide targeted geriatric assessment. However, ACR showed poor standalone discriminative ability for frailty across all definitions (AUC 0.50–0.54), establishing that it cannot serve as a frailty screening tool in isolation.

Journal of Clinical Medicine doi: 10.3390/jcm15124773

Authors: Samet Yavuz Şahhan Kilic Suha Asal Mert Babaoglu Cumaali Demirtaş Mehmet Yildirim Servet Altay Ahmet Lütfullah Orhan

Objective: Sodium–glucose cotransporter 2 (SGLT2) inhibitors, particularly empagliflozin, have attracted considerable attention because of their cardiovascular benefits beyond glycemic control. However, the interaction between empagliflozin and exercise-induced physiological cardiac remodeling in healthy individuals remains insufficiently understood. This study investigated the effects of different swimming exercise protocols (anaerobic, aerobic, and endurance), administered alone or in combination with empagliflozin, on cardiac structure and electrophysiology. Methods: Thirty-six male Sprague–Dawley rats were randomly assigned to six groups (n = 6 per group): anaerobic (An), aerobic (Ae), endurance (En), and the corresponding exercise groups combined with empagliflozin (An + Empa, Ae + Empa, and En + Empa). Empagliflozin was administered by oral gavage at a dose of 15 mg/kg/day for 30 days. Transthoracic echocardiography, electrocardiography (ECG), and gastrocnemius electromyography were performed at baseline and at the end of the study to assess cardiac remodeling, heart rate, and neuromuscular function. The study was carried out over a 30-day intervention period following ethics committee approval on 24 July 2024. Results: No significant between-group differences were observed in echocardiographic parameters before the intervention. On day 30, significant differences were identified among the groups in interventricular septal thickness at end-diastole (IVSd) (p = 0.027), left ventricular internal diameter at end-diastole (LVIDd) (p = 0.009), and end-diastolic volume (EDV) (p = 0.014). Bonferroni-corrected post hoc analysis showed that the aerobic exercise plus empagliflozin group differed from several exercise-only groups, particularly in parameters related to ventricular size and filling volume, including LVIDd and EDV (p < 0.008). On day 30, electrocardiographic repolarization-related parameters, including QT, QTc, JT, and Tpeak–Tend intervals, also differed significantly among the groups (all p < 0.05). In post hoc analysis, the anaerobic exercise group showed significant differences in QT and JT intervals compared with the aerobic and endurance groups (p < 0.008). In the anaerobic protocol, empagliflozin was associated with a reduction in heart rate compared with the corresponding control group (p = 0.019). No significant between-group differences were observed in EMG findings. Conclusions: Different exercise protocols induce distinct patterns of adaptation in cardiac structure and electrophysiology in healthy rats. Empagliflozin (15 mg/kg/day) may modulate exercise-induced cardiac responses in a modality-dependent manner; the most pronounced echocardiographic effects were observed in the aerobic protocol, whereas the effect on heart rate was observed in the anaerobic protocol. These findings highlight the need for longer-term and mechanistic studies to further clarify the effects of SGLT2 inhibitors on physiological cardiac remodeling.

Journal of Clinical Medicine doi: 10.3390/jcm15124771

Authors: Andrea Fabbri Ayca Begum Tascioglu Flavio Bertini Barbara Benazzi Roberto Martello Danilo Montesi

Background: Healthcare-associated bloodstream infections (HABSIs) are among the main categories of nosocomial infections. This analysis aims to identify the clinical characteristics of patients in the emergency department (ED) who will develop a HABSI during their hospital stay. Methods: Main outcome measures were HABSI and the cumulative survival rate at 30 days. The features tested in a logistic model were age, sex, vitals by the National Early Warning Score (NEWS), priority levels, main complaints, comorbidities by the Charlson Comorbidity Index (CCI), trauma-related disease, main diagnosis and ED length of stay. Results: In 414 (2.3%) out of 18,304 patients, aged 75 (16) years, mean (SD), a diagnosis of HABSI was recorded. HABSIs occurred in subjects with main diagnosis of diseases of the respiratory system (N = 116; 28.0%), digestive system (N = 72; 17.4%), and circulatory system (N = 68; 16.4%). The main key clinical features selected by the logistic model were: NEWS > 6, diagnosis of neoplasms, CCI > 4, and diagnosis of diseases of the digestive system. The ROC curve for the HABSI risk score was 0.703 ± 0.027 in predicting the outcome, (sensitivity 79%, specificity 51%, at optimal cut-off score). The overall hazard mortality risk was twofold higher in patients with HABSIs (hazard ratio: 2.319; 95% confidence interval: 1.871–2.875; p-value: <0.001). The overall 30-day survival rate was lower among patients with HABSIs (33%) vs. non-HABSI patients (62%). Conclusions: A group of main clinical features in subjects without suspect of infectious disease in the ED are associated with HABSIs. These features negatively impact survival rate during hospital stays.

Journal of Clinical Medicine doi: 10.3390/jcm15124770

Authors: Marcin Majos Artur Klepaczko Katarzyna Szychowska Weronika Banasik Ludomir Stefanczyk Ilona Kurnatowska

Introduction: Currently, chronic kidney disease (CKD) is detected based on glomerular filtration rate (GFR), proteinuria levels or kidney biopsy. However, the development of MRI techniques and AI algorithms gives hope to the assessment of CKD activity and kidney function with profound MRI image analysis. Methods: MRI images from healthy volunteers with no history of CKD were compared with those from CKD patients who had undergone both kidney MRI and kidney biopsy; the latter group was also divided into two subgroups based on CKD histopathological activity. Patients from both groups were scanned using either a 1.5 T or 3 T MRI scanner following sequential allocation (nine healthy controls and 28 CKD patients and 11 healthy volunteers and 43 CKD patients respectively for each scanner). Results: The final algorithm based on T1-weighted, T2-weighted and DWI images was able to distinguish patients with sensitivity ranging 77.78–87.50%, specificity 86.67–94.12% and precision 77.78–87.50%. Features of T1-weighted images and of T2-weighted images were found to correlate strongly with GFR with coefficients ranging from −0.5922 to −0.7090 and from 0.6126 to 0.6380, respectively. Conclusions: MRI image texture analysis may be suitable for assessing CKD activity, irrespective of the type of MRI scanner used. Furthermore, MRI image texture features correlate with eGFR values.

Journal of Clinical Medicine doi: 10.3390/jcm15124769

Authors: Adeolu Banjoko Nina Harris Sara Mousavi Stella Wang Ella Huszti Zachary M. Ferraro Claire Ann Jones

Background/Objectives: Shift work is a form of circadian dysregulation, which has been associated with adverse reproductive health outcomes. However, the association between circadian dysregulation and ovarian reserve remains uncertain. The present study examines whether shift work is associated with lower AMH levels in women seeking fertility treatment. Methods: This retrospective cohort study includes female patients aged 20–39 years presenting between February 2023 and June 2024. Patients were excluded if they had only one ovary, a current cancer diagnosis, or past chemotherapy use. Demographic and medical data were obtained from the electronic medical record. AMH levels were compared between daytime workers and shift workers. Results: A total of 1135 patients met inclusion criteria. The median age was 35 years (IQR 32–37). Of these, 89% (n = 1014) reported daytime work, and 11% (n = 121) reported shift work, comprising 102 working rotating shifts, seven working night shifts, and 12 working evening shifts. Daytime-only workers had a median AMH of 17.20 pmol/L (9.1–30.0). Combined shift workers had a median AMH of 17.10 pmol/L (8.1–31.0). There was no statistically significant difference in AMH levels between daytime workers and shift workers (p = 0.935). Although not significant, the odds of having low AMH levels (<7 pmol/L) were 25% higher among shift workers compared to daytime workers (OR 1.246, p = 0.345). Conclusions: In this cohort, AMH levels did not significantly differ between daytime and shift workers, offering reassurance to individuals required to engage in shift work. Future research should include larger cohorts and incorporate more comprehensive measures of circadian disruption.

Journal of Clinical Medicine doi: 10.3390/jcm15124767

Authors: Carlos López-Moreno Javier Conde-Pipó Antonio Martínez-Amat Alexander Achalandabaso-Ochoa

Background: Non-specific neck pain is associated with altered muscle mechanical properties, including increased stiffness. Radial extracorporeal shockwave therapy (rESWT) and orthopedic manual therapy (OMT) are commonly used interventions, although their combined effects on cervical muscle stiffness remain unclear. This study aimed to evaluate the short-term and within-session effects of adding rESWT to OMT on cervical muscle stiffness measured by means of shear wave elastography (SWE) in individuals with non-specific neck pain. Methods: A randomized controlled trial was conducted including 24 participants (mean age 34.36 years) allocated to an intervention group (IG, n = 12) or a control group (CG, n = 12). The IG received a combined protocol of rESWT (1500 impulses per point at 10 Hz, 2–4 bar) and OMT based on the Maitland concept, while the CG received OMT alone. Primary outcomes included cervical muscle stiffness assessed via SWE expressed in meters per second (m/s) and kilopascals (kPa). Secondary outcomes were pain intensity (VAS), pressure pain threshold (PPT), cervical range of motion (ROM), and shoulder elevation strength (SES). Treatment effects were estimated using ANCOVA adjusted for baseline values. Results: The combined intervention was associated with greater reductions in cervical muscle stiffness compared with the control group, with significant decreases in SWE values (m/s: β = −1.27, p < 0.001; kPa: β = −27.97, p < 0.001). Pain intensity was also reduced (β = −2.12, p = 0.012), while PPT increased (β = 18.84, p = 0.024). Improvements were observed in cervical extension ROM (β = 10.30, p = 0.014) and right SES (β = 3.85, p = 0.044). No significant differences were found for other ROM variables or left SES. Conclusions: The addition of rESWT to OMT was associated with greater short-term improvements in cervical muscle stiffness, pain intensity, and mechanical sensitivity compared with OMT alone in individuals with non-specific neck pain. However, these findings should be interpreted with caution due to the study limitations.

Journal of Clinical Medicine doi: 10.3390/jcm15124768

Authors: Mary Fronrath Carolyn Martz Kristin Griebe Michael Veve Zachary R. Smith

Introduction: Intravenous push (IVP) beta-lactam antibiotics have been adopted during parenteral solution shortages to conserve resources. Data evaluating the safety and efficacy of cefepime administered IVP versus intravenous piggyback (IVPB) infusion in Gram-negative bacteremia remain limited. We compared clinical outcomes of cefepime administered IVP versus IVPB in hospitalized patients with Gram-negative bacteremia. Methods: This was a retrospective cohort study across a five-hospital health system from 1 January 2014 through 31 December 2021. Adults receiving cefepime for Gram-negative bacteremia were included. The primary outcome was a tailored desirability of outcome ranking (DOOR) composite assessed through 30 days or hospital discharge, integrating clinical cure and cefepime-associated neurologic adverse effects. Clinical cure was defined as absence of recurrent bacteremia with the index pathogen after 48 h, no antibiotic escalation, and no in-hospital mortality. Results: A total of 254 met the inclusion criteria (127 IVPB; 127 IVP). Baseline severity was similar between groups. The primary outcome assessed by DOOR revealed no difference between IVPB and IVP groups (p = 0.656). Vasopressor support during therapy was more frequent in the IVP group (22.0% vs. 10.2%, p = 0.011), and median hospital length of stay was longer (10 vs. 7 days, p = 0.020). No differences were noted in other endpoints. General ward admission (OIR [aOR] 2.563, 95% CI 1.271–5.168; p = 0.009) and genitourinary source of bacteremia (aOR 3.398, 95% CI 1.509–7.652; p = 0.003) independently predicted clinical cure. Conclusions: In patients with Gram-negative bacteremia, cefepime administered IVP demonstrated similar safety and efficacy to IVPB infusion.

Journal of Clinical Medicine doi: 10.3390/jcm15124766

Authors: Valentina Blažinčić Anđela Grgić Kristina Kralik Ivica Ščurić Ivana Klepo Duško Cerovec

Background: In patients with traumatic brain injury (TBI), proteins are considered the main source of energy. Previous studies have suggested that an increase in the urea-to-creatinine ratio (UCR) indicates the onset of protein catabolism. Therefore, we aimed to investigate the associations of the UCR with the functional independence measure (FIM). Methods: This single-center retrospective study included 291 patients aged 17–87 years who underwent inpatient rehabilitation within the first 6 months post-TBI. Their demographic, clinical, neuroradiological, and laboratory data (eGFR, urea, creatinine, UCR) were collected. Spearman’s correlation and hierarchical multivariate regression analyses adjusted for clinical covariates were performed. Results: The strongest significant positive correlation was found between the Glasgow Coma Scale (GCS) and FIM at admission (ρ = 0.488, p < 0.001) and between GCS and FIM at discharge (ρ = 0.340, p < 0.001). A significant negative correlation was found between the discharge UCR and FIM at discharge (ρ = −0.262, p < 0.003), as well as with the change in FIM (ρ = −0.207, p < 0.02). Patients with UCRs ≥ 80 had a significantly lower discharge FIM compared to patients with UCRs < 80 (median 27 vs. 40; p = 0.02). The significant independent predictors of discharge FIM were the nutritional route (NGT/PEG), level of consciousness, and FIM at admission. The UCR did not remain independently associated with the discharge FIM (ΔR2 = 0.004, Cohen’s f2 = 0.014). Conclusions: Although UCR is associated with functional outcomes measured by FIM in TBI patients, it is not an independent predictor of these outcomes but rather a biomarker of catabolic burden.

Journal of Clinical Medicine doi: 10.3390/jcm15124765

Authors: Filippo Randelli Francesco Manzini Alberto Fioruzzi Jacopo Menini Giuseppe Fedele Clemente Caria

Background: Intraoperative periprosthetic proximal femoral fractures (PPFFs) represent a significant complication during total hip arthroplasty (THA), especially when using cementless stems via a direct anterior approach (DAA). Methods: This retrospective case series evaluated 10 patients with Vancouver A2 PPFFs treated with 2.7 mm lag screws alone or in combination with plates during DAA THA or partial hip arthroplasty between January 2021 and March 2024. Results: All fractures healed. One patient experienced 1 cm of stem subsidence without the need for revision. The mean Harris Hip Score improved from 35.4 preoperatively to 85.6 postoperatively. Functional recovery and radiological stability were comparable between fixation methods, though the screw-only group experienced slightly more postoperative pain. Patients in the screw-and-plate group were significantly older than those in the screw-only group (p = 0.026). No significant differences were found between groups regarding surgical time (p = 0.62) or BMI (p = 0.82). Due to the limited number of subsidence events, the statistical comparison of subsidence rates was inconclusive. Conclusions: In this preliminary retrospective case series, the use of 2.7 mm lag screws and small locking plates appeared feasible and was associated with favorable short-term outcomes in selected Vancouver A2 intraoperative PPFFs during DAA. These findings are hypothesis-generating and require confirmation in larger, prospective comparative studies.

Journal of Clinical Medicine doi: 10.3390/jcm15124764

Authors: Lenche Neloska Katerina Damevska Ordanche Ribarski Predrag Kovacevic

Background: In elderly patients with hypoalbuminaemia, hypoproteinaemia and advanced-stage PUs, chronic inflammation and wound-related protein loss contribute to a self-perpetuating circulus vitiosus, in which protein depletion drives deterioration of tissue repair processes, and in turn, ongoing wound-related catabolism further amplifies systemic protein loss. In this context, reduced serum albumin and total protein represent integrated indicators of systemic inflammatory and catabolic burden associated with delayed wound healing. Aim: This study evaluated the association between individualized nutritional replacement therapy and pressure ulcer healing in malnourished geriatric and palliative patients, using serum albumin, total protein, and PUSH score as longitudinal outcome indicators. Methods: A total of 78 malnourished geriatric and palliative patients with PUs, multiple comorbidities, and poor nutritional status (hypoalbuminemia and/or hypoproteinaemia) receiving patient-tailored nutritional replacement therapy participated in this study. PU assessment using the PUSH version 3.0 tool, as well as measurements of serum albumin and total protein concentrations, were performed on days 0, 30, 60, and 90. Results: Our study demonstrates significant improvement in the serum albumin levels, from 30.2 ± 6.19 at baseline to 42.1 ± 5.59 at day 90. Similarly, total protein concentrations increased from 57.8 ± 9.66 at baseline to 70.6 ± 7.03 at day 90. The improvement in protein status was accompanied by a significant reduction in the PUSH score, from 10.9 ± 2.94 at the first assessment to 2.9 ± 2.63 at the final assessment. Spearman’s rank-order correlation analysis between serum albumin, total protein, and PUSH score demonstrated a significant moderate inverse correlation at later assessment points (day 60 and 90). Conclusions: Individualized and targeted replacement therapy was associated with improved protein status and reduced pressure ulcer severity. Increases in serum albumin and total protein paralleled a marked reduction in PUSH scores, suggesting attenuation of the inflammatory-catabolic circulus vitiosus and a progressive shift toward wound healing in geriatric and palliative patients.

Journal of Clinical Medicine doi: 10.3390/jcm15124763

Authors: Ling Zhu Kim Chai Chua Daobo Wang Daniel Kanasa Arvin Wesley Karu Oriana Ng Noah Tapaua Yeow Leng Chua

Background/Objectives: Papua New Guinea has a population of over 10 million, with its public cardiac surgical service provided by only one tertiary center. Despite the climbing burden of ischemic heart disease, no CABG operation has been performed before 2025 due to limited local surgical capacity. An international collaboration was planned in order to launch a CABG program in the country. Methods: Three cases were shortlisted after a multidisciplinary team discussion. A team-based “On-the-job” mentoring strategy was employed to facilitate skill transfer. The operation was carried out in a “twinning” fashion, with each role of the surgical team being taken up by “a pair”—the trainer (visiting team) and the learner (local team). The trainer demonstrated key skills and tips in the first case, and the “pair” switched positions in the following cases to maximize hands-on learning. The last case was performed entirely by the local team. Results: Three patients underwent CABG operations in this pilot program. A total of 2.33 grafts/case were performed on average, with no 30-day mortality. There were no major complications except for one patient developing right middle cerebral artery infarct on postoperative day 5. The patient was discharged one month later after achieving functional recovery and was started on anticoagulation therapy. Conclusions: International collaborations with strategic planning can play a critical role in starting new cardiac surgical programs in low–middle-income countries, with acceptable surgical outcomes. History has been made with the first-ever CABG operation successfully performed in Papua New Guinea. The journey ahead to sustain local cardiac surgical capacity and to provide safe and accessible cardiac surgical care for the country remains challenging.

Journal of Clinical Medicine doi: 10.3390/jcm15124762

Authors: Kwannapas Saengsin Noraworn Jirattikanwong Pakpoom Wongyikul Phichayut Phinyo Thirasak Borisuthipandit Rekwan Sittiwangkul Suchaya Silvilairat Krit Makonkawkeyoon Saviga Sethasathien Tin Ayurag Nateewit Wiwatkamonchai Kanokkarn Sunkonkit

Background/Objectives: Post-extubation stridor (PES) is common in pediatric critical care and may contribute to extubation failure, particularly in children with heart disease. Prophylactic corticosteroids are frequently used before extubation, but their benefit in pediatric cardiac patients remains uncertain. We evaluated the association of prophylactic corticosteroids with PES and extubation failure and explored whether PES mediated any association with failure. Methods: We performed a retrospective, single-center, observational cohort study of extubation events in a pediatric cardiac critical care unit from July 2016 to June 2024. Exposure was prophylactic intravenous corticosteroids before planned extubation, most commonly dexamethasone (0.15–0.5 mg/kg per dose) or methylprednisolone (1–2 mg/kg per dose), administered 6–24 h before extubation in single- or multi-dose regimens. The primary outcome was clinically defined PES; the secondary outcome was extubation failure, defined as reintubation within 48 h. Confounding was addressed using propensity scores with inverse-probability weighting after common-support restriction. Causal interpretation of the weighted and mediation estimates was considered conditional on the no-unmeasured-confounding (ignorability) assumption. Subgroup analyses were stratified by PES status, and exploratory mediation analysis used structural equation modeling. Results: Among 494 extubation events, prophylactic corticosteroid use was not associated with lower odds of PES after weighting (OR 1.06, 95% CI 0.53–2.10) or extubation failure (OR 0.49, 95% CI 0.19–1.24). Among patients with PES, corticosteroid use was associated with a non-significant reduction in extubation failure (OR 0.70, 95% CI 0.14–3.43). Exploratory mediation analysis, interpreted under the ignorability assumption, did not support PES as a meaningful mediator. Conclusions: In this single-center cohort, prophylactic corticosteroid use was not associated with reduced PES or extubation failure. The findings do not support clinically defined PES as a key mediator of any potential treatment effect. Prospective studies are required for confirmation.

Journal of Clinical Medicine doi: 10.3390/jcm15124761

Authors: Atieh Karimzadeh Zahra Karimizadeh Nazila Heidari Samira Parviziomran Sepehr Ramezanipour Amirali Kalantari Shahdad Farokhmanesh Ibrahim Alkatout Leila Allahqoli

Background: Assisted reproductive technology (ART) is increasingly utilized worldwide, and approximately 30% of ART pregnancies result in twin gestations. Chorionicity strongly influences perinatal risk, yet its specific impact on ART-conceived twins has not been systematically clarified. Objective: To compare obstetrical and neonatal outcomes in assisted ART-conceived monochorionic (MC) versus dichorionic (DC) twin pregnancies and evaluate the impact of chorionicity on maternal and perinatal outcomes. Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD42024600292). PubMed, Scopus, and Web of Science were searched through October 2024 for studies comparing obstetrical and neonatal outcomes in ART-conceived monochorionic and dichorionic twin pregnancies. Eligible studies were qualitatively synthesized. Results: Thirty-five studies comprising 15,648 ART-conceived twin pregnancies were included, including 371 monochorionic and 15,277 dichorionic pregnancies. MC pregnancies consistently demonstrated less favorable perinatal outcomes compared with DC pregnancies, including an earlier gestational age at delivery, increased prematurity, lower birth weight, and higher rates of perinatal mortality. By contrast, maternal complications, such as hypertensive disorders, gestational diabetes mellitus, PROM, and cesarean delivery, varied considerably across the studies without a consistent association with chorionicity. The baseline maternal characteristics were generally comparable between the groups. Conclusion: Monochorionicity in ART-conceived twin pregnancies is associated with increased adverse neonatal and perinatal outcomes, particularly prematurity and perinatal mortality, while maternal outcomes appear less clearly influenced by chorionicity. Standardized prospective studies are needed to further clarify the chorionicity-specific risks in ART twin pregnancies.

Journal of Clinical Medicine doi: 10.3390/jcm15124760

Authors: Muhammed Ali Coşkuner Gökhan Köker Gizem Zorlu Görgülügil Gülhan Özçelik Köker Bilgin Bahadır Başgöz Asım Armağan Aydın Mustafa Yıldız

Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value of pretreatment hematologic inflammatory indices for overall survival (OS) and progression-free survival (PFS) in patients with non-metastatic NPC. Methods: This single-center retrospective cohort study included adult patients with non-metastatic NPC diagnosed at a tertiary referral center between 20 February 2014 and 2 May 2023, with outcomes ascertained through 12 December 2023. Pretreatment complete blood count and biochemical parameters were used to calculate the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value (PIV), and hemoglobin–albumin–lymphocyte–platelet score. Receiver operating characteristic analysis determined optimal cut-off values for mortality discrimination. Associations with OS and PFS were assessed using Cox regression models. Results: Forty-six patients were analyzed, including 37 males. Median OS and PFS were 45.90 and 37.05 months, respectively. Compared with survivors, non-survivors were older and had lower hemoglobin and albumin levels, higher PIV, NLR, PLR, and SII values, and lower HALP scores. Although NLR showed the highest conventional ROC performance for mortality discrimination, PIV retained prognostic significance in multivariable Cox models and showed stable time-dependent discrimination for PFS. Conclusions: These preliminary findings suggest that pretreatment inflammatory indices, particularly composite markers such as PIV, may provide adjunctive prognostic information in treatment-naïve non-metastatic NPC, pending larger prospective validation.

Journal of Clinical Medicine doi: 10.3390/jcm15124759

Authors: Michał Tarnowski Robert Morawiec Agata Galas Agata Tymińska Katarzyna Byczkowska Jarosław Kasprzak Aleksander Siniarski Anna Żarek-Starzewska Agnieszka Major Adrian Stefański Małgorzata Zachura Jarosław Drożdż Iwona Gorczyca-Głowacka

Background: Heart failure (HF) is a complex clinical syndrome, and its prognosis depends on many factors, including its etiology and the patient’s sex. We aimed to perform gendered evaluations on ischemic etiology’s impact on HF prognosis. Methods: Hospitalized patients and outpatients were enrolled in the Heart Failure Observational Study (HEROES), which is a prospective, multicenter cohort study, between April 2022 and January 2024. The primary endpoint was all-cause mortality. Results: Among 1410 patients included in the analysis (28.4% females and 71.6% males), 41.1% had ischemic HF etiology, and 58.9% had non-ischemic HF etiology. Ischemic etiology was identified in 28.5% of females and 46.0% of males; p < 0.001. The adjusted hazard ratio (aHR) was 1.16 (95% CI 0.85–1.58; p = 0.363) for all-cause mortality in the non-ischemic group relative to the ischemic reference category. The aHR for all-cause mortality in women relative to men was 1.14 (95% CI: 0.67–1.94; p = 0.633) for ischemic HF and 0.85 (95% CI: 0.56–1.27; p = 0.420) for non-ischemic HF. Conclusions: We found that ischemic and non-ischemic etiologies are associated with comparable all-cause mortality risk in patients with HF. Sex-stratified analyses revealed no significant mortality differentials between women and men within either etiologic category.

Journal of Clinical Medicine doi: 10.3390/jcm15124758

Authors: Mario Pacilli Giovanna Pavone Elizabeth Khoury Antonio Ambrosi Nicola Tartaglia

Background: The role of surgery in advanced thyroid cancer remains controversial, particularly in the setting of aggressive tumor behavior, local invasion, and limited therapeutic windows. Advanced thyroid cancer represents a heterogeneous clinical entity that includes anaplastic thyroid carcinoma as well as differentiated and poorly differentiated carcinomas with aggressive features. Methods: We conducted a retrospective case series of 10 consecutive patients who underwent surgical management for advanced thyroid cancer at a tertiary referral center over a 30-month period. Clinical presentation, surgical strategy, postoperative complications, adjuvant therapies, and outcomes were analyzed. Results: The cohort included 2 papillary, 5 poorly differentiated, and 3 anaplastic thyroid carcinomas. Most patients presented with locally invasive disease and compressive symptoms, including dysphonia and dyspnea. Complete resection (R0) was achieved in five patients and was associated with favorable outcomes, while patients with anaplastic histology experienced poor survival despite palliative interventions. Surgery provided meaningful symptom control in selected patients, particularly those with airway compromise. No perioperative mortality occurred. Conclusions: Surgical management of advanced thyroid cancer should be highly individualized and guided by tumor extent, symptom burden, and patient performance status. While surgery alone is insufficient as a standalone treatment, it plays a pivotal role when integrated within a multimodal strategy, offering both oncologic and palliative benefits. Early identification of candidates for surgical intervention and integration with systemic therapies represent key elements in the management of these complex malignancies.

Journal of Clinical Medicine doi: 10.3390/jcm15124757

Authors: Einav Koren Adar Yaacov Jamal Zidan Laila C. Roisman Nir Peled Noam Asna

Background: Pembrolizumab-based therapy is a standard first-line option for advanced non-small-cell lung cancer (NSCLC), yet pivotal clinical-trial populations may not reflect patients encountered in routine practice. Real-world cohorts enriched for Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and high metastatic burden remain underreported. We assessed real-world outcomes of first-line pembrolizumab in a heterogeneous cohort enriched for these. Methods: Retrospective cohort analysis of 45 patients with advanced NSCLC who received first-line pembrolizumab-based therapy (monotherapy or with platinum-based chemotherapy) at a single health maintenance organization in Israel between September 2017 and April 2020. Results: Mean age was 69.3 years (SD 9.0), 82.2% were male, 91.1% were current or former smokers, 37.8% had ECOG PS ≥2 (including 17.8% with ECOG ≥3), and 53.3% had three or more metastatic organ sites. PD-L1 expression was ≥50% in 46.7%, 1–49% in 13.3%, and <1% in 22.2%. After a median follow-up of 48.7 months (88.9% event rate), median overall survival (OS) was 8.87 months (95% CI, 5.88–14.32) and median progression-free survival (PFS) was 4.20 months (95% CI, 2.76–6.18), with an objective response rate of 46.7% and a disease control rate of 68.9%. On univariate Cox regression, the number of metastatic sites was most strongly associated with OS (HR 1.41 per site, 95% CI, 1.17–1.70, p = 0.0003). PD-L1 expression was significantly associated with both PFS (p < 0.0001) and OS (p = 0.0012), with the longest survival observed in patients with PD-L1 ≥50%. Conclusions: In this real-world cohort enriched for poor performance status and high metastatic burden, pembrolizumab-based therapy provided clinical benefit, but observed survival was substantially shorter than that reported in pivotal trials.

Journal of Clinical Medicine doi: 10.3390/jcm15124756

Authors: Lucrețiu Radu Marius-Bogdan Novac Ramona-Constantina Vasile Alexandra-Daniela Rotaru-Zăvăleanu Liviu Martin George-Alin Stoica

Background: Healthcare-associated infections (HAIs) remain a critical patient safety challenge. Hand hygiene is considered the most effective preventive measure, yet traditional monitoring captures only compliance, not technique quality. This prospective before–after study evaluated whether real-time visual feedback via the Semmelweis UV-fluorescence system is associated with improved hand hygiene quality, measured by ATP bioluminescence and microbiological culture. Methods: Three clinical departments (the Intensive Care Unit, Hematology, and Gynecology) at a Romanian tertiary hospital were purposively selected. Seventy-one healthcare workers (HCWs) were enrolled. The 12-week study comprised Phase 1 (baseline, weeks 1–4), Phase 2 (active intervention with Semmelweis feedback, weeks 5–8), a one-week washout (week 9), and Phase 3 (sustainability assessment, weeks 10–12). Paired ATP-CFU samples were collected weekly. Within-group comparisons used Kruskal–Wallis H tests with post hoc Dunn’s tests and Bonferroni correction. Secondary outcomes included Semmelweis global and zone-specific coverage and the correlation between subject-level Semmelweis coverage and ATP bioluminescence (Spearman’s rho). Results: A total of 781 paired ATP-CFU samples and 497 Semmelweis evaluations were analyzed. Mean ATP declined from 195.9 RLU at baseline to 148.2 RLU in Phase 2 (−24.4%) and 154.8 RLU in Phase 3 (−21.0%; Kruskal–Wallis H = 102.73, p < 0.001). CFU/mL declined from 84.8 to 66.2 (−21.9%) and 70.7 (−16.6%; H = 22.48, p < 0.001). Post hoc comparisons confirmed significant Phase 1 versus Phase 2 and Phase 1 versus Phase 3 differences for both markers (all p < 0.01), while Phase 2 versus Phase 3 was non-significant, indicating stabilization at an improved level. Subject-level Semmelweis coverage correlated negatively with ATP (rho = −0.665, 95% CI −0.778 to −0.510, p < 0.001), supporting construct validity at the operator level. Semmelweis global coverage was 93.1% (Phase 2) and 90.6% (Phase 3); interdigital spaces showed the highest inadequacy rate (73.9% protocol-based, 92.5% targeted). Conclusions: Real-time visual feedback via UV-fluorescence imaging was associated with significant and sustained improvements in hand hygiene quality beyond baseline. ATP, CFU, and Semmelweis assessments captured complementary, non-redundant dimensions, supporting multimodal evaluation. Interdigital spaces and fingertips remained persistent failure points requiring targeted educational reinforcement.

Journal of Clinical Medicine doi: 10.3390/jcm15124755

Authors: Ruslan A. Mammadov Henk P. Roest Gwenny M. Fuhler Junhong Su Thijmen Visseren Harry L. A. Janssen Robert J. Porte Sarwa Darwish Murad Bettina E. Hansen Luc J. W. van der Laan Maikel P. Peppelenbosch

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently requiring liver transplantation (LTx). The gut–liver axis, host genetics, and microbial dysbiosis are thought to contribute to disease progression and post-transplant outcomes. The FUT2 rs601338 polymorphism influences mucosal fucosylation, host–microbial interactions, and susceptibility to infection. This study aimed to investigate the association between FUT2 genotype, colonic mucosal microbiome composition, post-transplant bacteremia, and all-cause mortality in a retrospective single-center PSC cohort. Methods: This retrospective cohort study included PSC patients who underwent LTx at Erasmus MC University Medical Center (Rotterdam, The Netherlands) between 1987 and 2015. Pre-transplant archival formalin-fixed paraffin-embedded (FFPE) colonic biopsy specimens were available for microbiome analysis. Of 169 transplanted patients, FFPE tissue was available for 98 individuals, and FUT2 rs601338 genotyping was successfully performed in 87 patients. Patients were classified as FUT2 non-secretors (AA, n = 28) and secretors (GA/GG, n = 59). Post-transplant bacteremia was assessed based on clinically indicated blood cultures during follow-up. Colonic mucosal microbiome composition was analyzed using 16S rRNA gene sequencing. Results: FUT2 non-secretors showed a distinct colonic mucosal microbiome profile compared with secretors, characterized by differential abundance of selected taxa within Proteobacteria, Firmicutes, and Bacteroidetes. Post-transplant bacteremia occurred in 30 patients and was more frequent among non-secretors (43%) compared with secretors (15%). Both FUT2 non-secretor status and post-transplant bacteremia were associated with reduced all-cause post-transplant survival in Kaplan–Meier analysis and remained associated with mortality in multivariable regression models. Specific microbial taxa were also showed associations with bacteremia, mortality, and established prognostic scores, including the Amsterdam–Oxford Model and Mayo Risk Score. Conclusions: FUT2 genotype is associated with alterations in colonic mucosal microbiome composition, post-transplant bacteremia, and all-cause mortality in PSC patients undergoing liver transplantation. These findings suggest a potential interplay between host genetics, intestinal microbiota, and infectious complications after transplantation. Given the retrospective design, limited sample size, and use of archival FFPE tissue, all findings should be interpreted as exploratory and hypothesis-generating. Prospective multicenter studies using standardized sampling and high-resolution metagenomic approaches are warranted for validation.

Journal of Clinical Medicine doi: 10.3390/jcm15124754

Authors: A. Paradisi F. Brunetti G. M. Jeha S. N. Tolkachjov

Mohs micrographic surgery (MMS) is a highly specialized skin cancer procedure that combines complete microscopic margin assessment with maximal preservation of uninvolved tissue. The technique is based on staged excision of the tumor with systematic horizontal sectioning and real-time examination of the entire peripheral and deep surgical margins, allowing further tissue removal only in areas where residual tumor is identified. Its unique strength lies in the ability to detect subclinical tumor extensions that may be missed by conventional excision and standard vertical sectioning, thereby improving local control while minimizing unnecessary tissue sacrifice. Since its introduction in the 1930s by Frederic E. Mohs, the technique has evolved into a cornerstone of modern dermato-oncology, particularly for tumors arising in anatomically critical areas, recurrent neoplasms, and histologically aggressive malignancies. MMS is now widely regarded as the treatment of choice for high-risk basal cell carcinoma and cutaneous squamous cell carcinoma because of its superior cure rates and tissue-sparing approach. Beyond its oncologic advantages, MMS allows precise clinicopathologic correlation and immediate reconstruction tailored to the final defect, contributing to favorable functional and cosmetic outcomes. As experience with the technique has expanded, so too has interest in adjunctive tools for preoperative tumor delineation and margin control, further refining patient selection and surgical accuracy. Overall, MMS represents an essential advance over conventional excision for selected cutaneous malignancies, offering an optimal balance between radical tumor clearance and preservation of normal tissue.

Journal of Clinical Medicine doi: 10.3390/jcm15124753

Authors: Grant A. Bateman Alexander R. Bateman

Introduction: Decompressive craniectomy (DC) is often required to stabilize the intracranial pressure (ICP) in patients with traumatic brain injury (TBI). Both sinking flap syndrome (SFS) and hydrocephalus are known complications of DC. The pathophysiology of each is unknown. Case Report: We report on a patient who underwent DC for TBI who suffered both SFS and low-pressure hydrocephalus. We measured the changes in volumes of each hemisphere and the ventricles with CT and the cerebral blood flow (CBF) and aqueduct flow with phase-contrast MRI during different stages of the disease process. Discussion: The SFS in this patient was associated with a reduction in volume of both supratentorial cavities. There was a significant reduction in CBF bilaterally, which increased by an average of 26% following cranioplasty. During the low-pressure hydrocephalus phase of the patient’s illness, there was reversed CSF flow directed toward the ventricles. Once the ventricles returned to normal size, this reversed flow was lost. Conclusions: Lumped parameter modelling of the patients’ CSF and vascular systems suggested a new hypothesis, i.e., that the reduction in blood flow was due to reversible constriction of the arterioles secondary to a reset of the autoregulation rather than compression of the venous structures. We suggest there is an increase in CSF absorption efficiency despite the known CSF-absorption mechanisms being unlikely to function at such a low ICP. A hypothesis is put forward that CSF absorption occurs via the brain capillary bed in these diseases.

Journal of Clinical Medicine doi: 10.3390/jcm15124752

Authors: Bağnu Dündar Betül Özbek Fatma Bozkurt Asiye Gok Yurttas

Objective: Preanalytical errors account for the vast majority of preanalytical incidents and remain a fundamental threat to the reliability of test results. Although the types and frequencies of these errors have been extensively studied in the literature, their time-dependent variability has received comparatively little attention. This study aimed to evaluate how preanalytical specimen rejection rates vary across intraday time intervals and to assess the independent influence of time on preanalytical quality. Methods: This retrospective observational study included a total of 579,845 specimens accepted by the central laboratory of Istanbul Atlas University Hospital between January 2024 and December 2025. Specimens were analyzed with respect to preanalytical rejection reasons, the distribution and rate of these reasons across clinical units, and time of day. Each day was divided into six equal four-hour intervals: Z1 (00:00–04:00), Z2 (04:00–08:00), Z3 (08:00–12:00), Z4 (12:00–16:00), Z5 (16:00–20:00), and Z6 (20:00–24:00). Statistical analyses were performed using the Pearson chi-square test, and effect sizes were quantified using Cramér’s V coefficient. Results: Of the 579,845 specimens examined, 4365 were rejected, yielding an overall rejection rate of 0.79%. Rejection rates were found to be non-uniformly distributed across the day (p < 0.001). The highest rejection rate was observed during the Z2 interval (04:00–08:00) at 1.98%, whereas the lowest was recorded during Z3 (08:00–12:00) at 0.45%. Negative binomial regression analysis identified the Z2 interval as the only time period independently associated with an increased rejection risk Incidence Rate Ratio (IRR) = 1.63; 95% Confidence Interval (CI): 1.22–2.19. Among clinical units, the highest rejection rate was recorded in the emergency department (1.92%). Analysis of error types revealed that the majority of rejections were attributable to hemolysis (47.5%) and clotted specimens (26.3%). Hemolysis rates peaked in the emergency department, while clotted specimens occurred more frequently within intensive care units. Analysis of time and error interactions revealed that clotted specimens peaked during Z1 and Z2, whereas hemolysis became the primary cause of rejection during Z3 and Z4. Conclusions: Preanalytical specimen rejection rates exhibited significant variation according to time of day, clinical unit, and error type, with time emerging as a factor independently associated with preanalytical quality. The coexistence of elevated rejection risk during Z2 (04:00–08:00) and markedly low rejection rates during Z3 (08:00–12:00) indicates that the relationship between workload and error frequency is not linear. Although hemolysis and clotted specimens constituted the dominant error types, their distribution followed distinct patterns depending on the clinical unit and time interval. These results underscore the necessity of time-based monitoring to pinpoint unit-specific risks, providing a clear roadmap for targeted quality improvement interventions.

Journal of Clinical Medicine doi: 10.3390/jcm15124751

Authors: Miguel de Pedro Abascal Teresa Bas Paloma Bas Ghassan Elgeadi Saleh Alberto Caballero García Joint Halley Guimbard Perez Amparo Ortega Yago Miguel Ángel Castillo Soriano

Background/Objectives: To determine whether ESS provides superior clinical, radiologic, or perioperative outcomes compared with non-ESS surgical strategies in lumbar spondylolisthesis. Methods: We conducted a PRISMA-guided systematic review and meta-analysis comparing ESS with non-ESS strategies specifically for lumbar spondylolisthesis. PubMed, Web of Science, Scopus, and CENTRAL were searched from inception to December 2025, plus reference-list screening. Primary outcomes were mean change in VAS back pain, VAS leg pain, and Oswestry Disability Index (ODI); secondary outcomes included radiologic measures (disc height, lumbar lordosis angle, fusion rate) and perioperative outcomes (blood loss, operative time, length of stay, complications). Results: Eighteen studies (16 retrospective cohorts, 1 RCT, 1 case–control) involving 1200 patients with lumbar spondylolisthesis (2019–2025) were included. ESS showed no significant differences versus non-ESS in mean change in VAS back pain (13 studies; MD −0.07), VAS leg pain (14 studies; MD 0.08), or ODI (12 studies; MD 0.51). No statistically significant differences were detected in radiological outcomes (disc height, lumbar lordosis angle, and fusion rate). ESS was associated with reduced blood loss (MD −132.98) and shorter hospital stay (MD −2.86 days), with no difference in operative time (MD 3.96) or postoperative complications (RR 0.86). Subgroup analyses compared endoscopic fusion with MIS fusion, open fusion, and non-endoscopic decompression. Endoscopic versus MIS fusion showed lower blood loss (MD: −50.9 mL) and shorter hospital stay (MD: −1.4 days) but longer operative time (MD: +17.2 min), with no differences in clinical outcomes. Comparisons involving decompression and open fusion were limited by the small number of studies and should be considered exploratory. Conclusions: For lumbar spondylolisthesis, no statistically significant differences were detected between ESS and non-endoscopic approaches in pain, disability, radiologic outcomes, or complication rates, with potential perioperative advantages in blood loss and length of stay. However, these findings should be interpreted cautiously because the available evidence is predominantly retrospective, procedurally heterogeneous, and affected by substantial variation in follow-up duration.

Journal of Clinical Medicine doi: 10.3390/jcm15124750

Authors: Andra Patricia David Silviu Brad Laura-Cristina Rusu Ovidiu Tiberiu David Andra Ardelean Robert-Angelo Tuce Marius Traian Leretter

Background/Objectives: Implant placement in transnasal and paranasal regions of the severely atrophic maxilla is challenged by complex anatomy and proximity to critical structures, particularly the nasolacrimal duct (NLD). While cortical anchorage is considered important for implant stability, structured methods for evaluating anatomical eligibility and anatomical risk during planning remain limited. This proof-of-concept study aimed to describe a segmentation-assisted workflow for anatomical assessment of potential paranasal implant trajectories. Methods: A single-case proof-of-concept workflow was developed using CBCT imaging and multi-component anatomical bone segmentation (MCABS). Segmented anatomical structures were used to selectively visualize cortical pathways within the anterior maxilla. Implant planning was performed using axial, non-tilted trajectories. Particular attention was directed toward visualization of the spatial relationship between the planned implant pathway and the nasolacrimal duct. Workflow feasibility was further explored through study-model fabrication, guided implant insertion, and axis-based verification. Results: The proposed workflow enabled selective visualization of cortical structures and facilitated identification of anatomically favorable implant trajectories within the paranasal region. The relationship between the planned implant pathway and the nasolacrimal duct could be directly assessed using the segmented anatomical model. Guided insertion in the study model demonstrated concordance between planned and executed implant axes, supporting the technical feasibility of the workflow. Conclusions: Within the limitations of a single-case proof-of-concept study, the proposed segmentation-assisted workflow may contribute to preoperative anatomical assessment of potential paranasal implant trajectories and their relationship to adjacent anatomical structures. The workflow should be regarded as a methodological demonstration rather than a validated clinical protocol. Further anatomical, reproducibility, biomechanical, and clinical studies are required before broader clinical adoption can be considered.

Journal of Clinical Medicine doi: 10.3390/jcm15124748

Authors: Giovanni Inghilleri Massimo Franchini

Intravenous (IV) iron is used to replenish iron stores in patients with iron-deficiency anemia (IDA) who do not benefit from oral iron supplementation. Hypophosphatemia is an increasingly recognized adverse event associated with certain IV iron formulations. Mild/moderate hypophosphatemia may be asymptomatic or present with symptoms similar to those seen in patients with IDA, including fatigue, malaise, and muscle weakness. Persistent hypophosphatemia can cause osteomalacia due to reduced bone mineralization, leading to bone pain and pseudofractures. Ferric carboxymaltose (FCM) can impact phosphate homeostasis through an increase in fibroblast growth factor 23, leading to increased urinary phosphate excretion and hypophosphatemia. In clinical trials, rates of hypophosphatemia were significantly higher in patients receiving FCM compared with other IV iron formulations, such as ferric derisomaltose and ferumoxytol. Treatment guidelines recommend monitoring serum phosphate levels in patients receiving FCM who are at risk for low phosphate or who require repeat infusions, and alternative iron formulations should be considered in at-risk patients. This narrative review summarizes current evidence regarding IV iron-induced hypophosphatemia in individuals with IDA and examines the underlying pathophysiology and clinical evidence for IV iron-induced hypophosphatemia, particularly with FCM, the populations most at risk, and the clinical consequences of persistent hypophosphatemia.

Journal of Clinical Medicine doi: 10.3390/jcm15124749

Authors: Tomasz Karczewski Jennifer M. L. Stephens Dawid Karczewski Sahar Feizizadeh Avni K. Patel Merjorie M. A. Pinero Mihaela Olsen Melanie L. Thompson

Background/Objectives: Western Canadian and U.S. communities outside urban centres remain underserved by primary, specialist, emergency, mental health, and chronic-disease services. These access problems reflect distance, weather, workforce shortages, specialist maldistribution, primary care attachment gaps, broadband limitations, and the governance realities of Indigenous and Tribal communities. This scoping review with narrative synthesis examined how telehealth and virtual-care models affect rural access in western Canada and the western/frontier United States. Methods: Searches were completed on 21 May 2026 in PubMed/MEDLINE, Embase, CINAHL, Scopus, the Cochrane Library, and PubMed Central. Supplementary searches included Google Scholar, publisher platforms, reference-list checking, and official Canadian and U.S. health-system sources. Peer-reviewed evidence published from 1 January 2016 to 21 May 2026 was eligible when it addressed rural, remote, frontier, Indigenous, underserved, western, or northern healthcare settings and reported access, implementation, safety, continuity, equity, or service-use outcomes. Results: The search identified 112 records; 27 duplicates were removed, 85 records were screened, 37 full texts were assessed, and 28 peer-reviewed records were included. Seven official sources were retained separately. Evidence was mainly observational, qualitative, mixed-methods, implementation-focused, or review-level. Moderate confidence supported telehealth for travel reduction and specialist input, especially through eConsultation, provider-to-provider consultation, telementoring, and real-time emergency support. Confidence was low to moderate for hybrid primary care and telemental health, and low for durable reductions in emergency department use. Conclusions: Telehealth may be most appropriately implemented as a hybrid, locally anchored, culturally safe access model, not as a stand-alone substitute for rural primary care, specialist capacity, or emergency services. Implementation should include broadband support, local physical assessment capacity, documentation, continuity, patient education, and clear escalation pathways.

Journal of Clinical Medicine doi: 10.3390/jcm15124747

Authors: Brent Tai Chijioke Okonkwo Yaroslav Zuyev Derek Snyder

Background: Hospitalized adults with chronic kidney disease (CKD) experience high morbidity and mortality. Acute inpatient events frequently occur in combination, yet most studies evaluate individual conditions in isolation. Acute hemodynamic and vascular stressors may represent interacting physiological stressors that define heterogeneous patterns of inpatient risk. Methods: Acute hemodynamic stressors (sepsis, shock, acute decompensated heart failure, and mechanical ventilation) and vascular stressors (acute myocardial infarction, major bleeding, stroke, pulmonary embolism, and deep vein thrombosis) were identified using ICD-10-CM and ICD-10-PCS codes. Stressor burden was defined as the number of stressors (0, 1, 2, or ≥3). Hospitalizations were categorized into mutually exclusive domains: none, hemodynamic only, vascular only, or both. Survey-weighted multivariable regression models examined associations with mortality, acute kidney injury (AKI), length of stay (LOS), and hospital charges. Prespecified sensitivity analyses excluded inter-hospital transfers, and interaction analyses assessed modification by age. Results: Among 1,062,813 CKD hospitalizations, 66.1% experienced at least one acute stressor. Increasing stressor burden demonstrated a marked dose–response relationship with mortality, with adjusted odds ratios of 2.15 (95% CI: 2.08–2.23), 7.36 (95% CI: 7.09–7.64), and 31.65 (95% CI: 30.40–32.95) for 1, 2, and ≥3 stressors, respectively. Increasing stressor burden was also associated with higher odds of AKI, longer LOS, and greater hospital charges. Significant dose–response relationships were observed for all outcomes (all P-trend < 0.001). Isolated hemodynamic stressors were associated with greater mortality risk than isolated vascular stressors (aOR: 4.97 vs. 2.15), while hospitalizations experiencing both domains had the greatest risk (aOR: 13.10, 95% CI: 12.52–13.71). These findings were robust in sensitivity analyses excluding inter-hospital transfers. The relative increase in mortality associated with higher stressor burden was greater among patients younger than 65 years than among older adults (P for interaction <0.001). Conclusions: Acute hemodynamic and vascular stressors define heterogeneous patterns of inpatient risk among hospitalized adults with CKD. Both cumulative stressor burden and stressor domain are strongly associated with mortality, AKI, and resource utilization, with robust dose–response relationships that highlight acute physiological stress as an important determinant of inpatient outcomes in CKD.

Journal of Clinical Medicine doi: 10.3390/jcm15124746

Authors: Jure Bizjak Andraž Kondža Kosta Cerović Milan Medved Simon Hawlina

Background/Objectives: Robot-assisted partial nephrectomy (RAPN) has increasingly replaced laparoscopic partial nephrectomy (LPN) in the management of localized renal tumours. This study aimed to evaluate perioperative, functional and surgical margin outcomes during an institutional transition from LPN to RAPN in a high-volume centre. Methods: We performed a retrospective single-centre analysis of 100 consecutive patients undergoing minimally invasive partial nephrectomy. The last 50 LPN cases (August 2014–May 2018) were compared with the first 50 RAPN cases (June 2018–February 2020). Baseline characteristics, perioperative outcomes, early functional parameters and surgical margin status were analysed. Complications were classified according to the Clavien–Dindo system. Results: Tumours treated in the RAPN group were significantly larger (3.4 vs. 2.5 cm) and more complex (RENAL score of 6 vs. 5; p < 0.001). Operative time was longer in the RAPN group (143 vs. 122 min; p < 0.01), while warm ischaemia time did not differ significantly (16 vs. 15 min; p = 0.37). Estimated blood loss was lower (0 vs. 10 mL; p = 0.049) and the hospital stay was shorter (3 vs. 4 days; p < 0.001) in the RAPN group. Haemoglobin decrease and postoperative creatinine change were comparable between groups. Positive surgical margins were observed less frequently in the RAPN group (2.3% vs. 7.7%), but this difference was not statistically significant (p = 0.34). Complication rates were significantly lower in the RAPN group (4% vs. 22%; p < 0.05), with no major complications observed in the robotic cohort. Conclusions: In this institutional experience, RAPN was associated with favourable perioperative outcomes during the transition period, despite the treatment of larger and more complex renal tumours. The slightly longer operative and warm ischaemia times likely reflect a more comprehensive reconstruction strategy, which may contribute to improved haemostatic control and lower complication rates. Further studies with extended follow-up are required to evaluate oncological and renal functional outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124745

Authors: Anca-Iuliana Pîslaru Ramona Ștefăniu Mihaela-Cristina Panait (Baghiu) Mădălina Istrate Sabinne-Marie Albișteanu Bogdan-Cristian Brumă Ana-Maria Turcu Iulia-Daniela Lungu Adina-Carmen Ilie Ionuț Nistor

Background: Population ageing has increased the burden of geriatric syndromes among older adults with cardiovascular disease, where frailty is associated with adverse outcomes, including hospitalization, functional decline, and mortality. Digital technologies and Living Lab approaches offer new opportunities for the early detection, prevention, and monitoring of these conditions through user-centred innovation and stakeholder collaboration. Our purpose is to review the role of technology in the detection, prevention, and monitoring of geriatric syndromes in older adults with cardiovascular disease and to explore the potential of the Living Lab model for developing and implementing innovative solutions in geriatric care. Materials and Methods: A narrative review was conducted using PubMed, CINAHL, MEDLINE, and ScienceDirect. Eleven studies were included. Evidence on physical, cognitive, psycho-emotional, and social frailty, as well as technology-enabled assessment and monitoring approaches, was synthesized. Results: Digital technologies, including wearable sensors, telemonitoring platforms, mobile health applications, machine-learning models, and digital phenotyping tools, supported the early identification and monitoring of frailty, fall risk, cognitive decline, depressive symptoms, and functional deterioration. Technology-assisted interventions improved physical and cognitive performance and promoted social engagement. The Living Lab model facilitated the co-creation, evaluation, and validation of technologies in real-world settings, enhancing usability, acceptability, and implementation in clinical practice. Conclusions: Technology-supported assessment and monitoring can improve the management of geriatric syndromes in older adults with cardiovascular disease. Living Labs provide a valuable framework for the user-centred development and integration of these innovations, supporting personalized and proactive care strategies that promote healthy ageing.

Journal of Clinical Medicine doi: 10.3390/jcm15124744

Authors: Irmaleny Irmaleny Denny Nurdin Indra Primathena Huwaina Abd Ghani

Untreated dental caries in permanent teeth is the most frequent disease of all 371 diseases and traumas assessed by the Global Burden of Disease Study in 2021, and there are reported to be 2.24 billion cases worldwide. Demineralization is a disintegration process of minerals and apatite crystals in hard tissue, provoked by biofilm activities, dietary factors, and the micro-oral environment—the three main mechanisms of dental caries. Restoration of mineral ions in the crystal structure is defined as remineralization. Remineralization enables the deposition of new minerals within the crystal structure of demineralized enamel, aiming to increase mineral production. Environments suitable for remineralization and inhibiting demineralization could be created by using a caries prevention agent. Objectives: Providing scientific evidence regarding Aloe vera as an alternative agent for caries prevention. Materials and Method: The method used in this study is a scoping review, utilizing the PRISMA-ScR as a guideline to conduct article screening and further analysis, following a thematic analysis approach. Database searches were conducted in PubMed, EBSCOhost, and ScienceDirect, based on the keywords generated. Results: A total of 13 articles were gathered for further analysis. Conclusions: Aloe vera shows promising preliminary potential, but further standardized in vivo and randomized clinical studies are necessary to confirm its remineralizing efficacy and clarify its mechanisms of action as a cavity prevention agent. Clinical Relevance: Using Aloe vera as an alternative caries prevention agent.

Journal of Clinical Medicine doi: 10.3390/jcm15124743

Authors: Matyas Benyo Marie Al-Muhanna Zsuzsanna Molnar Janos Docs Tamas Takacs Jolan Harsfalvi

Venous thromboembolism (VTE) remains a clinically relevant complication of radical prostatectomy despite advances in surgical techniques and perioperative care. Current thromboprophylaxis strategies are largely based on fixed-duration approaches and static risk models focused on the early postoperative period. However, accumulating evidence suggests that postoperative hypercoagulability is a dynamic and prolonged process that may extend beyond this timeframe. This review summarizes the pathophysiological mechanisms and temporal dynamics of postoperative hypercoagulability after radical prostatectomy, with particular emphasis on biomarker-based evidence, including thrombin generation and von Willebrand factor. Clinical and laboratory findings suggest that haemostatic activation may persist after hospital discharge, supporting the concept of a biologically relevant post-discharge period during which insufficiently captured thrombotic risk may remain despite apparent clinical recovery. Current risk assessment models do not account for the time-dependent nature of postoperative haemostatic changes and do not incorporate biomarker data. This discrepancy highlights a gap between guideline-based thromboprophylaxis strategies and the underlying biological processes. To address this, we propose a conceptual framework in which postoperative thromboprophylaxis is considered in relation to the temporal evolution of hypercoagulability. This framework is hypothesis-generating and may help inform future studies aimed at identifying patients who could benefit from extended prophylaxis while avoiding unnecessary anticoagulation in those with more rapid haemostatic recovery. Further prospective studies are required to validate biomarker-guided strategies and to define clinically actionable thresholds for individualized thromboprophylaxis in prostate cancer patients undergoing radical prostatectomy.

Journal of Clinical Medicine doi: 10.3390/jcm15124742

Authors: Sandesh Shende Jaishriram Rathored

Background/Objectives: Vitamin D, universally recognized for its role in calcium–phosphate homeostasis and skeletal health, has emerged as a key immuno-endocrine modulator. Its active metabolite interacts with the vitamin D receptor (VDR) across immune and endocrine cell populations, influencing gene transcription, cytokine balance, and immune tolerance. This narrative review synthesizes mechanistic, epidemiological, and clinical evidence on the role of vitamin D in immune modulation across autoimmune and infectious diseases. Methods: This narrative review incorporated a structured and comprehensive literature search across PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar. Results: Vitamin D modulates both innate and adaptive immunity through antimicrobial peptide induction, macrophage and NK cell activation, and promotion of tolerogenic dendritic cells. Clinical and interventional trial outcomes remain heterogeneous and are influenced by baseline vitamin D status, dosing regimens, genetic variability, and disease context. Conclusions: Vitamin D functions in endocrine and immune regulation, contributing to host defense and immune tolerance. Current evidence supports that for autoimmune and infectious conditions, well-designed randomized trials are required to clarify effective dosing, identify responsive subpopulations, and elucidate genetic determinants of therapeutic benefit.

Journal of Clinical Medicine doi: 10.3390/jcm15124741

Authors: Christian Prangenberg Thomas Loy Alberto Alfieri Zellner Jonas Roos Sebastian Scheidt Lisa Roder Soufian Ben Amar Kristian Welle

Objective: Femoral head fractures are rare and severe injuries often associated with high-energy trauma. Early recognition and rapid, stable reduction are essential for successful treatment to prevent complications and morbidity. This retrospective study aims to describe and analyze long-term outcomes and survival rates of the femoral head after a Pipkin fracture. Methods: Between 2012 and 2021, all patients with a femoral head fracture who were treated in a Level I Trauma Center were assessed and analyzed. Two examiners performed a physical examination and radiological control of patients and called the patients for a final follow-up. Anterior and posterior fracture-dislocations and femoral head fractures were classified according to Pipkin’s classification system. The functional outcome was assessed using the Harris Hip Score (HHS). Results: Over a 10-year period, n = 15 patients were diagnosed with a femoral head fracture. All patients were male; the average age at admission was 41.3 years. The mean follow-up was 43.7 months ± 46 months. No complications occurred in three patients (20%). Twelve patients had complications. The most common complications were nerve lesions and posttraumatic osteoarthritis. Regarding the outcome, no data were available for two patients; one patient died, and two of four patients remained with a Girdlestone resection arthroplasty at the follow-up. The mean score in HHS was 76.69 ± 20.3 (mean ± standard deviation). Conclusions: An overall complication rate of 80% was observed; however, functional outcomes were generally moderate at final follow-up. These findings highlight the considerable risk of complications associated with femoral head fractures, particularly nerve injury and posttraumatic osteoarthritis. Notably, six of 15 patients no longer retained their native hip joint at the time of assessment. The study is a Level 2b study.

Journal of Clinical Medicine doi: 10.3390/jcm15124740

Authors: Ahmet Uzger Ahmet Rauf Goktepe Yasin Sahin

Objective: First-degree relatives, especially siblings, are at increased risk of developing celiac disease (CD). The aim of this study was to determine the prevalence of CD in siblings of children with CD, and to evaluate the applicability of the non-biopsy diagnostic criteria recommended in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2020 guidelines. Methods: Siblings of children with biopsy-confirmed CD who had not previously been diagnosed with CD were included in the study. According to the ESPGHAN 2020 guidelines, cases with elevated anti-tTG IgA levels (more than 10 times the upper limit of normal) were diagnosed without biopsy. Results: In total, 250 siblings of 81 children with biopsy-confirmed CD were included in the study. The median age of the siblings was 9.00 years. Anti-tTG IgA positivity was detected in 31 siblings. A total of 26 siblings (10.4%) were diagnosed with CD. Of the diagnosed cases, 21 (80.76%) were asymptomatic. In 12 cases with anti-tTG IgA levels more than 10× ULN, the diagnosis was done without biopsy. Conclusions: The prevalence of CD in siblings of celiac patients was found to be 10.4%. This rate is approximately 22 times higher than in the general population in our country. Since half of the diagnosed patients are asymptomatic, screening all siblings for CD, regardless of the presence of symptoms, is crucial for early diagnosis. Additionally, diagnosis can be done without biopsy in eligible cases meeting the ESPGHAN 2020 no-biopsy criteria. Note: This article abstract has been accepted for the 58th ESPGHAN congress as an E-poster presentation.

Journal of Clinical Medicine doi: 10.3390/jcm15124739

Authors: Merdan Orunoglu Ukbe Sirayder Oguzhan Yilmaz Murat Baloglu

Background: Three-level anterior cervical discectomy and fusion (ACDF) is widely used for multilevel cervical degenerative disc disease; however, the relationship between postoperative alignment trajectories, adjacent segment degeneration (ASD), and late patient-reported outcomes remains incompletely defined. This study evaluated plane-specific radiological alignment changes, MRI-based ASD, and late functional outcomes in a homogeneous three-level ACDF cohort. Methods: This single-center observational cohort included 29 patients who underwent three-level ACDF between January 2018 and December 2023 and had complete radiographic follow-up. Radiological data were collected retrospectively from institutional records and imaging archives. Cervical sagittal and coronal alignment were assessed using Cobb angles on radiographs obtained preoperatively and at 6 months, 1 year, and 2 years postoperatively. ASD was evaluated at the superior adjacent segment on 2-year MRI. Late patient-reported clinical outcomes were assessed at a mean follow-up of 42.6 ± 6.8 months using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Nottingham Health Profile (NHP). Results: Sagittal Cobb angle changed significantly over time (χ2(3) = 12.60, p = 0.006; Kendall’s W = 0.145), whereas coronal Cobb angle showed a statistically significant reduction over time, although the absolute magnitude of change was small (χ2(3) = 28.74, p < 0.001; Kendall’s W = 0.330). Lower sagittal Cobb angle correlated with worse NDI (r = −0.46, p = 0.004), and greater coronal Cobb angle correlated with worse physical activity scores (r = 0.52, p = 0.006). Higher Pfirrmann grade correlated with worse NDI (r = 0.49, p = 0.004) and pain scores (r = 0.44, p = 0.021). In exploratory regression analysis, sagittal Cobb angle and Pfirrmann grade were retained in the model for NDI, but these findings should be interpreted as hypothesis-generating. Conclusions: After three-level ACDF, sagittal and coronal alignment followed different postoperative trajectories. Lower sagittal alignment and greater adjacent disc degeneration were associated with worse late neck-related disability. However, given the modest sample size and exploratory nature of the regression analysis, these findings should be interpreted as hypothesis-generating. Larger prospective studies are needed to confirm whether sagittal alignment and MRI-based adjacent segment degeneration independently contribute to late functional outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124738

Authors: Joseph Hozayen Omar Hozayen Benjamin J. Behers Nicolas Riveros Anas Abu Jad Bashar Roumia Christoph A. Stephenson-Moe Matthew W. Miller Karen M. Hamad

Background: Infective endocarditis (IE) requires 4–6 weeks of intravenous antimicrobial therapy, and timely transition to outpatient parenteral antimicrobial therapy (OPAT) allows clinically stable patients to complete treatment outside the hospital. Because OPAT requires home infusion services or post-acute facility placement that typically depend on coverage, insurance status may strongly influence length of stay (LOS); national data on this association in IE remain limited. Methods: We performed a retrospective cross-sectional analysis of the 2016–2019 National Inpatient Sample (NIS) using ICD-10-CM codes I33 and I38 to identify adult IE hospitalizations. Patients were classified as insured (Medicare, Medicaid, or private insurance) or uninsured (self-pay or no charge). Outcomes included mean and prolonged LOS (>14 and >28 days), in-hospital mortality, discharge against medical advice (AMA), and hospitalization costs. Comparisons used chi-square and Student’s t-tests with appropriate NIS survey weighting. Multivariable Gamma regression (LOS, cost) and logistic regression (binary outcomes) were performed, adjusting for age, sex, race/ethnicity, income quartile, injection drug use (IDU), Elixhauser Comorbidity Index, and hospital characteristics, with an insurance × IDU interaction term. Results: Of 87,211 weighted IE hospitalizations, 81,667 (93.6%) were insured and 5544 (6.4%) were uninsured. Uninsured patients were younger (mean age 40.1 vs. 59.4 years) with lower comorbidity burden but higher injection drug use (IDU) prevalence (38.7% vs. 15.5%). Mean LOS was longer among the uninsured (15.5 vs. 12.4 days, p < 0.001); LOS > 14 days occurred in 35.8% vs. 26.6%, and LOS > 28 days in 18.5% vs. 9.2% (both p < 0.001). AMA discharge was four-fold higher among the uninsured (22.2% vs. 5.5%, p < 0.001), while unadjusted in-hospital mortality was similar (9.0% vs. 9.4%, p = 0.32). LOS and AMA disparities persisted in both IDU and non-IDU subgroups, with a six-fold AMA disparity among non-IDU patients (15.2% vs. 2.5%). Based on multivariable analysis, uninsured status remained independently associated with prolonged LOS > 28 days (adjusted odds ratio [aOR] 1.46, 95% CI 1.30–1.65), AMA discharge (aOR 3.51, 95% CI 3.10–3.97), and—after accounting for age and comorbidity differences—higher in-hospital mortality (aOR 1.25, 95% CI 1.10–1.43). Conclusions: Uninsured adults hospitalized with IE experienced longer stays, markedly higher AMA rates, and—after adjustment for age and comorbidity—higher in-hospital mortality than insured patients. These findings are consistent with nonclinical barriers to discharge—particularly limited OPAT and post-acute care access—and suggest that the younger, less comorbid profile of uninsured patients masks an underlying outcome disparity. The results identify uninsured IE patients as a population that may benefit from alternative care models and policy reforms expanding safe post-acute antimicrobial therapy.

Journal of Clinical Medicine doi: 10.3390/jcm15124737

Authors: Anna Maria Dworakowska Jolanta Małyszko Magdalena Bujalska-Zadrożny

Appropriate dose adjustment of renally eliminated medicines is central to safe pharmacotherapy in patients with chronic kidney disease; yet, in European primary care, it is systematically undermined not by lack of knowledge, but by structural misalignment between laboratory reporting, regulatory product information, and clinical guidelines. This Perspective argues that the core barrier to optimal renal dose adjustment is a mismatch between routinely reported indexed eGFR and dosing requirements based on absolute renal function, compounded by persistent regulatory reliance on the Cockcroft–Gault equation despite its known limitations. We show how these structural inconsistencies, together with patient-related factors such as frailty, ageing, and body size, generate uncertainty at the point of prescribing and contribute to persistent variability in dosing decisions. To address this challenge, we propose a structured, context-aware renal dosing framework designed for routine primary care. The framework integrates regulatory guidance, multiple methods of renal function estimation, and patient-specific modifiers into a stepwise decision process. Clinical vignettes illustrate how divergent renal function estimates and regulatory requirements can lead to different dosing decisions in everyday practice. By reframing renal dose adjustment as a context-driven clinical process rather than a purely equation-based task, this Perspective highlights the need for regulatory alignment and pragmatic decision tools to improve prescribing quality in patients with chronic kidney disease.

Journal of Clinical Medicine doi: 10.3390/jcm15124736

Authors: Ali İhsan Ökten Saygı Uygur Emre Bilgin Abdullah Kılıç Kemal Şüheda Özkavaklı Fatih Çiçek Erencan Kılcı Mehmet Babaoğlan Şahin Sancaktar Baran Uyanık Ali Harmanoğullarından

Background/Objectives: There is no consensus on whether it is possible to preserve implant retention during deep surgical site infections (SSIs), and there is no widely accepted treatment protocol to date for these patients. The aim of this study is to evaluate the efficacy of the debridement, antibiotics, and implant retention (DAIR) protocol in patients who were treated for degenerative thoracolumbar spinal disorder using spinal instrumentation. Methods: This retrospective study describes the 24-month outcomes of deep SSI that developed in 25 of 720 patients (3.5%) who underwent surgery for thoracolumbar degenerative spinal disorders (disc disease, spinal stenosis, and scoliosis) and were treated according to the DAIR protocol. Results: Of these 25 patients, 18 developed early infection (<1 month), 3 developed delayed infection (1–3 months), and 4 developed late-onset deep infection (>3 months). Staphylococcus aureus was isolated in 56% of the patients. The DAIR protocol was successful in 22 (88%) of the patients, while it failed in 3 (12%). Surgical implants were removed in 25% of patients with late-onset SSI, and only 11.1% with early onset and 0% with delayed SSI. All patients who failed DAIR were smokers. A significant association was found between the Charlson Comorbidity Index and the number of surgical interventions (p = 0.022). Conclusions: In this small retrospective cohort, the DAIR protocol appeared to be a feasible treatment option for deep SSI, particularly in early infections. Implant removal may be considered when infection persists after repeat DAIR or when implant loosening is observed.

Journal of Clinical Medicine doi: 10.3390/jcm15124735

Authors: Xiaofeng Huang Min Wang Da Wang Tao Li Zhanhua Liang

Background/Objectives: Brain dysfunction and symptoms can be improved with a sensory trick (ST) in more than 80% of patients with cervical dystonia (CD). This study aimed to investigate the functional connectivity (FC) of CD patients with different types of STs using functional near-infrared spectroscopy (fNIRS) and to explore the underlying neural mechanisms of STs. Methods: In this study, 35 CD patients (including 15 with classic STs, 15 with forcible STs, 5 with non-STs) and 29 healthy controls (HCs) underwent resting-state fNIRS. We subsequently analyzed FC differences between the groups and their correlations with clinical characteristics. Results: The grand-average FC was significantly higher in the non-ST group than in the forcible ST group. Furthermore, compared to the ST group, the non-ST group exhibited significantly increased FC, primarily involving the prefrontal and sensorimotor networks. In the forcible ST group, this hypoconnectivity was negatively correlated with disease severity scores. Conclusions: This study supports the concept of CD as a networkopathy, suggesting that both the severity and topology of cortical coherence impairment are modulated by the ST phenotype.

Journal of Clinical Medicine doi: 10.3390/jcm15124734

Authors: Zofia Pniakowska Sonia Czarkowska Natasza Kurys Maria Orłowska Piotr Jurowski

The progression of myopia in the pediatric population is currently highly prevalent. Thus, there is a need to look for new, effective methods that might suppress this pathological process. It not only affects visual comfort but also increases the risk of developing further ocular complications. The aim of the study is to review the literature and summarize contemporary methods for preventing the progression of myopia in children. The review is based on publications available on PubMed from the past 17 years, supplemented by the current literature on advanced digital technologies in ophthalmology. This article highlights that among other treatments such as orthokeratology, low-dose atropine or specialized lenses, there are also further beneficial options, including increased outdoor time, reduced screen time or the implementation of the latest medical innovations. The results indicate that defocus spectacle lenses may reduce myopia progression by approximately 50–67%, while orthokeratology has been associated with about a 46% reduction in axial elongation. Although there is a broad spectrum of therapeutic strategies, it is essential to develop novel approaches to myopia prevention in children to improve their quality of life from childhood into adulthood.

Journal of Clinical Medicine doi: 10.3390/jcm15124732

Authors: Irene M. de Graaf Annemarieke de Jonghe Nienke M. S. Golüke Esther J. M. de Brouwer Mariëlle H. Emmelot-Vonk Pim A. de Jong Lydia C. M. Kwekkeboom Huiberdina L. Koek

Background: Basal ganglia calcifications (BGCs) are frequently detected on brain CT scans in older adults, but their clinical relevance for mobility and fall risk is unclear. This study investigated the association of BGCs with impaired mobility and recurrent falls. Methods: In this cross-sectional study, all consecutive patients referred to the mobility clinic of a regional teaching hospital between 2019 and 2021 were included. Mobility was assessed using the Performance-Oriented Mobility Assessment (POMA) for balance, gait and overall mobility, and the Timed Up and Go (TUG) test for functional mobility. All assessments were performed by a trained physiotherapist. Recurrent falls were defined as self-reported occurrence of more than one fall in the past 12 months. Brain CT scans were evaluated for BGCs by a trained senior radiologist and were scored by severity. Univariable and multivariable logistic regression analyses were performed, adjusting for age, sex, and history of cardiovascular events. Results: A total of 253 participants were included (median age 82 years; 58% female), of whom 31% had BGCs. Falls data were available for 246 participants, and 70% reported recurrent falls. In both univariable and multivariable analyses, there was no evidence of a statistically significant association between the presence of BGCs and impaired balance, gait, overall mobility, functional mobility, or recurrent falls. Conclusions: No evidence of a statistically significant association was found between incidentally detected BGCs and impaired mobility or recurrent falls in older adults. Further longitudinal research is needed to confirm these findings and clarify whether BGCs are clinically relevant for mobility and fall risk assessment.

Journal of Clinical Medicine doi: 10.3390/jcm15124733

Authors: Liesbeth Van Dessel Peter Vanbrabant Liesbet Henckaerts Marc Sabbe

Background: International travel has increased over recent decades, leading to a rise in the number of patients presenting to emergency departments (EDs) with fever after returning from abroad. Evaluating fever in returning travelers is challenging because the differential diagnosis is broad, and exposure to tropical diseases limited, among most ED clinicians. Objective: This article aims to provide a practical overview of the most common travel-related causes of fever. The tool is intended to support targeted diagnostics and timely treatment and/or timely specialist referral, while emphasizing that non-travel-related infections must also be considered. Methods: We created a clinical summary of the most common causes of fever in returning travelers based on epidemiology, incubation periods, clinical features, and diagnostic approaches. A practical overview was created to aid ED clinicians in evaluating stable patients, incorporating travel history, exposure risks, and key clinical findings. Results: Malaria, dengue and typhoid fever are among the most common diagnoses in travelers returning from abroad, excluding non-travel-related diseases. These conditions share overlapping symptoms. Diagnosis relies on clinician awareness and a combination of exposure history, clinical evaluation, and targeted laboratory testing. Treatment depends on the causative pathogen and disease severity, but often requires early empiric therapy and supportive care. Conclusions: This article presents a systematic, pragmatic approach to the evaluation of fever in the returning traveler. This overview is designed to help ED clinicians recognize and make appropriate initial management and referral decisions when assessing a stable traveler. Nevertheless, we recommend specialist advice for most cases.

Journal of Clinical Medicine doi: 10.3390/jcm15124731

Authors: Małgorzata Dobrzycka Patryk Wołoszyn Magdalena Prud Ksawery Bieniaszewski Piotr Spychalski Katarzyna Gierat-Haponiuk Jarosław Kobiela

Background: Frailty is associated with adverse postoperative outcomes and functional decline in older adults undergoing colorectal cancer (CRC) surgery. The long-term course of frailty and functional outcomes among patients undergoing prehabilitation before CRC surgery remains insufficiently investigated. Methods: This prospective observational cohort study evaluated long-term functional and physiological outcomes in older adults with frailty syndrome undergoing colorectal cancer (CRC) surgery who participated in a structured prehabilitation program. Forty-one patients aged >70 years were assessed before prehabilitation and at one-year follow-up. Frailty (the Clinical Frailty Scale [CFS] and the 5-item Frailty Index [5-FI]), physical activity, postural function, respiratory parameters, and functional performance (the 6 min walk test [6MWT] and the Timed Up and Go [TUG] test) were evaluated. Results: Of the 93 eligible patients, 41 completed the one-year follow-up and were therefore included in the final analysis. A small but statistically significant increase in frailty was observed using 5-FI (mean difference = 0.029, p = 0.012), with no significant change in CFS. Postural function improved (p = 0.031), while physical activity and functional performance remained stable (6MWT: 392.71 vs. 384.36 m, p = 0.885; TUG: 12.36 vs. 10.42 s, p = 0.051). A significant reduction in pre- and post-exercise oxygen saturation was observed; however, the magnitude of change (before: −1.25%, p = 0.006; after: −0.91%, p < 0.001) was small and of uncertain relevance. Conclusions: Over a one-year follow-up of prehabilitated CRC patients with frailty, their functional performance remained stable despite a subtle progression of frailty. These findings suggest a dissociation between physiological vulnerability and functional status. Due to the observational design of the study and the lack of a control group, the results should be interpreted as descriptive rather than causal.

Journal of Clinical Medicine doi: 10.3390/jcm15124730

Authors: Titas Tiškevičius Egidija Kukarskytė Ignas Gaidamavičius Miglė Kulbokė Martyna Beitnerienė Rūta Dambrauskienė Milda Rudžianskienė Rima Jūratė Gerbutavičienė Audronė Vaitiekienė Rolandas Gerbutavičius Domas Vaitiekus

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and outcome. Results: The patient developed rapidly progressive epidermal detachment with severe oral, ocular, and genital mucosal involvement shortly after exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Disease severity was reflected by a SCORTEN score of 5, corresponding to a very high predicted mortality risk. The clinical picture raised concern for both TEN and severe acute GVHD, while histopathological findings favored TEN but were not definitive. Management included systemic corticosteroids, intravenous immunoglobulin, ruxolitinib, and intensive supportive care. The patient gradually re-epithelialized and recovered without long-term sequelae. Conclusions: This case underscores the diagnostic difficulty of distinguishing TEN from severe acute GVHD in the early post-transplant period. Careful assessment of drug exposure, clinical evolution, and multidisciplinary evaluation are essential to guide timely and appropriate management.

Journal of Clinical Medicine doi: 10.3390/jcm15124727

Authors: Gennaro Melone Paolo Luffarelli Ludovico Carbone Chiara Cascone Natale Calomino Marzio Angelo Zullo Valter Ripetti

Background: Idiopathic slow-transit constipation (STC) is a clinically significant event of chronic constipation. Total colectomy with ileorectal anastomosis is considered the standard surgical option for medically refractory STC but is associated with relevant morbidity and long-term functional impairment. This study aimed to evaluate safety and functional outcomes of partial colectomy (segmental or subtotal resection) as a potential alternative in patients with limited colonic involvement. Methods: A retrospective observational single-center study was conducted on patients with STC refractory to medical and rehabilitative treatment (1998–2021). Five-year follow-up data were collected. Results: On a cohort of 76 patients, 10 (13.2%) underwent total colectomy, 63 (82.9%) segmental, and 3 (3.9%) subtotal resections (left hemicolectomy). No perioperative mortality occurred. Overall, 30-day morbidity was 25.0%, with major complications observed in 12.1% after partial colectomy. Median hospital stay was three days longer after total colectomy. Constipation recurred in 20.3% of patients, exclusively after segmental resection, at a median follow-up of 7.7 years. Constipation severity significantly decreased postoperatively (p < 0.001), with the mean Wexner score improving from 21.5 to 6.1 (p < 0.001). Rates of diarrhea and fecal incontinence were comparable between segmental and total colectomy. Quality-of-life significantly improved in more than 75% of cases across all SF-36 domains. Conclusions: Segmental colectomy may be a safe and effective alternative to total colectomy in patients with limited STC, potentially offering durable symptom relief and favorable quality-of-life outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15124728

Authors: Jutikan Imsub Pasiri Sithinamsuwan Chanasak Hathaiareerugand Yarnisar Sakunchit Juthathip Suphanklang

Background/Objectives: Dysphagia is a prevalent consequence of neurological conditions, particularly stroke and Parkinson’s disease, leading to aspiration pneumonia and reduced quality of life. Currently, there are no specific recommendations for pharmacological therapy, although studies indicate that elevated substance P levels may improve swallowing function. While nicergoline is known to increase substance P, the role of its major metabolite, 10-methoxy-dihydro-lysergol (MDL), in this therapeutic effect remains unclear. This study examined the therapeutic effects of nicergoline and its correlation with substance P and MDL levels. Methods: This study conducted an open-label pilot study with historical controls in neurogenic patients with dysphagia. The primary outcome was improvement in the Gugging Swallowing Screen (GUSS) scores at week 12. Secondary outcomes included choking frequency, serum substance P levels, and the correlation between serum MDL levels and dysphagia enhancement. Inverse Probability Weighting (IPW) was employed to adjust for baseline confounders. Results: A total of 92 patients were analyzed: 26 in the nicergoline group (20 or 60 mg/day) and 66 in the historical control group. Compared to controls, the nicergoline group exhibited significantly higher median of GUSS scores (20 (IQR: 19–20) vs. 15 (IQR: 9–19), p < 0.001) and significantly lower median of choking frequency (6.43 (IQR 0–17) vs. 108 (IQR 13–201) 105.22, p < 0.001). The median substance P concentration in the therapy group was 4089.15 (IQR: 3336.13–4468.26) pg/mL. Patients receiving nicergoline showed a statistically significant elevation in substance P from baseline (p < 0.001). Pearson analysis revealed a negligible correlation between serum MDL and substance P levels (R2 = 0.0349). Conclusions: Preliminary findings suggest that nicergoline may be associated with improvements in swallowing function in neurogenic dysphagia and a potential increase in substance P levels. The lack of correlation with serum MDL suggests that efficacy may not linearly depend on circulating metabolite concentrations. Further large-scale randomized controlled trials are warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15124729

Authors: Sami Uyar Hatice Eyiol Ahmet Yılmaz Azmi Eyiol Yakup Alsancak

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis-3 definition), associated with high mortality in intensive care unit (ICU) patients. Composite immune–nutritional indices derived from routine laboratory data have emerged as accessible prognostic tools; however, their comparative value in critically ill septic patients remains insufficiently characterised. This study aimed to compare the prognostic performance of the haemoglobin–albumin–lymphocyte–platelet (HALP) score, pan-immune-inflammation value (PIV), and Naples Prognostic Score (NPS) for predicting in-hospital mortality in ICU patients with sepsis as the primary outcome, and to assess their incremental predictive value as the secondary objective. Methods: In this retrospective, two-centre cohort study, 1020 consecutive eligible adult patients fulfilling Sepsis-3 criteria (suspected or confirmed infection with an acute increase in SOFA score ≥ 2 points) admitted to the ICUs of Necmettin Erbakan University Hospital and Beyhekim Training and Research Hospital between January 2016 and June 2025 were included. HALP was calculated as haemoglobin (g/L) × albumin (g/L) × lymphocyte count (×109/L) ÷ platelet count (×109/L); PIV as (neutrophil × platelet × monocyte) ÷ lymphocyte (all ×109/L). NPS was computed from serum albumin, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio, with the total-cholesterol component imputed due to availability in only 31.7% of patients. Discriminative performance was evaluated by receiver operating characteristic (ROC) analysis, pairwise DeLong tests, bootstrap resampling (1000 iterations), Hosmer–Lemeshow calibration, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analyses. Five pre-specified nested multivariable logistic regression models were constructed. Results: Of 1020 patients (median age 76 years, IQR 67–83; 59.8% male), 521 (51.1%) died during hospitalisation. HALP showed the highest discriminative ability among individual indices (AUC 0.626, 95% CI 0.594–0.658), while PIV was non-discriminatory (AUC 0.504, p = 0.78) and NPS showed limited performance (AUC 0.563, 95% CI 0.531–0.595). HALP remained an independent predictor of mortality after multivariable adjustment (OR 0.98, 95% CI 0.97–0.99, p = 0.002). NRI and IDI analyses showed no incremental value with NPS addition. Conclusions: HALP demonstrated modest but independently consistent discrimination for in-hospital mortality in ICU patients with sepsis, outperforming PIV and NPS. However, an AUC of 0.626 does not support standalone clinical use; external validation and comparison with established severity models are required before integration into risk stratification frameworks.