Search Results (802)

Background: Overactive bladder (OAB) is a common functional disorder in paediatric populations and is associated with significant psychological burden and impaired quality of life. Although oxybutynin is widely used as first-line pharmacological therapy, a substantial proportion of children exhibit incomplete symptom control or limited tolerability. Emerging evidence suggests that targeting metabolic dysfunction, oxidative stress, and neuromuscular excitability may provide additional therapeutic benefit. This retrospective observational study evaluated the clinical impact of an adjunctive nutraceutical formulation containing myo-inositol, microlipodispersed magnesium, folic acid, and vitamin C (LEVIGON™ PRO, Sanitpharma; Milan, Italy) in children with OAB receiving oxybutynin. Methods: Medical records of children diagnosed with OAB were retrospectively reviewed. After applying inclusion and exclusion criteria, 120 patients aged 5–15 years were included and allocated to two groups based on documented treatment: oxybutynin plus LEVIGON™ PRO (Group A, n = 60) or oxybutynin alone (Group B, n = 60). The primary outcome was complete daytime urinary continence at Day 112. Secondary outcomes included weekly incontinence episodes, voiding frequency, bladder wall thickness, uroflowmetry parameters, and Patient Perception of Bladder Condition (PPBC) scores. An exploratory subgroup analysis was performed in 34 children with impaired fasting glucose (ifg), assessing fasting glucose, insulin, and homa-ir. results: by day 112, complete daytime continence was achieved in 61.7% of patients in group a and 48.3% in group b (absolute risk difference 13.4%; nnt ≈ 7.5; p = 0.14). across secondary endpoints, the combination therapy group showed significantly greater longitudinal improvements (group × time interaction, p < 0.05), including reductions in weekly incontinence episodes, voiding frequency, post-void residual volume, and ppbc scores, as well as increases in mean voided volume, qmax, and reductions in bladder wall thickness. in the ifg subgroup, greater reductions in fasting glucose, fasting insulin, and homa-ir were observed in group a compared with group b (p < 0.01). Both treatments were well tolerated, with no serious adverse events reported. conclusions: adjunctive nutraceutical therapy combined with oxybutynin was associated with greater improvements in several clinically relevant secondary outcomes in children with OAB, with a favourable tolerability profile. Although the primary endpoint did not reach statistical significance, the overall pattern of findings may suggest a possible additive benefit; however, these findings may be influenced by residual confounding inherent to the retrospective observational design. Therefore, the results should be considered hypothesis generating and require confirmation in prospective randomized controlled trials. Full article

Background: Cemented and cementless fixation techniques in total hip arthroplasty (THA) each present distinct biomechanical properties and perioperative risk profiles. While cementless fixation has gained increasing popularity, large-scale nationally representative comparisons of perioperative outcomes between cemented and cementless elective THA remain limited. This study aimed to compare complication rates, healthcare utilization, and temporal trends between cemented and cementless elective THA using the National Inpatient Sample. Methods: A retrospective cohort study was conducted using the National Inpatient Sample database from 2016 to 2021. Adult patients undergoing elective primary total hip arthroplasty were identified using ICD-10-PCS codes and categorized into cemented and cementless fixation groups. Patient demographics, comorbidities, indications, postoperative complications, length of stay, hospital charges, and in-hospital mortality were compared. Multivariate logistic regression analysis was performed to evaluate the independent association between fixation type and postoperative complications while adjusting for demographic, clinical, and hospital-level variables. Results: A total of 81,668 elective THAs were identified, including 40,290 cemented (49.33%) and 41,378 cementless (50.67%) procedures. Cemented THA was associated with a shorter length of stay (2.09 ± 1.88 vs. 2.26 ± 2.47 days, p < 0.001) and lower total hospital charges ($65,584.53 ± 48,797.21 vs. $72,186.84 ± 49,860.20, p < 0.001). Unadjusted analyses demonstrated higher rates of acute kidney injury and sepsis in the cementless group. After multivariate adjustment, cemented fixation was associated with lower odds of acute kidney injury (OR 0.87, 95% CI 0.79–0.96, p = 0.004). However, cemented THA was associated with higher odds of postoperative delirium (OR 1.20, 95% CI 1.02–1.42, p = 0.030), blood transfusion (OR 1.27, 95% CI 1.17–1.37, p < 0.001), and periprosthetic fracture (OR 1.32, 95% CI 1.02–1.71, p = 0.035). Rates of myocardial infarction, pneumonia, venous thromboembolism, urinary tract infection, and in-hospital mortality were similar between groups. Temporal analysis demonstrated comparable utilization trends, with a decline in elective procedures during 2020–2021. Conclusions: In this nationwide analysis, cemented total hip arthroplasty was associated with lower risk of acute kidney injury, shorter length of stay, and lower hospital charges, but higher odds of postoperative delirium, blood transfusion, and periprosthetic fracture compared with cementless fixation. These findings highlight distinct perioperative risk profiles between fixation strategies and may assist surgeons in individualized decision-making for elective total hip arthroplasty. Full article

The human virome, comprising eukaryotic viruses, bacteriophages, and viral genetic material, is a dynamic component of the microbiome with growing relevance in infectious diseases. This narrative review is structured to: (i) summarize the general composition of the human virome and methodological challenges, including the fraction of unclassified viral “dark matter”; (ii) describe virome alterations in chronic infections; and (iii) explore site-specific virome dynamics across respiratory, intestinal, and genito-urinary tracts in both chronic and acute infections. In chronic viral infections such as HIV, HBV, HCV, and HPV, a recurrent feature is the expansion of Anelloviridae—particularly torque teno virus—reflecting impaired immune surveillance rather than direct pathogenicity, suggesting their potential as surrogate biomarkers of immune competence. Evidence on virome changes in chronic bacterial and parasitic infections remains limited, highlighting a critical knowledge gap. Acute infections are associated with compartment-specific shifts in eukaryotic viruses and bacteriophage communities, often paralleling changes in bacterial populations and inflammatory responses, with implications for disease severity. Despite advances in metagenomic approaches, a substantial proportion of viral sequences remains unclassified, limiting functional interpretation. Nevertheless, virome profiling provides an ecosystem-level perspective, offering insights beyond single-pathogen detection and supporting emerging applications in diagnostics, immune monitoring, prognosis, and infectious disease surveillance. Full article

Chronic kidney disease is a global public health concern, representing a critical global public health challenge with increasing morbidity and mortality rates. The disease is a long-term condition characterized by the progressive loss of renal function. Early detection of declining kidney health and timely intervention are crucial to slow disease progression and improve prognosis, mitigating complications, including cardiovascular events. Current diagnostic standards are unable to detect early stages of kidney disease, reflecting early signs of glomerular and tubular damage. This creates an urgent need to identify reliable biomarkers for early detection, prognosis and therapeutic monitoring of kidney diseases. Novel biomarkers, including urinary microRNA, exosomal components, proteomic signatures and integrated multi-omics profiles, facilitated by up-to-date technologies offer strong promise for enhancing early diagnosis, risk assessment and monitoring of the disease. We focus on the fundamental biological significance and clinical application of these markers, discussing a critical evaluation of novel methodologies and clinical evidence supporting their potential for earlier and more precise diagnosis. This review summarizes innovative urinary biomarkers and advanced analytical technologies that can provide a more comprehensive and accurate assessment of the kidney status towards early diagnosis, better prognosis and better quality of life for patients with chronic kidney disease. Full article

Uropathogenic Escherichia coli (UPEC) is a leading cause of urinary tract infections (UTIs) in companion animals. This study characterized 42 UPEC isolates recovered from dogs and cats at the University of Florida, College of Veterinary Medicine Diagnostic Laboratories between 2023 and 2024, focusing on antimicrobial resistance (AMR), virulence gene profiles, biofilm-forming ability, and phylogroup distribution of the isolates. Antimicrobial susceptibility testing (AST) showed that 40.48% of the isolates were resistant to at least one of the tested antibiotics, and 9.52% exhibited multidrug resistance (MDR). Phylogroup B2 was predominant (69.05%), and 61.90% of isolates demonstrated strong biofilm formation in artificial human urine. Virulence gene analysis revealed the presence of genes mediating adhesion (fim, pap, sfa), iron acquisition (fyuA, iro), biofilm formation (csg, bcs, pga, ycg/ymg), motility (fli, mot, flh), and stress response (oxyR, soxR/S, kat). Multiple plasmids carrying AMR and virulence determinants were also identified. The co-occurrence of the traits underscores the potential for persistent and recurrent infections, which can complicate therapeutic outcomes and facilitate horizontal gene transfer (HGT). The detection of antimicrobial-resistant, highly virulent UPEC strains possessing human UPEC traits in companion animals suggests the risk of zoonotic and reverse-zoonotic transmission, particularly in households with close pet–owner interactions. These findings emphasize the importance of judicious antimicrobial use, routine molecular surveillance, and integrated One Health strategies to mitigate the veterinary and public health threats associated with UPEC infections in companion animals. Full article

Upper-tract urothelial carcinoma (UTUC) represents a biologically distinct and clinically challenging subset of urothelial malignancies, accounting for only 5–10% of urothelial cancers but carrying a disproportionately high risk of advanced disease and recurrence. Historically, management strategies for UTUC have been extrapolated from bladder cancer data, with limited prospective evidence specific to the upper urinary tract. However, recent years have witnessed an expanding number of UTUC-focused clinical trials that are reshaping treatment paradigms across localized, locally advanced, and metastatic disease states. This review examines the evolving landscape of clinical trials in UTUC, highlighting pivotal and ongoing studies that will inform contemporary management. We summarize evidence supporting perioperative systemic therapy, including neoadjuvant and adjuvant chemotherapy, and discuss the expanding role of immune checkpoint inhibitors in both perioperative and metastatic settings. Additionally, we review trials evaluating kidney-sparing approaches, intraluminal therapies, and novel drug-delivery platforms aimed at preserving renal function while maintaining oncologic control. Emerging trial designs incorporating molecular profiling, fibroblast growth factor receptor (FGFR)-targeted therapies, and biomarker-driven patient selection are also explored. Despite meaningful progress, significant gaps remain, including the underrepresentation of UTUC patients in large urothelial cancer trials, heterogeneity in risk stratification, and challenges in trial accrual for this rare disease. We conclude by outlining future directions for UTUC-specific clinical research, emphasizing the need for collaborative, multicenter trials, innovative endpoints, and integrated translational studies to further refine personalized treatment strategies. As the clinical trial ecosystem for UTUC continues to mature, these efforts hold promises for improving outcomes while balancing oncologic efficacy with renal preservation. Full article

Introduction: Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor with potent activity against multidrug-resistant Gram-negative pathogens, notably Pseudomonas aeruginosa. Its use is vital in the management of severe infections in ICU patients, especially where resistance limits first-line antibiotic options. This study aimed to describe the clinical characteristics, infection profiles, antimicrobial therapies, and hospital outcomes of ICU patients in Brazil who were treated with ceftolozane/tazobactam. Methods: A multicenter retrospective analysis was conducted on ICU patients treated with ceftolozane/tazobactam across twelve private hospitals in Brazil admitted between July 2018 and February 2023. Data were extracted from electronic medical records, including demographics, comorbidities, infection characteristics, antimicrobial usage, and hospital outcomes. Additionally, microbiological data and treatment details were evaluated. Descriptive statistics were used for analysis. Results: The study included 104 patients, with a median age of 78 years (IQR 61, 87) and 43% of whom were female. Pneumonia (57%) and urinary tract infections (19%) were the primary indications for treatment. Mechanical ventilation was required in 62 patients (60%). Pathogens were isolated in 44 cases, with ESBL-producing Gram-negative bacteria (34%) and carbapenem-resistant strains (18%) being the most common. Empirical therapy was initiated in 57% of cases, with a median treatment duration of 10 days. Concomitant antibiotics were used in 64% of patients. Mechanically ventilated patients exhibited higher mortality (66% vs. 29%) and prolonged ICU stays (57 vs. 20 days) as compared to non-ventilated patients. Conclusions: Ceftolozane/tazobactam demonstrates efficacy and safety in managing multidrug-resistant Gram-negative infections in ICU settings. However, its empirical use, driven by high resistance rates, underscores the importance of microbiology-guided therapy. The observed high mortality and prolonged ICU stay highlight the critical need for optimized infection management strategies and continued antimicrobial stewardship in critically ill populations. Full article

Purpose: The aims of this study were to evaluate the feasibility of time-restricted eating (TRE) in patients with Cushing’s disease (CD) and assess its effects on body weight and metabolic parameters. Methods: Twelve CD patients in remission with obesity were enrolled in a TRE program restricting food intake to 10:00–18:00. Anthropometric data, glycemic and lipid profiles, and circadian cortisol secretion were assessed at baseline and post-intervention. Serum cortisol levels were measured at multiple time points to evaluate diurnal patterns. Results: Nine patients completed the study. Over the 12-week period, participants showed a significant reduction in body weight, with median values decreasing from 93.8 kg [83.1–106.5] to 82.6 kg [76.9–100.3] (p = 0.011). Body mass index (BMI) also declined from 37.6 kg/m² [34.2–39.7] to 34.4 kg/m² [32.6–38.3] (p = 0.012). No statistically significant changes were observed in fasting glucose, HbA1c, or lipid parameters. Notably, 24 h urinary free cortisol levels significantly decreased (p = 0.01), and serum cortisol showed a downward trend at all measured time points, with the most pronounced reductions during mid-day and evening hours. No clinical or biochemical evidence of CD relapse was observed during the 12-month follow-up. Conclusions: Time-restricted eating is a feasible and well-tolerated dietary approach for patients with CD in remission, promoting weight loss and modest improvements in metabolic markers and cortisol rhythmicity. Full article

Urinary microRNAs (miRNAs) are promising noninvasive biomarkers for cancer detection, but their clinical utility is reduced by inconsistent normalization strategies, reducing reproducibility and comparability across studies. In this study, we assessed the stability of miR-20a as an endogenous normalizer for urinary miRNA profiling in clear cell renal cell carcinoma (ccRCC) while standardizing the pre-analytical phase using a urine stabilizing solution. Ninety-nine urine samples were analyzed: 47 from healthy individuals, 30 from ccRCC patients pre-surgery, and 22 post-operative patients. Six candidate miRNAs—miR-20a, miR-15b, miR-16, miR-15a, miR-210-3p, and miR-let-7b—were quantified via RT-qPCR. Stability analysis with RefFinder, integrating multiple algorithms (geNorm, normFinder, BestKeeper, and ΔCt methods), identified miR-20a as the most stable among the six candidates. Raw Ct values of miR-20a were normally distributed (Shapiro–Wilk test, p > 0.05), with no significant intergroup differences (one-way ANOVA, F(2.96) = 2.324, p = 0.103) and minimal intragroup variability (CV% 4.98–6.38). MiR-20a expression remained stable across different tumor staging, grading, and urine storage durations. These findings confirm miR-20a as a robust endogenous normalizer for urinary miRNA analyses and support the feasibility of developing reproducible urinary liquid biopsy workflows for ccRCC, even in settings where immediate sample processing is not feasible. Full article

Background: Complicated acute pyelonephritis (AP) is a severe upper urinary tract infection associated with systemic inflammation, organ dysfunction, and the risk of sepsis. The increasing prevalence of antimicrobial-resistant (AMR) organisms can alter clinical management. This study aimed to characterize the biological profile of inpatients with complicated AP and to eventually identify laboratory markers associated with risks of sepsis and AMR infections. Material and Methods: A retrospective observational analysis on 553 adult inpatients diagnosed with complicated AP between 2021 and 2025 was conducted in a tertiary center. Demographic, clinical, and biological parameters were analyzed, including inflammatory markers and renal and hepatic markers. Results: Group characteristics included a mean age of 63.82 ± 15.67 years, and 63% were female. At admission, inflammatory markers were raised, with leukocytosis (15.6 ± 5.8 × 10³/µL), neutrophilia (10.1 ± 4.7 × 10³/µL), and elevated C-reactive protein (CRP) (median 43.2 mg/dL). Coagulation activation was significant with elevated fibrinogen of 747 ± 145 mg/dL and D-dimer with a median level of 1249 ng/mL, of which 58% exceeded 1000 ng/mL. Mild to moderate renal impairment was frequently observed (creatinine 1.69 ± 0.76 mg/dL). In multivariate analysis, no biological parameter proved to be an independent predictor of AMR status among organisms. Discussion and Conclusions: Inpatients with complicated AP showed a pronounced inflammatory and procoagulant biological profile that did not vary between AMR pathogen and non-AMR pathogen infections. This suggests that the clinical value of biomarkers, such as leukocyte and neutrophile, CRP, D-dimer, fibrinogen, procalcitonin, urea, and creatinine, lies primarily in assessing disease severity rather than predicting antimicrobial resistance. The microbiological profile was dominated by Gram-negative pathogens, particularly Escherichia coli, although a heterogeneous spectrum of microorganisms was identified. Full article

The fruit of Aronia melanocarpa (Michx.) Elliott is a berry with multiple properties and was included as a new raw food material by the National Health Commission of China (NHC) in September 2018. This study focused on the immune regulatory properties and underlying mechanism of polysaccharides extracted from Aronia melanocarpa fruit (AMFP) by undertaking an integrated analysis of multiple endogenous metabolic pathways. An improvement in AMFP in immunosuppressed model mice at three levels of immune organs, immune cells, and immune factors was determined. The immunomodulatory role of AMFP was assessed through measurement of metabolomic and lipidomic profilings by UPLC-Q-TOF/MS. A total of 53 differential endogenous metabolites in the urinary, serum, and lipid metabolomics were identified, followed by KEGG pathway enrichment. Furthermore, the underlying mechanisms were elucidated by an integrated analysis of multiple metabolomics and lipidomics. Primarily, we found regulation of immune-related metabolic pathways, including nicotinate and nicotinamide metabolism, sphingolipid metabolism, glycerophospholipid metabolism, purine metabolism, steroid hormone biosynthesis, and arachidonic acid metabolism. The results also demonstrated the mutual validation of key pathways and mechanisms. AMFP potentiated both humoral and cellular immunity responses and protected the immune system from oxidative damage. This research provides a reference and a basis for the development and application of AMFP in the field of health foods that regulate immunity. Full article

Limited data exist on the prevalence of human epidermal growth factor receptor 2 (ERBB2/HER2) amplification in patients with all types of solid tumors. This retrospective, observational study (UMIN ID: UMIN000057382) analyzed the prevalence of HER2 amplification across all solid tumors using comprehensive genomic profiling (CGP) data from the Center for Cancer Genomics and Advanced Therapeutics database in Japan. We analyzed 89,374 eligible patients with solid tumors: HER2 amplification was detected in 5119 patients (5.7%). The highest rates of HER2 amplification were observed in patients with tumors of the esophagus/stomach (12.9%), followed by tumors of the bladder/urinary tract (10.6%), breast (9.5%), biliary tract (8.4%), and uterus (8.4%). Among the five assay platforms, FoundationOne CDx accounted for 69.7% of all CGP tests and had an HER2 amplification detection rate of 7.4%, compared to the other four platforms (range: 1.9–15.4% of all CGP tests [detection rates: 1.5–2.3%]). Substantial differences were observed in the mutation frequencies of multiple genes between HER2 amplified and HER2 non-amplified tumors. The results highlight that HER2 amplification extends beyond conventional tumor types and enables the identification, via CGP testing, of non-traditional tumor subsets (cancers other than breast and gastric cancer), including rare cancers, that could be candidates for HER2-targeting therapy such as trastuzumab deruxtecan in Japan. Full article

Background: Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of urinary tract infections (UTIs) worldwide. The emergence of strains combining high virulence with multidrug resistance (MDR) poses a significant challenge to public health. This study aimed to characterize the phylogenetic distribution, virulence profiles, and antimicrobial susceptibility of UPEC isolates recovered from patients in the metropolitan area of Buenos Aires (AMBA), Argentina. Methodology: Phylogenetic groups, the ST131 lineage, and virulence-associated genes were identified using PCR-based assays. Antimicrobial susceptibility testing (AST) was performed using automated methods and extended-spectrum beta-lactamase (ESBL) production was confirmed using the double-disk synergy test. Colistin (COL) resistance was evaluated by Colistin Drop Test and PCR screening for the mcr-1 (mobile colistin resistance gene 1). Biofilm formation was detected by the Tissue Culture Plate (TCP) method, whereas phenotypic virulence factors (VF) were assessed with Congo Red agar, hemagglutination, and hemolysis assays. Results: Phylogenetic groups B2 (43.8%) and D (26.7%), typically associated with extraintestinal infections, were the most frequent. The high-risk clone B2-ST131 was detected in 6.7% of isolates. Biofilm production was observed in 92.4% of the isolates, with curli fimbriae (87.6%) being the most frequently expressed VF. The highest resistance rates were observed for ampicillin (62.1%), ampicillin-sulbactam (39.8%), and trimethoprim-sulfamethoxazole (25.2%). Interestingly, 3.8% of isolates exhibited colistin resistance, despite the absence of the mcr-1 gene. Conclusions: This study highlights the detection of MDR-UPEC isolates that showed strong resistance to fluoroquinolones and were ESBL producers with high virulence in Argentina, justifying future research encompassing genomic and epidemiological monitoring of local UPEC, which is essential for managing infections and developing new therapeutic and preventive measures. Full article

Diabetes, a major global public health concern, requires early diagnosis and timely intervention. Glycated hemoglobin A1c (HbA1c) serves as a biomarker of glycemic management, with its levels showing a continuous relationship with the risk of developing diabetes. In this study, urinary proteome modifications were compared between each of the two patient groups with different HbA1c levels ([6.4 ± 0.7]% and [8.6 ± 1.6]%) and healthy controls. A total of 1954 and 5545 differentially modified peptides were identified in the two groups, respectively. Within each group, differentially modified peptides exhibiting changes from presence to absence or vice versa accounted for 48.8% and 86.5%, respectively. Additionally, results from the randomized grouping test indicated that at least 90.6% and 94.1% of these differentially modified peptides in each group were not randomly generated. In conclusion, urinary proteome modifications comprehensively and systematically reflect changes associated with elevated HbA1c levels, with distinct modification profiles corresponding to different HbA1c levels. These findings suggest that urinary proteome modifications have the potential to reflect HbA1c levels and offer a new perspective for research on the early diagnosis of diabetes. Full article

Chronic kidney disease (CKD) is a major global health burden leading to a loss of kidney function via podocyte damage, a non-regenerative renal cell type. Early detection of podocyte injury is crucial but remains limited, highlighting the need for non-invasive biomarkers. Therefore, we analysed urinary exosomal microRNAs (miRNAs) in relation to podocyte morphology in biopsies from 65 CKD patients, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and healthy controls. Global profiling distinguished CKD patients from controls, with miR-606 consistently upregulated and miR-431 downregulated. In podocytopathies, MCD displayed a predominantly suppressed miRNA profile, with miR-141, miR-429, and miR-660 as key candidates, whereas FSGS exhibited elevated miR-181c, miR-3610, miR-663b, miR-4651, and miR-429. Super-resolution morphometry revealed diffuse foot process effacement in MCD and heterogeneous, focally disrupted architecture in FSGS, providing a structural context for the molecular findings. Regression analyses linked these miRNAs to filtration slit density and length, proteinuria, and 25-Hydroxy-vitamin-D3 levels, integrating molecular, structural, and clinical readouts. These results define a coherent miRNA signature of podocyte injury that distinguishes CKD entities and correlates molecular changes with disease severity. Combining urinary exosomal miRNAs with morphometric analysis facilitates early, non-invasive identification of podocyte damage, enabling earlier therapeutic intervention in podocytopathies. Full article