Journal of Clinical Medicine最新文献

Background: Sepsis is one of the leading causes of early death after a liver transplant, with a frequency of up to 45% and a high death rate of 50% in more severe forms. Standard diagnostic and therapeutic algorithms are often not applicable to this specific population, where immunosuppression, reperfusion injury, and systemic inflammation overlap and generate a clinical picture that is significantly different from sepsis in immunocompetent patients. Methods: This paper analyzes the available literature and clinical experiences of characteristic immune and hemodynamic profiles of sepsis after liver transplants. Biomarkers (IL-6, IL-10, HLA-DR, lactate, and IgM) are discussed as tools for assessing immune status and guiding timely interventions, including the early application of continuous renal replacement therapy (CRRT) and the selective use of IgM-enriched immunoglobulins. Results: Sepsis after liver transplantation frequently unfolds in two phases, an initial hyper-inflammatory response driven by cytokine release and reperfusion injury and a second phase of secondary immunoparalysis characterized by reduced HLA-DR expression and increased anti-inflammatory signaling. The immunometabolic shift appears to influence the clinical course and may inform therapeutic decision-making. The immunoparalysis phase is accompanied by mitochondrial dysfunction and impaired vascular reactivity. This type of mechanism contributes to hemodynamic instability and a reduced response to standard therapy. Individualized monitoring and early use of hemofiltration and immunomodulatory measures can improve results in carefully selected patients. Conclusions: In this setting, an individualized immunometabolic approach may complement standard sepsis management in liver transplant recipients. The introduction of biomarkers of immune function into routine practice and the recognition of early signs of exhaustion of the immune response can assist in timely therapeutic decision-making and improve survival.

Background: Acute gastrointestinal bleeding (GIB) remains a major clinical emergency with substantial morbidity, mortality, and healthcare burden. We aimed to provide a comprehensive characterization of all GIB subtypes, including iatrogenic bleeding, which is underrepresented in previous studies. Methods: In this ambidirectional cohort study, 1021 consecutive adults with overt GIB were enrolled from two Hungarian tertiary centers. Standardized data collection included demographics, comorbidities, medication use, bleeding source, and in-hospital outcomes: mortality, rebleeding, intensive care unit (ICU) admission, length of hospitalization (LoH), endoscopic evaluation and haemostatic intervention, red blood cell transfusion, and surgical intervention. Group comparisons were performed using appropriate statistical tests, and survival was analysed using Kaplan-Meier curves (R v4.4.2; p < 0.05). Results: Non-variceal upper GIB was the most common subtype (51.0%), followed by lower GIB (29.7%), variceal GIB (8.9%), small bowel bleeding (2.3%), and iatrogenic bleeding (7.5%). Overall, in-hospital mortality was 10.6%, highest in variceal bleeding (22%). Rebleeding occurred in 5.3% of cases, most frequently in variceal bleeding. ICU admission was required in 8.9% of patients, again, most common in variceal bleeding (21.6%). The median LoH was 7 days (IQR 4-10), significantly shorter in cases of intraprocedural iatrogenic bleeding. Endoscopy was performed in 91% of cases, with haemostatic intervention in 57%. Surgery was required in 3.4% of patients. Conclusions: Gastrointestinal bleeding represents a heterogeneous clinical entity with distinct outcome profiles across subtypes. Variceal bleeding was associated with the most unfavorable outcomes, whereas intraprocedural iatrogenic bleeding had a favorable course. These findings support subtype-specific clinical management and warrant validation in larger multicenter cohorts.

Objective: To analyze multiple aspects of advanced bladder endometriosis surgery, based on the experience of an endometriosis reference center. Methods: This retrospective/prospective study included 80 consecutive patients with deep bladder endometriosis treated with laparoscopic surgery. Results: In 96.3% of cases, bladder endometriosis coexisted with other organ involvement: bowel (87.5%), uterus (61.3%), and ureters (37.5%); isolated bladder lesions occurred in 3.7%. Full-thickness bladder infiltration occurred in 36.4% of patients, and 71.8% had a history of surgery. The most frequent preoperative symptoms related to multiorgan involvement were dysmenorrhea (88.7%), dyschezia (75.0%), and dyspareunia (55.7%). Dysuria (55.7%), pollakiuria (17.9%), and urinary urgency (9.0%) were also reported. Shaving was performed in 45.0% of cases, resection in 40.0%, skinning in 15.0%, with two rare cases requiring bladder augmentation with bowel insert. Of all multiorgan surgeries (96.3% of cases), the most complex 30% were performed by a bi-disciplinary team of gynecologists and urologists. Postoperative complications occurred in 8 patients (10%) and were significantly associated with larger lesions, full-thickness infiltration, trigonum involvement, multiple organs opened, and prior surgery. Conclusions: Laparoscopic management of bladder endometriosis is feasible and effective, even in complex cases. Postoperative complications were linked to disease complexity but remained low, likely due to protective techniques used by the reference team. Optimal outcomes for the most difficult cases are more likely when procedures are performed by a bi-disciplinary team involving both oncological gynecologists specialized in deep endometriosis surgery and urologists. Given the heterogeneous clinical profiles of bladder endometriosis, treatment should be carried out in specialized centers where individualized surgical strategies can be implemented.

Background/Objectives: Real-world persistence of traditional oral migraine preventive medications is low in routine care. Prior large claims-based analyses demonstrated early discontinuation of oral prophylaxis, but such datasets neither included modern preventive options such as monoclonal antibodies (mAB) against calcitonin-gene-related peptide (CGRP), nor were able to capture clinically validated reasons for discontinuation. The primary aim was to compare real-world treatment persistence and discontinuation reasons due to adverse drug reactions (ADRs) or insufficient efficacy among three preventive therapy classes: subcutaneous CGRP mAB and oral high- (HEVP) and low-evidence preventive medications (LEVP). A secondary aim was to examine persistence patterns of individual substances within the HEVP cohort. Methods: This exploratory observational study used depersonalized real-world data from the German Pain e-Registry (GPeR), a national multicenter clinical registry. Persistence trajectories were evaluated over six months, together with cumulative proportions of ADR-related and inefficacy-related discontinuations. Pairwise comparisons across the three cohorts based on chi-square analyses, odds ratios, relative risks, effect sizes, and numbers needed to harm. Results: At six months, persistence was highest for CGRP monoclonal antibodies at 89.4%, compared with 43.0% for LEVP and 34.0% for HEVP (all p < 0.001). ADR-related discontinuation occurred in 7.0% with CGRP vs. 35.7/44.5% with LEVP/HEVP, and discontinuations due to insufficient efficacy occurred in 3.6% with CGRP vs. 21.3/21.5% with LEVP/HEVP, without influence of sex or migraine frequency. Substance-level analysis within HEVP showed the steepest early attrition for tricyclic antidepressants, followed by beta-blockers, with comparatively more favorable though still suboptimal persistence for topiramate and flunarizine. Conclusions: Real-world treatment persistence is markedly higher with CGRP mAB than with HEVP/LEVP. Oral preventives show high discontinuation rates due to both ADR and insufficient efficacy, indicating substantial limitations in real-world applicability. These findings highlight the clinical relevance of a modern mechanism-based migraine prevention with CGRP mAB.

Background/Objectives: Platelet-rich plasma (PRP) has become a therapeutic option for tendinopathies. Its clinical efficacy depends on several factors, including the target tendon. The aim of this study was to evaluate the PRP efficacy for tendinopathies in the rotator cuff (RC), Achilles tendon (AT), and patellar tendon (PT). Methods: We conducted a prospective cohort study including patients with RC, AT and PT tendinopathies. Each patient received three multitarget PRP (intratendinous and peritendinous) treatments at intervals of two weeks. Clinical outcomes were assessed at baseline and 6 months using tendon-specific scores (DASH for RC, VISA-A for AT and VISA-P for PT). Responders were identified based on the Minimal Clinically Important Improvement (MCII). Comparative statistical tests and multivariate regression were performed for the analysis. Results: A total of 49 patients were included (RC: 15, AT: 18, PT: 16). The number of responders at 6 months was 33 (67.4%), with 11 (73.3%) in the RC Group, 14 (75.0%) in the AT Group and 8 (50.0%) in the PT Group. The RC and AT patients experienced a significant improvement according to their scores (p < 0.001), which was not seen in the PT group (p = 0.065). The percentage of responders was higher in women (12/13, 92.3%) than men (21/36, 58.3%) (p = 0.025). Conclusions: Repeated intratendinous and peritendinous PRP injections in RC, AT, and PT tendinopathy improved joint-related function six months after treatment. This improvement was less pronounced in patients with PT and the proportion of responders was higher among women.

Background/Objectives: This study aimed to assess the prognostic significance of the glucose-lymphocyte ratio (GLR) prior to therapy in individuals with epithelial ovarian cancer. Methods: This retrospective cohort study included 326 patients with epithelial ovarian cancer who were treated from 2011 to 2025. The GLR was computed utilizing pre-treatment fasting blood glucose levels and absolute lymphocyte numbers. The optimal GLR cutoff value was established by receiver operating characteristic (ROC) analysis. Overall survival (OS) and disease-free survival (DFS) were assessed utilizing Kaplan-Meier analysis and Cox regression models. Additional sensitivity analyses were performed excluding patients with diabetes mellitus and by testing the interaction between GLR and neoadjuvant chemotherapy. Results: The optimal GLR cutoff value was 3.42. Patients were classified into low-GLR (≤3.42; n = 190) and high-GLR (>3.42; n = 136) groups. Patients with high GLR levels (>3.42) had a median OS of 58 months, which was significantly shorter than the 151 months for patients with low GLR levels (≤3.42) (p < 0.001). They also had a median DFS of 17 months, which was significantly shorter than the 49 months for patients with low GLR levels (p < 0.001). Multivariable Cox regression analysis showed that a higher GLR is an independent prognostic factor related to shorter overall survival (HR: 1.561; 95% CI: 1.078-2.261; p = 0.018). Findings remained consistent after excluding patients with diabetes mellitus. The group with a high GLR had a greater rate of disease progression (55.1% vs. 29.5%, p < 0.001). Conclusions: The pre-treatment GLR may serve as a simple and readily available prognostic biomarker in epithelial ovarian cancer, potentially supporting basic risk stratification; however, external validation is required.

Background/Objectives: Induction of labor at ≥41 weeks with an unfavorable cervix is challenging. Comparative evidence for double-balloon catheter (DBC)-based augmentation protocols is limited. We aimed to estimate the frequency of prolonged labor, compare four DBC-based protocols, and identify predictors of timely vaginal delivery in the study population. Methods: This retrospective cohort study analyzed 709 women with singleton, cephalic pregnancies at ≥41 weeks and a Bishop score of ≤6 who achieved vaginal delivery following DBC-based induction at a tertiary referral center (2017-2026). The protocols comprised DBC alone or in combination with oxytocin, dinoprostone, or misoprostol. The primary outcome was vaginal delivery within 24 h of DBC insertion. Multivariable logistic regression and Kaplan-Meier analyses were performed, adjusting for maternal age, parity, body mass index, and post-ripening Bishop score changes. Results: Prolonged labor (≥24 h) occurred in 10.2% of vaginal deliveries and was associated with significantly elevated maternal infectious morbidity and adverse neonatal respiratory outcomes. The median induction-to-delivery interval was shortest with DBC plus misoprostol and longest with DBC plus dinoprostone (p < 0.001). Uterine hyperstimulation was most frequent with misoprostol (21.2% of cases). Post-ripening Bishop score change emerged as the strongest predictor of timely delivery (adjusted OR 4.72, 95% CI 2.99-7.43), whereas advancing maternal age reduced the odds of timely delivery (adjusted OR 0.65 per year, 95% CI 0.57-0.75). The prediction model demonstrated excellent discrimination (AUC = 0.924). Conclusions: In late-term and post-term DBC-based inductions, prolonged labor affected 10% of vaginal deliveries and substantially increased maternal and neonatal morbidity. DBC combined with misoprostol achieved the shortest delivery interval but carried the highest risk of hyperstimulation, whereas DBC combined with oxytocin offered the most favorable uterine activity profile. Post-ripening cervical reassessment, particularly changes in the Bishop score, enables evidence-based risk stratification and may guide the selection of individualized protocols.

Background: Bacterial vaginosis and vaginal dysbiosis represent major causes of morbidity among women in sub-Saharan Africa, yet data from Madagascar remain scarce. This study aimed to assess the prevalence and determinants of vaginal bacterial infections among women in northern Madagascar and to explore how vaginal microflora composition reflects broader aspects of reproductive health. Methods: A cross-sectional study was conducted in April 2024 among 159 women (15-80 years) attending a rural second-referral clinic in Manerinerina, Ambatoboeny District. Sociodemographic and hygiene data were obtained through structured questionnaires. Vaginal pH was measured in situ, and Gram-stained smears were evaluated using the Nugent scoring system. The presence of Trichomonas vaginalis, Neisseria gonorrhoeae, and Candida spp. was assessed microscopically. Associations were analyzed using Chi-square or Fisher's exact tests, with p < 0.05 considered significant. Results: Abnormal vaginal flora was observed in 68.6% of women, including 43.4% with BV (Nugent 7-10) and 25.2% with intermediate flora. Elevated vaginal pH correlated strongly with higher Nugent scores (p < 0.01). T. vaginalis and N. gonorrhoeae were detected in 10.7% and 9.4% of women, respectively, and both were significantly associated with dysbiosis (p = 0.02 and p = 0.04). Poor hygiene practices, vaginal douching (79.1% vs. 64.5%; p = 0.04), and unsafe water sources (p = 0.04) were major behavioral and environmental determinants. Conclusions: Vaginal dysbiosis is highly prevalent among women in northern Madagascar and closely linked to modifiable hygiene behaviors and environmental conditions. In resource-limited settings, Gram-stained microscopy and Nugent scoring remain cost-effective tools for surveillance and patient care. Culturally adapted education, improved water access, and integration of low-cost diagnostics are essential for reducing the burden of vaginal infections in rural Madagascar.

Background/Objectives: Implantable loop recorders (ILRs) enable long-term electrocadiographic monitoring and are established diagnostic tools for syncope and atrial fibrillation (AF). However, their diagnostic yield and therapeutic impact in other clinical settings remain less well defined. We aimed to evaluate the diagnostic yield and clinical impact of ILR implantation across contemporary clinical indications. Methods: In this retrospective single-center study, 388 patients who underwent ILR implantation between 2011 and 2018 were included. Indications were categorized into seven groups: unexplained syncope, presyncope, cryptogenic stroke or transient ischemic attack (TIA), AF detection, AF recurrence after atrial flutter (AFL) ablation, risk stratification in structural or inherited heart disease, and palpitations. Results: Among 388 patients (median age 63 [51.8-71.8] years, 57.5% male; median follow-up 17.0 [IQR 6.4-32.4] months), ILRs were most frequently implanted for syncope (44.6%), AF (20.4%), and stroke/TIA (12.9%). ILR-detected arrhythmias occurred in 241 patients (62.1%), with the highest detection rates in AF (83.5%) and AFL (73.7%). Indication-fulfilling diagnoses were established in 155 patients (39.9%), most frequently in AF (73.4%) and AFL (71.1%), after a median of 4.4 months (IQR 2.4-12.5). Nearly three quarters (72.9%) of diagnoses were made within the first year. ILR findings prompted therapeutic interventions in 156 patients (40.2%), including pacemaker implantation in syncope and rhythm- or anticoagulation-based therapies in AF. AF and AFL independently predicted higher diagnostic yield, while diagnostic yield and AF history predicted ILR-triggered therapy. AF, AFL, stroke/TIA, and AF history were associated with shorter time to first arrhythmia detection. Arrhythmia-free survival differed significantly across indication groups (p < 0.0001) and was lowest in AF and AFL, which demonstrated the highest cumulative incidence of indication-fulfilling arrhythmias. Conclusions: ILRs provide substantial diagnostic and therapeutic value across a broad range of indications. Beyond established uses in syncope and AF, clinically relevant yields were observed in presyncope, risk stratification, and AFL post-ablation, supporting broader consideration of ILRs and optimized patient selection.

Background/Objectives: Chronic kidney disease (CKD) affects almost 800 million people worldwide. Cardiovascular disease is the main cause of death in this population. Although physical activity is fundamental to systemic health, the evidence regarding its impact on the clinical outcomes of CKD populations is inconclusive. This protocol outlines the methodology for a systematic review and meta-analysis aimed at evaluating the association between physical activity and intensity and all-cause mortality, cardiovascular mortality, and cardiovascular disease. Methods: This protocol adheres to PRISMA-P and Cochrane Handbook guidelines and has been registered with PROSPERO (CRD420261302904). A systematic search will be conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library until June 2026. Studies estimating the association between physical activity and all-cause mortality, cardiovascular mortality and cardiovascular disease in populations with CKD will be included. Two independent reviewers will perform study selection, data extraction and quality assessment using the Study Quality Assessment Tool from the United States National Institute of Health tool. The certainty of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation tool. Narrative synthesis and random-effects meta-analysis will be conducted to calculate pooled effect estimates. Random-effects meta-analyses will be performed according to the level of physical activity, and meta-regressions will be used to control for the association with major covariates. Ethical approval is not required for this study. Results: The results will provide a comprehensive synthesis of the evidence regarding the use of physical activity as a non-pharmacological intervention to modify CKD progression. Conclusions: The findings will be disseminated through peer-reviewed journals and international conferences.