Background/Objectives: Antibiotics are the recommended first-line therapy for acute uncomplicated lower urinary tract infections (cystitis), but antibiotic resistance and tolerability concerns require antibiotic-sparing strategies. This study evaluated D-mannose as a stand-alone alternative. Methods: This multicenter, randomized, controlled, double-blind study compared D-mannose to fosfomycin in women aged 18-70 with cystitis. Clinical cure (CC) was assessed using the Acute Cystitis Symptom Score (ACSS) up to day 8, with non-inferiority tested at the 15% margin. Post hoc analytical approaches accounted for potential bias due to low sample sizes and missing values. Results: The study randomized 118 patients. At baseline, severe symptoms (ACSS ≥ 12) were more frequent in the D-mannose group compared to fosfomycin (32.8% vs. 22.8%). Efficacy analyses were performed on the per-protocol set (D-mannose: N = 57; fosfomycin: N = 54). Median time to CC was 5.0 days (D-mannose) and 3.0 days (fosfomycin) overall, and 4.0 days vs. 3.0 days in the subgroup of moderate disease severity. The point estimate for the CC rate difference on day 8 (-10.1%) favored fosfomycin but was within the non-inferiority margin. Due to wide confidence intervals, non-inferiority was not statistically confirmed. The post hoc analysis yielded smaller confidence intervals with estimated CC rates of 84.2% (D-mannose) vs. 83.5% (fosfomycin) on day 8 and statistically demonstrated the comparability of both treatments. Recurrence rates were similar (13.2% vs. 13.3%), and there was no statistically significant difference for additional antibiotic use (19.3% vs. 11.1%). Investigators and patients favored D-mannose over fosfomycin for tolerability, and gastrointestinal adverse events were less frequent (9.8% vs. 24.6%). Conclusions: Post hoc analysis indicated that D-mannose treatment is comparable to fosfomycin in uncomplicated cystitis in line with the prespecified non-inferiority criteria. These findings warrant confirmation in an adequately powered trial but suggest that D-mannose is a promising alternative to antibiotics given its favorable risk-benefit ratio.

Chronic bladder inflammation and psychological stress are key contributors to lower urinary tract dysfunction and pelvic pain, yet the molecular stress responses engaged across bladder tissues and associated neural pathways remain poorly defined. Heat shock proteins (HSPs), critical regulators of cellular stress adaptation, may differentially respond to peripheral injury versus psychogenic stress. Using cyclophosphamide (CYP)-induced cystitis of varying duration, acute stress and repeated variate stress (RVS) paradigms in mice, we examined time-, tissue-, and segment-specific regulation of Hsp60, Hsp70, and Hsp90 transcripts across the urothelium, detrusor, dorsal root ganglia (DRG), and lumbosacral spinal cord. CYP-induced cystitis elicited a rapid, transient induction of all three Hsps examined in the urothelium and detrusor at 4 h, followed by normalization with longer duration of CYP-induced cystitis. In contrast, sensory (DRG) and central (spinal cord) responses were highly structured: sacral (S1) DRG showed early Hsp induction, whereas lumbar DRG and spinal cord segments exhibited delayed suppression of select Hsps during chronic cystitis. Psychogenic stress produced fundamentally different patterns. Longer duration RVS (2w, 4w), but not acute stress, caused progressive and sustained suppression of Hsp expression in the bladder, with earlier onset in the urothelium than detrusor. In contrast, longer duration RVS increased Hsp expression in select DRG and spinal cord segments, particularly L2, L6 DRG and L1, S1 spinal cord, with biphasic regulation. Together, these findings demonstrate that inflammatory and psychogenic stressors engage distinct, tissue-specific heat shock responses across bladder-neural pathways, revealing differential molecular responses that may underlie bladder dysfunction and pelvic pain.

Recurrent urinary tract infections (rUTIs) represent one of the most common infectious conditions worldwide, yet their pathophysiology extends far beyond repeated episodes of acute bacterial cystitis. Increasing evidence indicates that recurrence may arise through overlapping mechanisms including reinfection from intestinal or periurethral reservoirs, intracellular bacterial persistence, microbial dysbiosis, impaired mucosal immunity and chronic inflammatory remodelling of the bladder microenvironment. Current diagnostic frameworks remain largely based on symptom-based definitions and standard urine culture, approaches that incompletely capture the biological complexity of recurrent disease. This limitation is evident even at the definitional level, where clinically pragmatic categories often fail to reflect the heterogeneous mechanisms underlying recurrence. Advances in expanded urine culture techniques, metagenomics and metabolomics have reshaped the understanding of the urinary tract as a dynamic ecological system interconnected with vaginal, intestinal and prostatic microbial compartments. These approaches have identified diverse microbial communities, virulence-associated functional profiles and host-microbe interactions linked to recurrence-prone phenotypes. Significant challenges continue to persist in elucidating the biological mechanisms driving recurrence. Addressing these gaps is essential to improve disease characterization and support the development of more effective diagnostic and therapeutic approaches.

Urinary tract infections (UTIs) are highly prevalent across diverse populations, with uropathogenic Escherichia coli (UPEC) recognized as the leading cause, responsible for more than 85% of cystitis and acute pyelonephritis cases. Because bacterial attachment to the uroepithelium is the critical initial step in colonization and infection, blocking this adhesion represents one of the most effective preventive strategies. The PapG adhesin, located at the tip of P-fimbriae in P-type UPEC, is a key mediator of this attachment and therefore a promising vaccine target. In this study, a chimeric antigen was designed by fusing the 198-amino-acid receptor-binding domain of PapG (GenBank accession No. YP_543821.1) to the 85-amino-acid cell-wall anchoring domain of AcmA (accession No. NC_011751.1) via a pentameric EAAAK flexible linker, yielding a 314-amino-acid construct. The gene was subcloned into the pET21a expression vector and expressed in E. coli Origami (DE3) under 1 mM IPTG induction. The purified recombinant protein was verified by SDS-PAGE and Western blot analysis, and its surface association on Lactobacillus reuteri was confirmed by ELISA. Seventy BALB/c mice were allocated into five groups (14 mice per group) and received a triple-dose vaccination regimen at two-week intervals: alum-adjuvanted + PapG, PapG + formulated with Freund's adjuvant, PapG-AcmA-associated L. reuteri, PBS-treated L. reuteri, and PBS alone as a negative control. Antigen-specific antibody responses and cytokine secretion profiles were subsequently evaluated. The findings indicate that adjuvanted PapG formulations elicit robust systemic Th1 and Th2 immune responses. Meanwhile, oral administration of L. reuteri surface-associated PapG-AcmA provides partial mucosal protection against UPEC colonization, likely driven by localized immunomodulation, and may serve as a promising mucosal vaccine platform.

Late-onset sepsis secondary to urinary tract infection in preterm infants is frequently underdiagnosed and rarely reported. Establishing this diagnosis remains challenging, as clinical manifestations are often nonspecific, inflammatory markers may be inconclusive, and urinalysis is not routinely performed in many NICUs. We report a case of urosepsis originating from Klebsiella pneumoniae-associated cystitis in a 41-day-old preterm infant who had been admitted to our NICU since birth. The infant had multiple risk factors for sepsis, including prolonged mechanical ventilation and the presence of an indwelling central line. This case highlights the importance of maintaining a high suspicion index for urinary tract infection in preterm neonates with unexplained clinical deterioration and emphasizes the need for early urine evaluation as part of the sepsis workup.

Ruxolitinib is a cornerstone treatment for steroid-refractory graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) in children, yet longitudinal data on kidney function during such therapy remain limited. We retrospectively analyzed 38 pediatric patients (0-18 years) receiving ruxolitinib for acute or chronic GVHD between January 2018 and December 2025, assessing kidney function at six timepoints from baseline to month 6. Mean serum creatinine rose from 0.34 ± 0.16 mg/dL at baseline to 0.50 ± 0.34 mg/dL at month 3 (p < 0.001) and remained mildly elevated at month 6 (0.48 ± 0.23 mg/dL; p < 0.001). Acute kidney injury (AKI) occurred in 7 patients (18.4%) at a median of 2.36 months after ruxolitinib initiation, with 4 (57.1%) progressing to acute kidney disease; biopsies excluded BK virus nephropathy. BK virus reactivation, BKV-related hemorrhagic cystitis, CMV reactivation, older age at transplantation, and higher baseline creatinine were significantly associated with AKI, whereas ruxolitinib dose was not. Post-transplant AKI in this setting appears multifactorial; controlled studies including a ruxolitinib-unexposed comparator group are needed to clarify the specific contribution of the drug.

Urinary tract infections (UTIs) are a common cause of morbidity in the paediatric population, with prevalence varying according to age, sex, and circumcision status. Differentiating between upper and lower tract infections is crucial, as upper UTIs carry a greater risk of renal scarring and long-term complications. Accurate diagnosis and timely management reduce acute symptoms and prevent sequelae such as chronic kidney disease and hypertension. Current guidance recommends urgent referral for infants under 3 months of age, short-course oral antibiotics for uncomplicated cystitis in older children, and longer treatment for pyelonephritis. Preventive strategies emphasise addressing risk factors such as constipation, hydration and bladder dysfunction, while limiting prophylactic antibiotic use to high-risk cases. Education of parents and carers is central to early recognition and long-term management.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by bladder pain and lower urinary tract symptoms. Despite extensive investigation and numerous therapeutic candidates, few disease-modifying treatments have translated into clinical practice. Evidence indicates that IC/BPS comprises biologically distinct phenotypes, including inflammatory bladder-centric and systemic pain-associated phenotypes, creating challenges for experimental modeling and drug development.