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Abstract Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Purpose: To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections. Materials and Methods: Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization. Results: In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling. Conclusions: Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.

Ketamine, a dissociative anesthetic drug, has gained popularity as a recreational substance, particularly among young adults. However, chronic ketamine abuse can lead to various complications including ketamine-induced cystitis. We present the case of a 46-year-old Caucasian male with a history of HIV infection and daily recreational ketamine use for 7 months, who was admitted to the emergency room with hypogastric pain and hematuria. Laboratory examinations and contrast-enhanced abdominal CT tomography revealed significant irregular circumferential thickening of both ureters, substantial bilateral pyeloureteral ectasia, and a bladder with markedly thickened walls. Bilateral flexible ureteropyeloscopy, bladder transurethral resection, and bladder fulguration were performed, and pathology confirmed the diagnosis of ketamine-induced cystitis. Treatment consisted of ketamine withdrawal, pain relief, and support from psychiatrists and urologists. The patient's symptoms improved and he was discharged without complications. This case highlights the importance of recognizing the potential adverse effects of recreational ketamine use and the need for a multidisciplinary approach to managing ketamine-induced cystitis. Further research is necessary to elucidate the precise mechanisms underlying this condition and develop effective prevention and treatment strategies.

Purpose Previous studies have simply confirmed recurrence of acute cystitis negatively affects a patient’s psychological state. This study was performed to assess the impact of the recurrence of urinary tract infections on anxiety and depression and further assess whether there is a correlation between the number of recurrences and the degree of anxiety and depression. Methods This cross-sectional study enrolled patients with recurrent cystitis who visited a tertiary care center between April 2018 and June 2022. For eligible patients, depression and anxiety were assessed by the Patient Health Questionnaire-9 and State-Trait Anxiety Inventory. Among the clinical characteristics, factors that independently affected the degree of depression and anxiety were analyzed. Additionally, the relationship between the level of anxiety, depression, and the number of recurrent cystitis was assessed. Results A total of 112 female patients with recurrent cystitis were enrolled in this study. The proportion of patients with depression (moderate, 8%; severe, 0%) was relatively low compared with that of patients with anxiety (moderate, 22.3%; severe, 68.8%). Multivariate regression analysis showed that more recurrent episodes were significantly associated with higher anxiety scores (P

Abstract Background One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction. Methods Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice. Results Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan’s blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks. Conclusions Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.

Abstract One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p

Introduction: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. Methods: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. Results: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. Conclusion: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design, setting, and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria—Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p

Abstract Background Despite the publication of several meta-analyses regarding the efficacy of certain therapies in helping individuals with interstitial cystitis (IC) / bladder pain syndrome (BPS), these have not provided a comprehensive review of therapeutic strategies. The study aimed to determine the efficacy of various therapies for IC/BPS and identify potential moderating factors using randomized controlled trials (RCTs). Methods We queried the PubMed, Cochrane, and Embase databases to identify prospective RCTs using inclusion criteria: 1) patients diagnosed with IC, 2) interventions included relevant treatments, 3) comparisons were a specified control or placebo, 4) outcomes were mean differences for individual symptoms and structured questionnaires. The pairwise meta-analysis and network meta-analysis (NMA) were performed to compare the treatments used in IC/BPS. Hedges’ g standardized mean differences (SMDs) were used for improvement in all outcomes using random-effects models. Efficacy outcomes included individual symptoms such as pain, frequency, urgency, and nocturia, as well as structured questionnaires measuring IC/BPS symptoms. Results A comprehensive literature search was conducted which identified 70 RCTs with 3,651 patients. The analysis revealed that certain treatments, such as instillation and intravesical injection, showed statistically significant improvements in pain and urgency compared to control or placebo groups in traditional pairwise meta-analysis. However, no specific treatment demonstrated significant improvement in all outcomes measured in the NMA. The results of moderator analyses to explore influential variables indicated that increasing age was associated with increased nocturia, while longer follow-up periods were associated with decreased frequency. Conclusion This systematic review and meta-analysis provide insights into the efficacy of various treatments for IC. Current research suggests that a combination of therapies may have a positive clinical outcome for patients with IC, despite the fact that treatment for this condition is not straightforward. Trial registration PROSPERO CRD42022384024

Background: Research on acute cystitis in men is scarce and treatment guidelines differ between countries. Improved antibiotic stewardship is needed. Aim: To analyse antibiotic prescriptions and outcomes of Norwegian men diagnosed with cystitis in primary care. Design & setting: A nationwide retrospective study was undertaken in primary care in Norway. Method: We identified all episodes of acute cystitis in men diagnosed in Norwegian primary care during 2012–2019. Choice of antibiotic (from the Norwegian Prescription Database), treatment failure, re-prescription, and complications were stratified by age, calendar year, and risk factors. We used logistic regression to explore predefined risk factors (diabetes, prostate cancer, benign prostate hyperplasia [BPH], urinary retention, and any cancer) with complications (pyelonephritis, prostatitis, and hospitalisation) and re-prescriptions. Linear regression was used to explore time trends. Results: In total, 108 994 individuals contributed 148 635 episodes. Narrow-spectrum antibiotics were first-choice treatment in 71.0% of the episodes (52.5% of all prescriptions were pivmecillinam). More than 75% of the episodes with narrow-spectrum versus 82.2% of broad-spectrum treatment did not lead to any re-prescription or complication. Complications occurred in 1.8% of all episodes (0.5% prostatitis, 0.7% pyelonephritis, and 0.7% hospitalisation). BPH was associated with increased risk of complications and re-prescription. Diabetes was associated with a lower risk of re-prescriptions. Prostate cancer and urinary retention were associated with a lower risk of both complications and re-prescriptions. Conclusion: Our results support narrow-spectrum antibiotics as first-line treatment. Risk factor analyses warrants further investigation.

Immune checkpoint inhibitors (ICIs) including anti-programmed death cell protein 1 (anti-PD1) and anti-programmed cell death-ligand 1 (PD-L1), by disinhibiting the antitumor responses of lymphocytes, have extended survival benefits for patients in lung cancer. ICIs can also lead to a wide spectrum of immune-related adverse events (irAEs), due to dysregulation of immune reactions. Here, we report a 27-year-old female patient with adenocarcinoma of the lung treated with pembrolizumab-combined chemotherapy treatment, who complained of urinary irritation symptoms. No bacteria were found in multiple urine cultures. B-mode ultrasonography indicated a high echo in the right lateral wall of the bladder, about 5.6 × 4.5 mm in size. Transurethral bladder tumor resection (TURBT) was operated. At biopsy, we found CD3+ CD8+ lymphocyte, plasma cell, and eosinophil infiltration and lymphoid follicle formation in the bladder mucosal layer. This is a report of non-bacterial inflammation of the urinary tract caused by immunotherapy.

Abstract Background Prostate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics. Objective To compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC). Methodology We retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23. Results 114 patients were selected according to the inclusion criteria. Mean age was 68 years (61–75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant). Conclusion Hypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.

Abstract Background Uncomplicated urinary tract infections (uUTIs) are one of the most common community-acquired infections, particularly among women. Common symptoms of UTI include dysuria, urinary urgency and increased frequency, and lower abdominal pain. With appropriate treatment, symptoms may resolve in a few days. However, there is a lack of research on the emotional impact of this disease. We conducted a qualitative, interview-based study to gain a greater understanding of the emotional impact of uUTIs in women in China and Japan. Methods A qualitative, exploratory, in-depth, interview-based study was conducted between 19 November 2020 and 25 February 2021. Women aged ≥ 18 years who experienced ≥ 1 uUTI and received antibiotic treatment in the past year were eligible for inclusion. Participants must have experienced ≥ 1 of the following symptoms during a uUTI episode: urinary urgency, frequency, dysuria, or lower abdominal/suprapubic pain. Participants who reported back pain or fever (indicative of complicated UTI) were excluded. Participants with recurrent or sporadic UTIs were included, with specific screening criteria used to ensure capture of both groups. Following a screening call, a structured, in-depth telephone interview (~ 30 min in duration) was conducted by three female external moderators trained in qualitative interviewing, assisted by an interview guide. Interviews were analysed individually and thematically, with the results presented within the identified themes. Results A total of 65 women with uUTI completed the in-depth telephone interview: 40 (62%) from China and 25 (38%) from Japan. Participants reported that the symptoms of uUTI affected multiple aspects of their lives, and described feelings of embarrassment, frustration, guilt, dread, and loneliness associated with symptoms that interfered with relationships, work and daily activities, and sleep. Participants reported seeking healthcare from several different points of contact, from local pharmacies to hospitals. Conclusions Our analysis highlights the profound emotional impact of uUTIs in women in China and Japan, and the journey these participants take before their initial interaction with a healthcare professional. These insights emphasise the need to better understand the full impact of uUTI, and the role of healthcare professionals in improved patient education and support.

Abstract Background Ketamine is a novel and exciting putative antidepressant medication for patients with treatment-resistant depression. A complication commonly seen in frequent and heavy recreational use of ketamine is ulcerative cystitis, which presents with lower urinary tract symptoms (LUTS) and upper renal tract damage and can be seen in over 25% of regular users. Although Ketamine-induced cystitis (KIC) is a recognised complication in recreational use of ketamine, its occurrence in therapeutic use of ketamine in depression has so far not been reported. The exact pathogenesis of KIC is currently unknown, making treatment and prevention advice much more difficult. Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage. Case presentation We present a case of a 28-year-old female who was started on ketamine treatment for depression, and who then developed symptoms of KIC, which was confirmed by urine microscopy, culture and analysis. Conclusions To our knowledge, this is the first reported case of KIC in a patient receiving treatment-dose ketamine as part of their antidepressant therapy.

Objective: Due to the need for better treatments for infectious disorders, the antibacterial and anti-inflammatory potential of silver nanoparticles (AgNPs) of Mitracarpus scaber (M.scaber) extracts were assessed in this study. Methods: AgNPs were synthesized from 0.1M AgNO3 solution using M.scaber aqueous and ethanolic extracts as capping and reducing agents. FTIR, UV-VIS, FESEM and XRD studies were used to analyze the generated AgNPs. The Agar well diffusion method was used to evaluate their antibacterial activity against E. coli, while egg albumin and carrageenan-induced paw oedema assays were used to measure the anti-inflammatory activity of silver nanoparticles of aqueous and ethanol extracts of M.scaber (A.AgNPs and E.AgNPs). Result: The formation of A.AgNPs and E.AgNPs at λ max = 425 nm and 410 nm, respectively, were demonstrated by UV–vis spectroscopy. The XRD pattern showed that the crystalline phase of silver and the generation of A.AgNPs and E.AgNPs were well aligned. Agglomerated A.AgNPs and E.AgNPs with particle sizes ranging from 5 to 20 nm were seen in the FESEM micrograph. The antibacterial activity result showed that, in a dose-dependent manner, A.AgNPs had a significantly (P

Eosinophilic cystitis is a rare inflammatory condition of the bladder characterized by eosinophils infiltrating the bladder wall. It affects people of all ages and with no gender difference. Eosinophilic cystitis can mimic bladder tumors and other chronic cystitis, which makes it a challenging condition to diagnose. In this article, we will discuss the causes, symptoms, diagnosis, and treatment of eosinophilic cystitis, as well as how it might be mistaken for bladder tumors.

Background: The treatment of urinary tract infections (UTIs) has contributed to the rise of antibiotic resistance. Antibiotic appropriateness in the outpatient setting is lower than expected. We hypothesized that prescribing practices may vary based on the day of the week. We sought to determine the percentage of antibiotic prescriptions that met criteria for antibiotic appropriateness on Mondays vs. Fridays. Methods: This is a retrospective cohort study of adult females with simple cystitis presenting to the Emergency Department (ED) between 2019 and 2021. We defined antibiotic appropriateness based on the Infectious Diseases Society of America guidelines in conjunction with a regional outpatient UTI antibiogram. Each prescription was assessed for drug selection, dose, frequency, and duration. Categorical data is reported as counts (%) and compared with chi-square. Nonparametric continuous data is reported as median (range) and compared with Mann-Whitney. Results: 160 subjects were included: 80 came to the ED on a Monday and 80 on a Friday. Demographics were similar; except, more subjects had antibiotic allergies on Mondays. The number of appropriate antibiotic prescriptions was similar between Mondays and Fridays: 54 (68%) and 60 (75%), respectively (p=0.3). Overall, 44 subjects had an inappropriate duration of antibiotics and 14 subjects had an inappropriate antimicrobial prescribed, with no differences between Mondays and Fridays. Dose and frequency were always correct. In total, there were 46 (29%) antibiotics that failed to meet appropriateness criteria. Conclusions: There was no difference in antibiotic appropriateness between Mondays and Fridays; however, 29% of prescriptions did not meet criteria for appropriateness.

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, , may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered. On the other hand, non-antibiotic therapy has also become an option which should be discussed and offered to the patient. In patients suffering from recurrent uncomplicated cystitis, individual risk factors and ehavioral changes should first be taken into account. Non-antimicrobial prophylactic strategies shown to be successful in well-designed clinical studies are the next options. Long term antibiotic prophylaxis, however, should only be considered as a last option. For some of those patients self-diagnosis and self-treatment may be suitable, e.g. by using a recognized questionnaire.

Abstract Background The genus Corynebacterium comprises well-known animal and human pathogens as well as commensals of skin and mucous membranes. Species formerly regarded as contaminants are increasingly being recognized as opportunistic pathogens. Corynebacterium oculi has recently been described as a human ocular pathogen but has so far not been reported in dogs. Case presentation Here we present two cases of infection with a novel Corynebacterium sp., a corneal ulcer and a case of bacteriuria. The two bacterial isolates could not be identified by MALDI-TOF MS. While 16 S rRNA gene (99.3% similarity) and rpoB (96.6% identity) sequencing led to the preliminary identification of the isolates as Corynebacterium (C.) oculi, whole genome sequencing revealed the strains to be closely related to, but in a separate cluster from C. oculi. Antimicrobial susceptibility testing showed high minimal inhibitory concentrations of lincosamides, macrolides, tetracycline, and fluoroquinolones for one of the isolates, which also contained an erm(X) and tet-carrying plasmid as well as a nonsynonymous mutation leading to an S84I substitution in the quinolone resistance determining region of GyrA. Conclusions While the clinical signs of both dogs were alleviated by antimicrobial treatment, the clinical significance of these isolates remains to be proven. However, considering its close relation with C. oculi, a known pathogen in humans, pathogenic potential of this species is not unlikely. Furthermore, these bacteria may act as reservoir for antimicrobial resistance genes also in a One Health context since one strain carried a multidrug resistance plasmid related to pNG3 of C. diphtheriae.

Background: This study was designed to analyze the efficacy of a urine dipstick to detect urinary tract infection (UTI) in children and to correlate it with the urine culture. Methods: A prospective laboratory descriptive study was conducted at the Department of Pediatrics at Government General Hospital, Kadapa, from February 2022 to September 2023. Urine samples from 250 children of 2 and 12 years of age with UTI symptoms were analyzed using urine dipstick and other clinical/laboratory variables. Results: The urine culture was positive in 38.4% (n=96) of the children and negative in 61.6% (n=154) of the children using the dipstick. Urinary tract infection was more common among female than male children. It was common in children aged 6 to 10 years, accounting for 41.42%. The most prevalent organism isolated was Escherichia coli (24.8%), followed by Klebsiella (8.8%) and other Gram-negative bacilli (5.6%). Urine microscopy for pus cells revealed that 158 (63.2%) samples had no pus cells, 49 (19.6%) had up to 5 pus cells, 35 (14%) had 5-10 pus cells, and 8 (3.2%) had >10 pus cells. Pyuria was found in 56 of the 96 children in the culture-positive group, leukocyte esterase was positive in 123 cases, leukocyte esterase was negative in 88 cases, and the nitrite test was positive in 9 cases. However, the combined dipstick was positive in 121 (48.4%) of all cases. Among the culture-positive group, the combined dipstick was positive in 39 cases and negative in 3 cases. Among the culture-negative cases, the combined dipstick was positive in 28 cases and negative in 126 cases. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of leucocyte esterase and nitrite were 65%, 80%, 69%, and 78% for diagnosing UTI in our study, respectively. The sensitivity, specificity, PPV, and NPV of the combined dipstick compared with urine culture were 95.5%, 80%, 74.9%, and 95.9%, respectively. Conclusion: The combined dipstick + nitrite and leukocyte esterase show higher sensitivity and specificity, making it superior to leukocyte esterase or nitrite alone in diagnosing UTI. When compared to the urine culture, the combined dipstick has higher sensitivity, specificity, and positive and negative predictive values. Therefore, the combined dipstick can be used consistently as a quick screening tool for UTIs when culture facilities are not available.

Abstract Defects in the glycosaminoglycan layer (GAG) of the bladder mucosa have been identified as a significant contributor to the pathogenesis and clinical progression of chronic inflammatory diseases of the bladder, such as post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections. This narrative review aims to explore the contemporary evidence on the role of GAG reconstitution with intravesical installations of hyaluronic acid and chondroitin sulfate in the management of those patients, with a goal to provide valuable insights for clinical practice. The reviewed studies consistently demonstrate that GAG reconstitution can result in varying degrees of clinical improvement in patients with post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections, and is associated with a very favorable safety profile. While the available evidence is growing, its level is still limited, mainly by relatively low number of randomized controlled trials, with small sample sizes. Further research with larger, well-designed trials is needed to solidify the findings and optimize the clinical application of GAG reconstitution.

Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner’s interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management.

IntroductionBK virus-associated hemorrhagic cystitis (BK-HC) is a debilitating and poorly understood complication of hematopoietic stem cell transplantation (SCT). Hematuria, dysuria, and other symptoms associated with BK-HC are common in the immediate post-SCT period, making BK-HC difficult to distinguish from other conditions presenting with these symptoms. Despite published criteria for diagnosis, the degree to which these criteria are consistently applied to either clinical diagnosis or to studies informing BK-HC management is unclear. We present a case of BK-HC in a pediatric SCT recipient, and discuss the challenges associated with treatment in the absence of rigorous data to inform clinical management.MethodsWe reviewed all cases of BK viruria at our center in patients undergoing SCT between January 2015 and December 2019. We then performed a scoping review of publications in PubMed addressing BK-HC, specifically focusing on how BK-HC was defined. Publications using the keywords “BK polyomavirus” and “hemorrhagic cystitis” were included if they involved a clinical study of SCT recipients and a full-text article was available in English. Case reports were excluded. Analysis focused on whether BK-HC was explicitly defined and whether the definition incorporated elements of diagnostic criteria published by European Conference on Infections in Leukemia (ECIL).ResultsA total of 30 studies published between January 2018 and 30 June 2021 met criteria for review, including 4 clinical trials, 7 prospective observational studies, and 19 retrospective observational studies. Fifteen of these studies included pediatric patients (7 pediatric only, 8 combined adult and pediatric). Of the 30 publications, 19 included a definition of either BK-HC or BK cystitis, with only five using ECIL criteria, all of which were observational studies. Multiple interventions are described for treatment of BK-HC, including cidofovir, leflunomide, quinolones, hyperbaric oxygen, keratinocyte growth factor, and BK-specific cytotoxic T lymphocytes. However, evidence to support efficacy for any of these interventions is lacking.DiscussionAlthough BK-HC is a well-known complication of SCT, evidence to support available treatment options is limited. Well-controlled studies that incorporate clear diagnostic criteria are needed to better define the risk factors, natural history, and ideal interventions.

A 49-year-old female with multiple myeloma complicated by renal failure had dysuria. The urine culture revealed multidrug-resistant aeromonas caviae during her hospital stay. Her symptoms and signs significantly improved after receiving a seven-day course of piperacillin-tazobactam treatment. She had no history of urinary tract infections(UTIs). On follow-up, she felt clinically well. Aeromonas caviae is a rare cause of UTI. We review previous cases of aeromonas caviae UTIs. The purpose of this case report is to assist in the diagnosis and management of aeromonas caviae cystitis.

Non-muscle invasive bladder cancer (NMIBC) accounts for ~70–75% of total bladder cancer tumors and requires effective early intervention to avert progression. The cornerstone of high-risk NMIBC treatment involves trans-urethral resection of the tumor followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, BCG therapy is commonly accompanied by significant lower urinary tract symptoms (LUTS) including urinary urgency, urinary frequency, dysuria, and pelvic pain which can undermine treatment adherence and clinical outcomes. Despite this burden, the mechanisms underlying the development of BCG-induced LUTS have yet to be characterized. This review provides a unique perspective on the mechanisms thought to be responsible for the development of BCG-induced LUTS by focussing on the sensory nerves responsible for bladder sensory transduction. This review focuses on how the physiological response to BCG, including inflammation, urothelial permeability, and direct interactions between BCG and sensory nerves could drive bladder afferent sensitization leading to the development of LUTS. Additionally, this review provides an up-to-date summary of the latest clinical data exploring interventions to relieve BCG-induced LUTS, including therapeutic targeting of bladder contractions, inflammation, increased bladder permeability, and direct inhibition of bladder sensory signaling. Addressing the clinical burden of BCG-induced LUTS holds significant potential to enhance patient quality of life, treatment compliance, and overall outcomes in NMIBC management. However, the lack of knowledge on the pathophysiological mechanisms that drive BCG-induced LUTS has limited the development of novel and efficacious therapeutic options. Further research is urgently required to unravel the mechanisms that drive BCG-induced LUTS.

IntroductionFeline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations.MethodsThe current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug.ResultsHigher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson’s trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine.DiscussionPGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis.

Vulvitis is one of the most common disorders with which people come to visit obstetrician-gynecologist. nonspecific bacterial, atopic, infectious vulvitis and vulvitis associated with helminthiasis are most often found in girls under the age of 3 years. Hyperemic mucous membrane of the external genitalia, pain, burning, itching while urinating and at rest are specific clinical features of the disorder; abnormal genital discharge of various types can be also found. Vulvitis often comes along with perineal and perianal dermatitis. Labial fusion and urinary tract infections are common complications of nonspecific inflammation. obstetricians-gynecologists are recommended to conduct diagnosis, treatment, rehabilitation and further follow-up of such girls in cooperation with other related experts, involve pediatric urologist, gastroenterologist, pediatrician; if necessary – dermatovenerologist, enT physician, dentist, infectious disease specialist.

Abstract Background The importance of cystitis in pig production is controversial and sparse information is available on its frequency and etiology in sows. The aim of this study was to determine the prevalence of bacteriuria, macroscopical and histological lesions of the urinary bladder in culled sows. Urinary bladders and urine samples were obtained from 176 culled sows at slaughter. The urine samples collected by cystocentesis were analyzed to determine bacterial content and pathological findings, macroscopic as well as microscopic, of the bladder were recorded for each sow. Results The prevalence of bacteriuria, defined by bacterial concentrations ≥ 103 colony forming units per mL of urine, was 34%. Escherichia coli was isolated from 69% of the samples with bacteriuria. Redness of the mucosa was the most frequently observed macroscopic change of the bladder. Intense redness and presence of pus was considered significant pathological changes and occurred in 27% of the urinary bladders. The histopathological examination showed that mononuclear cells were the predominant type of cell infiltration in the bladder mucosa, while neutrophils occurred in very few samples. The criteria for cystitis determined by histopathology were met in 46% of the samples. The criteria were based on presence of hyperemia, edema, and inflammatory cell reaction defined as 40 or more neutrophils or mononuclear cells per high power field. All three indicators of cystitis were significantly associated with each other (p

Francesca Ambrosini,1,2 Niccolò Riccardi,3,4 Sara Occhineri,3,4 Tommaso Matucci,3,4 Irene Paraboschi,5 Alessandro Calarco,6 Alfredo Berrettini,5 Giusy Tiseo,3 Diana Canetti,7 André Van Der Merwe,8 Carlo Terrone,1,2 Guglielmo Mantica1,2 1IRCCS Ospedale Policlinico San Martino, Genova, Italy; 2Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy; 3Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 4StopTB Italia Onlus, Milan, Italy; 5Department of Pediatric Urology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 6Villa Pia Hospital, Via Folco Portinari 5, Rome, Italy; 7Infectious Diseases Unit, San Raffaele Scientific Institute, Milan, Italy; 8Department of Urology, Faculty of Medicine and Health Sciences, 26697 Stellenbosch University, Cape Town, South AfricaCorrespondence: Guglielmo Mantica, Department of Surgical and Diagnostic Intergrated Sciences (DISC), University of Genova, Genova, Italy, Tel +390105555960, Email guglielmo.mantica@gmail.comPurpose: Haemorrhagic cystitis may be due to different etiologies with infectious diseases representing an insidious cause to diagnose. The aim of this narrative review is to provide a comprehensive overview of less common but difficult-to-diagnose causes of infectious haemorrhagic cystitis of bacterial, mycobacterial, and parasitic origin, Moreover, we highlight possible diagnostic tools and currently available treatment options in order to give an updated tool for urologists to use in daily practice.Patients and Methods: The search engine PubMed was used to select peer-reviewed articles published from 1/Jan/2010 to 31/Aug/2022.Results: Bacteria, fungal, TB and schistosomiasis are uncommon causes of haemorrhagic cystitis burdened by high morbidity, especially if not promptly diagnosed.Conclusion: Because haemorrhagic cystitis ranges in severity from mild dysuria associated with pelvic discomfort to severe life-threatening haemorrhage, punctual diagnosis, and immediate treatment are essential to avoid further complications.Keywords: cystitis, haemorrhagic cystitis, schistosomiasis, tuberculosis, GUTB

Urinary tract infection (UTI) is one of the most common urological diseases and presents a problem for rational antibiotic therapy due to the growing antibiotic resistance. Fosfomycin is one of the older low molecular weight, broad-spectrum bactericidal antibiotics with activity against uropathogens, particularly Escherichia coli and others. Fosfomycin is administered as a single dose that achieves very high concentrations of the antibiotic in the urine and bladder, sufficient to eliminate most common uropathogens, including those with multidrug resistance (MDR). Many factors have contributed to the persistence of fosfomycin's antibacterial activity, including the use of a single dose, limited use for UTIs only, and very high and persistent urinary concentrations that rapidly kill bacteria, reducing the possibility of mutant selection. In addition to its antimicrobial properties, fosfomycin has an immunomodulatory effect by altering the function of lymphocytes, monocytes, and neutrophils. It affects the acute inflammatory cytokine response. New data have been obtained on the activity of fosfomycin against biofilms formed by uropathogens and against biofilm-associated bacterial strains with MDR. A new 2020 meta-analysis compared the efficacy of fosfomycin with equivalent antibiotics (β-lactams/cephalosporins, quinolones, sulfonamides, nitrofurantoin) in women in the broad categories of uncomplicated UTI or asymptomatic bacteriuria and found no difference in clinical and microbiological cure rates with comparison groups. A number of other studies in patients with UTIs with MDR or complicated course also showed a high sensitivity of uropathogens to fosfomycin and the effectiveness of treatment with multiple doses (2–3 doses with an interval of 48–72 hrs). Fosfomycin is being considered as a potentially useful antibiotic for the treatment of prostatitis. Current data indicate that sufficient concentrations in prostate tissue are achieved after a single dose of fosfomycin. Recent reviews in 2019 and 2022 present results of studies of fosfomycin for the prevention of infectious complications after transurethral prostate biopsy and in patients with chronic bacterial prostatitis whose pathogens are resistant to other antibiotics. Thus, the accumulation of new scientific data on the mechanisms of action and resistance of fosfomycin reveals more potential advantages of its practical application.

A urinary tract infection (UTI) is an immune response of the urothelium to bacterial invasion, bacteriuria (presence of bacteria in urine) and pyuria (presence of white blood cells in urine) are characteristic indicators of UTI. Prompt and effective management of UTIs is crucial to prevent complications, such as kidney infections and recurrent infections, and to alleviate symptoms, improve quality of life, and minimize antibiotic resistance. The aim of this study was to investigate the incidence, antibiotic resistance, medical treatment, causative agents, diagnosis, and prevention of urinary tract infections (UTIs) in Sulaymaniah city. A total of 60 patients from Sulaymaniah Teaching Hospital were included in the study. The most commonly diagnosed conditions were acute pyelonephritis and cystitis. Various evaluations were conducted, including history taking, physical examination, and diagnostic tests. Mid-stream urine samples were collected for culture and sensitivity analysis. The duration of symptoms such as dysuria, fever, and frequency varied, ranging from 1 to 3 days. During medical examinations, suprapubic tenderness was the most commonly observed finding. Dysuria was reported as the predominant symptom by 19 patients. The majority of patients fell within the age range of 21-40 years. The study findings indicated a higher prevalence of UTIs among females. The most frequently identified causative microorganism was Escherichia coli (E. coli), which accounted for approximately 90% of cases. Gentamycin emerged as the most commonly used antibiotic due to its effectiveness against E. coli. The high prevalence of antibiotic resistance among other pathogens necessitates ongoing surveillance and appropriate antibiotic stewardship to combat UTIs effectively. In conclusion, this study provides valuable insights into the incidence, antibiotic resistance, and management of UTIs in Sulaymaniah city. It emphasizes the need for tailored treatment approaches considering the prevalent causative agents and their susceptibility patterns.

Objective(s): To investigate the potential of Tropomyosin receptor kinase A (TrkA) for the treatment of interstitial cystitis/ bladder pain syndrome (IC/BPS).Materials and Methods: Sixty-four female rats were randomly assigned to the control and cyclophosphamide (CYP) groups. Quantitative reverse transcription polymerase chain reaction was utilized to detect the mRNA level of TrkA. Western blot analysis was used to measure the protein levels of TNF-α, IL-6, and TrkA. Immunostaining was used to detect the expression of TrkA in bladder sections. Contractility studies and urodynamic measurements were utilized to test the spontaneous contractions of detrusor muscle strips and the global bladder activity, respectively.Results: Rat models of chronic cystitis were successfully established. The mRNA and protein levels of TrkA were significantly increased in the bladders of CYP-treated rats. Also, results of immunohistochemical staining and immunofluorescence staining showed that increased TrkA expression in the CYP group was mainly observed in the urothelium layer and bladder interstitial Cajal-like cells (ICC-LCs) but not in the detrusor smooth muscle cells. The specific inhibitor of TrkA, GW441756 (10 μM), significantly suppressed the robust spontaneous contractions of detrusor muscle strips in the CYP group and alleviated the overall bladder overactivity of CYP-treated rats. However, the inhibitory effects of GW441756 (10 μM) on the spontaneous contractions of detrusor muscle strips and the overall bladder activity were eliminated after pretreatments with the specific blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, ZD7288 (50 μM).Conclusion: Our results suggested that increased TrkA expression during chronic cystitis promotes the development of bladder overactivity by targeting the HCN channels.

ABSTRACT Partial or complete bladder eversion is a rare condition of poor prognosis in cows, commonly associated with intense tenesmus observed in the peripartum period. A 14-year-old obese Nellore cow at 280 days of gestation was referred with 24-hour bladder prolapse. The bladder was complete eversion through the vulvar vestibule showing a thick congested wall and small residual urine volume. After clinical examination, the cow received scopolamine butylbromide and intercoccygeal epidural anesthesia, and the externalized bladder segment was partially reduced, remaining only 10 cm externalized. The cow was maintained with an intravesical human gastric tube number 16 and constant monitoring. The eversion was fully reduced after 12 hours of local treatment, and as the cow presented subclinical ketosis, hypocalcemia and cystitis, antibiotic, glucose, calcium and propylene glycol therapy were performed. We opted for induction of parturition, and after 24 hours, a healthy 52kg calf was born and the placenta was delivered 16 hours after calving. The cow and calf were discharged on the sixth day of hospitalization, with no recurrences or secondary complications after treatment.

Background. The purpose was stratification of factors that lead to the chronicity of inflammatory diseases of the urinary system in children, as well as creation of a mathematical model for predicting their course. Materials and methods. The research group consisted of 97 children (average age — 10.0 ± 1.3 years). The main group was divided into subgroups: the first one — 43 children with acute urinary tract infections (UTIs), the second one — 34 patients with chronic UTIs. The control group consisted of 20 conditionally healthy children. The content of 1,25(OH)2D3, vitamin D-binding protein, inducible nitric oxide synthase (NOS2), cystatin C, cathelicidin, hepcidin, lactoferrin, interleukins 6, 15 was investigated by immunoenzymatic analysis. The impact of factor characteristics on the process of UTI chronicity was evaluated using factor and cluster analyses. A logistic regression equation was used to predict the probability of developing chronic UTIs. The quality of the constructed model was assessed by its sensitivity and specificity, and receiver operator characteristic (ROC) analysis was also used. Results. It was found that 6 factors had the greatest significance: the factor of functional disorders of the urinary tract, the factor of comorbid conditions, the protective factor, the immune factor, chronic foci of the disease, and the NOS2 factor. According to the results of logistic regression, the model for predicting the probability of developing chronic UTI in children had the form of an equation that included 6 variables (early manifestation of the disease, vitamin D level, vesicoureteral reflux, dysmetabolic nephropathy, neurogenic bladder, UTI in the mother in childhood). The classification ability of the model was determined based on the data of the training sample and was 75.0 %. The sensitivity of the model was 78.3 %, and the specificity was 76.5 %. The area under the ROC curve that corresponded to our mathematical model was equal to 0.776. The Gini index was 55.2 %, which corresponds to the good quality of the model. Conclusions. The process of chronicity of the inflammatory process in the urinary system in children occurs under the conditions of the interaction of some pathological factors. The leading risk factors for the chronicity of the inflammatory process are the presence of functional disorders of the urinary tract, early manifestation of the disease, the level of vitamin D, intestinal dysfunction, and the presence of UTI in the mother in childhood.

Immune checkpoint inhibitor (ICI) is an up-to-date therapy for cancer with a promising efficacy, but it may cause unique immune-related adverse events (irAEs). Although irAEs could affect any organ, irAEs-induced whole urinary tract expansion was rarely reported. Herein, we reported a 27-year-old male patient with thymic carcinoma who received the treatment of tislelizumab, paclitaxel albumin and carboplatin. He was hospitalized for severe bellyache and lumbago after 6 courses of treatment. Antibiotic and antispasmodic treatment did not relieve his symptoms. The imaging examinations reported whole urinary tract expansion and cystitis. Therefore, we proposed that the patient’s pain was caused by tislelizumab-induced ureteritis/cystitis. After the discontinuation of tislelizumab and the administration of methylprednisolone, his symptoms were markedly alleviated. Herein, we reported a rare case of ICI-induced ureteritis/cystitis in the treatment of thymic cancer and reviewed other cases of immunotherapy-related cystitis and tislelizumab-related adverse events, which will provide a reference for the diagnosis and treatment of ICI-related irAEs.

Background: Cyclophosphamide is widely prescribed as an anti-cancer drug and used as an immunosuppressant. Hemorrhagic cystitis is one of the common complications of cyclophosphamide intake. We hypothesized that endoplasmic reticulum stress-related proteins could be altered in urothelium treated with cyclophosphamide. Objectives: We checked the effect of cyclophosphamide on the expression of various endoplasmic reticulum stress-related proteins in Vero cells. Methods: We treated Vero cells with varying doses of cyclophosphamide and observed its viability in flow cytometry using propidium iodide staining. We looked for changes in the expression of endoplasmic reticulum stress-related proteins in Vero cells treated with cyclophosphamide by western blot technique. Results: Cyclophosphamide at higher doses caused more death in Vero cells that could be attributed to an increase in apoptosis as evidenced by the changes in the morphology of cells and increased expression of endoplasmic reticulum specific caspase-12 proteins. Growth arrest/DNA damage 153 (GADD 153), one of the key transcription factors involved in the mediation of endoplasmic reticulum stress and apoptosis, was upregulated in Vero cells treated with cyclophosphamide. The protective effect of glucose-regulated protein GRP 78 against apoptosis was lost in Vero cells treated with a higher dose of cyclophosphamide, which is corroborated by decreased expression of GRP 78 in Vero cells treated with higher doses compared to Vero cells treated with lower doses of cyclophosphamide. Expression of disulfide isomerase protein, which guides misfolded proteins to fold properly, was downregulated in Vero cells treated with cyclophosphamide. Conclusion: To summarize, our study showed an alteration in the expression of key endoplasmic reticulum stress-related proteins in Vero cells treated with cyclophosphamide.

Purpose To investigate the effect of detrusor overactivity (DO) on the urethral expression of caveolin (CAV)-1, −2, and −3 of urethra in an animal model of cyclophosphamide (CYP)-induced cystitis rat. Methods Female Sprague-Dawley rats were divided into the control group (n=20) and the cystitis group (n=20). Cystitis was induced by intraperitoneal injection of CYP (200 mg/kg). An urodynamic study was done 3 days after the CYP injection to measure functional change of the urinary bladder and urethra. Cellular localization and expression of CAV-1, −2, and −3 in the rat urethra were determined by immunohistochemistry (IHC) and Western blot. Results Urodynamic experiments demonstrated a decreased contraction interval in the cystitis group compared to the control (3.9±1.0 minutes vs. 6.6±1.2 minutes, P

The proposed method aims to estimate the urinary Bladder Wall Thickness (BWT) from ultrasound (US) images to detect cystitis. Our method proposes a novel deep learning algorithm that segments the Bladder Wall from the ultrasound images of the urinary bladder, following which feature extraction and classification are performed to categorize the images as presence or absence of cystitis. The proposed study focused on a CYSNET CNN (Convolutional Neural Network) model for detecting cystitis in the urinary bladder and compares its accuracy with a transfer learning-based pre-trained model like ResNet50 and state-of-the-art Vision Transformer. Among the total population studied (N=250), 125 subjects with cystitis and 125 normal subjects, were included. The bladder wall thickness of cystitis was segmented using the U-Net semantic segmentation model. Eight features constituting contour and thickness were extracted from the segmented bladder wall. The best five features were selected using the Univariate feature selection method based on ANOVA F statistics as the scoring scale. The selected five features were classified into cystitis and normal using three different Machine Learning (ML) Classifiers such as AdaBoost, RepTree, and NaÏve Bayes. Three different CYSNET models with varying convolution layers were developed to detect cystitis in ultrasound images. The performance of the CYSNET models is compared with the ML classifiers, ResNet 50 model, and Vision Transformer. The CYSNET model 3 outperformed with the classification accuracy of 95% compared to the Adaboost network (90%), ResNet50 model (88.7%) and Vision Transformer (92.1%). Hence, the developed CYSNET model could be used as a computer-aided diagnostic tool for the detection of cystitis in ultrasound images.

Background: Urinary tract infection (UTI) has been a major burden on the community and the health-care systems all over the globe. It is the most common cause of bacterial infection in the pediatric age group, with an annual incidence of 3%. The aim of this study is to review and summarize all available guidelines on the diagnosis and management of children with UTI. Materials and Methods: This is a narrative review of the management of children with a UTI. All biomedical databases were searched, and any guidelines published from 2000 to 2022 were retrieved, reviewed, and evaluated to be included in the summary statements. The sections of the articles were formulated according to the availability of information in the included guidelines. Results: UTI diagnoses are based on positive urine culture from a specimen of urine obtained through catheterization or suprapubic aspiration, and diagnoses cannot be established on the bases of urine collected from a bag. The criteria for diagnosing UTI are based on the presence of at least 50,000 colony-forming units per milliliter of a uropathogen. Upon confirmation of UTI, the clinician should instruct parents to seek rapid medical assessment (ideally within 48 h) of future febrile disease to ensure that frequent infections can be detected and treated immediately. The choice of therapy depends on several factors, including the age of the child, underlying medical problems, the severity of the disease, the ability to tolerate oral medications, and most importantly local patterns of uropathogens resistance. Initial antibiotic choice of treatment should be according to the sensitivity results or known pathogens patterns with comparable efficacy of oral and parenteral route, for 7 days to 14 days duration. Renal and bladder ultrasonography is the investigation of choice for febrile UTI, and voiding cystourethrography should not be performed routinely unless indicated. Conclusion: This review summarizes all the recommendations related to UTIs in the pediatric population. Due to the lack of appropriate data, further high-quality studies are required to improve the level and strength of recommendations in the future.

Ketamine is illegally used as a recreational drug in many Asian countries. Long-term ketamine abusers often develop irritable bladder symptoms that gradually develop into more severe urinary frequency and urgency and eventually into a painful ulcerated bladder. These patients typically have reduced functional bladder capacity, increased bladder sensation, detrusor overactivity, severe urgency, urinary incontinence, and bladder contracture. Ketamine metabolites can cause severe inflammation of the urothelium, urothelial barrier deficits, vascular endothelial fibrinoid changes, increased oxidative stress, and bladder wall fibrosis. A decrease in bladder compliance, urinary tract infection, severe bladder pain with a full bladder, and painful micturition are also common symptoms. Finally, with continued abuse of ketamine, hydronephrosis, ureteral stricture, vesicoureteral reflux, and renal failure may develop. Cessation of ketamine is the mainstay of treatment. Lower urinary tract symptoms usually relapse if patients reuse ketamine after stopping. In cases of severe ketamine cystitis, only augmentation enterocystoplasty can relieve bladder pain and restore normal lower urinary tract function. This article reviews the underlying pathophysiology, clinical characteristics, and management of ketamine cystitis.

Background The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear. Methods We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation. Results We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG. Conclusions Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

Highlights: 1. In patients younger than one year old, cystitis was more frequent in boys. Meanwhile, in patients aged 1-5, girls were more frequent in pyelonephritis and cystitis. 2. In pyelonephritis, all patients had fever, followed by diarrhea and lethargy. 3. Urinary symptoms, such as dysuria and hematuria, were more frequent in cystitis than in pyelonephritis. Abstract Introduction: Urinary tract infection (UTI) is a common infection in children. Prompt diagnosis and treatment of this infection are important to prevent further damage to the kidney. This study aimed to examine the clinical profile of children with pyelonephritis and cystitis in Dr. Soetomo General Academic Hospital, Surabaya. Methods: This was a descriptive study conducted in Dr. Soetomo General Academic Hospital, Surabaya, from June 2013 until December 2015, using secondary data and presented by percentage. Samples included in this study were children aged two months to five years old with UTI as a primary or secondary diagnosis of diarrhea and had urine culture results ≥ 105 CFU/ml. Results: There were 30 patients with pyelonephritis and 27 patients with cystitis. The prevalence of pyelonephritis was 0.285% and of cystitis was 0.247%. In pyelonephritis patients younger than one-year-old, boys and girls were equal. However, boys (60%) were more frequent in cystitis patients. In both pyelonephritis and cystitis patients aged 1-5, girls were more frequent (56.3%; 64.7%). In pyelonephritis patients, all patients were found with fever, followed by diarrhea (60%) and lethargy (56.7%) as the two most common symptoms. The two most common symptoms in cystitis patients were lethargy (44.4%) and irritability (33.3%). Urinary symptoms, such as dysuria and hematuria, were more frequent in cystitis (11.1%; 7.4%) patients than in pyelonephritis patients. Conclusion: Boys were more frequent to suffer urinary tract infections. Systemic symptoms were frequently found in pyelonephritis patients, while urinary symptoms were more frequent in cystitis patients.

In non-muscle invasive bladder cancer, Bacillus Calmette–Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations.

The urinary system, primarily responsible for the filtration of blood and waste, is affected by several infectious and inflammatory conditions. Focusing on the lower tract, this review outlines the physiological and immune landscape of the urethra and bladder, addressing key immunological and microbiological aspects of important infectious/inflammatory conditions. The conditions addressed include urethritis, interstitial cystitis/bladder pain syndrome, urinary tract infections, and urosepsis. Key aspects of each condition are addressed, including epidemiology, pathophysiology, and clinical considerations. Finally, therapeutic options are outlined, highlighting gaps in the knowledge and novel therapeutic approaches.

Introduction: Due to its chemical properties, functional responses to nitric oxide (NO) are often difficult to examine. In the present study, we established a method to produce NO in an aqueous solution and validated its capacity to evoke functional responses in isolated rat bladders. Furthermore, we compared the NO responses to the commonly used NO donor sodium nitroprusside (SNP). We also investigated the impact of ongoing inflammation on the involvement of soluble guanylate cyclase (sGC) dependent signaling in NO relaxation.Methods: A setup to produce an aqueous NO solution was established, allowing the production of an aqueous solution containing a calculated NO concentration of 2 mM. Sixty male Sprague-Dawley rats received either no treatment (controls) or cyclophosphamide (CYP; 100 mg*kg−1 i.p., 60 h prior to the experiment) to induce experimental cystitis. Bladder strip preparations were mounted in organ baths and studied at basal tension or pre-contracted with methacholine (3 μM). Aqueous NO solution (40–400 μL; 2 mM corresponding to 4–40 μM) or SNP (1–1,000 μM) was added cumulatively in increasing concentrations. Relaxation to aqueous NO was also studied in the presence of the sGC inhibitor ODQ (0.25–25 μM). The expression of sGC was investigated by immunohistochemical analysis.Results: The NO solution caused functional relaxations in both controls and inflamed bladder preparations. NO-induced relaxations were significantly greater in inflamed bladder strips at basal tension, whereas no differences were seen in methacholine pre-contracted strips. In the presence of the sGC inhibitor ODQ in a high concentration, the NO-evoked relaxations were abolished in both control and inflamed preparations. At a lower concentration of ODQ, only NO relaxations in inflamed preparations were attenuated. Immunohistochemical analysis showed that sGC was expressed in the detrusor and mucosa, with a significantly lower expression in the inflamed detrusor.Conclusion: In the present study, we found that aqueous NO solution induces relaxation of the rat detrusor by activating soluble guanylate cyclase in both control and inflamed bladder strips. Induction of inflammation conceivably leads to decreased sGC expression in the detrusor, which may explain the different susceptibility towards inhibition of sGC in inflamed versus control tissue. The use of an aqueous NO solution should be further considered as a valuable complement to the pharmacological tools currently used.

ABSTRACT Recurrent cystitis is a common disease in women, mainly due to uropathogenic Escherichia coli (UPEC). For decades, typing methods now considered obsolete suggested that relapse by the same clone is dominant over reinfection, most UPEC strains being otherwise fully susceptible to antibiotics. We aimed to update these data. Thanks to a prospective study over 17 months, we recruited 323 women with cystitis. Of these, 251 of them had sporadic infection and 72 had recurrence, with 2 to 9 episodes per patient for a total of 131 UPEC isolates and 145 UPEC pairs at patient level. Phylogroups B2 (52.4%) and D (14.1%) were overall dominant, as expected due to their particular urovirulence. CH typing identified 119 distinct profiles with no CH type particularly associated with recurrence. Relapse was attested by CH typing for only 30.6% (22 out of 72), with very diverse situations ranging from all episodes due to the same clone to alternating reinfections and relapses. Next-generation sequencing confirmed the clonality for all but two of the 145 UPEC pairs. Antibiotic resistance was common for recurrent cystitis isolates (only 25 [17.2%] out of 145 UPEC pairs were fully susceptible), allowing us to predict UPEC clonality. Indeed, antibiotic susceptibility profile matched CH typing for 104 (71.7%) pairs. Finally, we demonstrated a large genetic diversity among UPEC isolates responsible for cystitis in women, even in cases of recurrence for which reinfection appeared dominant over relapse. Recurrent cystitis appears to be a heterogeneous disease requiring tailored treatment and prevention. IMPORTANCE More than half of women will experience cystitis during their lifetime. Among these women, 25% will experience a second episode within the following 6 months. It is epidemiologically important to discriminate relapses from reinfections. Relapse identification relies on long and laborious methods and might influence treatment. Therefore, the designation of time- and cost-effective strategies for this goal is of particular interest. Our work suggests using CH typing and antibiotic susceptibility profiles to type Escherichia coli, the main uropathogen.

Abstract Background Urinary tract infection (UTI) is particularly common in young women and the elderly. The Emergency Medical Services (EMS) in Copenhagen, Denmark can be reached by calling either of two dedicated telephone lines: 1–1-2 in case of an emergency and 1813 during general practitioner’s (GP) out-of-office hours (OOH). This study investigated characteristics of patients with symptoms of UTI calling the Copenhagen EMS and the response they received. Methods A retrospective observational cohort study was conducted in which 7.5 years of telephone data on UTI from the EMS in Copenhagen were analyzed. Descriptive statistics and multinomial logistic regression were used to analyze patient characteristics, the timing of the incident and response. Patients’ age and gender were assessed and the use of urinary catheters, the timing of the incident, and the impact on the response were evaluated. Results A total of 278.961 calls were included (78% female, mean age 47), with an average of 120 patients with UTI symptoms calling each day. Most people contacted the 1813-medical helpline (98%) and of those, the majority were referred to the emergency department (ED)(37%). Patients were more likely to be referred to the ED during the weekend compared to a weekday and less likely during OOH compared to in-office hours (IH). Patients with a urinary catheter were more likely to receive specialized care referred to as ‘other’. For the smaller proportion of patients calling 1–1-2, most people got a B (urgent) response (1.5%). The most likely response to be given was an A (emergency) or F (non-emergency) response during OOH compared to IH and on weekends compared to weekdays. Patients with a urinary catheter were more likely to receive a D (unmonitored transport) response. Conclusions Since 2015, there was a decrease in 1813 antibiotic prescription rates and a subsequent increase in referral to the ED of UTI patients. Patients were referred less to the ED during OOH as they were likely to be sent to their GP the next day. During the weekend, patients were referred more to the ED for the likely reason that their GP is closed.

We investigated the effect of green tea extract PEGylated gold nanoparticles (P-AuNPs) making use of its targeted and sustained drug delivery against cyclophosphamide (CYP)-induced cystitis. AuNPs were synthesized by reduction reaction of gold salts with green tea extract following the concept of green synthesis. Mostly spherical-shaped P-AuNPs were synthesized with an average size of 14.3 ± 3.3 nm. Pre-treatment with P-AuNPs (1, 10 mg/kg, i.p.) before CYP (150 mg/kg, i.p.) challenge suggested its uroprotective properties. P-AuNPs significantly reversed all pain-like behaviours and toxicities produced by CYP resulting in a decreased aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and creatinine level. P-AuNPs increased anti-oxidant system by increasing the level of reduced glutathione, glutathione-S-transferase, catalase and superoxide dismutase, and reduced nitric oxide production in bladder tissue. Additionally, it attenuated hypokalaemia and hyponatremia, along with a decrease in Evans blue content in bladder tissue and peritoneal cavity. CYP-induced bladder tissue damage observed by macroscopic and histological findings were remarkably attenuated by P-AuNPs, along with reduced fibrosis of collagen fibre in bladder smooth muscles shown by Masson’s trichrome staining. Additionally, alterations in hematological parameters and clinical scoring were also prevented by P-AuNPs suggesting its uroprotective effect.