Journal of Clinical Medicine最新文献

Background: Influenza is a common cause of hospitalization in young children, particularly infants. While most infections are self-limited, severe and life-threatening complications may occur. Diffuse alveolar hemorrhage (DAH) is a rare pulmonary manifestation of influenza, predominantly reported in adults, and is exceedingly uncommon in immunocompetent infants. Case Presentation: We report the case of an 8-month-old previously healthy female infant who presented with influenza A infection and rapidly progressed to acute respiratory failure and shock despite antiviral therapy. Bleeding was noted from the nasal cavity prior to clinical deterioration, and during emergent endotracheal intubation, blood was observed flooding the bronchial tree, consistent with massive pulmonary hemorrhage. Flexible bronchoscopy showed diffusely erythematous and friable airway mucosa without an identifiable focal bleeding source, and early bronchoalveolar lavage was nondiagnostic. Nasopharyngeal testing confirmed influenza A (H3). Laboratory findings revealed severe systemic inflammation, leukopenia with neutropenia, and anemia with normal coagulation parameters. Chest imaging demonstrated bilateral pulmonary infiltrates. After exclusion of autoimmune, coagulation, immunodeficiency, and alternative infectious causes, a diagnosis of diffuse alveolar hemorrhage secondary to influenza A infection was established. The patient was successfully managed with supportive care, antiviral therapy, tranexamic acid, and empiric antibiotics, without corticosteroid treatment, and made a full recovery. Conclusions: This case emphasizes that influenza-associated DAH in infants may occur without overt hemoptysis and may not demonstrate classical BAL findings early in the disease course. Clinicians should maintain a high index of suspicion in rapidly deteriorating infants with influenza and diffuse pulmonary infiltrates. The optimal role of corticosteroids remains uncertain and should be individualized.

The microbiota-gut-brain axis (MGBA) is a complex bidirectional communication network integrating neural, endocrine, immune, and metabolic pathways linking intestinal microbiota to central nervous system function. Increasing evidence indicates that microbiota-derived signals are critical regulators of neurodevelopment and may contribute to vulnerability to neurodegenerative disorders across the lifespan. In this narrative review, we synthesize experimental and clinical evidence to define the key biological mechanisms underlying microbiota-brain interactions. Converging data indicate that immune activation, barrier dysfunction, and microbial metabolites, particularly short-chain fatty acids and tryptophan-derived compounds, represent central mediators linking gut dysbiosis to neuroinflammatory and neurodegenerative processes. Early-life microbial perturbations, driven by factors such as antibiotic exposure, diet, and psychosocial stress, appear to induce long-term immunometabolic programming that may increase susceptibility to neurological disorders later in life. Clinical studies consistently associate dysbiosis with neurodevelopmental conditions and major neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease; however, causal relationships remain incompletely defined due to heterogeneity and the predominance of observational data. Overall, the available evidence supports a lifespan model in which microbiota-driven immune and metabolic dysregulation contributes to both early neurodevelopmental trajectories and late-life neurodegeneration. While microbiome-based biomarkers and therapeutic strategies show promise, their clinical translation requires validation in longitudinal and interventional studies.

Obesity, a heterogeneous metabolic disease, is linked with severe comorbidities, prominently increasing morbidity and mortality. A weight loss between 5% and 10% is already sufficient to induce clinically relevant improvements in human health. Activation of energy expenditure through an impact on the brown and beige adipose tissues has recently become an interesting new target in obesity treatment. Obeticholic acid (OCA) is a semisynthetic derivative of the primary human bile acid, chenodeoxycholic acid. The compound is an agonist of farnesoid X receptor (FXR) and Takeda G protein-coupled receptor (TGR5), activating the cellular pathways such as fibroblast growth factor-19, tissue-specific uncoupling protein 1, or type 2 iodothyronine deiodinase associated with energy expenditure and brown adipose tissue activity. So far, OCA has been approved to treat primary biliary cholangitis. Interestingly, the drug demonstrated therapeutic effects in animal models of obesity. Preliminary results from the human studies show that OCA administration holds potential as a treatment option in obesity, although some adverse effects may occur. Long-term administration of OCA might constitute an attractive therapeutic add-on approach, complementary to the currently approved treatments. The design of OCA derivatives targeting similar mechanisms, yet with a better pharmacological profile, seems to be an exciting pathway in the search of novel anti-obesity drugs. Further clinical trials involving larger cohorts of patients, with and without comorbidities, are warranted to confirm the benefits and safety of OCA administration.

Objective: To evaluate overall survival and to identify clinical, pathological, and demographic factors associated with survival in patients with stage III colon cancer. Methods: This retrospective cross-sectional study included 452 patients with stage III colon cancer who were followed at Ankara Bilkent City Hospital between 2005 and 2025. Patient data, including age, sex, ECOG performance status, comorbidities, tumor characteristics, treatment-related toxicities, and recurrence, were analyzed using PASW Statistics 18.0 (SPSS Inc., Chicago, IL, USA). Kaplan-Meier and log-rank tests were used for survival analysis. Prognostic factors, survival, mortality, and recurrence predictions were evaluated using machine learning algorithms, including coarse tree, bagged trees, support vector machines, and k-nearest neighbors. Furthermore, an explainable artificial intelligence framework was incorporated to improve model transparency and reveal clinically meaningful feature contributions. Model performance was assessed using accuracy, sensitivity, specificity, and F-score. Results: According to statistical analyses, older age, ECOG performance score ≥ 2, stage IIIC disease, N2-level lymph node metastasis, and the presence of comorbidities-particularly diabetes mellitus-were significantly associated with worse survival (p < 0.05). Machine learning analyses identified key prognostic factors, including positive surgical margins, rash, mucositis, thrombocytopenia, number of chemotherapy cycles, pathological tumor subtype, diarrhea, age at diagnosis, and anemia. SHAP analysis further demonstrated that treatment-related variables, particularly surgical margin positivity and chemotherapy-associated toxicities, were among the most influential predictors of survival. Several machine learning models outperformed traditional statistical methods in predicting mortality and recurrence, with the highest accuracy observed in ensemble methods such as coarse tree (87%) and bagged trees. Conclusions: This study identifies key prognostic factors influencing survival in stage III colon cancer and demonstrates that machine learning-based approaches can complement conventional statistical methods. The integration of clinical and treatment-related variables may improve individualized risk stratification and support clinical decision-making. These findings may also guide future large-scale, multicenter, and prospective studies.

Background/Objectives: Growing evidence suggests that disruption of circadian rhythms contributes to the pathogenesis of inflammation and inflammatory bowel disease; however, clinical data linking circadian gene variants to ulcerative colitis remain limited. In this study, we aimed to investigate associations between key circadian rhythm gene polymorphisms and clinical and treatment-related characteristics in ulcerative colitis. Methods: A total of 107 patients with ulcerative colitis and 80 healthy controls were included in this single-center cross-sectional study. The BMAL1 rs7950226, CLOCK rs1801260, and CRY1 rs2287161 polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype and allele frequency distributions were compared between patients and controls, and associations with clinical characteristics were evaluated within the ulcerative colitis cohort. Results: Genotype distributions of BMAL1 rs7950226 and CLOCK rs1801260 were similar between patients with ulcerative colitis and healthy controls; however, the G allele of BMAL1 was more frequent in patients (p = 0.028). Within the ulcerative colitis cohort, CLOCK rs1801260 genotypes were significantly associated with inflammatory and treatment-related characteristics, with the CC genotype linked to higher C-reactive protein levels (p = 0.021) and the TT genotype associated with increased azathioprine use (p = 0.006). Conclusions: These findings suggest a potential association between circadian rhythm gene variants and clinical features of ulcerative colitis, particularly in relation to inflammatory activity and treatment requirements, and provide preliminary clinical insight that warrants further investigation in larger and longitudinal studies.

Background/Objectives: We evaluated the clinical outcomes of two commonly used approaches for managing oligoprogression arising during first-line therapy for metastatic hormone-sensitive prostate cancer (mHSPC): metastasis-directed radiotherapy (RT) with continuation of the ongoing systemic regimen and immediate transition to another systemic treatment. Methods: A total of 81 patients with mHSPC who experienced radiologically confirmed oligoprogression during first-line systemic therapy were retrospectively evaluated. Oligoprogression was defined as progression involving three or fewer metastatic sites. Patients were categorized into an RT group (metastasis-directed RT with continuation of the same regimen) or a treatment-change group (immediate switch in systemic therapy without RT). Post-oligoprogression radiologic progression-free survival (rPFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Results: Thirty-one patients received metastasis-directed RT, whereas fifty underwent a change in systemic therapy. The median post-oligoprogression rPFS was 25.8 months (95% CI, 16.3-35.2) in the entire cohort and did not differ significantly between the treatment-change (26.8 months) and RT groups (22.7 months; p = 0.828). The median OS was 42.6 months overall, with comparable outcomes between the treatment-change (42.6 months) and RT groups (52.4 months; p = 0.452). Conclusions: In patients with mHSPC who developed oligoprogression during first-line systemic therapy, metastasis-directed RT with continuation of the same regimen and immediate change in systemic treatment were associated with comparable post-oligoprogression outcomes in our cohort. These findings suggest that both strategies may be feasible in selected patients. Prospective studies may help clarify which patients are more likely to benefit from each strategy.

Background: Frailty is a major determinant of adverse outcomes in older adults with cardiovascular disease. Automated digital tools may facilitate routine frailty assessment in hospital settings; however, their validity and prognostic relevance in acutely hospitalized patients remain insufficiently established. Methods: In this prospective cohort study, 113 hospitalized cardiology patients underwent frailty assessment using both manual Short Physical Performance Battery (mSPPB) and an automated electronic SPPB (eSPPB) system. Agreement between methods was evaluated using Pearson correlation, intraclass correlation coefficients (ICCs), and Bland-Altman analysis. Frailty was defined as SPPB < 5. The association between frailty and 30-day mortality was assessed using logistic regression and Kaplan-Meier survival analysis. Results: Seventeen patients (15.0%) were classified as frail. Automated and manual SPPB scores were highly correlated (r = 0.994, p < 0.001) and demonstrated good agreement (ICC = 0.80). Bland-Altman analysis showed a mean difference of -1.63 points (95% limits of agreement -4.41 to 1.16). Frailty was associated with significantly higher 30-day mortality (17.6% vs. 2.1%, p = 0.009), corresponding to a tenfold increase in mortality odds (OR 10.07; 95% CI 1.5-67.5). An exploratory model showed apparent discriminative performance (AUC 0.83; 95% CI 0.71-0.95). Conclusions: Automated eSPPB demonstrated good agreement with manual assessment and was significantly associated with short-term mortality in hospitalized cardiovascular patients. These findings support the validity and potential clinical utility of automated frailty assessment for risk stratification in acute cardiology settings.

Objectives: To characterize paraspinal muscle asymmetry using quantitative CT parameters in adolescent idiopathic scoliosis (AIS) and to examine the associations among muscle asymmetry, vertebral rotation, and curve severity. Methods: A retrospective analysis of 68 AIS patients was conducted. Quantitative CT measured the fatty infiltration rate (FIR) of paraspinal muscles at apical and stable vertebral levels. A muscle asymmetry index was calculated based on the FIR difference between concave and convex sides. Pearson and Spearman correlations and linear regression were used as the main analyses. AVR across upper, pedicle, and lower levels was evaluated using repeated-measures analysis, and SEM was performed as an additional analysis. Inter-observer repeatability of the apical muscle measurements was additionally assessed using an independently repeated segmentation dataset. Results: Paraspinal muscles at the apical region exhibited significant asymmetry, with concave FIR (33.4 ± 14.0%) being significantly higher than convex FIR (15.8 ± 6.8%; p < 0.001). In contrast, the stable vertebra showed no significant asymmetry. Muscle asymmetry was significantly associated with Cobb angle in both Pearson and Spearman analyses (r = 0.456, p = 0.0001; rho = 0.430, p = 0.0003). Its association with AVR was weaker (Pearson r = 0.232, p = 0.058; Spearman rho = 0.302, p = 0.013). In multivariable linear regression, both AVR (β = 1.222, 95% CI 0.827 to 1.617, p < 0.001) and muscle asymmetry (β = 0.375, 95% CI 0.167 to 0.583, p = 0.0006) remained independently associated with Cobb angle. Inter-observer repeatability for the apical muscle asymmetry index remained excellent (ICC(2,1) = 0.958, 95% CI 0.933 to 0.974). Conclusions: Significant asymmetric CT-derived low-attenuation change was observed in the apical paraspinal muscles of patients with AIS, predominating on the concave side. In this severe AIS cohort, paraspinal muscle asymmetry was consistently associated with Cobb angle and showed a weaker, more method-dependent association with AVR. These findings suggest a relationship between paraspinal muscle asymmetry and the severity of three-dimensional deformity.

Background/Objectives: This study aimed to determine the inguinal hernia recurrence rate after transabdominal preperitoneal (TAPP) repair, particularly considering the effect of simultaneous umbilical hernia repair. The secondary aim was to assess whether closing the 10 mm midline supraumbilical port-site fascia affects the incidence of trocar-site hernia (TSH) following inguinal TAPP. Methods: We reviewed medical records of consecutive patients undergoing inguinal TAPP at the Department of Surgery, University Hospital Centre Zagreb, between 1 January 2014 and 30 June 2022, and supplemented the data with telephone follow-up. Demographic, clinical, and operative variables were compared between patients who did and did not report inguinal hernia recurrence. Patients were also grouped by operating surgeon to compare TSH rates. Surgeon A routinely closed the 10 mm supraumbilical fascial defect with a single suture, while Surgeon B mostly did not, deciding on a case-by-case basis. Results: The analysis included 281 patients with a median follow-up of 60 months. The overall recurrence rate was 10.6%. Baseline demographic and clinical characteristics did not differ significantly between patients who reported recurrence and those who did not. A prior hernia repair was more common in the recurrence group (34.1% vs. 17.2%; p = 0.007). Concomitant umbilical hernia repair was performed in 12.5% of cases. Patient-reported recurrence was higher after combined TAPP and umbilical hernioplasty than after TAPP alone (14.3% vs. 12.2%), but this difference was not statistically significant (p = 0.784). Surgeon A had a lower observed TSH rate than Surgeon B (1.0% vs. 3.6%), although this difference did not reach statistical significance (p = 0.242). Conclusions: Concurrent TAPP and umbilical hernioplasty is not associated with a higher recurrence rate, but further research on a larger cohort is necessary. Routine closure of the 10 mm midline supraumbilical fascial defect could reduce the TSH rate, although the difference was not statistically significant. The side of the hernia does not influence recurrence after TAPP.