Urinary Research Articles

Real-life data on the tolerability of SGLT2 inhibitors in elderly patients with heart failure

Abstract Introduction Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated their effectiveness in improving the prognosis of heart failure. However, there is some hesitation in clinical practice to prescribe them to elderly patients due to a lack of long-term safety data. The SafeGLT2 study aims to evaluate the tolerance of SGLT2i in elderly patients with heart failure in real-life settings. Methods This is a prospective study conducted in acute geriatric units in the Île-de-France region between February 2020 and May 2023. All patients admitted for acute heart failure (AHF), aged 75 years and older, were included. The diagnosis was confirmed by an expert committee, and patients were followed for one year. Treatments were recorded upon admission and discharge, along with demographic characteristics and medical history. SGLT2i tolerance data were collected and analyzed, including renal insufficiency, hypovolemia, genital infections, urinary infections, hypoglycemia, diabetic ketoacidosis, fractures, amputations, etc. A comparison of tolerance data between heart failure patients treated with SGLT2i and those not receiving SGLT2i was performed. Results 288 patients were included in the study with a mean age of 88 years, 53% (n=153) were female, and a median Charlson Comorbidity Index (CCI) of 8.77 [2.71]. 44.1% (n=127) of patients had neurocognitive disorders, 39.6% (n=114) were malnourished, 32.6% (n=94) were fallers, 53.8% (n=155) had renal insufficiency (eGFR < 60 ml/min), and 11.5% (n=33) lived in institutions. A total of 33% (n=95) were treated with SGLT2i upon discharge. No serious adverse effects were found in this very frail population receiving SGLT2i compared to the group not receiving SGLT2i (severe hypotension, hypovolemia, ketoacidosis, hypoglycemia, fracture, amputation). Beneficial effects on renal function (improvement of renal function at 6 months) were observed in the SGLT2i group despite a temporary decrease in glomerular filtration rate of less than 30% after SGLT2i initiation. However, a statistically significant increase in urinary tract infections (16.8% vs 4.15%), genital infections (12.6% vs 1.5%), and constipation (10% vs 1%) was found in the SGLT2i group compared to the group without SGLT2i. Conclusion These data indicate that SGLT2i are well tolerated in very elderly frail heart failure patients. However, the occurrence of urogenital infections appears to be more frequent in this population and requires particular surveillance.

Risks of incident genitourinary malignancies in anticoagulated atrial fibrillation patients experiencing hematuria

Abstract Background When managing oral anticoagulant (OAC)-related bleeding in patients with atrial fibrillation (AF), the possibility of occult malignancies should be kept in mind, as suggested by guidelines. In this study, we aimed to investigate the incidence of genitourinary (GU) trat cancer in anticoagulated AF patients experiencing hematuria. Also, we aimed to report the prevalence of other causes of hematuria beside malignancy. Methods We conducted a nationwide, retrospective cohort study in Taiwan. A total of 19,974 AF patients aged ≥ 20 years on OAC treatment (warfarin 9232, non-vitamin K antagonist OACs [NOACs] 10,742) experiencing hematuria were enrolled. Risk of newly diagnosed GU malignancy within one year after hematuria was reported and compared between patients receiving warfarin and NOACs. Results A total of 738 patients (3.99%) were diagnosed to have GU tract cancers within 1 year after OAC-related hematuria, with prostate cancer (52.30%) being as the commonest subtype, followed by bladder cancer (31.71%) and kidney/ureter/urethra in origin (15.99%)(Figure 1). The risk of GU tract cancer was higher for warfarin compared to NOAC users (4.10% versus 3.89%; odds ratio 1.169, p = 0.041)(Figure 1). For patients without diagnosed GU tract cancers, urinary tract infection (42.3%) was the leading cause of hematuria followed by benign prostate hyperplasia (37.6%), GU tract stone (16.7) and cystitis (9.2%)(Figure 2). Overall, 27.5% of patients whose causes of hematuria could not be identified (Figure 2). Conclusions Incident GU cancers were diagnosed in 1 of 25 AF patients at 1 year after OAC-related hematuria. Detailed examinations for occult GU cancers and other etiologies are necessary.

Is it worth using the Comprehensive Complication Index over the Clavien-Dindo classification in elderly patients who underwent percutaneous nephrolithotomy?

To compare the Comprehensive Complication Index (CCI) to the Clavien-Dindo classification (CDC) in an elderly population who underwent percutaneous nephrolithotomy (PCNL) and to identify predictors of postoperative complications in this population. We conducted a retrospective cohort study involving patients 60years and older who underwent PCNL at our Institution between 2009 and 2020. Postoperative complications were considered up to 30days after surgery. Both CDC and CCI were calculated to assess patient outcomes. Length of stay (LOS) and admission to the emergency room (ER) were used as surrogates of postoperative complications. We included 244 patients with a median age of 65 [63-69] years. 15.6% presented postoperative complications, and 2.5% multiple complications. LOS had a correlation coefficient of 0.29 (p < 0.001) and ER admissions had a coefficient of 0.27 (p < 0.001) with both CDC and CCI. Cost of hospitalization based on CDC underestimated CCI-based cost of hospitalization in 0.8% (p = 0.049). Higher American Society of Anesthesiology (ASA) physical status (p = 0.02), Charlson Comorbidity Index (p = 0.008), Guy's classification (p = 0.005), and history of urinary tract infection (UTI, p = 0.047) exhibited significant correlations with postoperative complications. Both CDC and CCI equally correlate with LOS and ER admissions following PCNL in elderly patients. However, CDC underestimates cost of hospitalization in comparison to CCI. We found higher ASA physical status, Charlson Comorbidity Index, Guy's classification, and history of UTI as predictors of postoperative complications after this procedure in this population.

Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation

BackgroundProstate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa.MethodsClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson’s correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis.ResultsWe constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion.ConclusionBuilding on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion.

Pattern of Birth Defects, Association And Their Outcomes Among Neonates In A Tertiary Care Hospital In Bangladesh

Introduction: Birth defects are one of the major cause of stillbirths and neonatal mortality in developed and developing countries. The prevalence of birth defects varies in different parts of the world. In many cases, the causes are unknown; however, several factors known to be associated are genetic factors, maternal age, health, dietary factors, maternal infections, geographical factors, drugs, smoking and irradiation. Objectives: To identify the pattern of birth defects, association and their outcomes among neonates Methodology: This observational cross-sectional study was conducted in the department of neonatology, Dhaka Medical College Hospital, Dhaka from 1st July 2019 to 30th June 2021. Sample was collected by purposive sampling technique. Total 407 babies were enrolled. Out of them 207 babies were with birth defects in group-A and 200 babies had no birth defects in group-B. Detail demographic data were collected from the informant and recorded in structured case report form. Clinical examination and relevant investigations were done. Data processing work consist of registration schedules, editing computerization, preparation of dummy table, analyzing and matching of data. Results: In this study the two study groups were almost similar with respect to their demographic characteristics like sex, residence, place of delivery, mode of delivery, gestational age, parity and maternal age. The total number of admission during this period was 3050 and total number of birth defects was 207 (6.78%0). In this study on evaluation of maternal risk factors, group-A maternal high blood pressure were in 25.12% cases( OR=1.62;p=.002), maternal diabetes were in 15.46% cases( OR=1.12;p=.001), poor maternal nutritional status was 14.50%( p=.001), history of taking folic acid was 9.66%(OR=0.10;p=.001), 5.80% of the patient had history of exposure to antenatal radiation(OR=.06;p=.001), 4.43% had history of consanguinity(OR=.05;p=.001), 2.420% of women noticed that exposure to pesticides(OR=.025;p=.001), H/O of taking anticonvulsant was 2.420%(OR=.025;p=.001). Group-B was maternal high blood pressure in 7.25% cases(OR=.078;p=.001), maternal diabetes were in 6.28% cases(OR=.067;p=.001), poor maternal nutritional status was 5.80%(p=.001), history of taking folic acid was 4.83% (OR=.051;p=.001), 1.45% of the patient had history of exposure to antenatal radiation(OR=.015;p=.001) and 0.97% had history of consanguinity(OR=.01;p=.001). In this study pattern of birth defects summarized as the cardiovascular system defects was the most commonly affected(26.57%), followed by defects in the head, neck ear,- and eye(19.32%), Syndromes(14.50%), gastrointestinal defects(12.56%), musculoskeletal system defects(10.14%), central nervous system defects (8.70%) and genitourinary system(4.83%) of total defects. In group-A 78.26% of the patients recovered and 23 patients expired during hospital stay (p=.001). In group-B 85.99% of the patients recovered and 17 patients expired. Conclusion: Congenital cardiac defects were the most prevalent anomaly detected. Maternal high blood pressure and diabetes are the risk factors of birth defects in neonates. Antenatal diagnosis and proper management can improve the outcome of these neonates. J Dhaka Med Coll. 2023; 32(1) : 43-50

Transanal total mesorectal excision: Understanding indications, managing complications, and effective prevention methods

AbstractTransanal total mesorectal excision (TaTME) has emerged as a surgical method for treating rectal malignancies in the middle and lower third of the rectum over the past 15 years. This approach was adopted because of the challenges encountered in secure total mesorectal excision (TME). Patient selection criteria and the rationale for TaTME have evolved, leading to improved oncological outcomes and patient quality of life. The procedure includes inserting a unique platform through the anus, forming a purse‐string closure, and endoscopically sealing the lower rectum. The mesorectum is then removed laparoscopically following a ‘down‐to‐up’ approach, finalised with a transabdominal laparoscopic phase and anastomosis. Pelvic anatomy complexity poses challenges, including potential injuries to the urinary tract, surgical site leakage, sinus damage, sagittal vein harm, nerve injury, carbon dioxide embolism, bowel function disturbance, sphincter mechanism issues, and rectal abscess formation. Proficient anatomy knowledge, precise surgical techniques, and advanced technologies contribute to their prevention. In conclusion, TaTME offers a promising approach to rectal surgery with satisfactory oncological outcomes. However, vigilance is required to eliminate potential complications.

Laparoscopic colon surgery: time to leave the urinary catheter in the operating room?

'Fast track' guidelines have incorporated multimodal measures to optimize perioperative outcomes in surgery, with laparoscopy being a pivotal component for its advantages in early recovery. In this setting,current recommendations regarding the use of aurinary catheter suggest its removal within the first 24-hours postoperatively. However,few studies have assessed the feasibility of leaving the operating room without it. The purpose of this study is to compare the perioperative outcomes of patients undergoing elective laparoscopic colonic resections leaving the operating room with and without a urinary catheter. A retrospective study was conducted utilizing prospectively collected data from patients undergoing elective colon resections over a 17-month period. The patients were classified into two groups based on the presence or absence of a urinary catheter upon leaving the operating room, and subsequently, their perioperative outcomes were compared. A total of 107 patients met the inclusion criteria (n = 28 with a urinary catheter and n = 79 without). Cancer was the most prevalent diagnosis (83.2%), and right hemicolectomy the most frequently performed surgery (32.7%). Two events of urinary catheter reinsertions were reported, both in the no-catheter group (0% vs 2.53%, p = 0.969), andthere were no cases of urinary tract infections. The overall and severe complications ratesexhibited no significant differences (25% vs. 26.6%, p = 1, and 7.14% vs. 5.06%, p = 1)and the length of stay was similar (p = 0.220). Removing the urinary catheter before leaving the operating room appears to be safe and associated with very low rates of urinary retention in selected patients undergoing laparoscopic colonic or upper rectal resections.

Emphysematous pyelonephritis caused by Raoultella ornithinolytica: a case report

BackgroundEmphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica.Case presentationAn 86-year-old man presented with severe back pain of 3 days’ duration. He had a history of hypertension and diabetes for more than 20 years, and his infection indicators and serum creatinine were elevated. Abdominal computed tomography revealed an abnormal gas shadow around his right kidney and the anterior edge of his right psoas muscle. Consequently, he was initially diagnosed with emphysematous pyelonephritis. There was no evidence of nephrolithiasis or other anatomical or structural abnormalities that could have precipitated this focal renal infection. Both blood and drainage fluid cultures revealed R. ornithinolytica. After early anti-infection treatment, percutaneous drainage and moderate control of blood glucose, the patient gradually recovered.ConclusionsEmphysematous pyelonephritis caused by R. ornithinolytica is rare but has a high drug resistance rate potentially and may cause severe infections. Early diagnosis, prompt use of antibiotics that are sensitive to the organism, and decompression drainage could be the key to treatment.

Pathology-Based Animal Cancer Registry of Abruzzo and Molise Regions (Central Italy): A Ten-Year Retrospective Study (2014–2023)

Pets have a crucial role in cancer research. Specifically, dogs and cats share the same environment as their owners and thus may serve as sentinels of naturally occurring tumors that are linked to the exposure to environmental hazards. Quantitative comparison of tumor types may reveal unusual cancer frequencies, providing directions for research and generation of hypotheses of cancer causation in a specific area and identification of risk factors. The aim of this study was to describe the data collected by the pathology-based animal cancer registry, managed by Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise (IZSAM), during 10 years of activity (2014–2023) and to assess its potential epidemiological relevance. Frequencies of tumor topography and morphology in dogs and cats were described, analyzed and compared. Proportional morbidity ratios (PMRs) were calculated, taking into consideration some potential risk factors such as species, breed, sex, diet and living environment. The database comprises 5311 tumors (n = 4719 in dogs and n = 592 in cats), with a higher prevalence in females (67.3% in dogs and 61.2% in cats). The mean age at the first diagnosis of tumors was similar between sexes and slightly lower in dogs compared to cats. PMRs highlighted certain risk and “protective” factors for the development of tumors in specific topography. The risk of developing tumors of the blood and hematopoietic system (PMR = 0.44; 95% CI: 0.21–0.94), skin and subcutaneous tissues (PMR = 0.70; 95% CI: 0.61–0.80), oral cavity and pharynx (PMR = 0.60; 95% CI: 0.24–0.89), urinary organs (PMR = 0.33; 95% CI: 0.11–0.99) and bones, joints and cartilage (PMR = 0.72; 95% CI: 0.22–0.98) was lower in non-neutered male dogs than in neutered male dogs. Non-spayed female dogs had a greater risk of developing tumors of the mammary gland (PMR = 1.75; 95% CI: 1.57–1.96), female sexual organs (PMR = 2.12; 95% CI: 1.01–4.36) and respiratory system (PMR = 2.25; 95% CI: 1.55–6.74) but less risk for cutaneous and subcutaneous tissue tumors (PMR = 0.44; 95% CI: 0.38–0.51) and blood/hematopoietic system tumors (PMR = 0.47; 95% CI: 0.26–0.85) compared to spayed female dogs. Compared with mixed breed, purebred dogs had a significantly greater risk of developing mammary gland tumors (PMR = 1.36; 95% CI: 1.20–1.54) and lower risk for respiratory (PMR = 0.15; 95% CI: 0.07–0.32), gastrointestinal (PMR = 0.63; 95% CI: 0.34–0.94) and oral (PMR = 0.59; 95% CI: 0.36–0.96) neoplasia. Non-neutered male cats had a lower risk of developing skin and subcutaneous tumors (PMR = 0.68; 95% CI: 0.50–0.92) compared with neutered cats. The risk of developing skin and subcutaneous tissues tumors was higher for dogs and cats that lived mostly outdoor (PMR dogs = 1.21; 95% CI: 1.10–1.33; PMR cats = 1.18; 95% CI: 1.08–1.47), while dogs that live mainly indoor had a greater risk to develop mammary gland tumors (PMR = 0.78; 95% CI: 0.68–0.89). Results described herein highlight the fundamental role of animal cancer registration initiatives. These efforts would contribute to the possibility of conducting multicentric collaborative studies to deepen the knowledge of the epidemiology of tumors in dogs and cats from a comparative perspective, thus fulfilling the One Health approach.

Kidney Transplantation in Patients with Polycystic Kidney Disease: Increased Risk of Infection Does Not Compromise Graft and Patient Survival

Abstract Background Patients with autosomal dominant polycystic kidney disease (ADPKD) represent &amp;gt;10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear. Methods Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients we assessed the occurrence, frequency and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses. Results During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, p=0.022; 0.8±1.4 vs. 0.5±1.1 episodes, p&amp;lt;0.001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; p&amp;lt;0.001) and recipient age (RR 1.05; p=0.003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral: RR 0.60; p=0.088; bilateral: RR 0.45; p=0.020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients (HR 0.67; p=0.047) due to a lower risk of death-censored graft loss (HR 0.47; p=0.014). Donor age (HR 1.34; p=0.002) and rejection (HR 8.47; p&amp;lt;0.001) were risk factors for death-censored graft loss. Conclusions ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better.

Analysis of the efficacy of Prostatic Artery Embolization in the treatment of Benign Prostatic Hyperplasia.

To investigate the safety and efficacy of prostatic artery embolization (PAE) in the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), and to investigate predictors of clinical success of PAE. A retrospective analysis was used to collect 107 patients [median age 81.0 (73.0,85.0)] with BPH-related LUTS treated with PAE from September 2014 to February 2022 in a hospital. Repeated measurement ANOVA was used to compare the efficacy evaluation indicators at different times before and after PAE. Univariate and multivariate analyses were used to identify potential predictors of PAE clinical success and establish the optimal joint prediction model. The Receiver Operating Characteristic curves of the quantitative predictors and multivariate model prediction probability values significantly correlated with clinical success were plotted. Of the 107 cases, 103 (96.3%) successfully underwent PAE. The International Prostate Symptom Score (IPSS) decreased from a baseline mean of 24.94 to 10.19 (P < 0.05) 3 months after PAE, and the mean IPSS at 6 months, 12 months and 24 months was 10.12, 11.30 and 11.86, respectively, which were statistically significant compared with baseline (P<0.05). Predictors of clinical success were greater prostate volume (> 65 ml, P = 0.018), adenomatous-dominant benign prostatic hyperplasia (AdBPH)(P = 0.030), indwelling catheterization due to urine retention (P = 0.028), and bilateral embolization (P = 0.018). PAE was able to significantly improve BPH-related LUTS and the outcome indicators remained stable at long-term follow-up. Preoperative urinary retention catheters, AdBPH, larger prostate volume (> 65ml) and bilateral embolization suggest better clinical efficacy.

Influence of Diabetes Mellitus on Postoperative Complications After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

Background and Objectives: Total knee arthroplasty (TKA) is an effective treatment option for severe knee osteoarthritis. Understanding the impact of diabetes mellitus (DM) on postoperative outcomes is crucial for improving patient satisfaction after TKA. This study aimed to investigate the influence of DM on postoperative complications and mortality after TKA. Materials and Methods: We conducted a systematic review and meta-analysis by searching relevant studies published before December 2023 in the PubMed, EMBASE, Cochrane Library, Medline, and Web of Science databases. The assessment included demographic data, comorbidities, and postoperative complications after primary TKA for both DM and non-DM patients. The odds ratio (OR) was used to represent the estimate of risk of a specific outcome. Results: Thirty-nine studies were finally included in this meta-analysis. Patients with DM had higher rates of periprosthetic joint infection (OR: 1.71, 95% confidence interval [CI]: 1.46–2.00, p &lt; 0.01) and prosthesis revision (OR: 1.37, 95% CI: 1.23–1.52, p &lt; 0.01). Moreover, patients with DM showed an elevated incidence of pneumonia (OR: 1.54, 95% CI: 1.15–2.07, p &lt; 0.01), urinary tract infection (OR: 1.86, 95% CI: 1.07–3.26, p = 0.02), and sepsis (OR: 1.61, 95% CI: 1.46–1.78, p &lt; 0.01). Additionally, the postoperative risk of cardiovascular (OR: 2.49, 95% CI: 1.50–4.17, p &lt; 0.01) and cerebrovascular (OR: 2.38, 95% CI: 1.48–3.81, p &lt; 0.01) events was notably higher in patients with DM. The presence of DM increased the risk of deep vein thrombosis (OR: 1.58, 95% CI: 1.22–2.04, p &lt; 0.01), but did not lead to an increased risk of pulmonary embolism. Most importantly, DM was associated with a higher mortality rate within 30 days after TKA (OR: 1.27, 95% CI: 1.02–1.60, p = 0.03). Conclusions: Patients with DM exhibited a higher rate of postoperative complications after TKA, and DM was associated with a higher mortality rate within 30 days after TKA. It is crucial to educate patients about the perioperative risk and develop evidence-based guidelines to prevent complications after TKA.

Urogenital colonization and pathogenicity of E. Coli in the vaginal microbiota during pregnancy

This study explores the role of the vaginal microbiota (VM) in the pathophysiology of asymptomatic bacteriuria (ASB) in a cohort of 1,553 pregnant women. Worldwide, E. coli remains the most common etiological agent of bacteriuria during pregnancy and also a major causative agent of newborn infections. A healthy VM is typically characterized by low diversity and is dominated by lactic acid-producing species, notably those from the Lactobacillus genus. Our results point to decreases in Lactobacillus spp associated with an increase of gut-microbiota-associated species from the Enterobacterales order. Escherichia coli exhibited the most pronounced increase in abundance within the VM during bacteriuria and was notably associated with ASB. Molecular typing and antimicrobial resistance characterization of 72 metagenome assembled E. coli genomes (MAGs) from these pregnant women revealed a genomic signature of extraintestinal pathogenic E. coli (“ExPEC”) strains, which are involved in various extraintestinal infections such as urinary tract infections, newborn infections and bacteremia. Microbial diversity within the vaginal samples from which an E. coli MAG was obtained showed a substantial variation, primarily marked by a decrease in abundance of Lactobacillus species. Overall, our study shows how disruption in key bacterial group within the VM can disrupt its stability, potentially leading to the colonization by opportunistic pathogens.

Mimicking Urinary Tract Infections Caused by Uropathogenic Escherichia coli Using a Human Three-Dimensional Tissue Engineering Model

Uropathogenic Escherichia coli are the main causal agent of urinary tract infections. These diseases can affect more than half of women during their lifetime. Moreover, recurrent urinary tract infections can affect up to 30% of patients, leading to higher social and economic costs for the community. No efficient treatment against the recurrent form of the disease has been discovered. Due to the low average rate of successful translation from 2D cell culture and in vivo animal models into clinical trials, new models that mimic pathologies, such as those produced by tissue engineering, are needed. A model of human-derived 3D bladder mucosa was produced by tissue engineering techniques using collagen gels and organ-specific primary human stromal and epithelial cell populations. This model was used to mimic the different steps of a urinary tract infection: adhesion, invasion, intracellular bacterial community and quiescent intracellular reservoir formation and, finally, bacteria resurgence after umbrella cell exfoliation through chitosan exposure to mimic the recurrent infection. The uropathogenic strain UTI-89-GFP was used as infectious bacteria and BL-21-GFP strain as a control. Our model is unique and is the first step toward mimicking the different phases of a UTI in a human context.

Clinical determination of the natural distensibility of the human ureter: initial study.

To define the natural distensibility of the human ureter and evaluate the impact of other possibly favourable factors on ureteric distensibility. A total of 101 patients undergoing ureteroscopic stone removal or percutaneous nephrolithotomy underwent ureteric sizing using sequential passage of 37-cm urethral dilators in 2-F increments while attached to a unique force sensor. Insertion forces were limited to 6 N. After 6 N was attained, an appropriately sized ureteric access sheath was passed. At the conclusion of each procedure, Post-Ureteroscopic Lesion Scale score was determined. Urethral dilators were passed in 61% of patients at ≤14 F; 39% of patients accepted urethral dilators of ≥16 F. The mean dilator size was 14 F. Multivariate logistic regression analysis revealed that preprocedural ureteric stenting and antibiotic use favoured passage of 16-F dilators (odds ratio [OR] 5.16, 95% confidence interval [CI] 1.70-15.62 [P = 0.004] and OR 5.15, 95% CI 1.743-15.243 [P = 0.003], respectively). Neither tamsulosin nor prior urinary tract infection had an impact on ureteric size (OR 0.765, 95% CI 0.281-2.084 [P = 0.601], OR 1.049, 95% CI 0.269-4.089 [P = 0.945], respectively). Using continuous insertion force monitoring and a 6-N threshold, the majority of unstented adult human ureters within our patient population safely accommodated a 14-F dilator. Safe passage of a 16-F dilator at the 6-N threshold was more likely among patients with a preexisting indwelling ureteric stent or patients who were treated with antibiotics within a week of the procedure.

Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway

Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.

Clinical characteristics and nomogram model for predicting the risk of recurrence of complicated urinary tract infection in pediatric patients

Complicated urinary tract infection (cUTI) has higher incidences of antibiotic resistance, recurrence, chronicity, and progression. There exist differences in the immune functions, anatomical structures and physiological functions of urinary tract system between children and adults. In addition, the immature stage of hygiene habit development and the inability to express discomfort accurately all contribute to cUTI recurrence in pediatric patients. cUTI recurrence in children can lead to serious consequences such as growth and development delay, renal scars, and progression to end-stage kidney diseases. Despite the high incidence of cUTI recurrence, no predictive model currently exists to guide targeted intervention in pediatric patients. This study aimed to establish a nomogram to predict the risk of cUTI recurrence in children, thereby facilitating targeted prevention and treatment strategies in pediatric patients. The nomogram was developed based on a retrospective cohort that included 421 pediatric patients with cUTI at West China Second University Hospital from January 2020 to August 2023. The patients were randomly divided into a training set and a validation set in a 3:1 ratio. Logistic regression analysis was used to identify risk factors and construct the nomogram for predicting the risk of cUTI recurrence, followed by validation and performance analysis. Of the 421 children with cUTI, the recurrence rate of cUTI was 68.4% (288 cases) during an average follow-up duration of 22.9 months. The nomogram comprised female gender, history of urinary tract surgery, Escherichia coli in urine culture, renal dysfunction, and vesicoureteral reflux as predictors of cUTI recurrence in pediatric patients. The model showed favorable performance with C-index values of 0.735 and 0.750 in the training dataset and the validation dataset, respectively. The decision curve analysis revealed that the nomogram might be clinically useful. The reliable nomogram would be beneficial for clinicians to identify children with high risks of cUTI recurrence for targeted intervention.

Risk factors associated with multidrug-resistant Klebsiella pneumoniae infections: a multicenter observational study in Lebanese hospitals

BackgroundKlebsiella pneumoniae is a significant global public health burden, especially in low-income countries and regions with fragile healthcare infrastructures, due to its ability to cause severe infections, increase mortality rates, and its rising antimicrobial resistance. This study aimed to estimate the proportion of multidrug-resistant (MDR) K. pneumoniae infections and identify associated risk factors.MethodsData were retrospectively collected from three academic hospitals in Beirut, Lebanon, between January 2021 and September 2023 using a standardized form. Binary logistic regression was used to determine risk factors associated with MDR, extended-spectrum beta-lactamase (ESBL)-producing, and carbapenem-resistant K. pneumoniae (CRKP) infections.ResultsOut of 2,655 K. pneumoniae cases, 410 met the inclusion criteria. The primary infection sources were the urinary tract (58.3%) and the respiratory tract (12.4%). Among the isolates, 61% were MDR K. pneumoniae, with 7.3% being extensively drug-resistant, and 0.5% pandrug-resistant. Additionally, 36.8% were ESBL-producing, while 6.3% were CRKP. Predictors significantly associated with MDR K. pneumoniae infections included male sex (adjusted odds ratio [AOR] = 3.46, 95% CI = 1.01–11.86, P = 0.04), recent antibiotics use (AOR = 4.52, 95% CI = 1.65–12.36, P = 0.003), and recent cancer chemotherapy (AOR = 3.43, 95% CI = 1.25–9.42, P = 0.01). ESBL-producing infections were associated with age ≥ 65 years, higher Charlson Comorbidity Index (CCI), and recent antibiotic use. CRKP infections were linked to male sex, prior antibiotic use, and longer hospital stays prior to infection (all P < 0.05).ConclusionsMDR K. pneumoniae infections are steadily rising in Lebanon, along with an increase in ESBL-producing and CRKP cases. The main risk factors for MDR K. pneumoniae infections were male sex, recent antibiotic use, and cancer chemotherapy. ESBL-producing infections were associated with advanced age, higher CCI, and recent antibiotic use, while CRKP infections were linked to male sex, prior antibiotic use, and prolonged hospital stays. This situation is further exacerbated by inadequate healthcare infrastructure and suboptimal national surveillance. Strengthening local surveillance and implementing effective antibiotic stewardship programs are critical to managing this growing threat..

Imperforate Hymen: Rare Types

When the hymen, a thin membrane of stratified squamous epithelium circumscribing the vaginal introitus, does not spontaneously rupture during neonatal development, it is referred to as an imperforate hymen. An imperforate hymen is a rare cause of primary amenorrhea and can present with obstructive symptoms of the female genital and urinary tracts during the perinatal, pediatric, or adolescent years. Timely diagnosis and prompt treatment are critical. Specific pediatric and gynecologic knowledge and skills are necessary to provide comprehensive, patient-centered care. In addition to the anatomical and physiological aspects of imperforate hymen, its clinical presentation, and potential complications, the psychological impact on affected individuals must be understood. Best practices will ultimately improve patients’ quality of life and reproductive health outcomes. This activity reviews the evaluation and treatment of imperforate hymen and highlights the role of the interprofessional team in improving care for patients with this condition.

Phototriggered Hydrogen Persulfide Donors via Hydrosulfide Radical Formation Enhancing the Reactive Sulfur Metabolome in Cells.

Hydrogen persulfide (H2S2) is an important sulfur-containing signaling molecule that plays a crucial role in the homeostasis of various organ systems, such as the renal, cardiovascular, liver, and gastrointestinal systems. However, research on H2S2 in biological settings is still challenging due to its instability and high reactivity. Compounds that can controllably release H2S2 (also known as donors) are thus crucial research tools. Currently, available H2S2 donors are still very limited, with most of them relying on modified disulfide templates. These templates possess an unavoidable limitation of being susceptible to cellular disulfide exchange which can compromise their efficacy. In this work, we explored nondisulfide-based and nonoxidation-dependent templates for the design of H2S2 donors. We found that tertiary naphthacyl thiols could undergo phototriggered C-S homolytic cleavage to form H2S2 via hydrosulfide (HS) radicals. In addition, the release of H2S2 was associated with the formation of a product with strong blue fluorescence, which allowed for real-time monitoring of the release process. This reaction was demonstrated to proceed effectively in both buffers and cells, with the ability to enhance intracellular production of persulfides, including GSSH, CysSSH, H2S2, H2S3, etc. It provides a unique photocontrolled H2S2 donor system with distinct advantages compared to known H2S2 donors due to its good stability and spatiotemporal control ability.