Search Results (31)

Background/Objectives: Kidney injury is a frequent complication of multiple myeloma (MM) and monoclonal gammopathies. Podocyte stress markers, such as urinary nephrin and podocin, have been studied in other renal diseases but their utility in paraprotein-related kidney disease remains unclear. This pilot study investigated the association of urinary nephrin and podocin levels with albuminuria and biopsy-proven podocytopathy in patients with paraprotein-related diseases. Methods: We retrospectively analyzed 75 patients with plasma cell dyscrasias, including MM and MGRS, along with 11 healthy controls. Urinary podocin and nephrin mRNA levels were measured using qPCR, and urinary podocin protein levels were quantified via ELISA. Associations were assessed between these biomarkers and urinary protein-to-creatinine ratio (uPCR), albumin-to-creatinine ratio (uACR), and histologically confirmed podocytopathia. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Results: Higher urinary podocin protein levels were significantly associated with lower uACR (p = 0.007) and uPCR (p = 0.026). Neither podocin nor nephrin mRNA showed significant associations with proteinuria metrics. ROC analysis indicated that podocin ELISA (AUC = 0.350) and podocin mRNA (AUC = 0.510) lacked diagnostic accuracy for predicting renal involvement. The presence of urinary tract infection (UTI) was a significant confounder, leading to increased levels of podocin and nephrin mRNA. Conclusions: Urinary podocin shows a trend toward elevation in MM/MGRS patients with histological podocyte injury. The study revealed an unexpected inverse association between urinary podocin and albuminuria, suggesting complex release kinetics or stage mismatches in this population. Given the confounding effect of UTIs, and the pilot nature of this study, further research is required to validate these podocyte proteins as biomarkers in paraprotein-related kidney disease. Full article

Importance: Uncomplicated urinary tract infections (uUTIs) are among the most common bacterial infections and are typically treated with existing oral antibiotics. In 2024–2025, the FDA approved two new oral agents, sulopenem etzadroxil/probenecid and gepotidacin, via expedited review pathways, for the treatment of uUTIs. Objective: To assess the clinical significance and regulatory evidence supporting FDA approval of sulopenem/probenecid and gepotidacin for uUTI, and to analyze the adherence of pivotal phase III trials to regulatory standards for approval and FDA guidelines. Design, Setting, and Participants: Comparative descriptive analysis of publicly available data from phase 3 randomized, double-blind, active-controlled clinical trials submitted to the FDA for approval. Pivotal phase III clinical trial data and FDA integrated reviews, guidance for the industry, and approved drug labels. Adult women with uUTI enrolled in pivotal phase III clinical trials, with subgroup analysis stratified by pathogen susceptibility to comparator antibiotics. Interventions: Sulopenem/probenecid was compared to ciprofloxacin and to amoxicillin/clavulanate and gepotidacin was compared to nitrofurantoin. Main Outcomes and Measures: Primary endpoints were clinical and microbiological responses assessed in the microbiologic modified intention-to-treat (micro-MITT) subjects. Safety outcomes and FDA regulatory determinations were also assessed. Results: Sulopenem/probenecid was inferior to ciprofloxacin and noninferior to amoxicillin/clavulanate in subjects with susceptible pathogens, and superior in subjects with resistant pathogens. Gepotidacin showed noninferiority to nitrofurantoin in one trial and superiority in another. Trials excluded randomized subjects, included post-randomization subgroup analyses, and enrolled control-arm subjects with resistant pathogens. Clinical cure rates were lower than historical comparators. Both new antibiotics had higher adverse event rates than controls. Conclusions and Relevance: Pivotal clinical trials for sulopenem/probenecid and gepotidacin for uUTI had significant design limitations and relied on surrogate endpoints of limited clinical interpretability, undermining reliability and clinical relevance. Future antibiotic development for uUTI should prioritize representative populations, standard-of-care comparators, clinically meaningful outcomes and robust, well-controlled trial designs to ensure meaningful clinical evidence of safety and efficacy. Full article

Background: Serious bacterial infections (SBIs) in neonates present a significant diagnostic challenge due to nonspecific symptoms and immature immune responses. Early identification is essential to ensure timely treatment and prevent adverse outcomes. This study investigates clinical, laboratory, and epidemiological parameters associated with SBI in febrile neonates. Methods: A retrospective analysis was conducted on neonates hospitalized for suspected SBI at University Hospital Split from 1 January 2023 until 31 December 2024). The data was analyzed using descriptive statistics, Mann–Whitney U test and Chi-square test. Results: The study included 71 neonates hospitalized with suspected SBI, of whom 38 (53.5%) had a confirmed SBI. Neonates with SBI had a significantly longer hospital stay (p < 0.001). C-reactive protein (CRP) levels at admission were significantly higher in the SBI group (p = 0.020), while other laboratory parameters showed no significant differences. The most common diagnosis in the SBI group was urinary tract infection (50%). In urine analysis, abundant bacterial presence, strongly positive leukocyte esterase (3+), and positive nitrite findings were significantly associated with the presence of urinary tract infection (UTI). Conclusions: In neonates with suspected SBI, elevated CRP levels and prolonged hospital stay were significantly associated with confirmed SBI. Among specific diagnoses, UTI were most frequent, with urinalysis parameters (bacteria, leukocyte esterase, and nitrites) proving useful in identifying affected cases. However, individual clinical signs showed limited diagnostic value, highlighting the importance of combining clinical and laboratory data in early recognition of SBI. Full article

Background and Objectives: Urinary tract infections (UTIs) are a major cause of emergency department (ED) visits and hospital admissions among older adults. Although most seniors present hemodynamically stable, a sizeable fraction deteriorate during hospitalization, and no ED-specific tool exists to identify those at greatest risk. We sought to determine risk factors for in-hospital mortality in this population and to develop a predictive model. Materials and Methods: We analyzed the MIMIC-IV-ED database (2011–2019) and enrolled culture-confirmed UTI patients aged ≥ 65 years who were hemodynamically stable—defined as a systolic blood pressure ≥ 100 mm Hg without vasopressor support. Demographics, comorbidities, triage vital signs, and initial laboratory tests were extracted. Least Absolute Shrinkage and Selection Operator (LASSO) regression with 10-fold cross-validation was performed for variable selection. Discrimination was quantified with the C-statistic, calibration with the Hosmer–Lemeshow test, and clinical utility with decision curve analysis. Internal validation was assessed via 1000-sample bootstrap resampling. Results: Among 1571 eligible encounters (median age 79 years, 33% male), in-hospital mortality was 4.5%. LASSO selected eight variables; six remained significant in multivariable analysis: age, systolic blood pressure, oxygen saturation, white blood cell count, red cell distribution width, and blood urea nitrogen. The predictive nomogram demonstrated a C-statistic of 0.73 (95% CI 0.66–0.79) and outperformed traditional early warning scores. Conclusions: A six-variable nomogram may stratify mortality risk in hemodynamically stable older adults with UTI. Because the model was developed in a single U.S. tertiary-care ED, it remains hypothesis-generating until validated in external, multicenter cohorts to confirm generalizability. Full article

Objectives: This study aimed to identify differences in risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infections across different anatomical sites and to explore risk factors associated with mortality in CRE-infected patients. Methods: Patients who underwent CRE screening and were subsequently diagnosed with CRE infections were included and categorized by infection site: respiratory tract (RTI), urinary tract (UTI), and bloodstream (BSI). Forty ICU patients without CRE infection were randomly selected as controls. Statistical comparisons were performed using the Mann–Whitney U or Chi-square test, as appropriate. Potential risk factors were evaluated via univariate and multivariate analyses, and a predictive model was constructed, with its performance assessed using ROC curve analysis. Results: CRE colonization was identified as a common independent risk factor across all three groups (RTI, UTI, and BSI). Infection-site-specific analyses revealed independent risk factors: RTI was associated with mechanical ventilation, UTI with trauma, and BSI with gastrointestinal injury. Predictive models for RTI, UTI, and BSI demonstrated good discrimination, with ROC AUCs of 0.94, 0.94, and 0.95, respectively. In the analysis of Survived versus Deceased patients, the BSI group had the highest mortality, though the difference was not statistically significant. Deceased patients exhibited significantly higher PCT levels than Survived patients (p = 0.005). Prior use of carbapenems and antifungal agents, as well as Ln(PCT), were independently associated with mortality in CRE-infected patients. Conclusions: Risk factors for CRE infections vary across anatomical sites, with CRE colonization, mechanical ventilation, trauma, and gastrointestinal injury playing key roles. Overuse of antibiotics and elevated inflammatory responses are associated with increased mortality. These findings provide evidence for early identification of high-risk patients and optimization of individualized treatment strategies. Full article

Antimicrobial resistance (AMR) has reached a critical situation globally, prompting urgent national responses to this escalating crisis, including the prioritization of novel antibiotic research. In 2016, Japan initiated a national AMR action plan that promoted appropriate antibiotic use in the country and encouraged a national environment conducive to mitigation measures. However, tackling AMR remains difficult. From an epidemiological perspective, this challenge now extends beyond severe infections, impacting common community-acquired infections, including uncomplicated urinary tract infections (uUTls) and gonorrhea. In uUTIs, the rising prevalence of extended-spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli diminishes the effectiveness of current, routinely used oral antibiotics, necessitating an exploration into innovative solutions. Similarly, the growing resistance of Neisseria gonorrhoeae to antibiotics such as azithromycin raises concerns about the efficacy of current therapeutic options for gonorrhea, which is a highly prevalent sexually transmitted infection. In Japan, since the removal of azithromycin as the recommended first-line treatment, there are no oral first-line antibiotics available to treat gonorrhea. Therefore, novel oral antibiotics are urgently needed for both serious and commonly occurring community-acquired infections. This narrative review discusses the limited availability of novel antibiotics in Japan, the distinctive features of the Japanese antibiotic repertoire and AMR epidemiology, and potential alternative oral treatments for community-acquired infections, including uUTIs and gonorrhea. Japan has been making significant advances toward tackling the AMR crisis through an updated national action plan, AMR policy changes, and innovative approaches to developing novel antibiotics. Substantial international cooperation and the engagement of diverse industry sectors are essential to address the pressing issue of AMR. Full article

Background/Objective: Voiding cystourethrography is the gold-standard diagnostic tool for detecting vesicoureteral reflux and is commonly requested by pediatricians, pediatric nephrologists, emergency pediatricians, and pediatric urologists. However, VCUG is invasive, exposes patients to radiation, and carries a risk of iatrogenic urinary tract infection (UTI). This study aimed to assess the correlation between VCUG findings and factors such as age, gender, referring specialist, and clinical indication for the procedure to identify opportunities to reduce unnecessary VCUG examinations. Methods: A retrospective analysis of 197 pediatric patients who underwent VCUG over 12 months at the Institute for Child and Youth Health Care of Vojvodina was conducted. Results: The Mann–Whitney U test showed no statistically significant age difference between patients with normal (median: 2.5 years) and pathological (median: 3 years) VCUG findings (Z = −0.415, p = 0.678). The chi-square test showed that patients with a single urinary tract infection (10 patients) and other clinical indications (24 patients) had a higher chance of normal VCUG findings (0.041 and 0.011, respectively). Binary logistic regression analysis showed that patients referred by pediatric urologists were 2.06 times more likely to have pathological VCUG findings than those referred by pediatric nephrologists (p = 0.013, OR = 2.059; 95%CI: 0.166–3.634). Regarding clinical indications, the chance that VCUG findings would be normal was 2.7 times higher in patients with other indications than in patients with recurrent UTIs (p = 0.038, OR = 2.729; 95% CI: 1.055–7.059). Conclusions: Pediatric urologists tend to refer patients for VCUG more selectively than pediatric nephrologists. Avoiding VCUG in cases of a single UTI or non-specific clinical indications could significantly reduce the number of unnecessary procedures, minimizing patient exposure to radiation and potential complications. Full article

Background/Objectives: Radical prostatectomy is a standard treatment for localized prostate cancer. We aimed to compare perioperative outcomes and functional results between laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Methods: A retrospective analysis was conducted on 120 patients who underwent LRP (n = 60) or RARP (n = 60). Perioperative parameters, including operative time, hospitalization duration, blood transfusion rate, wound healing complications, urinary catheterization duration, urinary tract infections (UTIs), and urinary incontinence, were assessed. Statistical analyses included Student’s t-, Mann–Whitney U, and χ² tests. Results: RARP was associated with significantly shorter operative time, compared with LRP (147.25 vs. 188.30 min, p < 0.0001). No significant differences were observed in hospitalization duration, transfusion rates, or overall complication rates. However, impaired wound healing was less frequent in the RARP group, with a 10% lower incidence, compared with the LRP group (p = 0.0946). Similarly, UTIs occurred less often in the RARP group (six vs. one cases; p = 0.0544). Urinary incontinence was significantly less frequent following RARP, with its incidence being more than twice as low, compared with the LRP group (p = 0.0032). Additionally, the RARP group had significantly lower International Prostate Symptom Scores, with a mean difference of 7.83 points, indicating improved urinary function. No significant differences were found in sexual function (IIEF-5 scores). Conclusions: RARP offers advantages over LRP, including reduced operative time, lower rates of wound healing complications, decreased incidence of urinary incontinence, and improved postoperative urinary function. Further studies with larger cohorts are warranted to confirm these findings and assess long-term functional and oncological outcomes. Full article

Background/Objectives: The management of urinary tract infections (UTIs) has become an increasingly challenging medical intervention. This study explores whether adoption of a precision medicine model could improve the management of acute uncomplicated pyelonephritis (uAPN) or complicated UTIs (cUTIs) compared with the standard of care approach, in hospitalized patients. Methods: From January 2022 to March 2024, all patients affected by uAPN or cUTIs and attending our urological institution were randomized to receive the following: antibiotic treatment according to guidelines and recommendations (standard of care group) or antibiotic treatment according to the precision medical model (intervention group). The main outcome measures were the rates of clinical success and the length of hospitalization. The time until switching to oral treatment was regarded as a secondary outcome measure. Results: Eighty-three patients were enrolled in the standard of care group, while seventy-nine patients were enrolled in the intervention group. While the overall clinical success rate was similar in the two groups (75 vs. 72; p = 0.97), a statistically significant difference was observed between the two groups in terms of length of hospitalization (8 days vs. 5 days; p = 0.03) and time to switch to oral treatment (96 h vs. 72 h; p = 0.04). A statistically significant difference was found between the two groups regarding the need to change antimicrobial therapy during hospitalization [12 out of 80 vs. 6 out of 77; p = 0.04]. Conclusions: Adoption of the precision medicine model appears as a valuable means to improve the management of patients with uAPN and cUTIs. By reducing the period of hospitalization and the time to switch to oral treatment, the precision medicine model also improves antimicrobial stewardship in the management of UTIs. Full article

Urinary tract infections (UTIs) represent a prevalent health concern among the female population, with anatomical and physiological determinants such as a shorter urethra and its proximity to the rectum augmenting vulnerability. The presence of Escherichia coli and various other pathogens plays a significant role in the etiology of these infections, which can be aggravated by sexual intercourse and disturbances to the vaginal microbiome. The physiological alterations associated with pregnancy further elevate the likelihood of UTIs, with untreated cases potentially leading to severe complications such as pyelonephritis, preterm labor, and stillbirth. Furthermore, postmenopausal women encounter an augmented risk of UTIs attributable to estrogen deficiency and vaginal atrophy, as well as conditions including pelvic organ prolapse (POP) and urinary incontinence (UI), which hinder optimal bladder functionality. The aforementioned factors, in conjunction with the rising prevalence of cesarean deliveries and catheterization, complicate the management of UTIs. While precise diagnosis is paramount, it remains a formidable challenge, notwithstanding advancements in molecular diagnostic techniques. Management strategies encompass antibiotic-sparing therapies; however, the increasing incidence of multidrug resistance represents an alarming trend. Diverse guidelines from various medical specialties endeavor to standardize treatment approaches, yet significant inconsistencies continue to exist. This study systematically appraises the extant guidelines, evaluating the quality of evidence while identifying areas of agreement and discord to supply practitioners with effective strategies for UTI management. Full article

Urinary tract infections (UTIs) are among the most common pediatric infections. This study evaluated the antimicrobial susceptibility patterns of 3511 uropathogenic E. coli (UPEC) isolated from pediatric patients in the United States from 2014 to 2023. The database from the SENTRY antimicrobial surveillance program from 89 medical centers was utilized as a data source. The antimicrobial susceptibility was tested using the microbroth dilution technique against 24 antimicrobial agents. MICs were determined using the CLSI/EUCAST/FDA breakpoint criteria. All the antimicrobials reported susceptibility rates above 80% except for tetracycline (76.2%), trimethoprim–sulfamethoxazole (69.7%), and ampicillin–sulbactam (55.7%). During the study period, the susceptibility rates remained stable for most antimicrobial agents. However, significant differences were observed among age, gender, and U.S. census regions, with the Middle Atlantic showing the lowest and the Mountain region the highest susceptibility rates, for most antimicrobials. The incidence of ESBL UPEC increased from 7.1% to 10.8% between 2014 and 2023, while the prevalence of the MDR phenotype remained relatively stable. The prevalence of both ESBL and MDR phenotypes was highest among infants and young children (0–24 months), with the highest resistance rates from the Pacific region. Knowledge of the landscape of antibiotic resistance in pediatric UPEC will help healthcare providers to better tailor empiric treatment regimens for most UTI infections. Full article

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA’s safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified). Full article

Background: Urinary tract infections (UTIs) are very common bacterial infections in children. Early detection of renal parenchymal involvement in this setting can help clinicians make more effective treatment choices. The aim of this pilot study was to assess the ability of plasma and urinary neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL) levels, measured using an automated system, to accurately predict renal parenchymal involvement in children with febrile UTIs. Methods: This prospective single-center study included 28 children aged ≥ 4 years with a first episode of febrile UTIs. All patients underwent magnetic resonance imaging. pNGAL, uNGAL, procalcitonin, C-reactive protein (CRP), and white blood cells were measured before antibiotic therapy. Results: The receiver operating characteristic (ROC) area under the curve for predicting acute pyelonephritis was 0.6 for pNGAL, 0.8 for CRP, 0.4 for PCT, and 0.4 for uNGAL. The ROC analyses showed an optimal cutoff of 141.0 ng/mL for pNGAL (sensitivity, 54.2%; specificity, 75.0%; positive predictive value, 92.9%; and negative predictive value, 21.4%). Conclusion: pNGAL and uNGAL did not effectively aid the early prediction of renal parenchymal involvement in children ≥ 4 years with febrile UTIs. The novelties of this study were the use of MRI as the gold standard and an automated biochemical method to measure NGAL. Full article

Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with neurological lesions in the central nervous system (CNS). Medical treatment usually cannot adequately relieve NLUTD. This study reported the real-life treatment outcome of botulinum toxin A (BoNT-A) for overactive bladders (OAB) and voiding dysfunction in patients with CNS lesions. Methods: We retrospectively analyzed the first-time treatment outcome of 74 patients who received detrusor 100 U BoNT-A for OAB and 45 patients who received a urethral sphincter 100 U BoNT-A injection for voiding dysfunction. The treatment outcome, therapeutic duration, and adverse events (AE) after BoNT-A were compared among different CNS lesions and among patients with different urodynamic characteristics. Results: The study included 74 patients receiving detrusor injections for OAB (36 with cerebrovascular accidents, 13 with Parkinson’s disease, and 25 with dementia) and 45 patients receiving a urethral sphincter injection for voiding dysfunction (26 with cerebrovascular accidents, 7 with Parkinson’s disease, and 12 with dementia). After detrusor BoNT-A treatment, urinary continence was achieved in 28.4% of patients with neurogenic OAB, postoperative difficult urination in 59.5%, acute urinary retention (AUR) in 9.5%, and urinary tract infection (UTI) in 14.9%, with a therapeutic duration of 6.43 months. There were no differences among subgroups or between patients with detrusor overactivity (DO) and DO with detrusor underactivity (DU) in terms of treatment outcomes and AEs. The improvement rate of urethral sphincter BoNT-A injections was 75.6% without any difference among subgroups. After treatment, 24.4% of the patients had exacerbated urinary incontinence, 33.3% had persistent difficult urination, and 15.6% had UTI. Patients with dementia had higher rates of difficult urination and UTI, higher postvoid residual volume, and a shorter therapeutic duration. Patients with DU and those without urethral sphincter dyssynergia had less favorable outcomes after their urethral sphincter BoNT-A injection. Conclusions: The therapeutic efficacy of detrusor BoNT-A injection for OAB due to CNS lesions is limited, with high rates of difficult urination, AUR, and UTI. Although urethral sphincter BoNT-A injection is effective in treating voiding dysfunction; however, exacerbated urinary incontinence and persistent difficult urination remain a problem, particularly in patients with dementia. Full article

Chemotherapy and cyclooxygenase inhibitors (COXi) are primary treatments for canine urethral transitional cell carcinoma (uTCC), a tumor known for its aggressiveness and poor prognosis. This retrospective study aimed to evaluate the clinico-pathological characteristics, treatment modalities, and prognostic factors of 35 dogs with confirmed uTCC that received chemotherapy and COXi. Upon admission, urethral obstruction (UO) and urinary tract infection (UTI) were observed in seven (20%) dogs each. Gemcitabine (n = 20; 57.1%) and vinblastine (n = 10; 28.6%) were commonly used as first-line therapies, with four dogs also receiving radiation therapy. Based on RECIST, one (2.9%) dog achieved complete remission, nine (25.7%) partial remission, 20 (57.14%) showed stable disease, and five (14.3%) progressed. Among dogs with UO, six (85.7%) showed resolution or improvement after the first chemotherapy dose. The median time to local progression was 171 days (range: 107–235), and the median survival time was 333 days (range: 158–508). Dogs with UO upon admission had a higher risk of local progression, while both UO and UTI were associated with an increased risk of overall disease progression and tumor-related death. Additionally, gemcitabine significantly improved metastatic control. This study identified UO and UTI as negative prognostic factors, highlighting the importance of a multimodal approach in managing uTCC. Full article