Journal of Clinical Medicine

22 pages, 4100 KiB

Open AccessArticle

Investigation of the CTLA-4–CD28 Axis in Oral Squamous Cell Carcinoma

by Ferdinand Feldmeier, Manuel Weber, Franca Pacelli, Christoph Vogl, Jacek Glajzer, Leah Trumet, Mayte Buchbender, Carol Geppert, Marco Kesting and Jutta Ries

J. Clin. Med. 2025, 14(14), 5171; https://doi.org/10.3390/jcm14145171 - 21 Jul 2025

Viewed by 694

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in [...] Read more.

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article

(This article belongs to the Special Issue Oral Cancer: Clinical Updates and Perspectives)

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15 pages, 703 KiB

Open AccessSystematic Review

Total Arch Replacement with Ascyrus Medical Dissection Stent Versus Frozen Elephant Trunk in Acute Type A Aortic Dissection: A Meta-Analysis

by Massimo Baudo, Fabrizio Rosati, Michele D’Alonzo, Antonio Fiore, Claudio Muneretto, Stefano Benussi and Lorenzo Di Bacco

J. Clin. Med. 2025, 14(14), 5170; https://doi.org/10.3390/jcm14145170 - 21 Jul 2025

Viewed by 496

Abstract

Background: Acute Stanford Type A aortic dissection (ATAAD) often requires total arch replacement (TAR) with frozen elephant trunk (FET) to address entry tears and support aortic remodeling. In select cases, AMDS may provide a simpler option. The present meta-analysis aims to compare [...] Read more.

Background: Acute Stanford Type A aortic dissection (ATAAD) often requires total arch replacement (TAR) with frozen elephant trunk (FET) to address entry tears and support aortic remodeling. In select cases, AMDS may provide a simpler option. The present meta-analysis aims to compare surgical outcomes between these two approaches. Methods: A comprehensive search in the Pubmed, ScienceDirect, SciELO, DOAJ, and Cochrane library databases was performed until February 2025. We included studies that reported the outcomes of patients with ATAAD undergoing TAR with AMDS or FET. To enable a meaningful comparison, we only included FET studies where patients met the same inclusion criteria as those with the AMDS. Results: Thirty-eight articles met our inclusion criteria, with a total of 319 patients in the AMDS group and 4129 in the FET group. Patients undergoing an AMDS procedure experienced significantly higher bleeding requiring surgery (21.2% vs. 6.4%, p < 0.001) and a higher hospital mortality (14.5% vs. 10.0%, p = 0.037) compared to FET. The individual patient data of 1411 patients were constructed. Overall survival at 1 and 3 years was 81.9% ± 3.3% vs. 88.8% ± 0.9% and 81.9% ± 3.3% vs. 85.2% ± 1.0% between AMDS and FET, respectively. A flexible parametric survival model demonstrated a significant mortality drawback for AMDS compared to FET up to 31 days, beyond which the difference was no longer evident. Conclusions: The comparison between AMDS and FET for ATAAD treatment remains debated, with FET favored for its lower mortality and stronger long-term evidence. AMDS, as a newer technique, shows promise but lacks sufficient data to confirm its safety and efficacy. Full article

(This article belongs to the Special Issue Advances in Aortic Surgery)

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10 pages, 470 KiB

Open AccessReview

Emergency Department Discharges Following Falls in Residential Aged Care Residents: A Scoping Review

by Gigi Guan, Kadison Michel, Charlie Corke and Geetha Ranmuthugala

J. Clin. Med. 2025, 14(14), 5169; https://doi.org/10.3390/jcm14145169 - 21 Jul 2025

Viewed by 368

Abstract

Background: Falls in residential aged care facilities (RACFs) have a significant impact, often leading to costly and unnecessary emergency department (ED) transfers. This scoping review examined the ED discharge proportions and patient characteristics of RACF residents presenting to the ED following a fall, [...] Read more.

Background: Falls in residential aged care facilities (RACFs) have a significant impact, often leading to costly and unnecessary emergency department (ED) transfers. This scoping review examined the ED discharge proportions and patient characteristics of RACF residents presenting to the ED following a fall, to identify factors that could reduce unnecessary ED transfers. Methods: The databases MEDLINE, CINAHL, Scopus, and Web of Science were searched, resulting in an initial 1385 articles. Nine of these articles met the inclusion criteria and were included in this review. Results: The median age of patients reported in the nine papers ranged from 80.8 to 88 years. Discharge proportions from ED back to RACF ranged from 36% to 91%, with an average of 63%. The studies that reported on computed tomography of the brain (CTB) showed that CTB findings did not significantly influence discharge decisions. Conclusions: Many RACF residents transferred to EDs following falls are discharged without hospital admission. The heterogeneity of study methods makes it challenging to draw definitive conclusions about factors that may help identify patient groups that do not require transfer to the ED following a fall. However, this scoping review highlights potential opportunities to reduce ED transfers from RCAFs. These findings highlight a need for geriatric-specific, person-centred protocols that reduce unnecessary ED transfers while safeguarding quality of care and respecting residents’ advance care preferences. Full article

(This article belongs to the Special Issue Geriatric Diseases: Management and Epidemiology)

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16 pages, 630 KiB

Open AccessReview

The Role of Probiotics in Preventing Gestational Diabetes: An Umbrella Review

by Simone Cosmai, Sara Morales Palomares, Cristina Chiari, Daniela Cattani, Stefano Mancin, Alberto Gibellato, Alessandra Valsecchi, Marco Sguanci, Fabio Petrelli, Giovanni Cangelosi, Diego Lopane and Beatrice Mazzoleni

J. Clin. Med. 2025, 14(14), 5168; https://doi.org/10.3390/jcm14145168 - 21 Jul 2025

Viewed by 591

Abstract

Background/Objectives: Gestational diabetes (GD), which affects approximately 15% of pregnancies worldwide, poses significant risks to both maternal and fetal health, underscoring the need for effective prevention and management strategies. This umbrella review aims to evaluate the role of probiotics in the prevention [...] Read more.

Background/Objectives: Gestational diabetes (GD), which affects approximately 15% of pregnancies worldwide, poses significant risks to both maternal and fetal health, underscoring the need for effective prevention and management strategies. This umbrella review aims to evaluate the role of probiotics in the prevention of GD. Methods: The review was conducted in accordance with the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. A comprehensive literature search was performed in November 2024 across four databases: PubMed/Medline, Cochrane Library, Embase, and CINAHL. A total of 307 articles were identified, of which 6 met the inclusion criteria and were included in the final synthesis. Results: Probiotic supplementation was associated with a significant reduction in the incidence of GD in selected populations, particularly in women with a body mass index (BMI) < 26, age < 30 years [Relative Risk (RR): 0.58], and p < 0.05 in the other studies included, alongside improvements in several metabolic parameters. However, consistent benefits on maternal or neonatal complications were not observed but a 33% reduction in GD was confirmed (RR 0.67). The combination of probiotics with healthy lifestyle behaviors appeared to exert a stronger protective effect against GD and its potential complications. Conclusions: This umbrella review suggests that probiotics—particularly multi-strain formulations—may have a potential role in reducing the risk of GD in certain populations. However, the findings across the included studies are inconsistent and sometimes conflicting. While probiotics are generally considered safe and have recognized benefits for metabolic health, their efficacy as an adjunct intervention for GD prevention remains not fully clear. Further well-designed research is needed to clarify which specific probiotic interventions may be effective and to better guide clinical practice. Full article

(This article belongs to the Special Issue Gestational Diabetes: Cutting-Edge Research and Clinical Practice)

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13 pages, 329 KiB

Open AccessArticle

Postoperative Morbidity Is Not Associated with a Worse Mid-Term Quality of Life After Colorectal Surgery for Colorectal Carcinoma

by Maximilian Brunner, Theresa Jendrusch, Henriette Golcher, Klaus Weber, Axel Denz, Georg F. Weber, Robert Grützmann and Christian Krautz

J. Clin. Med. 2025, 14(14), 5167; https://doi.org/10.3390/jcm14145167 - 21 Jul 2025

Viewed by 409

Abstract

Objectives: The aim of the present study was to investigate the impact of postoperative morbidity on mid-term quality of life and patient-related outcome (PRO) parameters after colorectal surgery for colorectal carcinoma. Methods: Quality of life and perioperative data were prospectively collected [...] Read more.

Objectives: The aim of the present study was to investigate the impact of postoperative morbidity on mid-term quality of life and patient-related outcome (PRO) parameters after colorectal surgery for colorectal carcinoma. Methods: Quality of life and perioperative data were prospectively collected from 99 adult patients treated for colorectal carcinoma—56 patients with colonic carcinoma and 43 with rectal carcinoma, all of whom underwent R0 colorectal resection, at the University Hospital Erlangen between 2018 and 2021. Quality of life data (EQL C29 and C30) were assessed before the start of treatment and one year after. Patients were grouped based on the presence or absence of postoperative morbidity, and their quality of life was compared between the two groups. Results: In the colonic carcinoma cohort, global quality of life and emotional functioning showed significant improvement from pre-treatment to the one-year follow-up (63 vs. 72, p = 0.012 and 63 vs. 76, p = 0.009, respectively). Among the symptom scales, five items improved, while two worsened. Patients who experienced postoperative morbidity (32% in the colonic carcinoma group) did not exhibit worse outcomes in functioning or symptom scales compared to those without morbidity (4 items improved and 1 worsened in the morbidity group vs. 3 improved and 1 worsened in the no-morbidity group). The rectal carcinoma cohort demonstrated a decline in quality of life from pre-treatment to the one-year follow-up. Two functioning scales worsened significantly (physical function: 89 vs. 83, p < 0.001; role function: 81 vs. 68, p = 0.009), and twelve symptom scales showed deterioration, with only two symptom scales improving. Postoperative morbidity (33% in the rectal carcinoma group) did not result in more pronounced impairments compared to those without morbidity. The morbidity group experienced 2 worsened and 0 improved items, while the no-morbidity group had 10 worsened and 1 improved item. Conclusions: Postoperative morbidity was not significantly associated with a worse quality of life at one-year follow-up after treatment of colorectal carcinomas, including colorectal resections, compared to patients who did not develop postoperative morbidity. Full article

(This article belongs to the Section Oncology)

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14 pages, 787 KiB

Open AccessArticle

Preimplantation Genetic Testing for Aneuploidy Versus Morphological Selection in Women Aged 35–42: Results of a Pilot Randomized Controlled Trial

by Yusuf Beebeejaun, Daniela Bakalova, Anastasia Mania, Timothy Copeland, Ippokratis Sarris, Kypros Nicolaides, Antonio Capalbo and Sesh K. Sunkara

J. Clin. Med. 2025, 14(14), 5166; https://doi.org/10.3390/jcm14145166 - 21 Jul 2025

Viewed by 749

Abstract

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women [...] Read more.

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)

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16 pages, 729 KiB

Open AccessArticle

Cross-Sectional and Quasi-Longitudinal Examination of Childhood and Adult Cognitive Disengagement Syndrome, Depression, Anxiety, Stress, and Insomnia

by Dena Sadeghi-Bahmani, Larina Eisenhut, Thorsten Mikoteit, Nico Helfenstein, Annette Beatrix Brühl, Kenneth M. Dürsteler, Jean-Marie Bizimana, Stephen P. Becker and Serge Brand

J. Clin. Med. 2025, 14(14), 5165; https://doi.org/10.3390/jcm14145165 - 21 Jul 2025

Cited by 1 | Viewed by 357

Abstract

Background: Longitudinal studies on cognitive disengagement syndrome (CDS) are scarce, and only one study has investigated the trajectory of CDS from childhood to early adulthood. Given this, the aims of the present study were to explore, with a quasi-longitudinal design, (1) whether scores [...] Read more.

Background: Longitudinal studies on cognitive disengagement syndrome (CDS) are scarce, and only one study has investigated the trajectory of CDS from childhood to early adulthood. Given this, the aims of the present study were to explore, with a quasi-longitudinal design, (1) whether scores for childhood CDS were associated with scores for CDS during early adulthood; (2) whether childhood CDS scores were associated with childhood and adult scores for depression, anxiety, stress, and insomnia; (3) whether childhood CDS, depression, anxiety, stress, and insomnia and adult depression, anxiety, stress, and insomnia were independently associated with adult scores for CDS, and (4) whether childhood CDS scores were directly and indirectly associated with adult CDS scores via adult depression and stress in two conditional effect models. Methods: A total of 246 young adult students (mean age = 22.62; 56.3% females) participated in a cross-sectional and quasi-longitudinal study. The participants completed questionnaires assessing CDS (Adult Concentration Inventory; ACI), depression, anxiety, stress, and insomnia for the following two developmental periods: for the present time point as young adults and for a past time point, when they were about eight years old. To enable retrospective past recall, the participants undertook a standardized imagination exercise. Results: Childhood scores for CDS, depression, anxiety, stress, and insomnia were highly associated with adult scores for CDS, depression, anxiety, stress, and insomnia. In the regression model, higher childhood scores for CDS, depression, and anxiety and higher adult scores for depression, stress, and insomnia, but not adult anxiety, were strongly and independently associated with adult scores for CDS. In the two conditional effects models, childhood CDS was associated with adult CDS directly and indirectly via adult depression and adult stress. Conclusions: In this quasi-longitudinal study, childhood scores for CDS were associated with adult scores for CDS, suggesting a potentially stable trajectory of CDS from childhood to early adulthood. Further, the two conditional effects models suggested that childhood and adult CDS were both directly and indirectly associated via adult depression and stress. As such, symptoms of depression, anxiety, stress, and insomnia should be considered in conceptualizations of adult CDS. Next, given that standardized psychotherapeutic interventions for depression, stress, and insomnia are available, such interventions might also favorably impact CDS symptoms. These findings further underscore the importance of prospective longitudinal and intervention studies on adult CDS. Full article

(This article belongs to the Section Mental Health)

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17 pages, 5672 KiB

Open AccessArticle

The Effect of Dienogest on Deep Endometriosis Nodules Involving the Recto-Sigmoid Colon: A Prospective Longitudinal Long-Term Study

by Carlos Andrés Contreras, Ignacio Brunel, Mónica Restrepo, Claudia Patricia Franco, María Clara Soto, José Carlos Vilches, Rodrigo Orozco, Stefano Guerriero and Juan Luis Alcázar

J. Clin. Med. 2025, 14(14), 5164; https://doi.org/10.3390/jcm14145164 - 21 Jul 2025

Viewed by 535

Abstract

Objective: To assess the long-term effects of Dienogest on clinical complaints and nodule sizes in women affected by recto-sigmoid deep endometriosis (DE). Methods: This was a single-center longitudinal prospective observational study comprising a consecutive series of women affected by recto-sigmoid DE, who underwent [...] Read more.

Objective: To assess the long-term effects of Dienogest on clinical complaints and nodule sizes in women affected by recto-sigmoid deep endometriosis (DE). Methods: This was a single-center longitudinal prospective observational study comprising a consecutive series of women affected by recto-sigmoid DE, who underwent medical treatment with Dienogest (2 mg daily continuous). All women underwent clinical visits and transvaginal sonography (TVS) with bowel preparation prior to starting therapy and at 3–6-month intervals for at least 12 months. Clinical complaints such as dysmenorrhea, dyspareunia and dyschezia were assessed using a visual analog scale (VAS). The DE recto-sigmoid lesion was measured in the three orthogonal planes. The lesion’s volume was estimated using the prolate ellipsoid formula. The maximum diameter and lesion volume were used for analysis. Patients’ complaints and lesion sizes before starting the treatment and at final follow-up were compared. Results: From January 2017 to July 2020, 125 patients were consecutively recruited (mean age: 37 years, ranging from 20 to 50 years). The median follow-up period was 47.8 months (range: 12–74 months). We did not observe a significant correlation between the severity of the symptoms and the lesion size prior to starting therapy. Clinical complaints improved significantly during treatment (88% of women were symptomatic at initial visit, versus 53% at final follow-up, p < 0.001). The median lesion volume significantly decreased (median initial volume vs. final volume: 1.1 mL vs. 0.9 mL, p = 0.017). However, the median maximum lesion diameter did not change significantly (26.0 mm vs. 25.0 mm, p = 0.779). Conclusions: Long-term Dienogest therapy significantly relieves clinical symptoms related to recto-sigmoid DE. This is accompanied by a significant reduction in the lesion volume but not the maximum lesion diameter. Full article

(This article belongs to the Special Issue Challenges in Fertility Preservation)

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13 pages, 789 KiB

Open AccessArticle

Vitamin D Deficiency as an Independent Predictor for Plaque Vulnerability and All-Cause Mortality in Patients with High-Grade Carotid Disease

by Stephanie Kampf, Olesya Harkot, Rodrig Marculescu, Svitlana Demyanets, Markus Klinger, Wolf Eilenberg, Johann Wojta, Christoph Neumayer and Stefan Stojkovic

J. Clin. Med. 2025, 14(14), 5163; https://doi.org/10.3390/jcm14145163 - 21 Jul 2025

Viewed by 615

Abstract

Objectives: The mechanisms linking vitamin D deficiency to carotid artery stenosis (CAS) remain unclear. Data on cardiovascular outcomes in CAS patients with vitamin D deficiency are limited. We investigated the association of vitamin D deficiency with carotid plaque morphology and patient outcomes in [...] Read more.

Objectives: The mechanisms linking vitamin D deficiency to carotid artery stenosis (CAS) remain unclear. Data on cardiovascular outcomes in CAS patients with vitamin D deficiency are limited. We investigated the association of vitamin D deficiency with carotid plaque morphology and patient outcomes in high-grade CAS. Methods: A total of 332 patients undergoing carotid endarterectomy for symptomatic (n = 113, 34%) or asymptomatic (n = 219, 66%) CAS were included. Preoperative vitamin D levels were measured, and duplex sonography was used to assess luminal narrowing. Associations of vitamin D with clinical presentation were analyzed using univariate and multivariate linear regression. For vitamin D deficiency and the prediction of major adverse cardiovascular events (MACE) and all-cause mortality, the Cox proportional hazard regression model was used. Results: The median age was 69 years (interquartile range (IQR) 64–74), and 94 (29.3%) patients were female. Vitamin D deficiency was present in 84 (25%) patients. Symptomatic patients had significantly lower vitamin D levels (41.2 nmol/L, IQR 25.1–63.5) than asymptomatic patients (51.6 nmol/L, IQR 30.5–74.3, p = 0.011). Patients with echolucent (44.9 nmol/L, IQR 27.4–73.7) or mixed plaques (39.2 nmol/L, IQR 22.9–63.5) had lower vitamin D levels than those with echogenic plaques (52.3 nmol/L, IQR 34.1–75.7). Vitamin D deficiency predicted MACE and all-cause mortality with an adjusted HR of 1.6, 95% CI of 1.1–2.6, and p = 0.030 and an HR of 2.2, 95% CI of 1.3–3.6, and p = 0.002, respectively, in a multivariable Cox proportional hazard regression model. Conclusions: A deficiency in vitamin D was correlated with unstable plaque characteristics and symptomatic CAS. Furthermore, vitamin D deficiency was associated with long-term adverse cardiovascular outcomes and mortality, suggesting its potential as a modifiable risk factor for improved risk stratification in patients undergoing carotid endarterectomy. Full article

(This article belongs to the Section Cardiovascular Medicine)

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16 pages, 1317 KiB

Open AccessSystematic Review

Association Between Oral Dysbiosis and Depression: A Systematic Review

by Paula García-Rios, Miguel R. Pecci-Lloret, María Pilar Pecci-Lloret, Laura Murcia-Flores and Nuria Pérez-Guzmán

J. Clin. Med. 2025, 14(14), 5162; https://doi.org/10.3390/jcm14145162 - 21 Jul 2025

Viewed by 482

Abstract

Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various [...] Read more.

Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various studies are exploring a possible association between oral dysbiosis and depression—an increasingly relevant topic, as confirmation of such a relationship could position the oral microbiota as a potential etiological or diagnostic factor for depression, given its accessibility and ease of analysis. Aim: To present a qualitative synthesis of studies addressing how oral dysbiosis influences the onset of depression, as well as the importance of controlling this alteration of the oral microbiota to aid in the prevention of the disease. Materials and Methods: The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) outline the procedures to be followed for conducting this systematic review. The article search was carried out on 22 May 2025, across the PubMed, Scopus, Scielo, and The Cochrane Library databases, using terms related to “depression” and “oral dysbiosis”. Studies published within the last 10 years that addressed the potential association between oral dysbiosis, and depression were included. Furthermore, the quality of the studies was assessed using various tools depending on their design: the Newcastle–Ottawa Scale (NOS) was applied to case-control and cohort studies; the Joanna Briggs Institute (JBI) critical appraisal checklist was used for cross-sectional studies; and experimental studies were evaluated using SYRCLE’s Risk of Bias Tool. Results: A total of eleven studies were included in this systematic review. The findings suggest the presence of alterations in the oral microbiota of patients with depression, particularly in terms of composition, structure, and diversity. A reduction in alpha diversity—an indicator of local microbial balance—was observed, along with an increase in beta diversity, indicating greater inter-individual variability, which may be associated with inflammatory processes or immunological dysfunctions. Some studies reported differing results, which may be attributable to methodological variability regarding study design, or the populations sampled. Conclusions: This systematic review suggests that the oral microbiome could be considered a diagnostic biomarker and therapeutic target for depression, as the analyzed studies demonstrate a significant association between oral microbiome dysbiosis and this mental disorder. However, the methodological heterogeneity among the studies highlights the need for further research to confirm this potential relationship. Full article

(This article belongs to the Special Issue Endodontic and Periodontal Medicine: Systemic Implications of Oral Infections)

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13 pages, 233 KiB

Open AccessArticle

Exploring the Perceived Value of Standing in Individuals with Lower Limb Impairments

by Yukiyo Shimizu, Hideki Kadone, Yosuke Eguchi, Kai Sasaki, Kenji Suzuki and Yasushi Hada

J. Clin. Med. 2025, 14(14), 5161; https://doi.org/10.3390/jcm14145161 - 21 Jul 2025

Viewed by 387

Abstract

Background: Standing has medical and psychosocial benefits for people with lower limb impairments; however, systemic, logistical, and economic barriers often limit opportunities to stand in daily life. This study explored how users perceive standing and standing-assistive technologies. Methods: This study used a [...] Read more.

Background: Standing has medical and psychosocial benefits for people with lower limb impairments; however, systemic, logistical, and economic barriers often limit opportunities to stand in daily life. This study explored how users perceive standing and standing-assistive technologies. Methods: This study used a mixed-methods approach: in-person interviews (n = 18) and a nationwide web-based survey (n = 125; 74.4% male, mean age 52.2 ± 13.9 years, diagnoses: spinal cord injury 37.6%, cerebrovascular disease 27.2%, and cerebral palsy 16.8%). Results: Participants described the psychosocial values of standing, such as feeling more confident and being able to interact with others at eye level. The web survey revealed that most participants believed that standing was beneficial for health (76.8%) and task efficiency (76.0%), although only 49.6% showed an interest in standing wheelchairs. The multivariate analysis revealed that ongoing standing training was the strongest predictor of positive perceptions of health benefits, task efficiency, and interest in standing wheelchairs. Younger participants showed a greater interest in standing wheelchairs. The reported barriers include a lack of awareness, high costs, and difficulty in accessing training. Conclusions: These findings suggest the need for a user-centered design and improved support systems to integrate standing into the daily lives of people with mobility impairments. Full article

(This article belongs to the Section Clinical Rehabilitation)

26 pages, 2610 KiB

Open AccessReview

Immunosuppressants/Immunomodulators and Malignancy

by Norishige Iizuka, Yoshihiko Hoshida, Atsuko Tsujii Miyamoto, Hotaka Shigyo, Akira Nishigaichi, Gensuke Okamura and Shiro Ohshima

J. Clin. Med. 2025, 14(14), 5160; https://doi.org/10.3390/jcm14145160 - 21 Jul 2025

Viewed by 858

Abstract

Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a [...] Read more.

Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a high incidence of virus-associated cancers, and are reversible in some cases. Notably, immunosuppressive agents influence the frequency and type of malignancies, as well as their clinicopathological features. Organ transplant recipients receive long-term immunosuppressants to prevent acute rejection. Post-transplant malignancies vary depending on the type of drug administered before the onset of these diseases. Patients with rheumatoid arthritis (RA) are treated with long-term immunosuppressive medications, such as methotrexate (MTX). MTX is widely recognized as being associated with a specific type of lymphoproliferative disorder (LPD), known as MTX-associated LPD. Our recent report indicated that the clinicopathological features of rheumatoid arthritis-associated lymphoproliferative disorder (RA-LPD) also vary based on the other anti-RA agents used, such as tacrolimus and tumor necrosis factor inhibitors. Therefore, the clinicopathological characteristics of post-transplant LPD and RA-LPD evolve alongside the changes in the immunosuppressants/immunomodulators administered. Understanding the various characteristics and time trends of immunosuppressive neoplasms, particularly LPDs, in relation to different immunosuppressant/immunomodulator medications is highly valuable in clinical practice. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)

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14 pages, 561 KiB

Open AccessReview

Current Evidence and Surgical Strategies in the Management of Greater Tuberosity Fracture–Dislocations: A Narrative Review

by Gabriele Colò, Federico Fusini, Luca Faoro, Giacomo Popolizio, Sergio Ferraro, Giorgio Ippolito, Massimiliano Leigheb and Michele Francesco Surace

J. Clin. Med. 2025, 14(14), 5159; https://doi.org/10.3390/jcm14145159 - 21 Jul 2025

Viewed by 555

Abstract

Background: Greater tuberosity fracture–dislocations (GTFDs) represent a distinct subset of proximal humerus fractures, occurring in up to 57% of anterior glenohumeral dislocations. Malreduction may result in impingement, instability, and functional limitation. Treatment is influenced by the displacement magnitude and direction, bone quality, [...] Read more.

Background: Greater tuberosity fracture–dislocations (GTFDs) represent a distinct subset of proximal humerus fractures, occurring in up to 57% of anterior glenohumeral dislocations. Malreduction may result in impingement, instability, and functional limitation. Treatment is influenced by the displacement magnitude and direction, bone quality, and patient activity level. Methods: This narrative review was based on a comprehensive search of PubMed, Scopus, and Web of Science for English-language articles published between January 2000 and March 2025. Studies on pathomechanics, classification, diagnosis, treatment, and outcomes of GTFDs in adult and pediatric populations were included. Data were analyzed to summarize the current evidence and identify clinical trends. Results: A displacement ≥ 5 mm is the standard surgical threshold, though superior or posterosuperior displacement ≥ 3 mm—and ≥2 mm in overhead athletes—may justify surgery. Conservative treatment remains appropriate for minimally displaced fractures but is associated with up to 48% subacromial impingement and 11% delayed surgery. Surgical options include arthroscopic repair for small or comminuted fragments and open reduction and internal fixation (ORIF) with screws or plates for larger, split-type fractures. Locking plates and double-row suture constructs demonstrate superior biomechanical performance compared with transosseous sutures. Reverse shoulder arthroplasty (RSA) is reserved for elderly patients with poor bone stock, cuff insufficiency, or severe comminution. Pediatric cases require physeal-sparing strategies. Conclusions: GTFDs management demands an individualized approach based on fragment displacement and direction, patient age and activity level, and bone quality. While 5 mm remains the common threshold, lower cutoffs are increasingly adopted in active patients. A tiered treatment algorithm integrating displacement thresholds, fracture morphology, and patient factors is proposed to support surgical decision making. The incorporation of fracture morphologic classifications further refines fixation strategy. Further prospective and pediatric-specific studies are needed to refine treatment algorithms and validate outcomes. Full article

(This article belongs to the Special Issue Orthopedic Trauma Surgery: Current Challenges and Future Perspectives)

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17 pages, 360 KiB

Open AccessArticle

High Antenatal Psychosocial Risk Among Pregnant Women in Bulgaria: Evidence to Support Routine Mental-Health Screening

by Elitsa Gyokova, Eleonora Hristova-Atanasova and Georgi Iskrov

J. Clin. Med. 2025, 14(14), 5158; https://doi.org/10.3390/jcm14145158 - 21 Jul 2025

Viewed by 428

Abstract

Background: Antenatal depression and anxiety contribute significantly to maternal morbidity and adverse pregnancy outcomes. However, structured screening and targeted interventions are largely absent from standard prenatal care in many Eastern European countries, including Bulgaria. This study examines the prevalence and psychosocial predictors of [...] Read more.

Background: Antenatal depression and anxiety contribute significantly to maternal morbidity and adverse pregnancy outcomes. However, structured screening and targeted interventions are largely absent from standard prenatal care in many Eastern European countries, including Bulgaria. This study examines the prevalence and psychosocial predictors of antenatal psychosocial risk using the validated Antenatal Risk Questionnaire–Revised (ANRQ-R) in a nationally underrepresented population. Methods: A cross-sectional survey was conducted among 216 third-trimester pregnant women in Bulgaria. Data on sociodemographic characteristics, health behaviours, and reproductive history were collected. Multivariate logistic regression identified predictors of elevated psychosocial risk. Results: A total of 65.7% of participants met the criteria for elevated psychosocial risk. Significant risk factors included passive smoking exposure during pregnancy (OR = 5.03, p < 0.001), physical activity prior to pregnancy (OR = 1.81, p = 0.004), and a family history of hereditary disease (OR = 42.67, p < 0.001). Protective factors were better self-rated current health (OR = 0.37, p = 0.004), the presence of chronic illness (OR = 0.42, p = 0.049), previous childbirth experience (OR = 0.11, p = 0.032), and residence in Northwestern Bulgaria (OR = 0.31, p = 0.028). Despite the high prevalence of psychosocial vulnerability, only 9.5% of affected women sought professional help. Conclusions: While our findings point to important unmet needs in antenatal mental health, further research is required before national screening policies can be implemented. Pilot programs, cultural validation of tools, and system-level readiness assessments should precede broad adoption. Full article

(This article belongs to the Section Mental Health)

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8 pages, 974 KiB

Open AccessBrief Report

Current Antithrombotic Prescribing Habits for Extended Secondary Prevention in Patients with Peripheral Artery Disease and Unprovoked Venous Thromboembolism: A Survey Among Specialists in Angiology and Vascular Surgery

by Elena Butera, Frederikus Albertus Klok, Jamilla Goedegebuur, Angelo Porfidia, Behnood Bikdeli, Walter Ageno and Roberto Pola

J. Clin. Med. 2025, 14(14), 5157; https://doi.org/10.3390/jcm14145157 - 21 Jul 2025

Viewed by 380

Abstract

Background: Venous thromboembolism (VTE) is conventionally treated with anticoagulant therapy. In contrast, the core treatment for peripheral artery disease (PAD) is antiplatelet therapy. VTE and PAD share common risk factors and may occur in the same patient. Nonetheless, there is little evidence of [...] Read more.

Background: Venous thromboembolism (VTE) is conventionally treated with anticoagulant therapy. In contrast, the core treatment for peripheral artery disease (PAD) is antiplatelet therapy. VTE and PAD share common risk factors and may occur in the same patient. Nonetheless, there is little evidence of the best antithrombotic regimen to use when the two conditions coexist, especially in terms of the extended prevention of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and VTE recurrences. Methods: We conducted an online survey of members of the Italian Society of Angiology and Vascular Medicine (SIAPAV) to explore current prescribing habits for extended antithrombotic therapy in patients with PAD and unprovoked VTE. The survey included four clinical scenarios with variations in age, gender, bleeding risk, index VTE event, and severity of PAD. In all cases, patients had received anticoagulation for 6 months, and the key question was how to continue treatment beyond 6 months from the index VTE event. Results: A total of 174 clinicians participated to the survey. The most common choice was combining antiplatelet therapy with a direct oral anticoagulant (DOAC) at a low dose. Full-dose DOAC alone or antiplatelet therapy alone were less frequently chosen. Older age and high bleeding risk increased the preference for antiplatelet therapy alone. Conclusions: This survey highlights the marked variability in antithrombotic prescribing patterns among specialists in vascular medicine for patients with unprovoked VTE and concomitant PAD, reflecting the lack of evidence on optimal management in this specific setting. More research is needed to define the safest and most effective treatment strategies for patients with concurrent PAD and VTE. Full article

(This article belongs to the Section Cardiovascular Medicine)

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10 pages, 839 KiB

Open AccessArticle

Ex Vivo Thrombocyte Function and Its Response to NO/Sildenafil in Patients Undergoing Hemodialysis

by Vera Bonell, Christoph Schmaderer, Georg Lorenz, Roman Günthner, Susanne Angermann, Quirin Bachmann, Claudius Küchle, Lutz Renders, Uwe Heemann, Thorsten Kessler and Stephan Kemmner

J. Clin. Med. 2025, 14(14), 5156; https://doi.org/10.3390/jcm14145156 - 21 Jul 2025

Viewed by 280

Abstract

Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate [...] Read more.

Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate analyzer (Roche), which is based on multiple electrode impedance aggregometry. Platelet aggregation was induced using adenosine diphosphate (ADP), and the area under the curve (AUC) served as the primary endpoint. In addition, platelet counts and C-reactive protein (CRP) levels were measured. To further evaluate nitric oxide (NO)-mediated inhibition of platelet aggregation, blood samples were incubated with the NO donor, sodium nitroprusside (SNP), and the phosphodiesterase 5A (PDE5A) inhibitor, sildenafil. Results: A total of 60 patients undergoing HD and 67 healthy controls were included in the analysis. Patients receiving HD treatment had significantly lower platelet counts compared to healthy controls (226.9 ± 53.47 vs. 246.7 ± 47.21 G/L, p = 0.029). Platelet aggregation was markedly reduced in patients undergoing HD compared to controls (462.0 ± 266.54 vs. 644.5 ± 254.44 AU × min, p < 0.001) with a significant correlation for platelet count (r = 0.42, p = 0.001) and systemic inflammation as indicated by CRP levels (r = 0.28, p = 0.035). Following SNP and sildenafil administration, inhibition of platelet aggregation remained more pronounced in patients undergoing HD. However, the change in platelet aggregation after SNP/sildenafil treatment did not differ significantly between the groups. Conclusions: Patients undergoing HD exhibit altered platelet function, indicated by reduced aggregation and platelet counts, as well as an association with systemic inflammation. Multiple electrode impedance aggregometry appears to be a feasible method for detecting platelet function alterations in patients receiving HD treatment. Responsiveness to NO donors was preserved in patients undergoing HD. Further studies are needed to identify the underlying mechanisms, particularly the role of NO signaling in platelet dysfunction in patients undergoing HD. Full article

(This article belongs to the Section Nephrology & Urology)

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16 pages, 249 KiB

Open AccessArticle

The Role of Echocardiographic Right Atrial Strain Parameters in Evaluating Atrial Fibrillation Recurrence in Patients Undergoing Atrial Fibrillation Ablation

by Hasan Can Konte, Emir Dervis, Idris Yakut and Dursun Aras

J. Clin. Med. 2025, 14(14), 5155; https://doi.org/10.3390/jcm14145155 - 21 Jul 2025

Viewed by 396

Abstract

Background: Atrial fibrillation (AF) recurrence following catheter ablation remains a significant clinical challenge despite technological advancements, with recurrence rates in the range of 20–40%. While left atrial parameters have been extensively studied as predictors of recurrence, the contribution of right atrial mechanical function [...] Read more.

Background: Atrial fibrillation (AF) recurrence following catheter ablation remains a significant clinical challenge despite technological advancements, with recurrence rates in the range of 20–40%. While left atrial parameters have been extensively studied as predictors of recurrence, the contribution of right atrial mechanical function has received limited attention. The hypothesis that the combined assessment of right and left atrial strain parameters may provide superior predictive value represents an important clinical question with potential implications for post-ablation risk stratification and follow-up strategies. Methods: This single-center, retrospective cohort study included 100 consecutive adult patients who underwent AF ablation between May 2022 and June 2024 with at least one-year follow-up. Patients were divided into two groups: those with recurrence (n = 13) and those without recurrence (n = 87). A comprehensive echocardiographic assessment, including the speckle-tracking strain analysis of both atria, was performed. Results: The median follow-up was 365 days [range: 150–912 days] in patients with recurrence. In the multivariable analysis, right ventricular diameter (OR: 0.74; 95% CI: 0.61–0.90; p = 0.001), left ventricular end-diastolic volume (OR: 1.04; 95% CI: 1.00–1.08; p = 0.022), and left ventricular global longitudinal strain rate (OR: 1.22; 95% CI: 1.05–1.40; p = 0.007) emerged as independent predictors of recurrence. Conclusions: The significant association of right atrial longitudinal reservoir strain with recurrence in univariable analysis, although not retained as an independent predictor in the multivariable model, suggests the importance of comprehensive cardiac assessment including right heart parameters in predicting AF recurrence. Full article

(This article belongs to the Section Cardiology)

12 pages, 1184 KiB

Open AccessArticle

Diagnostic Potential of Serum Circulating miRNAs for Endometriosis in Patients with Chronic Pelvic Pain

by Tomas Kupec, Julia Wittenborn, Chao-Chung Kuo, Laila Najjari, Rebecca Senger, Philipp Meyer-Wilmes, Elmar Stickeler and Jochen Maurer

J. Clin. Med. 2025, 14(14), 5154; https://doi.org/10.3390/jcm14145154 - 21 Jul 2025

Viewed by 436

Abstract

Background: Endometriosis is a chronic gynecological condition marked by ectopic endometrial-like tissue, leading to inflammation, pain, and infertility. Diagnosis is often delayed by up to 10 years. Identifying non-invasive biomarkers could facilitate earlier detection. MicroRNAs, known for their stability in biological fluids [...] Read more.

Background: Endometriosis is a chronic gynecological condition marked by ectopic endometrial-like tissue, leading to inflammation, pain, and infertility. Diagnosis is often delayed by up to 10 years. Identifying non-invasive biomarkers could facilitate earlier detection. MicroRNAs, known for their stability in biological fluids and role in disease processes, have emerged as potential diagnostic tools. This pilot study investigated whether serum miRNA profiling can differentiate endometriosis from other causes of chronic pelvic pain. Methods: Serum samples from 52 patients (36 with laparoscopically confirmed endometriosis and 16 controls) treated for chronic pelvic pain at a University Endometriosis Centre were analyzed. High-throughput miRNA sequencing was performed. Feature selection reduced 4285 miRNAs to the 20 most informative MiRNAs. Machine learning models, including logistic regression, decision tree, random forest, and support vector machine, were trained and evaluated. Results: Among the tested machine learning models, support vector machine achieved the best overall performance (accuracy 0.71, precision 0.80), while logistic regression and random forest showed the highest AUC values (0.84 and 0.81, respectively), indicating strong diagnostic potential of serum miRNA profiling. Conclusions: This study demonstrates the feasibility of using serum miRNA profiling combined with machine learning for the non-invasive classification of endometriosis. The identified miRNA signature shows strong diagnostic potential and could contribute to earlier and more accurate detection of the disease. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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23 pages, 1017 KiB

Open AccessArticle

The Impact of Oral Health and Dental Care on Pregnancy: A Cross-Sectional Study Among Women of Reproductive Age

by Paulina Adamska, Hanna Sobczak-Zagalska, Zuzanna Gromek, Barbara Wojciechowska, Paulina Doroszkiewicz, Marek Chmielewski, Dominika Cichońska, Adam Zedler and Andrea Pilloni

J. Clin. Med. 2025, 14(14), 5153; https://doi.org/10.3390/jcm14145153 - 20 Jul 2025

Viewed by 805

Abstract

Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related [...] Read more.

Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related to the mother, such as smoking, alcohol drinking, drug use, malnutrition, or certain diseases. It is imperative to educate women of reproductive age (15–49) about the basic factors influencing embryonic development, such as oral health, diet, medicine intake, and harmful habits. Even though most women are aware of the negative impact of harmful habits on the fetus, still too little attention is paid to oral health in pregnant women. Poor oral health may influence the well-being of the future mother, as well as of the child. Therefore, women of reproductive age and those who are pregnant must have adequate knowledge on this subject. The aim of this study was to assess the knowledge of Polish women of reproductive age (15–49) regarding oral health during pregnancy, including the impact of dental treatment, oral hygiene, and maternal oral conditions on pregnancy outcomes and the health of the newborn. Materials and Methods: This was a cross-sectional study of 508 women, in the reproductive age, whose age ranged from 18 to 49 years old. The surveys were conducted from April 2020 to November 2020. The questionnaire was originally developed based on the available literature and consisted of seven sections: basic information, general health and habits, pregnancy status and dental care, knowledge of treatment options during pregnancy, oral health status and its association with the risk of preterm birth, prematurity and the child’s oral health, and breastfeeding and oral development. Results: After excluding incomplete questionnaires, a total of 499 questionnaires were included in the analysis. Women participating in the study had a fairly good understanding of the impact of oral health on the fetus and the role of breastfeeding in the development of the stomatognathic system (from 50% to 70% correct answers). However, even though most respondents had completed higher education (344/68.94%), their knowledge of oral health, preterm birth, and low birth weight was very limited (including the impact of inflammation on the intrauterine development of the child or bacteria and transfer across the placenta). In these sections, the percentage of correct answers ranged from less than 20% to 50%. When analyzing knowledge by age, education, number of births, and place of residence, the highest levels of knowledge were observed among respondents with higher education, particularly those aged 27–32. Conclusions: Respondents had a fairly good understanding of the general impact of oral health during pregnancy and recognition of the importance of breastfeeding for infants. However, their knowledge about the impact of bacteria and inflammation in the mother’s oral cavity on prematurity and low birth weight was limited. Therefore, educating women of reproductive age and pregnant women on this topic is essential, as it may help reduce the adverse consequences of prematurity. Full article

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

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23 pages, 587 KiB

Open AccessReview

Immune Checkpoint Inhibitors and Allograft Rejection Risk: Emerging Evidence Regarding Their Use in Kidney Transplant Recipients

by Muhammad Ali Khan, Munir Mehmood, Hind EL Azzazi, Samiullah Shaikh, Bhavna Bhasin-Chhabra, Prakash Gudsoorkar, Sumi Sukumaran Nair, Lavanya Kodali, Girish Mour, Sundararaman Swaminathan and Bassam G. Abu Jawdeh

J. Clin. Med. 2025, 14(14), 5152; https://doi.org/10.3390/jcm14145152 - 20 Jul 2025

Viewed by 773

Abstract

The indications for immune checkpoint inhibitor (ICI) use in cancer treatment continue to expand. This is attributable to their proven anticancer activity in addition to their tolerability and favorable toxicity profile as compared to conventional chemotherapeutic agents. ICIs work by blocking the inhibitory [...] Read more.

The indications for immune checkpoint inhibitor (ICI) use in cancer treatment continue to expand. This is attributable to their proven anticancer activity in addition to their tolerability and favorable toxicity profile as compared to conventional chemotherapeutic agents. ICIs work by blocking the inhibitory signals between tumor cells and T-cells, thereby enhancing the T-cell cytotoxic activity to inhibit tumor growth. Because of their immune-stimulating effect, ICIs are linked to adverse renal outcomes in both native and transplanted kidneys. The risk of kidney allograft rejection in the setting of ICI use has been reported to be around 40%, leading to an increased risk of graft loss. In this report, we review the literature examining outcomes in kidney transplant recipients receiving ICIs for various oncologic indications. Full article

(This article belongs to the Special Issue Clinical Advancements in Kidney Transplantation)

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13 pages, 4206 KiB

Open AccessCase Report

Comparison of Symptoms and Disease Progression in a Mother and Son with Gorlin–Goltz Syndrome: A Case Report

by Agnieszka Adamska, Dominik Woźniak, Piotr Regulski and Paweł Zawadzki

J. Clin. Med. 2025, 14(14), 5151; https://doi.org/10.3390/jcm14145151 - 20 Jul 2025

Viewed by 562

Abstract

Background: Gorlin–Goltz syndrome (GGS), also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare genetic disorder caused by mutations in the PTCH1, PTCH2, or SUFU genes, leading to an increased risk of neoplasms. Craniofacial [...] Read more.

Background: Gorlin–Goltz syndrome (GGS), also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare genetic disorder caused by mutations in the PTCH1, PTCH2, or SUFU genes, leading to an increased risk of neoplasms. Craniofacial anomalies are among the most common features of GGS. This paper aimed to highlight the similarities and differences in clinical presentation across different ages and to emphasize the importance of including all family members in the diagnostic process. The diagnosis can often be initiated by a dentist through routine radiographic imaging. Case Presentation: We present a 17-year longitudinal follow-up of a male patient with recurrent multiple odontogenic keratocysts and other manifestations consistent with GGS. Nearly 20 years later, the patient’s mother presented with similar clinical features suggestive of GGS. Diagnostic imaging, including contrast-enhanced computed tomography (CT), cone-beam CT, magnetic resonance imaging, and orthopantomography, was performed, and the diagnosis was confirmed through genetic testing. Interdisciplinary management included age-appropriate surgical and dermatological treatments tailored to lesion severity. Conclusions: Given the frequent involvement of the stomatognathic system in GGS, dentists play a critical role in early detection and referral. Comprehensive family-based screening is essential for timely diagnosis, improved monitoring, and effective management of this multisystem disorder. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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15 pages, 508 KiB

Open AccessReview

The Role of Artificial Intelligence in the Diagnosis and Management of Diabetic Retinopathy

by Areeb Ansari, Nabiha Ansari, Usman Khalid, Daniel Markov, Kristian Bechev, Vladimir Aleksiev, Galabin Markov and Elena Poryazova

J. Clin. Med. 2025, 14(14), 5150; https://doi.org/10.3390/jcm14145150 - 20 Jul 2025

Viewed by 954

Abstract

Background/Objectives: Diabetic retinopathy (DR) is a progressive microvascular complication of diabetes mellitus and a leading cause of vision impairment worldwide. Early detection and timely management are critical in preventing vision loss, yet current screening programs face challenges, including limited specialist availability and [...] Read more.

Background/Objectives: Diabetic retinopathy (DR) is a progressive microvascular complication of diabetes mellitus and a leading cause of vision impairment worldwide. Early detection and timely management are critical in preventing vision loss, yet current screening programs face challenges, including limited specialist availability and variability in diagnoses, particularly in underserved areas. This literature review explores the evolving role of artificial intelligence (AI) in enhancing the diagnosis, screening, and management of diabetic retinopathy. It examines AI’s potential to improve diagnostic accuracy, accessibility, and patient outcomes through advanced machine-learning and deep-learning algorithms. Methods: We conducted a non-systematic review of the published literature to explore advancements in the diagnostics of diabetic retinopathy. Relevant articles were identified by searching the PubMed and Google Scholar databases. Studies focusing on the application of artificial intelligence in screening, diagnosis, and improving healthcare accessibility for diabetic retinopathy were included. Key information was extracted and synthesized to provide an overview of recent progress and clinical implications. Conclusions: Artificial intelligence holds transformative potential in diabetic retinopathy care by enabling earlier detection, improving screening coverage, and supporting individualized disease management. Continued research and ethical deployment will be essential to maximize AI’s benefits and address challenges in real-world applications, ultimately improving global vision health outcomes. Full article

(This article belongs to the Section Ophthalmology)

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10 pages, 2235 KiB

Open AccessArticle

Obstetrical Follow-Up in Pregnancies After Radical Trachelectomy—Our Case Series and Proposed Cervical Length Measurement Protocol

by Șerban Nastasia, Adina-Elena Nenciu, Adrian Valeriu Neacșu, Manuela-Cristina Russu and Nicoleta-Adelina Achim

J. Clin. Med. 2025, 14(14), 5149; https://doi.org/10.3390/jcm14145149 - 20 Jul 2025

Viewed by 394

Abstract

Background/Objectives: Obstetrical monitoring following radical trachelectomy (RT) for cervical cancer is marked by the lack of a standardized protocol, which may lead to delays in the intervention for cervical shortening. In light of the typical cervical remodeling process that occurs at the [...] Read more.

Background/Objectives: Obstetrical monitoring following radical trachelectomy (RT) for cervical cancer is marked by the lack of a standardized protocol, which may lead to delays in the intervention for cervical shortening. In light of the typical cervical remodeling process that occurs at the onset of labor, we hypothesized that the onset of premature cervical shortening in patients who have undergone radiotherapy commences at the internal ostium. Methods: We introduced the concepts of internal distance (distance between internal cervical ostium and cerclage thread) and the latent shortening of internal distance, which is characterized as a painless reduction in the internal distance, serving as an early marker of preterm contractions, thus enabling timely tocolytic intervention. Results: Three patients spontaneously conceived after RT. They were obstetrically followed-up after RT, using a combined approach of transvaginal ultrasound cervical markers and cardiotocography. Active tocolysis was used if internal distance shortening was observed. All patients delivered term healthy babies. Conclusions: The consistent ultrasound evaluation of both internal and external distances permits the proactive diagnosis of premature contractions and enables swift therapeutic measures. Full article

(This article belongs to the Special Issue Adverse Pregnancy Outcomes: Current Status, Challenges and Future Directions)

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12 pages, 366 KiB

Open AccessArticle

Acute Respiratory Distress Syndrome in Patients with Lymphopenia: Results from the National Inpatient Sample (2017–2021)

by Arnav Garyali, Trishna Parikh, Dhruv Kumar, Ishan Gupta, Adishwar Rao, Akriti Agrawal, Sabiha Armin, Rishi Panjala, Rohan Patil, Nikhil Sriram, Sruthi Parthasarathy, Aarohi Parikh and Bindu Akkanti

J. Clin. Med. 2025, 14(14), 5148; https://doi.org/10.3390/jcm14145148 - 20 Jul 2025

Viewed by 452

Abstract

Background: Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population. Methods: Patients [...] Read more.

Background: Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population. Methods: Patients ≥ 18 years of age with lymphopenia were identified in the National Inpatient Sample (2017–2021) and stratified according to ARDS diagnosis. Predictors of in-hospital mortality were determined using multivariate analyses with a logistic regression model. Results: From 183,185 patients with lymphopenia, 10,420 (5.7%) had ARDS, of which 92.8% had coronavirus disease 2019. The patients with ARDS suffered from more in-hospital mortality (47% versus 6.7%, p < 0.001). ARDS increased the odds of in-hospital mortality by eight-fold (odds ratio [OR]: 7.91 [7.06–8.86], p < 0.001). Age ≥ 65 years (OR: 4.88 [3.98–5.99]), moderate/severe liver disease (OR: 2.53 [1.87–3.42]), and metastatic cancer (OR: 2.18 [1.68–2.82]) were among the strongest positive predictors of in-hospital mortality (all p < 0.001). Conclusions: Patients with lymphopenia who have ARDS have higher in-hospital mortality, likely due to the condition’s clinical course. Lymphopenia may be a marker of immune dysregulation and systemic involvement in ARDS. Full article

(This article belongs to the Section Respiratory Medicine)

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25 pages, 1308 KiB

Open AccessReview

Targeting the Substrate: Mechanism-Based Ablation Strategies for Persistent Atrial Fibrillation

by Gabriela-Elena Marascu, Alexandru Ioan Deaconu, Raluca-Elena Mitran, Laura Adina Stanciulescu and Radu Gabriel Vatasescu

J. Clin. Med. 2025, 14(14), 5147; https://doi.org/10.3390/jcm14145147 - 20 Jul 2025

Viewed by 654

Abstract

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, especially effective in patients with paroxysmal AF, where the pulmonary veins (PVs) are the primary triggers. More complex arrhythmogenic mechanisms are involved in persistent AF (PsAF), and PVI alone may not [...] Read more.

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, especially effective in patients with paroxysmal AF, where the pulmonary veins (PVs) are the primary triggers. More complex arrhythmogenic mechanisms are involved in persistent AF (PsAF), and PVI alone may not be sufficient. Personalized, substrate-based ablation strategies are increasingly used and can significantly enhance outcomes in PsAF patients. While radiofrequency ablation remains the gold standard, cryoablation provides effective PVI, and pulsed field ablation is emerging as a safer, promising alternative. Advanced mapping techniques may better target scar areas responsible for arrhythmogenesis, optimizing procedural results. While still in development, artificial intelligence and machine learning enable more personalized and precise ablation strategies and may improve long-term outcomes. Full article

(This article belongs to the Special Issue Catheter Ablation of Atrial Fibrillation: Current Progress and New Challenges)

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8 pages, 5186 KiB

Open AccessCase Report

Ectopic Intramural Isthmic Pregnancy: Case Report

by Eloisa Maria Mariani, Diletta Guglielmi, Paola Camponovo, Erika Gambino, Alessandra Inzoli, Davide Leni, Paolo Passoni and Anna Locatelli

J. Clin. Med. 2025, 14(14), 5146; https://doi.org/10.3390/jcm14145146 - 20 Jul 2025

Viewed by 439

Abstract

Background/Objectives: Intramural pregnancy (IMP) is a rare type of ectopic pregnancy where the embryo implants within the uterine myometrium. This condition carries a high risk of massive hemorrhage, uterine rupture, and potentially life-threatening complications. Methods: We present a case of a 35-year-old patient [...] Read more.

Background/Objectives: Intramural pregnancy (IMP) is a rare type of ectopic pregnancy where the embryo implants within the uterine myometrium. This condition carries a high risk of massive hemorrhage, uterine rupture, and potentially life-threatening complications. Methods: We present a case of a 35-year-old patient who underwent in vitro fertilization (IVF) and was diagnosed with an IMP located in the back-isthmian portion of the uterus by ultrasound scan. Results: We performed a conservative treatment approach based on the gestational sac location and the patient’s stable clinical condition and desire for future fertility. We first administered mifepristone 600 mg, followed by intracavitary methotrexate under ultrasound guidance. Although originally planned, a uterine artery embolization was not performed due to the evidence of bilateral anastomoses between the uterine and ovarian arteries. Progressive reabsorption of pregnancy was observed over the course of 8 months. Conclusions: Non-surgical management can be considered for IMP, thus allowing fertility preservation. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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14 pages, 5817 KiB

Open AccessArticle

Recent Changes in Sexually Transmitted Infection in Korea: A Population-Based Analysis

by Jae Yen Song, Kang Seob Kim, Chang Hee Han and Sangrak Bae

J. Clin. Med. 2025, 14(14), 5145; https://doi.org/10.3390/jcm14145145 - 20 Jul 2025

Viewed by 976

Abstract

Background: The objective of this study is to investigate the prevalence and epidemiological changes of major sexually transmitted infections (STIs) in Korea over the past decade. Methods: From 2010 to 2021, patients diagnosed with STIs based on ICD-10 codes were analyzed [...] Read more.

Background: The objective of this study is to investigate the prevalence and epidemiological changes of major sexually transmitted infections (STIs) in Korea over the past decade. Methods: From 2010 to 2021, patients diagnosed with STIs based on ICD-10 codes were analyzed using Korean Health insurance data. The analysis included the number of patients, prevalence, and age-specific prevalence (in 5-year intervals) over this period. We examined changes in disease patterns over time by analyzing the annual trends and age-specific prevalence of bacterial STIs such as chlamydia, mycoplasma, gonorrhea, and syphilis; viral STIs such as genital herpes, human papillomavirus (HPV), and human immunodeficiency virus (HIV); and other infections including scabies, pubic lice, and trichomoniasis. Results: In 2010, the STI with the highest prevalence due to an infectious pathogen was trichomoniasis (256.65/100,000), while latent syphilis had the lowest prevalence (5.29/100,000). In 2021, the STI with the highest prevalence was genital herpes (254.54 per 100,000 persons), and latent syphilis continued to have the lowest prevalence. Bacterial STIs showed a decreasing trend. Viral STIs showed a continuous increase throughout the study period, with anogenital warts (AGW) having the highest rate of increase. Other infections showed a decreasing trend. HIV and AGW in men showed a rapid increase. Gender differences varied depending on the disease. Conclusions: While bacterial STIs have gradually declined, viral STIs have continued to increase during last decade. The characteristics of each pathogen vary according to age and gender, necessitating the establishment of risk groups for each pathogen and the development of prevention policies accordingly. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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27 pages, 2740 KiB

Open AccessReview

Outcomes in Adults with Celiac Disease Following a Gluten-Free Diet

by Daniel Vasile Balaban, Iulia Enache, Marina Balaban, Răzvan Andrei David, Andreea-Diana Vasile, Alina Popp and Mariana Jinga

J. Clin. Med. 2025, 14(14), 5144; https://doi.org/10.3390/jcm14145144 - 20 Jul 2025

Viewed by 779

Abstract

Background/Objectives: Histological follow-up still lacks consensus in the long-term management of adult patients with celiac disease (CD) adhering to a gluten-free diet (GFD). Despite clinical and serological improvement, a significant proportion of patients continue to have persistent villous atrophy. We aimed to [...] Read more.

Background/Objectives: Histological follow-up still lacks consensus in the long-term management of adult patients with celiac disease (CD) adhering to a gluten-free diet (GFD). Despite clinical and serological improvement, a significant proportion of patients continue to have persistent villous atrophy. We aimed to synthesize current evidence regarding histological outcomes after GFD treatment in adult CD, focusing on mucosal healing rates, assessment methods, and remission criteria. Methods: We conducted a literature search with extraction and analysis of published cohort studies that included adult patients with CD on GFD with follow-up biopsy data. Extracted parameters included demographic details, baseline histology, GFD duration and adherence, serologic status, and histologic recovery rates with corresponding remission criteria. Results: Data from 46 studies comprising 15,530 patients were analyzed. The overall mean age was 41 years, and 73.3% were female. Mean histologic remission across cohorts was 58.8%, with considerable interstudy variation. Remission criteria also varied widely, ranging from strict Marsh 0 control histology to more inclusive definitions that considered Marsh 1 or even non-atrophic mucosa (Marsh < 3) as indicative of recovery, while some studies relied on quantitative villous height-to-crypt depth ratio thresholds, substantially influencing reported remission rates. Longer GFD duration and rigorous diet adherence assessment using validated questionnaires and accurate laboratory tools were associated with higher remission rates. Conclusions: Histologic remission in GFD-treated adult patients with CD is highly variable and strongly influenced by remission definitions and adherence assessment methods. Standardized reporting using validated metrics for histologic outcome and dietary compliance is essential for harmonizing follow-up strategies in adult CD. Full article

(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)

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Open AccessArticle

Clinical Predictors of Polyautoimmunity in Autoimmune Liver Diseases: Insights into Disease Complexity

by Özge Güçbey Türker, Çağdaş Kalkan, Gülden Bilican, Emra Asfuroğlu Kalkan, Ali Atay, İhsan Ateş and İrfan Soykan

J. Clin. Med. 2025, 14(14), 5143; https://doi.org/10.3390/jcm14145143 - 20 Jul 2025

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Abstract

Background: Autoimmune liver diseases (ALDs) are a diverse group of chronic inflammatory disorders. Individuals with a history of one autoimmune disease (AD) are at a substantially increased risk of developing additional autoimmune conditions. Polyautoimmunity has increasingly been recognized as a factor associated [...] Read more.

Background: Autoimmune liver diseases (ALDs) are a diverse group of chronic inflammatory disorders. Individuals with a history of one autoimmune disease (AD) are at a substantially increased risk of developing additional autoimmune conditions. Polyautoimmunity has increasingly been recognized as a factor associated with a more complex disease course and poorer long-term outcomes. Methods: This retrospective, cross-sectional observational study reviewed medical records of patients diagnosed with ALDs who had been admitted to the gastroenterology clinic. Results: A total of 457 patients with ALDs were included. Polyautoimmunity was present in 194 patients (42.5%), and multiple autoimmune syndrome (MAS) was diagnosed in 26 of these patients (5.7%). Serological comparisons revealed that antinuclear antibody (ANA) positivity was significantly more common in the polyautoimmunity group. Only 22.2% of the patients with polyautoimmunity were ANA-negative, compared with 52.9% in those without. An ROC curve analysis was conducted to assess the predictive value of clinical and laboratory variables for polyautoimmunity. Among all the tested parameters, ANA positivity (>+2) had the strongest predictive value (AUC: 0.724). A disease duration longer than 6.5 years followed, with a moderate discriminative capacity (AUC: 0.677). Additionally, lower albumin levels (<3.0 g/dL) and elevated erythrocyte sedimentation rates (ESRs) (>29.5 mm/h) were significantly associated with polyautoimmunity. Conclusions: In our cohort, 42.5% of patients had at least one additional autoimmune disorder, highlighting the need for a systemic and comprehensive approach to patient care. Simple and accessible markers—such as ANA titers, disease duration, albumin levels, and ESRs—may help to identify patients at greater risk. Full article

(This article belongs to the Section Immunology)

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13 pages, 248 KiB

Open AccessArticle

An Evaluation of Polish Women’s Knowledge of Perineal Incision: A Cross-Sectional Study

by Romana Buchert, Katarzyna Wszołek, Kinga Bednarek, Marcin Wierzchowski, Maciej Wilczak and Karolina Chmaj-Wierzchowska

J. Clin. Med. 2025, 14(14), 5142; https://doi.org/10.3390/jcm14145142 - 19 Jul 2025

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Abstract

Background/Objectives: A perineal incision (episiotomy) is a surgical procedure involving the controlled cutting of perineal tissues to widen the vaginal outlet during the second stage of labor. The aim of this study was to assess Polish women’s knowledge regarding perineal incision. Methods [...] Read more.

Background/Objectives: A perineal incision (episiotomy) is a surgical procedure involving the controlled cutting of perineal tissues to widen the vaginal outlet during the second stage of labor. The aim of this study was to assess Polish women’s knowledge regarding perineal incision. Methods: This study was conducted using an unvalidated, anonymous questionnaire created in Google Forms. Results: Women with higher education, those who had undergone childbirth, and those who identified the Internet, medical personnel, medical personnel on social media, and medical journals as sources had significantly higher levels of knowledge. Respondents aged 25 years or younger had significantly lower knowledge levels compared to those aged over 26. Additionally, respondents living in cities with populations of up to 500,000 had significantly lower levels of knowledge compared to women living in larger cities. Conclusions: The level of women’s knowledge about perineal incision varies and is influenced by several factors. Significant determinants of higher levels of knowledge were higher education, having a history of obstetric delivery, being over 25 years old, and using information provided by medical personnel, including those present on social media. Full article

(This article belongs to the Special Issue Clinical Challenges in Obstetrics and Gynecology: Interactions Between Gynecological and Obstetric Disorders, Quality of Life, and Mental Health in Women)

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J. Clin. Med., Volume 14, Issue 14 (July-2 2025) – 360 articles

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