Journal of Clinical Medicine

15 pages, 600 KB

Open AccessArticle

Survival Outcomes of Open Versus Robot-Assisted Radical Cystectomy: A Large-Scale Multicenter Propensity Score Matched Study

by Jong Ho Park, Sangchul Lee, Seung-Hwan Jeong, Ja Hyeon Ku, Kyung Hwan Kim, Jong Kil Nam, Bumjin Lim, BumSik Hong, Wook Nam, Sung Gu Kang, Seok Ho Kang, Tae Gyun Kwon, Tae-Hwan Kim, Jieun Heo, Won Sik Ham, Geehyun Song, Ho Kyung Seo, Wan Song, Hyun Hwan Sung, Byong Chang Jeong and Jong Jin Oh Show full author list Hide full author list

J. Clin. Med. 2026, 15(9), 3559; https://doi.org/10.3390/jcm15093559 - 6 May 2026

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Abstract

Background/Objectives: While robot-assisted radical cystectomy (RARC) is widely adopted, its long-term survival impact relative to open radical cystectomy (ORC) remains uncertain. We compared survival outcomes between ORC and RARC using a propensity score-matched multicenter cohort. Methods: We retrospectively analyzed 3972 radical [...] Read more.

Background/Objectives: While robot-assisted radical cystectomy (RARC) is widely adopted, its long-term survival impact relative to open radical cystectomy (ORC) remains uncertain. We compared survival outcomes between ORC and RARC using a propensity score-matched multicenter cohort. Methods: We retrospectively analyzed 3972 radical cystectomy patients from 11 Korean tertiary centers between 2003 and 2024. After stratifying by surgical approach (ORC vs. RARC), 1:1 propensity score matching (PSM) mitigated baseline imbalances. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were evaluated using Kaplan–Meier and multivariable Cox analyses. Results: PSM yielded 473 well-balanced patients per group. Compared to ORC, RARC was associated with a longer operative time but demonstrated a superior perioperative profile, including reduced estimated blood loss, lower intraoperative transfusion rates, shorter hospital stays, higher lymph node yields, and lower positive margin rates. RARC significantly improved OS (5-year: 75.4% vs. 56.1%; 10-year: 68.3% vs. 44.5%; p < 0.001) and CSS (5-year: 88.1% vs. 71.6%; 10-year: 82.7% vs. 67.7%; p < 0.001), with comparable RFS (5-year: 59.6% vs. 54.8%; 10-year: 51.1% vs. 47.4%; p = 0.155). Multivariable analyses confirmed RARC as an independent predictor of improved OS (hazard ratio [HR] 0.564, p < 0.001) and CSS (HR 0.474, p < 0.001). Conclusions: RARC demonstrated superior perioperative outcomes and favorable survival trends compared to ORC, with no difference in RFS. Although RARC appears to be an oncologically safe alternative, these exploratory survival benefits require cautious interpretation due to potential residual confounding. Further prospective validation is warranted. Full article

(This article belongs to the Special Issue Innovations in Surgical and Medical Approaches of Urologic Oncology)

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22 pages, 999 KB

Open AccessArticle

Systemic Inflammatory and Hematologic Biomarkers in Pediatric Dental Caries: Clear Group Differences with Limited Independent Association with DMFT

by Ștefania Alice Petrache, Mihail Virgil Boldeanu, Oana Andreea Diaconu, Adelina Smaranda Bugălă, Mădălina Olteanu, Ionela Teodora Dascălu, Andreea Gabriela Nicola, Maria Cristina Beznă, Marilena Bătăiosu and Mihaela Jana Țuculină

J. Clin. Med. 2026, 15(9), 3558; https://doi.org/10.3390/jcm15093558 - 6 May 2026

Cited by 2 | Viewed by 725

Abstract

Background: Dental caries in children has been explored not only as a local oral condition but also in relation to potential systemic inflammatory changes. This study evaluated systemic inflammatory biomarkers and hematologic indices in children with dental caries and examined their association with [...] Read more.

Background: Dental caries in children has been explored not only as a local oral condition but also in relation to potential systemic inflammatory changes. This study evaluated systemic inflammatory biomarkers and hematologic indices in children with dental caries and examined their association with caries severity, as assessed by the DMFT index. Methods: In this exploratory cross-sectional sibling-controlled study, 114 participants were included: 75 children with dental caries and 39 unaffected siblings serving as controls. All participants underwent blood testing, including inflammatory biomarkers (TNF-α, NGAL) and hematologic indices (NLR, LMR, PLR, IIC, MCVL, SII, SIRI, AISI). Group comparisons were performed using parametric or nonparametric tests, depending on data distribution. Correlation analyses were conducted within the caries group. Age- and sex-adjusted univariate and multivariable linear regression models were used to identify predictors of DMFT, and logistic regression was applied to evaluate associations with high caries burden (DMFT ≥ 6). Results: Children with caries showed higher NGAL, PLR, and MCVL, and lower LMR than controls, while IIC showed a non-significant upward trend. Correlation analysis revealed strong associations among several inflammatory indices, largely reflecting shared computational components. DMFT showed a modest positive correlation with LMR, whereas associations with classical inflammatory biomarkers such as TNF-α and NGAL were weak or absent. In age- and sex-adjusted models, several markers showed borderline associations with DMFT, but none remained independently significant in multivariable analyses. Age was the strongest predictor of DMFT, while sex showed no significant effect. Logistic regression for high DMFT confirmed age as the only significant determinant. Conclusions: In this exploratory pediatric cohort, children with dental caries showed differences in selected systemic inflammatory and hematologic biomarkers compared with unaffected siblings. However, most biomarkers showed only limited independent associations with caries severity after adjustment, with age emerging as the primary determinant of DMFT. These findings suggest that systemic inflammatory markers have limited independent explanatory value for caries severity and should be interpreted as exploratory rather than clinically definitive. Full article

(This article belongs to the Special Issue Oral Health and Dental Care: Current Advances and Future Options)

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13 pages, 404 KB

Open AccessArticle

Low HPV16 E6 Seroprevalence in HNSCC: A Prospective Study in Brazil

by Enes Buck Mutiua Cantala Xavier, Camila Batista Daniel, Priscila Marinho de Abreu, Isabella Bittencourt do Valle, Brena Ramos Athaydes, Frederico Firme Figueira, Agenor Sena, Evandro Duccini de Souza, Tim Waterboer and Sandra Ventorin von Zeidler

J. Clin. Med. 2026, 15(9), 3557; https://doi.org/10.3390/jcm15093557 - 6 May 2026

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Abstract

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) remains a global public health challenge with significant morbidity and mortality. Emerging epidemiological data indicate a rising global incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Serology for early HPV antigens has been [...] Read more.

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) remains a global public health challenge with significant morbidity and mortality. Emerging epidemiological data indicate a rising global incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Serology for early HPV antigens has been highlighted as a relevant biomarker for HPV-associated OPSCC. This study aimed to determine the seroprevalence of HPV16 E6 antibodies in HNSCC patients in the state of Espírito Santo, Brazil. Methods: This is a prospective longitudinal cohort study in which 287 patients with HNSCC were enrolled, recruited from two oncology centers in Espírito Santo between 2011 and 2018, along with 68 cancer-free individuals. Serum samples were analyzed using the HPV16 E6 GST Capture ELISA assay. Statistical analysis was performed using SPSS. Binary logistic regression was employed to identify independent predictors of seropositivity. Results: The overall seroprevalence of HPV16 E6 antibodies was 7.3%. Seropositivity was observed in tumors of the oral cavity (6.2%) and oropharynx (13.3%). Patients with OPSCC demonstrated a significantly higher likelihood of seropositivity compared to those with tumors of the oral cavity, larynx, and hypopharynx (OR = 2.96, 95% CI: 1.21–7.28, p = 0.018). The highest frequency of HPV16 E6-positive cases occurred in tumors of the palatine tonsils (OR = 6.00; 95% CI: 1.58–22.89; p < 0.009). No seropositive cases were observed in hypopharyngeal or laryngeal tumors. Among patients with OPSCC and oral cavity squamous cell carcinoma (OCSCC), HPV16 E6 serostatus did not significantly correlate with sociodemographic, behavioral, or clinical tumor characteristics. Conclusions: Our findings reinforce the predilection of HPV-associated carcinogenesis for the oropharynx, more specifically in the palatine tonsils. In addition, this study highlights HPV16 E6 serology as a potential biomarker for HPV-driven OPSCC and underscores Brazil’s epidemiological heterogeneity, warranting standardized clinical validation. Full article

(This article belongs to the Section Oncology)

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15 pages, 288 KB

Open AccessArticle

Artificial Intelligence vs. Human Readers in Contrast-Enhanced Harmonic Imaging Endoscopic Ultrasound Interpretation of Solid Pancreatic Masses: A Multicenter Interobserver Study

by Nicoleta Podină, Lucian Gheorghe Gruionu, Anca Udriștoiu, Elena Codruța Gheorghe, Voicu Rednic, Alina Liliana Constantin, Maria Simona Badiu, Cristian George Țieranu, Nona Bejinariu, Cristina Pojoga, Claudia Hagiu, Andrada Seicean and Adrian Săftoiu

J. Clin. Med. 2026, 15(9), 3556; https://doi.org/10.3390/jcm15093556 - 6 May 2026

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Abstract

Background/Objectives: Contrast-enhanced harmonic imaging endoscopic ultrasound (CHI-EUS) is a valuable tool for characterizing solid pancreatic tumors. However, interobserver variability remains a significant limitation in clinical interpretation. Artificial intelligence (AI) may offer objective, reproducible assessments, potentially enhancing diagnostic performance. This study compared the diagnostic [...] Read more.

Background/Objectives: Contrast-enhanced harmonic imaging endoscopic ultrasound (CHI-EUS) is a valuable tool for characterizing solid pancreatic tumors. However, interobserver variability remains a significant limitation in clinical interpretation. Artificial intelligence (AI) may offer objective, reproducible assessments, potentially enhancing diagnostic performance. This study compared the diagnostic accuracy and interobserver agreement of nine physicians with varying CHI-EUS experience levels vs. a dedicated AI system and a general-purpose large language model (ChatGPT) on the same 118 histologically confirmed cases. Methods: We conducted a prospective, multicenter, observer-blinded study involving 118 CHI-EUS video cases of histologically confirmed (EUS-FNB) focal pancreatic masses from three tertiary care centers in Romania. Nine readers were stratified into three groups: trainees (<5 years CHI-EUS experience), intermediates (5–10 years), and experts (>10 years). All readers and two AI models received standardized, anonymized 2 min CHI-EUS video clips. A dedicated AI system used a convolutional neural network (CNN) for lesion segmentation and time–intensity curve (TIC) extraction, followed by a feedforward neural network (FNN) for classification. ChatGPT was separately evaluated on the same videos. Diagnostic metrics (accuracy, sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and AUROC) were calculated. Interobserver agreement was assessed using Fleiss’ and Cohen’s kappa statistics. Results: The dedicated AI system achieved an overall accuracy of 95.8% (sensitivity 96.6%; specificity 94.1%) in diagnosing pancreatic adenocarcinoma. Expert readers had a mean accuracy of 78.8% (sensitivity 86%, specificity 61%, and AUROC 0.74), intermediates 80.8% (sensitivity 83%, specificity 75%, and AUROC 0.84), and trainees had a mean accuracy of 67.2% (sensitivity 70%, specificity 60%, and AUROC 0.67). For the most-likely-diagnosis parameter, interobserver agreement was similar between intermediates (Fleiss’ κ = 0.407) and experts (κ = 0.389), while trainees showed lower agreement (κ = 0.203). ChatGPT correctly classified only 14.1% of PDAC cases. Conclusions: A specialized AI model for CHI-EUS video analysis can achieve expert-level performance and reduce diagnostic variability across experience levels. Integration of dedicated AI systems into CHI-EUS interpretation may enhance accuracy and serve as a valuable decision support tool in clinical and training settings. Full article

(This article belongs to the Special Issue Pancreatic Disorder, Pancreatitis, and Pancreatic Cancer: Interconnections, Clinical Challenges, and Therapeutic Advances)

15 pages, 411 KB

Open AccessArticle

Peripapillary Vessel Density Mediates the Relationship Between Axial Length and Visual Field Damage in Glaucoma

by Samuel Potash, Alon Harris, Alice Verticchio Vercellin, Keren Wood, Gal Yaakov Cohen, Adam Rosen, Minwoo Kwon, Jacob Rothstein, Yash Lahoti, Lucia Tanga, Carmela Carnevale and Brent A. Siesky

J. Clin. Med. 2026, 15(9), 3555; https://doi.org/10.3390/jcm15093555 - 6 May 2026

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Abstract

Objectives: Axial myopia is a risk factor for glaucoma, yet the mechanism(s) linking axial length (AL) to visual field (VF) damage remain unclear. This pilot study investigates to what extent peripapillary vessel density (pVD) mediates the relationship between AL and VF outcomes in [...] Read more.

Objectives: Axial myopia is a risk factor for glaucoma, yet the mechanism(s) linking axial length (AL) to visual field (VF) damage remain unclear. This pilot study investigates to what extent peripapillary vessel density (pVD) mediates the relationship between AL and VF outcomes in patients with primary open-angle glaucoma (POAG). Methods: This cross-sectional pilot study included a primary cohort of 26 POAG eyes with directly measured AL, with an exploratory expanded cohort of 71 POAG eyes used to assess the consistency of findings. Optical coherence tomography angiography quantified pVD across eight sectors. VF outcomes included mean deviation, pattern standard deviation, and visual field index. Mediation analyses used ordinary least squares regression adjusted for age, intraocular pressure, and scan quality. Indirect effects were assessed via bias-corrected bootstrap confidence intervals. Results: In both primary and expanded cohorts, inferior-temporal pVD mediated the relationship between AL and all VF outcomes. Additional sectors emerged as mediators in the expanded cohort, suggesting broader vascular involvement. Conclusions: Peripapillary microvascular compromise significantly mediates the impact of AL on glaucomatous VF loss, supporting a possible biomechanical–vascular model of POAG eyes across a range of axial lengths. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases—Mechanisms, Diagnostics, and Emerging Therapies)

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12 pages, 2985 KB

Open AccessArticle

Clinicopathological Characteristics of Acute Antibody-Mediated Rejection in Pediatric Liver Transplantation—A Single-Center Study

by Sylwia Szymanska, Barbara Piątosa, Mateusz Ciopiński, Artur Kijewski, Piotr Kaliciński and Małgorzata Markiewicz-Kijewska

J. Clin. Med. 2026, 15(9), 3554; https://doi.org/10.3390/jcm15093554 - 6 May 2026

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Abstract

Introduction: Presently, liver transplantation is becoming a more common treatment option for adults and children suffering from liver failure. Antibody-mediated rejection (AMR), a phenomenon that is exceedingly uncommon and inadequately comprehended, may induce graft dysfunction. The objective of the investigation was to evaluate [...] Read more.

Introduction: Presently, liver transplantation is becoming a more common treatment option for adults and children suffering from liver failure. Antibody-mediated rejection (AMR), a phenomenon that is exceedingly uncommon and inadequately comprehended, may induce graft dysfunction. The objective of the investigation was to evaluate the clinical and histopathological manifestations of AMR in pediatric patients. Material and methods: The retrospective study comprised sixty-two liver core biopsies from forty-two pediatric patients. In a total of 10 biopsies, 7 children were diagnosed with AMR, while 35 of them exhibited features of acute T-cell-mediated rejection (TCMR) in 52 biopsies. The C4d binding assay was conducted in all biopsies using the immunohistochemical (IHC) method. Bilirubinostasis, steatosis and acute and chronic rejection were re-assessed in all specimens. The 6-grade Ishak scale was employed to evaluate fibrosis. The TCMR activity was established using the Banff classification. AMR was assessed according to a novel histopathological grading system that was developed by the authors. Depending on the type of rejection, the relationship between histopathological grading, morphological characteristics, and laboratory parameters was established for each group. Standard methods were implemented to conduct statistical analysis. Results: At the time of biopsy, the median age of patients was 47.6 months (15.03–98.83) and the median time from transplantation was 0.9 months (0.3–7.6). The study’s findings provided evidence that histopathological lesions were the least specific manifestation, which supported the presence of AMR. A positive C4d staining statistically increases the likelihood of AMR diagnosis, whether or not there are associated morphological abnormalities. The type of rejection and laboratory tests did not exhibit any statistically significant correlation. Conclusions: The diagnosis of AMR in a transplanted liver is intricate and requires a multifaceted approach. However, the proposed histopathological grading may be a helpful method for selecting patients who should be assessed for donor-specific antibodies (DSAs) or in whom AMR should be suspected when DSAs cannot be determined. Full article

(This article belongs to the Special Issue Clinical Advances in Pediatric Critical Care Medicine)

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13 pages, 1088 KB

Open AccessArticle

Evaluating Dry Eye Disease Subtypes Based on Whole-Area Lipid Layer Thickness Assessment

by Hyunmin Ahn, Young Joon Choi, Ikhyun Jun, Tae-im Kim and Kyoung Yul Seo

J. Clin. Med. 2026, 15(9), 3553; https://doi.org/10.3390/jcm15093553 - 6 May 2026

Cited by 1 | Viewed by 585

Abstract

Background/Objectives: Lipid layer thickness (LLT) is widely used to assess tear film status in dry eye disease (DED), but single-point measurements may not adequately reflect spatial lipid distribution driven by tear film dynamics. This study evaluated whether the combined assessment of inferior and [...] Read more.

Background/Objectives: Lipid layer thickness (LLT) is widely used to assess tear film status in dry eye disease (DED), but single-point measurements may not adequately reflect spatial lipid distribution driven by tear film dynamics. This study evaluated whether the combined assessment of inferior and superior corneal LLT provides additional clinical relevance for interpreting DED subtypes. Methods: This cross-sectional study included 614 eyes of 614 patients with DED. Inferior corneal LLT (LLT_inf) was measured using a tear interferometer, and superior corneal LLT (LLT_sup) was graded using an LED-based slit-lamp assessment. DED parameters, including meibomian gland expressibility (MGE), meibum quality, tear meniscus height, Schirmer I test, and fluorescein tear break-up patterns, were analyzed. Results: Low LLT_inf showed worse meibomian gland function, with higher MGE scores than in the high LLT_inf group (1.9 ± 0.8 vs. 1.2 ± 0.9, p < 0.001). Higher LLT_inf was associated with lower aqueous parameters, and aqueous deficiency was observed in 57.4% of the high LLT_inf group increasing to 83.0% when LLT_sup was low. Combined LLT_inf–LLT_sup assessment improved the prediction of aqueous deficiency compared with LLT_inf alone (AUC, 0.719 vs. 0.559). Improvement for moderate-to-severe MGD was smaller (AUC 0.731 vs. 0.653). Conclusions: LLT reflects not only lipid secretion, but also aqueous-driven distribution. The combined assessment of LLT_inf and LLT_sup may improve the interpretation of LLT findings and provide additional insight into tear film dynamics in DED. However, its predictive performance remains moderate, suggesting that this approach is considered a complementary interpretive framework rather than a standalone diagnostic tool. Full article

(This article belongs to the Special Issue Meibomian Gland Dysfunction and Dry Eye Diseases)

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13 pages, 930 KB

Open AccessCase Report

Phenotypic Heterogeneity in Titinopathies with Peripheral Nerve Involvement in Pediatric Age: Two Case Reports

by Carlo Alberto Cesaroni, Giulia Pisanò, Massimiliano Marton, Stefano Giuseppe Caraffi, Susanna Rizzi, Agnese Pantani, Diletta Ziveri, Marzia Pollazzon, Juha Koskenvuo, Daniele Frattini and Carlo Fusco

J. Clin. Med. 2026, 15(9), 3552; https://doi.org/10.3390/jcm15093552 - 6 May 2026

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Abstract

Background/Objectives: Titin (TTN; OMIM 188840) is the largest known human sarcomeric protein, and pathogenic variants in the TTN gene cause a broad spectrum of inherited myopathies and cardiomyopathies. The extent to which TTN variants may also involve the peripheral nervous system remains poorly [...] Read more.

Background/Objectives: Titin (TTN; OMIM 188840) is the largest known human sarcomeric protein, and pathogenic variants in the TTN gene cause a broad spectrum of inherited myopathies and cardiomyopathies. The extent to which TTN variants may also involve the peripheral nervous system remains poorly defined. We aimed to describe two pediatric patients carrying heterozygous truncating TTN variants with neurophysiological evidence of peripheral nerve involvement, and to review the existing literature on this underrecognized association. Pathogenic variants in the TTN gene are associated with a wide spectrum of inherited myopathies and cardiomyopathies. To date, peripheral neur opathy has not been recognized as a defining feature of TTN-related disorders, and neurophysiological investigations in affected individuals typically demonstrate normal or myopathic findings without evidence of a primary neuropathic process. Here, we report two pediatric patients with heterozygous truncating TTN variants and neurophysiological evidence of bilateral axonal involvement of the deep peroneal nerve. Methods: This case report was structured and reported according to the CARE guidelines. Genetic testing was performed using whole-exome sequencing (Blueprint Genetics Whole Exome Family Test). Nerve conduction studies and needle electromyography were performed using the Galileo NT system. Variant classification followed current ACMG guidelines. Results: The first patient, a 10-year-old girl, presented with a symptomatic distal motor phenotype characterized by bilateral pes cavus, anterior compartment muscle atrophy, areflexia, and steppage gait with onset in early childhood. The second patient, an 8-year-old boy, had subclinical bilateral axonal neuropathy identified during neurophysiological evaluation prompted by intermittent lower limb pain; his father, carrying the same variant, showed concordant neurophysiological abnormalities. In both cases, nerve conduction studies demonstrated reduced compound muscle action potential amplitudes with preserved conduction velocities and distal latencies, consistent with axonal neuropathy. Whole-exome sequencing excluded other established genetic causes of inherited neuropathy in both probands. Conclusions: Although a causal relationship cannot be established, these observations raise the possibility that peripheral nerve involvement may represent an underrecognized feature of the titinopathy spectrum. Prospective studies in larger cohorts of TTN variant carriers are needed to clarify the prevalence and pathophysiological basis of neuropathy in this context. Full article

(This article belongs to the Section Clinical Pediatrics)

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12 pages, 1532 KB

Open AccessArticle

Clinical Characteristics and Treatment Outcomes of Pediatric Glaucoma: A Retrospective Cohort Study

by Nancy N. Hanna, Doris Canes Napoles, Aaron Flickinger, Carter L. Carlos, Richard W. Hertle and Xiaoming Gong

J. Clin. Med. 2026, 15(9), 3551; https://doi.org/10.3390/jcm15093551 - 6 May 2026

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Abstract

Objectives: This study aimed to evaluate clinical characteristics and treatment outcomes in a cohort of pediatric patients with glaucoma over 10-year period at a tertiary referral center. Methods: Medical records of patients younger than 18 years diagnosed with glaucoma between 1 [...] Read more.

Objectives: This study aimed to evaluate clinical characteristics and treatment outcomes in a cohort of pediatric patients with glaucoma over 10-year period at a tertiary referral center. Methods: Medical records of patients younger than 18 years diagnosed with glaucoma between 1 January 2013 and 31 December 2023 were retrospectively reviewed. Diagnoses were classified according to the Childhood Glaucoma Research Network (CGRN). Demographic data, clinical characteristics and surgical outcomes were analyzed. Statistical analyses included Student’s t-test, one-way ANOVA, and corresponding non-parametric methods (α = 0.05). Results: A total of 105 patients (168 eyes) were included, with a mean age of 5.52 ± 5.61 years, and a mean duration of follow-up of 5.41 ± 3.37 years. Mean baseline intraocular pressure (IOP) was 24.41 ± 10.85 mmHg. Secondary glaucoma was the predominant category (69%), led by glaucoma following cataract surgery (26%). Bilateral disease occurred in 60% of cases, more frequently in secondary forms. Surgery was performed in 57.4% of glaucomatous eyes. All subtypes except glaucoma following cataract surgery (GFCS) achieved significant reductions in IOP from baseline (p < 0.01). Despite effective IOP control, final visual acuity remained limited in many patients, especially those with glaucoma associated with non-acquired ocular anomalies or following cataract surgery. Worse baseline vision and higher presenting IOP were associated with poorer final acuity. Conclusions: Secondary glaucoma, particularly GFCS, was the most common form of pediatric glaucoma in this cohort. Although IOP control was generally successful, visual outcomes frequently remained suboptimal, highlighting the importance of early detection, comprehensive management, and close long-term monitoring. Full article

(This article belongs to the Special Issue Clinical Outcomes of Glaucoma Surgery: Visual Acuity, Effectiveness and Quality of Life)

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18 pages, 619 KB

Open AccessReview

Cognitive Impairment as a Putative Mechanism of Self-Management Failure in Chronic Obstructive Pulmonary Disease: A Conceptual Narrative Review

by Maryam M. Almulhem and Rayan A. Siraj

J. Clin. Med. 2026, 15(9), 3550; https://doi.org/10.3390/jcm15093550 - 6 May 2026

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Abstract

Background/Objectives: Chronic obstructive pulmonary disease (COPD) management increasingly relies on patient self-management; however, medication non-adherence, inhaler misuse, delayed exacerbation recognition, and suboptimal engagement in pulmonary rehabilitation remain highly prevalent across disease stages. Cognitive impairment is increasingly recognised in this population, particularly in moderate-to-severe [...] Read more.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) management increasingly relies on patient self-management; however, medication non-adherence, inhaler misuse, delayed exacerbation recognition, and suboptimal engagement in pulmonary rehabilitation remain highly prevalent across disease stages. Cognitive impairment is increasingly recognised in this population, particularly in moderate-to-severe disease and in those with greater systemic burden, yet it is most often treated as a descriptive comorbidity rather than a determinant of disease control. Methods: This conceptual narrative review synthesises biological, neuropsychological, and clinical evidence to examine the extent to which cognitive impairment contributes to variability in self-management performance and clinical outcomes, and to propose a structured framework linking disease burden, neurocognitive vulnerability, behavioural execution, and downstream outcomes. Results: COPD-related processes—including chronic hypoxaemia, hypercapnia, systemic inflammation, oxidative stress, vascular comorbidity, and recurrent exacerbations—provide biologically plausible pathways to neurocognitive vulnerability. Reported deficits in executive function, attention, working memory, processing speed, and visuomotor integration may affect the execution of cognitively demanding tasks central to disease management, including inhaler technique, medication adherence, symptom appraisal, and sustained participation in pulmonary rehabilitation. Across studies, cognitive impairment is consistently associated with inhaler errors, reduced adherence and independence, rehabilitation dropout, impaired symptom recognition, increased healthcare utilisation, functional decline, and mortality. Conclusions: Collectively, these findings support the interpretation that cognitive vulnerability may act as an intermediary mechanism through which disease burden translates into behavioural instability and adverse outcomes. Although this framework remains hypothesis-generating, it provides a coherent basis for future longitudinal and interventional studies to formally evaluate the mediating role of cognition in disease management and outcome trajectories. Full article

(This article belongs to the Special Issue Advances in the Management and Understanding of Adult Respiratory Diseases)

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17 pages, 931 KB

Open AccessArticle

Pre-Transplant Prognostic Nutritional Index Independently Predicts Progression-Free Survival After Autologous Stem Cell Transplantation in Lymphoma

by Hüseyin Atacan, Volkan Aslan, Alper Topal, Nurlan Mammadzada, Gizem Yıldırım, Gökçe Gül Güneysu, Berkan Karadurmuş, Esmanur Kaplan Tüzün, Ömer Faruk Kuzu, Efe Cem Erdat, Musa Barış Aykan, İsmail Ertürk and Nuri Karadurmuş

J. Clin. Med. 2026, 15(9), 3549; https://doi.org/10.3390/jcm15093549 - 6 May 2026

Cited by 1 | Viewed by 473

Abstract

Background: Autologous stem cell transplantation (ASCT) is a standard treatment for relapsed or high-risk lymphoma. While disease-related factors are well-known, the impact of host-related factors like nutritional status remains less defined. We aimed to evaluate the prognostic value of the prognostic nutritional index [...] Read more.

Background: Autologous stem cell transplantation (ASCT) is a standard treatment for relapsed or high-risk lymphoma. While disease-related factors are well-known, the impact of host-related factors like nutritional status remains less defined. We aimed to evaluate the prognostic value of the prognostic nutritional index (PNI) and other factors in lymphoma patients undergoing ASCT. Methods: We conducted a single-center retrospective cohort study including adult patients with Hodgkin and non-Hodgkin lymphoma who underwent ASCT between January 2015 and December 2023. Pre-transplant clinical, laboratory, and transplant-related variables were analyzed. The prognostic nutritional index (PNI) was calculated using serum albumin and absolute lymphocyte count and dichotomized according to the cohort median. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier and Cox regression analyses. We conducted a retrospective single-center cohort study including adult patients with Hodgkin and non-Hodgkin lymphoma who underwent ASCT between January 2015 and December 2023. Results: A total of 43 patients were included. Median age was 38 years, and 72.1% were male. Patients transplanted in complete remission (CR) had significantly longer PFS compared with those transplanted in partial remission (PR) (log-rank p = 0.022). Patients with higher pre-ASCT PNI demonstrated significantly improved PFS (median 45 vs. 7 months; log-rank p = 0.021). In multivariable Cox regression analysis, both higher PNI (HR 0.39; 95% CI 0.16–0.97; p = 0.043) and complete remission prior to ASCT (HR 0.41; 95% CI 0.17–0.98; p = 0.046) remained independently associated with improved PFS. Higher infused CD34⁺ (hematopoietic stem cell) dose was associated with shorter hospitalization but showed no statistically significant association with engraftment kinetics or survival. No variable was independently associated with OS, likely due to the limited number of death events. Conclusions: Pre-transplant prognostic nutritional index and disease response independently predict progression-free survival after ASCT in lymphoma. These findings highlight the complementary role of host-related and disease-related factors in transplant outcomes and suggest that PNI may serve as a practical tool for pre-transplant risk stratification and patient optimization. Given the small sample size and limited number of events, these findings should be interpreted with caution. Full article

(This article belongs to the Section Oncology)

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13 pages, 1584 KB

Open AccessFeature PaperArticle

Suture Versus Non-Suture Closure of the Cystic Duct Orifice During Fenestrating Laparoscopic Subtotal Cholecystectomy: A Single-Center Retrospective Study

by Hiroto Sakurai, Kei Nakagawa, Shingo Tsujinaka, Kenichiro Yambe, Kazuhiro Takami, Noriko Kondo, Kuniharu Yamamoto, Chikashi Shibata and Yu Katayose

J. Clin. Med. 2026, 15(9), 3548; https://doi.org/10.3390/jcm15093548 - 6 May 2026

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Abstract

Background/Objectives: Laparoscopic subtotal cholecystectomy (LSC) can be performed using either the fenestrating or reconstituting method. In the fenestrating method, some surgeons additionally perform suture closure of the cystic duct orifice, whereas others do not. However, evidence regarding the clinical significance of suture closure [...] Read more.

Background/Objectives: Laparoscopic subtotal cholecystectomy (LSC) can be performed using either the fenestrating or reconstituting method. In the fenestrating method, some surgeons additionally perform suture closure of the cystic duct orifice, whereas others do not. However, evidence regarding the clinical significance of suture closure remains limited. Methods: Between April 2018 and December 2023, 934 patients underwent cholecystectomy at our institution. Among them, 37 underwent LSC because standard cystic duct control could not be achieved intraoperatively. Of these, 34 were treated with the fenestrating method. Among these 34 patients, 27 did not undergo suture closure of the cystic duct orifice (non-suture group), while 7 underwent suture closure (suture group). Perioperative outcomes were retrospectively compared between the groups. Results: No statistically significant differences were observed between the groups in operative time, drain retention period, postoperative hospital stay, postoperative bile leakage, or the need for postoperative endoscopic treatment. Similar findings were observed in exploratory subgroup analyses among patients with intraoperative bile flow from the cystic duct orifice (IBF) and within the non-suture group according to the presence or absence of IBF. No reoperations, readmissions, or deaths occurred in either group. However, postoperative bile leakage (11/27 [40.7%] vs. 1/7 [14.3%]) and endoscopic treatment (7/27 [25.9%] vs. 1/7 [14.3%]) were more frequent in the non-suture group, although not statistically significant. Conclusions: In this small retrospective single-institution cohort, no statistically significant differences in perioperative outcomes were observed between patients with or without suture closure of the cystic duct orifice during fenestrating LSC. However, the non-suture group showed a trend toward higher rates of postoperative bile leakage and endoscopic treatment. These hypothesis-generating findings should be interpreted cautiously. Full article

(This article belongs to the Special Issue Approaches to Prevention and Management of Postoperative Complications in Minimally Invasive Surgery)

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21 pages, 4756 KB

Open AccessReview

A Scoping Review of Gut Dysbiosis and Malnutrition in Neurological Disorders: Implications, Indications, and Promising Therapeutic Approaches

by Thana’ Aljaraedah, Sameeha Al-Thnaibat, Abd Al-Rhman Nawasreh, Wesal Alraei and Esra’a Al-Trad

J. Clin. Med. 2026, 15(9), 3547; https://doi.org/10.3390/jcm15093547 - 6 May 2026

Viewed by 535

Abstract

Background/Objectives: Neurological diseases are increasing worldwide, but the biological processes underlying these diseases remain poorly understood, and existing treatments have been ineffective at arresting disease progression. Emerging data indicate that dysbiosis of the microbiota–gut–brain axis and malnutrition are comorbid factors in neurological [...] Read more.

Background/Objectives: Neurological diseases are increasing worldwide, but the biological processes underlying these diseases remain poorly understood, and existing treatments have been ineffective at arresting disease progression. Emerging data indicate that dysbiosis of the microbiota–gut–brain axis and malnutrition are comorbid factors in neurological dysfunction. Methods: An extended search strategy was developed using a multifaceted approach across various databases to identify eligible studies published between January 2010 and February 2026. Results: Results showed uniform relationships among neurological conditions, loss of microbial richness, loss of short-chain fatty acid-producing bacteria, neuroinflammation, and nutritional susceptibility. The review also identifies methodological trends in microbiome profiling and nutritional assessment and suggests an integrative framework of symptom-linked microbial imbalance, malnutrition, and inflammatory processes. Conclusions: Although dietary modulation and microbiome-targeted interventions appear promising, the evidence is mostly correlational. Longitudinal and interventional studies should be well-designed to elucidate causal mechanisms and to provide effective clinical strategies. Full article

(This article belongs to the Topic Environmental Influences on Dietary Patterns and Disease Risk: Nutritional Pathways and Health Implications)

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11 pages, 724 KB

Open AccessArticle

Atherosclerosis Progression Evaluation in Coronary Arteries by Computed Tomography Compared to Peripheral Vessels Using 3D Ultrasonography

by Maria Noflatscher, Michael Schreinlechner, Philip Sommer, Julian Freiberger, Fabian Plank, Pietro G. Lacaita, Markus Theurl, Rudolf Kirchmair, Axel Bauer, Gudrun Feuchtner and Peter Marschang

J. Clin. Med. 2026, 15(9), 3546; https://doi.org/10.3390/jcm15093546 - 6 May 2026

Viewed by 1193

Abstract

Background: Cardiovascular disease remains the leading cause of mortality worldwide. In recent years, several non-invasive imaging techniques have been introduced to improve the assessment of atherosclerotic burden and cardiovascular risk, including computed tomography and vascular ultrasound. Three-dimensional ultrasound has emerged as a promising [...] Read more.

Background: Cardiovascular disease remains the leading cause of mortality worldwide. In recent years, several non-invasive imaging techniques have been introduced to improve the assessment of atherosclerotic burden and cardiovascular risk, including computed tomography and vascular ultrasound. Three-dimensional ultrasound has emerged as a promising method for the non-invasive quantification of plaque volume in peripheral arteries. Methods: In this prospective single-centre study, 63 patients with low to moderate cardiovascular risk (6–20% according to the Framingham Risk Score) were included. All participants underwent baseline examinations, and 38 patients completed follow-up after a mean period of 2 years. The assessment included coronary artery calcium scoring (CACS) by computed tomography and three-dimensional ultrasound to measure peripheral plaque volume in carotid and femoral arteries. Baseline values and progression of coronary and peripheral atherosclerosis were analysed using Spearman’s correlation. Results: Sixty-three patients were included in the final analysis. A significant correlation was observed between baseline CACS and peripheral plaque volume (r = 0.32; p = 0.010). In addition, the progression of coronary calcium scores was significantly associated with the progression of peripheral plaque volume (r = 0.34; p = 0.037). Conclusions: Coronary artery calcium is significantly associated with peripheral plaque burden, both at baseline and over time. The parallel progression of coronary and peripheral atherosclerosis suggests that peripheral plaque volume assessed by 3D ultrasound may serve as a surrogate marker for coronary disease progression. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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13 pages, 1043 KB

Open AccessArticle

Weekly Variability of an Objective Bradykinesia Score in Parkinson’s Disease—An Observational Longitudinal Study

by Marcus Dalsgaard Hansen, Filip Bergquist and Trine Hørmann Thomsen

J. Clin. Med. 2026, 15(9), 3545; https://doi.org/10.3390/jcm15093545 - 6 May 2026

Viewed by 498

Abstract

Background: Parkinson’s Disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Effective management is critical to improving patient outcomes but is limited by the subjectivity of retrospective assessments of motor symptom burden. The objectives were to describe the weekly variability [...] Read more.

Background: Parkinson’s Disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Effective management is critical to improving patient outcomes but is limited by the subjectivity of retrospective assessments of motor symptom burden. The objectives were to describe the weekly variability of objective bradykinesia score (BKS) derived from a wrist-worn device and assess the correlation between BKS variability and the Quality of Life (QoL) of People with Parkinson’s disease (PwP). Method: This observational, longitudinal study is part of the overall self-management project, Empower-PD. The study population consists of 80 PwP. Participants wore a wrist-worn accelerometer watch that measures movement during daily activities to evaluate the degree of bradykinesia as the bradykinesia score (BKS). Weekly median BKSs were collected over a 10-week period. Quality of life was assessed with the PDQ-39 questionnaire at baseline and after 10 weeks. Descriptive statistics assessed BKS variation and distribution. Linear and logistic regression models examined correlations between variability in BKS and QoL. Results: Results showed that 95% of BKS weekly changes were in a range between −4.3 and +4.4 points, with a central tendency near zero. The distribution of BKSs over time indicated that most participants exhibited stable BKSs. No significant correlation was found between BKS changes and QoL at 10 weeks. Conclusions: This study successfully described weekly BKS variations over ten weeks in PwP using objective measurements. The results showed that 95% of all value changes in BKS ranged from −4.3 to 4.4, values which may serve as preliminary distribution-based reference bounds that could inform the design of future studies examining clinically significant changes in BKS. Full article

(This article belongs to the Special Issue Innovations in Parkinson’s Disease)

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16 pages, 1869 KB

Open AccessArticle

Personality Disorders in Functional and Idiopathic Dystonia

by Violetta Aleksandrovna Tolmacheva, Vladimir Anatolyevich Parfenov, Dmitry Vladimirovich Romanov, Ekaterina Dmitrievna Spektor, Beatrisa Albertovna Volel and Ekaterina Vladimirovna Silina

J. Clin. Med. 2026, 15(9), 3544; https://doi.org/10.3390/jcm15093544 - 6 May 2026

Viewed by 826

Abstract

Background: Distinguishing functional dystonia (FD) from idiopathic dystonia (ID) remains a major clinical challenge because both conditions are diagnosed primarily on clinical grounds and may be accompanied by non-motor psychiatric symptoms. Although personality abnormalities have been described in functional neurological disorders, their [...] Read more.

Background: Distinguishing functional dystonia (FD) from idiopathic dystonia (ID) remains a major clinical challenge because both conditions are diagnosed primarily on clinical grounds and may be accompanied by non-motor psychiatric symptoms. Although personality abnormalities have been described in functional neurological disorders, their relevance in the differential diagnosis of dystonia remains insufficiently studied, and comparative data on FD and ID are lacking, particularly in the Russian population. Patients and Methods: A total of 178 patients with idiopathic dystonia (focal and segmental dystonia, ID) and 32 patients with functional dystonia (FD) were observed. A clinical interview by a psychiatrist was conducted; the SCID-II-PD questionnaire and the Five-Factor Personality Questionnaire (5-PFQ) were used to assess PD. Results: Patients with FD more often than patients with ID had such PD as dependent, paranoid, passive–aggressive, borderline, schizoid and schizotypal (p < 0.001), as well as obsessive–compulsive (p < 0.013) and avoidant (p < 0.049) according to SCID-II-PD. In FD, personalities of the eccentric cluster A predominate; patients with FD are characterized in personality terms by significantly greater introversion, detachment, naturalness (irresponsibility, impulsivity, carelessness), emotional restraint and practicality (conservatism, low sensitivity, rigidity) according to 5-PFQ. Conclusions: Patients with FD differ from patients with ID in both categorical and dimensional personality characteristics. The predominance of cluster A personality pathology and the identified pattern of personality-related variables may have potential value as adjunctive markers in the clinical differentiation of FD from ID. Further external validation is required before these findings can be incorporated into diagnostic algorithms. Full article

(This article belongs to the Special Issue Neuro-Psychiatric Disorders: Updates on Diagnosis and Treatment—2nd Edition)

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16 pages, 2616 KB

Open AccessSystematic Review

Safety and Efficiency of Various Pancreatic Enucleation Procedures: A Systematic Review and Meta-Analysis

by Deqiang Zhou, Feng Tan, Zihe Wang, Ning Xia, Xing Huang, Li Wang, Shijie Cai, Bole Tian and Junjie Xiong

J. Clin. Med. 2026, 15(9), 3543; https://doi.org/10.3390/jcm15093543 - 6 May 2026

Viewed by 683

Abstract

Objective: This study aimed to systematically compare the short-term outcomes of minimally invasive pancreatic enucleation (MI-pEn), including laparoscopic and robotic-assisted approaches, and open pancreatic enucleation (O-pEn). Methods: A systematic search of PubMed, MEDLINE, Embase, and Web of Science was conducted for [...] Read more.

Objective: This study aimed to systematically compare the short-term outcomes of minimally invasive pancreatic enucleation (MI-pEn), including laparoscopic and robotic-assisted approaches, and open pancreatic enucleation (O-pEn). Methods: A systematic search of PubMed, MEDLINE, Embase, and Web of Science was conducted for studies published between January 1990 and December 2025 that compared various types of pancreatic enucleation. The literature screening, data extraction, and quality assessment followed the PRISMA guidelines. The meta-analysis was performed using RevMan 5.4.1 and R 4.3.0. Results: Fifteen studies were included, with thirteen comparative studies (463 MI-pEn, 547 O-pEn) incorporated into the meta-analysis. Two studies comparing laparoscopic and robot-assisted enucleation were also included. No significant difference in clinically relevant postoperative pancreatic fistula (CR-POPF) was detected between MI-pEn and O-pEn (OR = 0.78; 95% CI: 0.56–1.07; p = 0.12). However, MI-pEn was associated with significantly reduced operation time (MD = −21.24; p = 0.01), blood loss (MD = −75.88; p < 0.00001), hospital stay (MD = −2.07; p = 0.001), and wound infection (OR = 0.3; p = 0.03). Direct comparisons between robotic and laparoscopic enucleation revealed no significant differences in any outcomes. Conclusions: MI-pEn is safe and feasible and offers advantages in terms of operative time, blood loss, and recovery without increasing complications. Robotic and laparoscopic approaches yield comparable short-term outcomes in pancreatic enucleation, although the potential advantage of robotic surgery in reducing pancreatic fistula risk warrants further validation. Full article

(This article belongs to the Section General Surgery)

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20 pages, 2918 KB

Open AccessReview

Aortopathy in Bicuspid Aortic Valve: Pathophysiology, Risk Stratification and Surgical Decision-Making—A Narrative Review

by Sebastian Krych, Julia Gniewek, Michał Jurkiewicz, Paweł Kowalczyk, Dariusz Waniczek and Tomasz Hrapkowicz

J. Clin. Med. 2026, 15(9), 3542; https://doi.org/10.3390/jcm15093542 - 6 May 2026

Cited by 2 | Viewed by 3138

Abstract

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects, introducing significant hemodynamic disturbances to the circulatory system. This narrative review analyzed articles published between 2012 and 2025 and indexed in PubMed. The aim was to synthesize key information on [...] Read more.

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects, introducing significant hemodynamic disturbances to the circulatory system. This narrative review analyzed articles published between 2012 and 2025 and indexed in PubMed. The aim was to synthesize key information on the etiopathogenesis of BAV, its potential complications and associated risks, as well as available pharmacological and surgical treatment strategies, with emphasis on indications and contraindications for specific surgical techniques. Analyses demonstrate that isolated BAV with typical valvular aortopathy is associated with a more favorable prognosis compared to valvular aortopathy syndromes. Valve phenotype shows important sex-related relationships in its presentation and progression. From a hemodynamic perspective, BAV alters blood flow angles, which may contribute to weakening of the aortic wall and secondary valve changes. BAV is also frequently associated with genetic disorders such as Marfan syndrome. The heterogeneity of aortopathies linked to BAV creates significant challenges for echocardiographers, cardiologists and cardiac surgeons, particularly in determining the optimal timing and strategy for surgical intervention. Full article

(This article belongs to the Special Issue Global Expert Views on Aortic Valve Repair and Replacement: 2nd Edition)

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29 pages, 384 KB

Open AccessReview

Percutaneous Cryoneurolysis for Upper Limb Spasticity: A Systematic Scoping Review of Current Evidence, Safety Profile, and Implications for Hand and Upper Extremity Practice

by Marco Passiatore, Luciano Maria Bissolotti, Marta Starnoni, Luca Pecori, Anna Paola D’Apolito, Francesco De Santis and Rocco De Vitis

J. Clin. Med. 2026, 15(9), 3541; https://doi.org/10.3390/jcm15093541 - 6 May 2026

Cited by 2 | Viewed by 1290

Abstract

Background/Objectives: Percutaneous cryoneurolysis (CNL) has emerged as a minimally invasive neuromodulatory technique for focal spasticity management, with growing international clinical adoption since 2018. Its application to upper limb motor nerve targets—including branches of the musculocutaneous, radial, median, ulnar, pectoral, and thoracodorsal nerves—is of [...] Read more.

Background/Objectives: Percutaneous cryoneurolysis (CNL) has emerged as a minimally invasive neuromodulatory technique for focal spasticity management, with growing international clinical adoption since 2018. Its application to upper limb motor nerve targets—including branches of the musculocutaneous, radial, median, ulnar, pectoral, and thoracodorsal nerves—is of direct relevance to clinicians involved in the surgical and non-surgical management of hand and upper extremity spasticity. The existing literature lacks a comprehensive systematic appraisal of its evidence base. This systematic scoping review aimed to map all published evidence on CNL for spasticity across all aetiological groups and anatomical regions, with particular attention to upper limb and hand-relevant targets; appraise methodological quality using design-appropriate tools; characterise the safety profile; apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to key outcome domains; and identify critical evidence gaps. Methods: A systematic scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines (search through February 2026). PubMed/MEDLINE, Embase (via Ovid), Scopus, and the Cochrane Library were searched. Methodological quality was assessed using JBI Critical Appraisal Checklists, Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), and A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2). Certainty of evidence was evaluated using GRADE. Results: Twenty-five studies met inclusion criteria; no randomised controlled trials (RCTs) were identified. In the largest prospective observational cohort (n = 59, 12-month follow-up), CNL produced statistically significant improvements in passive range of motion (ROM), Modified Ashworth Scale (MAS) scores, and pain in patients with upper limb spasticity refractory to botulinum toxin type A (BoNT-A). A prospective safety study (n = 113 patients; 277 nerves) documented that 96.75% of nerve treatments produced no post-procedural sensory disturbance; the risk was approximately 10-fold higher for mixed sensorimotor than purely motor nerve targets (7.1% vs. 1.1%). Certainty of evidence was Very Low (⊕◯◯◯) for all efficacy outcomes and Low (⊕⊕◯◯) for safety. Conclusions: CNL represents a mechanistically sound second-line or complementary intervention for refractory focal spasticity. In the upper extremity context, it may additionally serve as a reversible functional evaluation tool before irreversible surgical decisions—including selective neurotomy—are made. The evidence base is critically constrained by the absence of RCTs, confirmed cohort overlap between the two largest primary studies, financial conflicts of interest with the primary device manufacturer identified in ≥48% of included studies (≥12/25), and single-institution concentration of primary evidence (≥69% of primary clinical studies from one research group). Multiple ongoing controlled trials are expected to provide higher-quality evidence to inform guideline development. Full article

(This article belongs to the Special Issue Innovation in Hand Surgery)

15 pages, 1030 KB

Open AccessArticle

First Clinical Results of Novel Haemodynamic Simulation Software for Patient-Specific Qp:Qs Quantification in Patients with Atrial Septal Defect Using Routine 2D Echocardiographic Data

by Florian Gross, Robert Dragendorf, Teresa Lerach, Alexandra Hinke, Felix Berger, Raphael Seiler and Stanislav Ovrutskiy

J. Clin. Med. 2026, 15(9), 3540; https://doi.org/10.3390/jcm15093540 - 6 May 2026

Viewed by 625

Abstract

Background/Objectives: Accurate quantification of left-to-right shunt volume is central to clinical decision-making in patients with atrial septal defect (ASD). Conventional echocardiographic Qp:Qs estimation is widely used but limited by operator dependency, Doppler alignment sensitivity, and the quadratic amplification of diameter measurement errors in [...] Read more.

Background/Objectives: Accurate quantification of left-to-right shunt volume is central to clinical decision-making in patients with atrial septal defect (ASD). Conventional echocardiographic Qp:Qs estimation is widely used but limited by operator dependency, Doppler alignment sensitivity, and the quadratic amplification of diameter measurement errors in flow calculations. These factors contribute to clinically relevant variability, particularly in paediatric populations with small vessel dimensions. Simulation-based haemodynamic modelling offers an alternative approach by integrating structural and functional cardiac parameters within a patient-specific computational framework, independent of direct Doppler flow measurements. Methods: This retrospective single-centre study evaluated agreement between conventional Doppler-derived and software-based Qp:Qs quantification using a three-dimensional haemodynamic simulation model. Transthoracic echocardiographic datasets from patients with isolated secundum ASD undergoing defect closure between 2018 and 2024 were analysed. Conventional Qp:Qs was calculated using pulmonary and aortic valve diameter and velocity–time integral measurements, while software-derived Qp:Qs was computed from patient-specific haemodynamic modelling based on cardiac chamber geometry and physiological parameters. Mean values were compared using Student’s t-test. Agreement was assessed using Bland–Altman analysis. A predefined ± 20% deviation threshold was considered clinically acceptable according to the study protocol. Results: A total of 98 echocardiographic examinations from 94 patients were included. Mean Qp:Qs was 1.83 ± 0.45 by echocardiography and 1.73 ± 0.47 by simulation modelling, with no statistically significant difference between methods (p Using the predefined ± 20% deviation criterion, 53.1% of examinations fell within the acceptable range. Larger ASD diameter was associated with increased inter-method deviation. Conclusions: This study provides an initial feasibility evaluation of a novel haemodynamic simulation approach enabling patient-specific three-dimensional modelling of cardiac structures and shunt physiology based on routine echocardiographic data. Simulation-derived Qp:Qs estimates demonstrated no systematic difference in comparison with conventional Doppler-based quantification and were feasible within routine clinical workflows. Ongoing prospective validation against invasive haemodynamic reference standards will further define analytical accuracy and potential clinical applicability. Full article

(This article belongs to the Special Issue Management of Congenital Heart Disease (CHD))

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20 pages, 1972 KB

Open AccessArticle

Real-World Data on Halting Radiographic Progression with Antifibrotics in Connective Tissue Disease-Associated Interstitial Lung Disease: A Two-Center Study from Hungary

by Zsuzsanna Gyetkó, Edit Végh, Dóra Nemes-Tömöri, Lilla Andó, Edit B. Nagy, Judit Maráz, Angéla Mikáczó, Anna Sárközi, Ildikó Horváth, István Takács, László Tóth, Gabriella Szűcs, Zoltán Szekanecz, Bernadett Bói, Gyöngyike Majai and Szilvia Szamosi

J. Clin. Med. 2026, 15(9), 3539; https://doi.org/10.3390/jcm15093539 - 6 May 2026

Cited by 1 | Viewed by 745

Abstract

Background/Objectives: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is linked to substantial morbidity and mortality. While nintedanib (NTB) slows lung function decline in progressive pulmonary fibrosis (PPF), real-world data—particularly regarding radiographic outcomes—remain limited. We aimed to evaluate the real-world effectiveness and tolerability [...] Read more.

Background/Objectives: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is linked to substantial morbidity and mortality. While nintedanib (NTB) slows lung function decline in progressive pulmonary fibrosis (PPF), real-world data—particularly regarding radiographic outcomes—remain limited. We aimed to evaluate the real-world effectiveness and tolerability of antifibrotic therapy—predominantly NTB—on radiographic and functional outcomes in a Hungarian CTD-ILD cohort. Methods: We conducted a retrospective observational cohort study including 72 patients with progressive CTD-ILD who initiated antifibrotic therapy at two Hungarian tertiary centers between January 2021 and June 2025. The primary endpoint was the proportion of patients without significant radiographic progression at 6–12 months, based on blinded assessment of paired high-resolution computed tomography (HRCT) scans by two thoracic radiologists. Secondary endpoints included changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) at 6 and 12 months, safety and tolerability, and correlations between lung function and disease-related factors. Results: The cohort comprised systemic sclerosis–ILD (n = 25), rheumatoid arthritis–ILD (n = 23), and other CTD-ILD (n = 24). Radiographic stability was observed in 65.8–78.9% of patients, with improvement most commonly seen in ground-glass opacities, while traction bronchiectasis remained largely unchanged. Radiographic disease extent showed the strongest inverse correlation with baseline FVC and DLCO (p < 0.05). Significant improvements in FVC and DLCO were observed at 6 and 12 months (p < 0.001). Antifibrotic therapy was well tolerated, including in combination with immunosuppressive treatment. Conclusions: These real-world data support the effectiveness and safety of NTB in PPF–CTD-ILD and highlight radiologic disease burden as a key determinant of functional impairment. Full article

(This article belongs to the Section Immunology & Rheumatology)

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18 pages, 4852 KB

Open AccessReview

Functionally Single-Ventricle Complications After Fontan Palliation—A Narrative Review

by Małgorzata Kowalczyk and Mirosław Kowalski

J. Clin. Med. 2026, 15(9), 3538; https://doi.org/10.3390/jcm15093538 - 6 May 2026

Viewed by 898

Abstract

Functionally single-ventricle (FSV) defects are complex congenital heart anomalies that require Fontan palliation, a surgical procedure redirecting systemic venous blood directly to the pulmonary arteries, bypassing the heart. Despite improvements in surgical techniques and perioperative care leading to enhanced survival rates, patients remain [...] Read more.

Functionally single-ventricle (FSV) defects are complex congenital heart anomalies that require Fontan palliation, a surgical procedure redirecting systemic venous blood directly to the pulmonary arteries, bypassing the heart. Despite improvements in surgical techniques and perioperative care leading to enhanced survival rates, patients remain vulnerable to significant long-term complications, due to the unique Fontan circulation physiology. This circulation relies on low pulmonary vascular resistance and preserved single-ventricle function but predisposes patients to venous congestion and reduced cardiac output, resulting in multi-organ dysfunction. Key cardiovascular complications include systolic and diastolic dysfunction of the single ventricle, atrioventricular valve regurgitation, arrhythmias, pulmonary vascular disease, and thromboembolic events. Systemic complications encompass Fontan-associated liver disease (FALD), protein-losing enteropathy (PLE), plastic bronchitis (PB), renal impairment, and endocrine and psychosocial burdens. All the problems induce frequent hospitalizations, psychological challenges, and impaired educational and employment opportunities. Comprehensive management requires multidisciplinary approaches addressing the complex interplay of hemodynamic, organ-specific problems, and psychosocial factors inherent to Fontan physiology. Full article

(This article belongs to the Special Issue Congenital Heart Disease in Adults (ACHD): Diagnosis, Therapy, and Clinical Management)

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10 pages, 469 KB

Open AccessArticle

Use of Novel 6.3 Fr Ureteroscope in Endoscopic Combined Intrarenal Surgery (ECIRS): Comparative Experience with Conventional Ureteroscopes

by Theodoros Spinos, Vasileios Tatanis, Angelis Peteinaris, Fani Moultsia, Dimitrios Diamantopoulos Kogkas, Paraskevi Katsakiori, Vasiliki Tsekoura, Theofanis Vrettos, Evangelos Liatsikos and Panagiotis Kallidonis

J. Clin. Med. 2026, 15(9), 3537; https://doi.org/10.3390/jcm15093537 - 6 May 2026

Viewed by 650

Abstract

Background/Objectives: Recently, a 6.3 Fr single-use flexible ureteroscope (f-URS) was introduced to the market. The purpose of this pilot study is to present our experience with it during Endoscopic Combined Intrarenal Surgery (ECIRS) and to compare its performance with the conventional 7.5 [...] Read more.

Background/Objectives: Recently, a 6.3 Fr single-use flexible ureteroscope (f-URS) was introduced to the market. The purpose of this pilot study is to present our experience with it during Endoscopic Combined Intrarenal Surgery (ECIRS) and to compare its performance with the conventional 7.5 Fr scope. Methods: For percutaneous access, renal puncture was performed in a nonpapillary approach. Regarding retrograde access, for the first group, a 7.5 Fr single-use f-URS was used, while for the second group, a 6.3 Fr single-use f-URS was utilized. Lithotripsy was primarily performed in an antegrade manner, using the Lithoclast Trilogy^®. In cases where stones could not be reached with a nephroscope, retrograde lithotripsy was performed with either a Holmium:YAG laser or a Thulium Fiber Laser. Results: In total, 45 patients were included. Of these, 23 patients underwent ECIRS with the 6.3 Fr f-URS and 22 with the 7.5 Fr f-URS. The mean operative time, fluoroscopy time and lasing time were 59.5 ± 5.6 min, 139.7 ± 14.2 s and 18.4 ± 2.7 min in the 6.3 Fr group and 57.1 ± 3.9 min, 133.8 ± 29.7 s and 18.6 ± 1.9 min in the 7.5 Fr group, respectively. Two patients in the 6.3 Fr group and three patients in the 7.5 Fr group experienced Grade II complications. Stone-free rates were 91.3% in the 6.3 Fr group versus 86.4% in the 7.5 Fr group. Conclusions: The use of a 6.3 Fr f-URS during ECIRS is potentially a feasible, safe and efficient approach. Both the 6.3 Fr and 7.5 Fr scopes were associated with comparable outcomes during ECIRS. Additional studies are needed so as to draw safer conclusions. Full article

(This article belongs to the Section Nephrology & Urology)

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24 pages, 591 KB

Open AccessSystematic Review

Antipsychotic Drugs and the Risk of Diabetic Complications: A Systematic Review of Observational Studies

by Nisrine Haddad, Nawal Farhat, Christopher A. Gravel, Yue Chen, Franco Momoli, Donald R. Mattison, Jeannette Goguen and Daniel Krewski

J. Clin. Med. 2026, 15(9), 3536; https://doi.org/10.3390/jcm15093536 - 6 May 2026

Viewed by 971

Abstract

Background: In recent years, case reports and case series have suggested an association between the use of second- (SGAs), but not first-generation antipsychotics (FGAs), also known as atypical and typical APDs, respectively, and hyperglycemic complications, notably diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state [...] Read more.

Background: In recent years, case reports and case series have suggested an association between the use of second- (SGAs), but not first-generation antipsychotics (FGAs), also known as atypical and typical APDs, respectively, and hyperglycemic complications, notably diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). Although this evidence is informative, there is a need for more observational studies to strengthen this body of knowledge. Objective: To conduct a systematic review of evidence established in observational studies on adverse drug events, specifically DKA and HHS, associated with the use of FGAs and SGAs. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using appropriate index phrases and keywords through October 17, 2025. Exposure included at least one United States Food and Drugs Administration (US FDA)-approved antipsychotic drug (APD); outcomes were limited to DKA and HHS. Results: A total of 15 observational studies were included in this review, including seven analytical and eight descriptive studies. These studies varied in scope and used different case definitions, study populations, exposures, and outcomes. The observational studies support existing evidence of an association between atypical APDs and DKA, mainly. As a class, typical APDs were associated with an increased risk of DKA, when compared to non-antipsychotic drug use. Although some studies evaluated this association in relation to HHS, there is insufficient information to draw conclusions for this outcome at this time. Conclusions: This analysis provides additional evidence of an association between use of atypical APDs and DKA. Additional analytical studies using administrative health databases are needed to clarify this association. Full article

(This article belongs to the Section Pharmacology)

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13 pages, 1156 KB

Open AccessArticle

Hidden Burden of Hypertension in Türkiye: A Multi-Center DAHUDER World Hypertension Day Study Reveals Gaps in Awareness, Adherence, and Control

by Hilmi Erdem Sumbul, Ihsan Solmaz, Esref Arac, Ismail Demir, Seyit Uyar, Kamil Konur, Ersin Kuloglu, Ahmed Bilal Genc, Celalettin Kucuk, Kubilay Issever, Nizameddin Koca, Alihan Oral, Ozden Yıldırım Akan, Huseyin Ali Ozturk, Bektas Isik, Fatih Necip Arici, Bercem Berent, Hatice Beyazal Polat, Nazif Yalcin, Deniz Cekic, Selcuk Yaylaci and Ramazan Azim Okyay Show full author list Hide full author list

J. Clin. Med. 2026, 15(9), 3535; https://doi.org/10.3390/jcm15093535 - 6 May 2026

Viewed by 827

Abstract

Background: Hypertension remains the single most important modifiable risk factor for cardiovascular disease, stroke, and premature mortality worldwide. Despite major pharmacological advances, awareness, treatment, and control rates remain globally inadequate, particularly in low- and middle-income settings. Türkiye occupies a unique epidemiological position [...] Read more.

Background: Hypertension remains the single most important modifiable risk factor for cardiovascular disease, stroke, and premature mortality worldwide. Despite major pharmacological advances, awareness, treatment, and control rates remain globally inadequate, particularly in low- and middle-income settings. Türkiye occupies a unique epidemiological position at the intersection of European and Asian cardiovascular risk patterns, with national surveys documenting a stable hypertension prevalence of approximately 30% but persistent deficits in disease control. Methods: This cross-sectional study was conducted on World Hypertension Day (17 May 2025) across nine provinces in Türkiye representing five geographic regions (Marmara, Aegean, Mediterranean, Black Sea, and Southeastern Anatolia). A total of 1967 adult volunteers were enrolled. Blood pressure was measured following standardized protocols and classified per ESH 2023 guidelines. A structured questionnaire captured sociodemographic data, lifestyle factors, medication adherence, and hypertension-related awareness. Results: The median participant age was 51 years; 55.4% were female. Screening-detected hypertension (BP ≥ 140/90 mmHg) was identified in 26.6% and above-optimal blood pressure in 41.6%. A prior hypertension diagnosis was reported by 35.1%. Among the 1277 participants without a known diagnosis, 51.1% had above-optimal or hypertension-range blood pressure readings, including 11.6% with screening-detected hypertension-range blood pressure. Independent predictors in multivariate analysis included age (OR = 1.048), male sex (OR = 1.528), BMI (OR = 1.096), and alcohol consumption (OR = 1.536); regular exercise was protective (OR = 0.796). Among known hypertensive patients, only 50% monitored blood pressure regularly, 30% skipped doses, and awareness of renal (40.4%) and visual (30.6%) complications was notably low. Conclusions: This large multi-center screening study reveals a substantial proportion of previously undetected hypertension-range blood pressure readings and persistent management gaps in a volunteer-based Turkish community sample. The observed screening rate below national prevalence averages likely reflects a healthy volunteer effect inherent to this study design. World Hypertension Day offers an effective framework for simultaneous multi-center screening. Targeted interventions should address non-cardiovascular complication awareness, sodium intake, and medication adherence. Full article

(This article belongs to the Section Cardiovascular Medicine)

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14 pages, 560 KB

Open AccessArticle

Contrast-Associated Acute Kidney Injury and Mortality Risk After Coronary Angiography for Acute Coronary Syndromes: A Retrospective Cohort Study

by Eva Maria Olivas-Flores, Alberto Daniel Rocha-Muñoz, Angelita del Socorro Valencia-López, Roberto Rojas-Castillo, Jorge Guillermo Delgado-Gutiérrez, Karina Patricia Pizarro-Gonzales, Mario Alberto Mireles-Ramírez, J. Ahuixotl Gutiérrez-Aceves, Nicte Selene Fajardo-Robledo, Adrian Esau De La Cruz-Estrella, Claudia Lorena Mariscal-Chavez, Maria Luisa Vazquez-Villegas, Fabiola Gonzalez-Ponce, Ernesto German Cardona-Muñoz, David Cardona-Müller, Jorge Ivan Gamez-Nava and Laura Gonzalez-Lopez

J. Clin. Med. 2026, 15(9), 3534; https://doi.org/10.3390/jcm15093534 - 6 May 2026

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Abstract

Background/Objectives: Contrast-associated acute kidney injury (CA-AKI) is a frequent complication after coronary angiography (CAG) that may adversely affect outcomes in patients with acute coronary syndrome (ACS). We aimed to estimate the incidence of CA-AKI and evaluate its association with 30-day all-cause mortality in [...] Read more.

Background/Objectives: Contrast-associated acute kidney injury (CA-AKI) is a frequent complication after coronary angiography (CAG) that may adversely affect outcomes in patients with acute coronary syndrome (ACS). We aimed to estimate the incidence of CA-AKI and evaluate its association with 30-day all-cause mortality in adults with ACS undergoing CAG. Methods: We conducted a retrospective cohort study; CA-AKI was defined as an increase in serum creatinine ≥0.5 mg/dL or ≥25% from baseline within 72 h after contrast exposure, according to KDIGO criteria. The primary outcome was 30-day all-cause mortality. Survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models. Results: Including 374 consecutive adults with ACS who underwent diagnostic or therapeutic CAG at a tertiary referral center. The mean age was 68.8 ± 11.2 years, and 72.6% were male. CA-AKI occurred in 17.4% of patients, and 11.7% died within 30 days. In multivariable analysis, age (HR 1.04; 95% CI 1.00–1.07), CA-AKI (HR 2.81; 95% CI 1.48–5.33), stress hyperglycemia ≥180 mg/dL (HR 2.88; 95% CI 1.54–5.38), and delirium (HR 7.20; 95% CI 2.40–20.92) were independent predictors of mortality. Conclusions: age, CA-AKI, stress hyperglycemia, and delirium independently predict short-term mortality after CAG in ACS, supporting integrated risk-stratified peri-procedural management. These observations suggest that mortality in these patients may be related to an inflammatory process secondary to ischemia/reperfusion, which is probably induced by dysregulation of the central autonomic network and activation of the hypothalamic–pituitary–adrenal axis which is currently underdiagnosed. Full article

(This article belongs to the Section Cardiovascular Medicine)

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17 pages, 503 KB

Open AccessArticle

Beyond Breathlessness Intensity: A Prospective Psychometric Validation of the Multidimensional Dyspnea Profile in Heart Failure with Reduced and Mildly Reduced Ejection Fraction

by Monira I. Aldhahi, Rakan I. Nazer and Ali M. Albarrati

J. Clin. Med. 2026, 15(9), 3533; https://doi.org/10.3390/jcm15093533 - 5 May 2026

Viewed by 554

Abstract

Background/Objectives: Dyspnoea in heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) is multidimensional, yet conventional unidimensional scales do not capture its sensory and affective components. The Multidimensional Dyspnea Profile (MDP) addresses this gap; however, its psychometric properties have not been established [...] Read more.

Background/Objectives: Dyspnoea in heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) is multidimensional, yet conventional unidimensional scales do not capture its sensory and affective components. The Multidimensional Dyspnea Profile (MDP) addresses this gap; however, its psychometric properties have not been established in a dedicated HFrEF/HFmrEF cohort. We assessed structural validity, internal consistency, test–retest reliability, and construct validity of the MDP using COSMIN methodology. Methods: In this prospective, single-centre psychometric validation study, 101 clinically stable adults with HFrEF or HFmrEF were enrolled at a tertiary outpatient cardiac clinic in Riyadh, Saudi Arabia. Participants completed the MDP alongside Dyspnea-12, modified Medical Research Council scale, Kansas City Cardiomyopathy Questionnaire-12, Fatigue Severity Scale, and 6 min walk test. Test–retest data were obtained at 12 days in patients confirmed stable by the Global Rating of Change (n = 87). Psychometric evaluation included Cronbach’s α, intraclass correlation (ICC₂,₁), standard error of measurement, minimum detectable change (MDC₉₅), confirmatory factor analysis (comparative fit index [CFI], root mean square error of approximation [RMSEA], standardised root mean square residual [SRMR]), and 12 a priori construct hypotheses. A preliminary minimal clinically important difference (MCID) was estimated using anchor- and distribution-based methods. Results: The mean age was 55 ± 11 years and 80% were male. CFA supported the two-factor model (CFI = 0.96; RMSEA = 0.061; SRMR = 0.058). Cronbach α was 0.92 for the full scale, 0.88 for immediate perception, and 0.91 for emotional response. ICC_2,1 was 0.94 (95% CI: 0.91–0.96), and MDC₉₅ was 4.2 points. All 12 hypotheses were confirmed. The preliminary MCID was 8 points. Conclusions: The MDP is a reliable, valid, and clinically interpretable multidimensional dyspnoea measure in HFrEF/HFmrEF. The 8-point MCID is preliminary and requires confirmation in larger longitudinal intervention studies. Full article

(This article belongs to the Section Cardiology)

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14 pages, 897 KB

Open AccessArticle

Symptom Improvement and Interrelated ESAS Domains Following Outpatient Palliative Care in Hungarian Cancer Patients

by Nóra Frank, Csilla Busa, Eszter Sághy, Éva Pozsgai and Ágnes Csikós

J. Clin. Med. 2026, 15(9), 3532; https://doi.org/10.3390/jcm15093532 - 5 May 2026

Viewed by 498

Abstract

Background: Outpatient palliative care effectively alleviates symptom burden in advanced cancer patients, yet data from Central–Eastern Europe remain scarce. This retrospective study examined changes in revised Edmonton Symptom Assessment Scale (ESAS) scores from initial outpatient palliative consultation to first follow-up in Hungarian cancer [...] Read more.

Background: Outpatient palliative care effectively alleviates symptom burden in advanced cancer patients, yet data from Central–Eastern Europe remain scarce. This retrospective study examined changes in revised Edmonton Symptom Assessment Scale (ESAS) scores from initial outpatient palliative consultation to first follow-up in Hungarian cancer patients, assessing clinically meaningful improvement and inter-symptom associations. Methods: Revised ESAS scores from 119 patients attending an outpatient palliative care clinic (2017–2020) were analyzed using paired baseline and first follow-up assessments (7–30 days). Symptom changes (Time 2–Time 1) were evaluated using Wilcoxon signed-rank tests. Clinically meaningful improvement was assessed with minimal clinically important difference thresholds (0.5× baseline SD). Sankey diagrams visualized symptom transitions, and multivariable linear regression examined inter-symptom associations. Results: Baseline pain was highest (mean 6.29, median 7), followed by fatigue, sleep disorder, and impaired well-being. At follow-up, significant reductions were observed in pain (mean 4.52, p = 0.001), nausea, dyspnea, constipation, sleep disorder, depression, and anxiety (all p < 0.05). Sankey diagrams showed shifts from severe to mild/moderate pain (50% to 24%) and constipation. Clinically meaningful improvement occurred in pain, nausea, and constipation, with 59–65% achieving ≥1-point pain reduction. Regression analyses showed that pain reduction was associated with concurrent improvements in sleep disorder (β = 0.31), depression (β = 0.20), fatigue (β = 0.20), and anxiety (β = 0.14), while dyspnea reduction was associated with concurrent improvements in depression (β = 0.22) and anxiety (β = 0.14). Conclusions: Outpatient palliative care in Hungarian cancer patients resulted in clinically meaningful symptom reductions, particularly pain and dyspnea. Improvements in these core symptoms were associated with concurrent improvements in other symptom domains, underscoring the clinical relevance of inter-symptom associations and supporting early, integrated outpatient palliative care and symptom cluster-based management. Full article

(This article belongs to the Section Oncology)

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12 pages, 1066 KB

Open AccessArticle

The CALLY Index May Reflect Systemic Inflammatory Burden Rather than Patient-Reported Disease Activity in Ankylosing Spondylitis: A Medical Record-Based Cross-Sectional Study

by Altuğ Güner, Taner Dandinoğlu, Sümeyye Tuna Güner and İlknur Aykurt Karlıbel

J. Clin. Med. 2026, 15(9), 3531; https://doi.org/10.3390/jcm15093531 - 5 May 2026

Cited by 2 | Viewed by 644

Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease in which accurate assessment of disease activity remains challenging. Although composite indices such as BASDAI and ASDAS are widely used, they may not fully capture systemic inflammatory burden. The C-reactive protein–albumin–lymphocyte (CALLY) index is [...] Read more.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease in which accurate assessment of disease activity remains challenging. Although composite indices such as BASDAI and ASDAS are widely used, they may not fully capture systemic inflammatory burden. The C-reactive protein–albumin–lymphocyte (CALLY) index is an emerging composite biomarker integrating inflammatory, nutritional, and immunological components. This study aimed to evaluate the association of the CALLY index with disease activity, functional status, and quality of life in AS. Methods: This medical record-based cross-sectional study included 65 patients with AS. Disease activity was assessed using BASDAI and ASDAS-ESR, functional status using BASFI, and quality of life using the 12-Item Short Form Health Survey (SF-12). The CALLY index was calculated from serum CRP, albumin levels, and lymphocyte counts. Correlation and multivariable linear regression analyses were performed. Results: The mean CALLY index was 58.43 ± 66.20. The index showed moderate negative correlations with ESR and ASDAS-ESR and a positive correlation with lymphocyte count. Its strong inverse correlation with CRP was expected because CRP is part of the formula and was therefore interpreted cautiously. No significant associations were found with BASDAI, BASFI, or SF-12. In multivariable analysis, BMI (β = −0.299, p = 0.012) and NSAID use (β = −0.298, p = 0.011) were independent predictors. Conclusions: The CALLY index was associated mainly with objective inflammatory markers rather than patient-reported outcomes, suggesting a dissociation between biochemical and clinical disease domains in AS. These findings are preliminary and require confirmation in larger longitudinal studies before clinical application. Full article

(This article belongs to the Section Immunology & Rheumatology)

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17 pages, 1864 KB

Open AccessSystematic Review

Therapeutic Efficacy of Hyperbaric Oxygen in Central Retinal Artery Occlusion: A Systematic Review and Meta-Analysis

by Hani Basher ALBalawi, Moustafa S. Magliyah, Naif M. Alali, Mohammed M. Alshehri, Abdullah Alhewiti, Faisal Almarek, Ibrahim Shajry, Mohammad A. Hazzazi and Yousef A. Alotaibi

J. Clin. Med. 2026, 15(9), 3530; https://doi.org/10.3390/jcm15093530 - 5 May 2026

Viewed by 1179

Abstract

Background/Objectives: Central retinal artery occlusion (CRAO) is a vision-threatening condition with limited evidence-based treatment options. Hyperbaric oxygen therapy (HBOT) has emerged as a potential intervention, but its efficacy remains debated. This systematic review and meta-analysis evaluated the therapeutic efficacy and safety of HBOT [...] Read more.

Background/Objectives: Central retinal artery occlusion (CRAO) is a vision-threatening condition with limited evidence-based treatment options. Hyperbaric oxygen therapy (HBOT) has emerged as a potential intervention, but its efficacy remains debated. This systematic review and meta-analysis evaluated the therapeutic efficacy and safety of HBOT in CRAO. Methods: Relevant studies were identified across seven databases using optimized Boolean and MeSH-based strategies. Eligible studies evaluated HBOT in CRAO and reported visual or safety outcomes. Extracted data included demographics, intervention details, treatment timing, visual acuity outcomes, and adverse events. Risk of bias was assessed using ROBINS-I. Visual acuity outcomes were standardized to logMAR whenever directly reported or convertible, and subgroup analyses were stratified by HBOT initiation time (<12 h vs. >12 h), study type, and baseline visual severity when reported. A random-effects model was used, and pooled estimates were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results: Twelve studies were included. The pooled efficacy analysis favored HBOT (OR = 0.47; 95% CI: 0.26–0.87; p = 0.02), although heterogeneity was substantial (Tau² = 0.64; I² = 78%). Stratified synthesis showed that studies in which HBOT was initiated within 12 h consistently reported greater visual improvement, whereas delayed or variably timed treatment showed attenuated and inconsistent benefits. After outcome harmonization, studies reporting logMAR-compatible data generally demonstrated clinically relevant visual improvement, while adverse-event rates did not differ significantly between HBOT and non-HBOT groups (OR = 0.70; 95% CI: 0.43–1.16; p = 0.17; I² = 0%). Conclusions: HBOT appears most beneficial when initiated early, particularly within the first 12 h. However, heterogeneity in treatment timing, study design, and baseline severity reporting limits the certainty of these results and supports the need for standardized outcome reporting and protocol-driven prospective studies. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases—Mechanisms, Diagnostics, and Emerging Therapies)

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J. Clin. Med., Volume 15, Issue 9 (May-1 2026) – 382 articles

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