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To determine the incidence of radiation cystitis on prostate cancer (PCa) patients undergoing pelvic radiotherapy (RT), evaluating the most used management strategies, and identifying potential risk factors associated with the development of this condition. A retrospective analysis was conducted using the PearlDiver Mariner database, containing patient records compiled between 2011 and 2022. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify population and outcomes. We evaluated patients who underwent RT for PCa and subsequently developed radiation cystitis. Primary objective was to determine the overall incidence of radiation cystitis. Furthermore, we investigated its associated risk factors and management. A total of 274,865 PCa patients underwent RT during the study period. Of these, 48,713 (17.7%) experienced hematuria following RT, while 7721 (2.8%) were diagnosed with radiation cystitis. After the diagnosis, 2307 patients (29.9%) received diagnostic or therapeutic endoscopic interventions. Only 59 patients (0.76%) underwent endovascular embolization, while 151 patients (1.95%) required cystectomy. Hyperbaric oxygen therapy, administered to 1287 patients (16.67%), was the only treatment that displayed a significant upward trend. Multivariate logistic regression identified obesity (OR 1.29; 95% CI 1.23-1.35), smoking (OR 1.27; 95% CI 1.22-1.33), and diabetes (OR 1.32; 95% CI 1.26-1.39), as significant risk factors for radiation cystitis (all P -values <.001). Radiation cystitis represents a rare complication after pelvic RT with significant clinical impact. Its incidence has remained stable throughout the study period. The identified risk factors corroborate the pathophysiology of radiation cystitis. Hyperbaric oxygen therapy was the only treatment to show an upward trend during the study period. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTI) are a common problem in childhood. The clinical presentation is variable depending on age and whether there is pyelonephritis or cystitis. UTI are diagnosed by culturing an appropriately collected urine sample. Most children with UTI can be managed safely with oral antibiotics irrespective of whether they have cystitis or pyelonephritis. Following a single UTI a significant proportion of children will develop recurrent UTI and many of these children will have identifiable risk factors. Treating children with recurrent UTI with repeated courses of antibiotics or long term prophylactic antibiotics puts patients at risk of infections with multi-resistant organisms. Furthermore recurrent UTI are also associated with the risk of renal parenchymal damage with long term health implications. It is therefore essential that management of children with UTI focuses not only on early diagnosis and treatment but also on UTI prevention. [ABSTRACT FROM AUTHOR]

The 2024 European Association of Urology guidelines on urological infections provide evidence-based recommendations for the diagnosis, treatment, and prevention of urinary tract infections and male accessory-gland infections. Recommendations emphasise the importance of thorough assessment, antimicrobial stewardship, and individualised treatment approaches to combat antimicrobial resistance and improve patient outcomes. Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) is a typical cystitis-causing organism that can migrate from the vagina to the bladder and cause recurrent cystitis (RC). Few reports have compared the characteristics of urinary and vaginal UPEC in patients with RC. We carried out molecular biological analyses of Escherichia coli (E. coli) strains and their antimicrobial susceptibility to assess the association between urinary and vaginally UPEC. We included E. coli isolated from urinary and vaginal samples at the onset of cystitis in postmenopausal women with RC between 2014 and 2019 in our hospital. Pulsed-field gel electrophoresis (PFGE) was performed using a restriction enzyme (Xba I). These sequences were compared with 17 antimicrobial susceptibilities determined by a micro-liquid dilution method. Multilocus sequence typing (MLST) and classification of extended-spectrum β-lactamase (ESBL) genotypes by multiplex polymerase chain reaction (PCR) were performed on ESBL-producing E. coli. We analyzed 14 specimens (each seven urine and vaginal) from seven patients in total. On PFGE, the similarity of urinary and vaginal E. coli per patient ranged from 89.5 to 100 %, including four patients with 100 % matches. MLST demonstrated that 29 % (4/14 specimens) were strain sequence type 131. Two specimens contained ESBL-producing strains and identified the CTX-M-27 genotype for each specimen. For each patient, antimicrobial susceptibilities between urinary and vaginal E. coli were mostly identical. Thus, urinary- and vaginally-derived E. coli were identical in postmenopausal women with RC. Management targeting both urinary and vaginal UPEC is essential for RC, indicating the importance of a vagina-targeted approach. [ABSTRACT FROM AUTHOR]

We report a case of adenovirus nephritis (ADVN) in a kidney transplant recipient (KTR) occurring within 8 days post-transplantation. The patient, a 35-year-old male, displayed systemic symptoms, high-grade fever, and acute kidney injury (AKI) without signs of hemorrhagic cystitis (HC). Extensive diagnostic workup revealed widespread necrotizing granulomatous inflammation in the allograft, leading to the identification of adenovirus (ADV) via histopathology and polymerase chain reaction (PCR) testing. The source of ADV transmission remained uncertain, raising questions about the potential donor-derived infection. Unlike typical ADVN cases, the patient exhibited no hematuria or urinary symptoms. The case underscores the atypical presentation of ADVN in KTRs, challenging the conventional understanding of its timeline, transmission routes, and associated clinical features. We discuss the diagnostic challenges, histological findings, and management strategies for ADVN, emphasizing the importance of considering this entity in KTRs with unexplained fever and AKI, even in the absence of classical urinary symptoms or hematuria. [ABSTRACT FROM AUTHOR]

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum β-lactamase (ESBL)-producing E. coli , respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli , respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan. [ABSTRACT FROM AUTHOR]

To assess the incidence, cumulative healthcare burden, and financial impact of inpatient admissions for radiation cystitis (RC), while exploring practice differences in RC management between teaching and nonteaching hospitals. We focused on 19,613 patients with a diagnosis of RC within the National Inpatient Sample (NIS) from 2008 to 2014. ICD-9 diagnosis and procedure codes were used. Complex-survey procedures were used to study the descriptive characteristics of RC patients and the procedures received during admission, stratified by hospital teaching status. Inflation-adjusted cost and cumulative annual cost were calculated for the study period. Multivariable logistic regression was used to study the impact of teaching status on the high total cost of admission. Median age was 76 (interquartile range 67-82) years. Most of the patients were males (73%; P <.001). 59,571 (61%) patients received at least one procedure, of which, 24,816 (25.5%) received more than one procedure. Median length of stay was 5 days (interquartile range 2-9). Female patients and patients with a higher comorbidity score were more frequently treated at teaching hospitals. A higher proportion of patients received a procedure at a teaching hospital (64% vs 59%; P <.001). The inflation-adjusted cost was 9207 USD and was higher in teaching hospitals. The cumulative cost of inpatient treatment of RC was 63.5 million USD per year and 952.2 million USD over the study period. The incidence of RC-associated admissions is rising in the US. This disease is a major burden to US healthcare. The awareness of the inpatient economic burden and healthcare utilization associated with RC may have funding implications. [ABSTRACT FROM AUTHOR]

To elucidate the mechanism of Lactobacillus crispatus (L. crispatus) suppositories to prevent patients from recurrent cystitis (RC), independent from viable-Lactobacilli-bacteria- and acid-dependent ones such as hydrogen peroxide and lactate. We used the GAI98322 strain of L. crispatus in all experiments and pH-matched. cell-free culture supernatant of L. crispatus (CFCS) was collected. The growth inhibitory activity and the biofilm formation inhibitory activity of the CFCS against uropathogenic Escherichia coli (UPEC), Extended Spectrum beta (β) Lactamase producing (ESBL+) UPEC , and Pseudomonas aeruginosa (P. aeruginosa) was assessed by agar-disk diffusion tests and crystal violet assay. Also, CFCS was subjected to mass spectrometry to specify ingredients. The CFCS suppressed the proliferation of E. coli , ESBL + E. coli , and P. aeruginosa. Also, the CFCS at a concentration of 40% significantly impeded the biofilm formation of these three bacteria. The aggregation-promoting factor and Lysin was detected from CFCS. The cell-free supernatant from the GAI98322 strain of L. crispatus inhibits the growth/biofilm formation of broad pathogens by aggregation promoting factor and lysin, which may prevent hosts from RC regardless of the antimicrobial resistance of the pathogens and even under pH modulation. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are the most common infection among pregnant women and have been associated with maternal and foetal complications. Antimicrobial exposure during pregnancy is not without risk. International guidelines recommend a single screen-and-treat approach to asymptomatic bacteriuria (ASB); however, this approach has been questioned by recent studies. The aim of this narrative review was to assess the pathophysiology, current risk factors and management of UTI during pregnancy, its impact on pregnancy outcomes, and to develop recommendations on the best use of antimicrobials. PubMed, Cochrane database, and ClinicalTrials.gov. Owing to the physiological changes related to pregnancy, pregnant women are at higher risk of UTI. All types of UTIs combined have been estimated to affect approximately 2% to 15% of women. ASB affects 2% to 7% of pregnant women. Recent studies do not provide good-quality evidence for an association between ASB and acute pyelonephritis if ASB is untreated. There is low-to-moderate–quality evidence that treatment of ASB results in a reduction in the incidence of low birth weight and preterm birth, which justifies screening practices for ASB with only a single urine culture in the first trimester. If the clinician opts for treatment, a short course of β-lactams, nitrofurantoin, or fosfomycin should be favoured. Studies on cystitis during pregnancy are limited. Acute pyelonephritis has been shown to be associated with increased maternal complications and in some studies has also been associated with preterm delivery and low birth weight. Preferred antimicrobials for the management of pyelonephritis are amoxicillin combined with an aminoglycoside, third-generation cephalosporins, or carbapenems. Studies on recurrent UTIs during pregnancy are limited, making it difficult to draw conclusions regarding prophylactic measures. Further research is required to understand the true incidence of ASB-related complications and the benefit and modalities of screening for ASB and to further explore prophylactic measures. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) pose a significant health care burden. Outpatient antibiotic geospatial factors (eg, geographic prescribing and geographic resistance) may be associated with inpatient outcomes. This study examined the relationship between these factors, severe UTI, and hospitalization for severe UTI. The first cohort included hospitalized, female, Medicare beneficiaries, aged >50 years. The primary outcome was severe UTI (defined as CSS diagnosis code of 159 with an APR-DRG severity of illness code of 3 or 4). The association between geospatial first-line prescribing (FLP) and severe UTI was assessed. The second cohort examined the association between these geospatial FLP and risk of hospitalization with severe UTI. Multivariable regression was used to produce adjusted odds ratios and adjusted risk ratios. In the first cohort (n = 14,474), low FLP was not associated with severe UTI (P =.87) in univariable analysis. In multivariable analysis, low FLP was associated with severe UTI was (aOR: 1.08 [95% CI 1.00, 1.16]). In the second cohort (n = 2,972,174), the admission rate was 47.0 and 49.8 per 10,000 (low FLP vs high FLP, respectively [ P <.001]). The aRR for admission was 1.26 (95% CI 1.14, 1.39) in areas with low FLP. This study suggests that geospatial antibiotic factors may influence inpatient outcomes in women aged >50 with UTI. Further research is needed to corroborate our findings. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have changed the landscape of advanced cancer treatment. However, immune checkpoint inhibitors can trigger effector T cells against self-antigens as well as tumor antigens, resulting in immune-related toxicities in normal organs, referred to as immune-related adverse events (irAEs). A 56-year-old man with undifferentiated gastric carcinoma received sintilimab plus paclitaxel and tegafur therapy. After five cycles of treatment, the patient was referred to the hospital for sudden onset urinary frequency, micturition pain, and urinary incontinence. Cystoscopy revealed the entire bladder mucosa was red and edematous but there was no evidence of tumor. Oral administration of Chai-Ling-Tang (Sairei-To) alleviated lower urinary tract symptoms (LUTS). Histological analysis revealed numerous infiltrates of CD3-positive and CD8-positive cells into the urothelium but no atypia, indicating a diagnosis of immune-related cystitis. Interestingly, the urothelial epithelium infiltrated by lymphocytes and subepithelial inflammatory cells strongly expressed cell boundary PD-L1. The dose of Chai-Ling-Tang was maintained and stopped 2 months later without recurrence of LUTS. Since recovering from cystitis, the patient remains alive with no disease progression. This report shows that Chai-Ling-Tang is safe and effective for treating immune-related cystitis. The detailed mechanism of action requires further investigation. [ABSTRACT FROM AUTHOR]

Urinary tract infections are amongst the most common bacterial infections. They can occur in either an uncomplicated host setting, where there is no underlying structural or functional abnormality of the patient's genitourinary tract, or complicated, where there is. For the latter, common predisposing factors are the presence of a foreign body, including urinary catheter, or disruption of normal urinary flow by obstruction or retention. Bacteria vary widely in their ability to successfully invade the urinary tract; the vast majority of such infections being due to a small number of species. The route is usually ascension from the urethra. Certain uropathogenic strains of Escherichia coli are the most proficient as measured by their frequency of being the identified cause. Such strains display a number of virulence factors which enable them to occupy this niche – which with increasing understanding, may promote different methods of treating. Other species are often implicated only in the presence of an underlying urological abnormality. The presence of a urinary catheter, or other urine drainage device, provides a ready scaffold for organisms to develop a biofilm, which in turn shields them from being eradicated successfully. Renal calculi similarly can be linked to biofilm production. [ABSTRACT FROM AUTHOR]

Glycosaminoglycan (GAG) replenishment therapy consists of the instillation of GAG solutions directly in the bladder to alleviate Bladder Painful Syndrome/Interstitial Cystitis (BPS/IC). However, several issues were reported with this strategy because the GAG solutions are rapidly eliminated from the bladder by spontaneous voiding, and GAG have low bioadhesive behaviors. Herein, GAG nanomaterials with typical flattened morphology were obtained by a self-assembly process. The formation mechanism of those nanomaterials, denoted as nanoplatelets, involves the interaction of α-cyclodextrin cavity and alkyl chains covalently grafted on the GAG. Three GAG were used in this investigation, hyaluronan (HA), chondroitin sulfate (CS), and heparin (HEP). HA NP showed the best anti-inflammatory activity in an LPS-induced in vitro inflammation model of macrophages. They also exhibited the best therapeutic efficacy in a BPS/IC rat inflammation model. Histological examinations of the bladders revealed that HA NP significantly reduced bladder inflammation and regenerated the bladder mucosa. This investigation could open new perspectives to alleviate BPS/IC through GAG replenishment therapy. [Display omitted] • Bladder Painful Syndrome/Interstitial Cystitis is a chronic disease. • Glycosaminoglycan solution administered in the bladder is the first-line treatment of BPS/IC. • However, intravesical instillation is limited by rapid drug elimination. • Herein, we demonstrated that hyaluronan particles that have a typical flat morphology significantly reduce inflammation. • This investigation could open opportunities for efficient intravesical drug delivery. [ABSTRACT FROM AUTHOR]

BK virus associated hemorrhagic cystitis(BKV-AHC) is a serious complication observed after allogeneic stem cell transplantation and the current therapeutic options are scarce with substantial renal side effects. Although the guidelines recommend intravenous cidofovir application with caution to nephrotoxicity, there are few studies which investigated intravesical administration and reported similar therapeutic results with less renal side effects. Methods: We administered low dose, daily and consecutive (75 mg/day, for 5 days) intravesical cidofovir to 25 patients with BKV-AHC that developed after (ASCT). Results: The response rate in our cohort was 92% and relapse was not encountered in 84% of the patient population during one year of follow-up. The median BK urine viral load significantly decreased from 260,000,000 IU/mL to 53,000,000 IU/mL after a week of treatment (p = 0.0001). Rise in serum creatinine was observed in 5 patients during treatment and post-treatment nephrotoxicity was seen in only 1 patient. Conclusions: Daily low dose intravesical cidofovir might be an effective treatment option for BKV-AHC after ASCT with favorable less systemic side effects. [ABSTRACT FROM AUTHOR]

A small-colony variant (SCV) of carbon dioxide-dependent Escherichia coli was isolated from a patient with acute bacterial cystitis. After the urine sample was inoculated on 5% sheep blood agar and incubated overnight at 35 °C in ambient air, no colony formation was observed. However, after overnight incubation at 35 °C in 5% CO 2 -enhanced ambient air, numerous colonies were obtained. We failed to characterize or identify the SCV isolate using the MicroScan WalkAway-40 System because the isolate did not grow in the system. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing were useful for identifying this SCV isolate. Genome sequencing analysis of the isolates revealed the presence of an 11-bp deletion mutation leading to premature translational truncation in the carbonic anhydrase gene, can, and the presence of 10 known antimicrobial resistance genes. The results of the antimicrobial susceptibility tests performed under CO 2 -enhanced ambient air were consistent with the presence of antimicrobial resistance genes. Our results also showed that Can is important to grow E. coli in ambient air, and that antimicrobial susceptibility testing of carbon dioxide-dependent SCVs should be performed in 5% CO 2 -enhanced ambient air. A revertant strain was obtained by passaging the SCV isolate, but the deletion mutation in can remained. To the best of our knowledge, this is the first case in Japan of acute bacterial cystitis caused by carbon dioxide-dependent E. coli with a deletion mutation in can. [ABSTRACT FROM AUTHOR]

Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI). To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies. MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials. RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care. We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD. We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7–5.5; Bayesian p-value (p B) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1–5.8; p B = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3–13.9; p B = 0.0003). Conversely, they decreased overall antibiotic use by 63%. Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1–10.8; p B = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3–2.0; p B = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis. Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate office flexible cystoscopy findings in the evaluation and management of postmenopausal women with recurrent urinary tract infections (RUTIs).Methods: An IRB-approved, prospectively maintained database of women evaluated for RUTIs at a tertiary care center was retrospectively reviewed by an independent investigator for flexible cystoscopy (FC) findings and related treatment decisions over three consecutive years. Data reviewed in the electronic medical record (EMR) included demographics, UTI history, history of diabetes, hormone replacement therapy (HRT), prior urological surgeries, sexual activity, coital antibiotic prophylaxis use, urine culture findings, antibiotic resistance/allergies, cystoscopy, and treatment plan.Results: Between 2017 and 2019, 113 consecutive postmenopausal women, mostly Caucasian, underwent flexible office cystoscopy to complete their RUTI evaluation. Eighty-four women (74%) had abnormal cystoscopy findings. The rate of overall abnormal findings on cystoscopy increased yearly, including findings of trigonitis (p = 0.022). Other abnormal cystoscopy findings, as well as post-evaluation treatment plans, did not significantly differ over time. Trigonitis was the most common (67%) finding on cystoscopy. RUTI management included exposed urethral/bladder mesh removal and/or electrofulguration of chronic cystitis areas.Conclusions: Flexible cystoscopy, as an office diagnostic procedure, can provide valuable information of underlying etiology of RUTIs and allow directed management. [ABSTRACT FROM AUTHOR]

• tFNA-Que can alleviate radiation-induced oxidative stress and inflammation. • tFNA-Que presents a straightforward and efficient synergistic delivery nano-system. Radiation cystitis (RC) has impacted millions globally with high morbidity and a dearth of effective strategies. Earlier research indicated that quercetin (Que) could alleviate radiation-induced bladder damage. However, Que's limited application arises from issues such as poor water solubility, rapid degradation, and low oral bioavailability. To address these challenges, a nano-system, named tFNA-Que, has been developed for Que delivery, utilizing the tetrahedral framework nucleic acid (tFNA). Due to the anti-inflammatory, antioxidant, and delivery capabilities of tFNA, it is purposefully designed as an efficient carrier for delivering Que. The tFNA-Que formulation exhibits an easily synthesized structure, stable performance, sustained release, good water solubility, robust cellular internalization ability, desirable biocompatibility, and biosafety. As a result, tFNA-Que can alleviate radiation-induced oxidative stress and inflammation while promoting angiogenesis in RC. In summary, the synthesis of tFNA-Que presents a straightforward and efficient synergistic delivery nano-system, making it as a promising candidate for RC treatment. [ABSTRACT FROM AUTHOR]

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Although the results on acute and late toxicity of ultrahypofractionation are encouraging, data on safety in prostate cancer patients with a medical history of transurethral resection of the prostate (TURP) or adenomectomy remain scarce, especially in cases of repeated procedures. The aim of the present study was to report on long-term toxicities after stereotactic body radiotherapy (SBRT) of prostate cancer patients with previous surgical treatment of benign prostatic hyperplasia. Among 150 patients treated with SBRT (median dose 36.25 Gy in five fractions) realised from 2014 to 2019 in a single-centre institution, data of 24 men with a history of TURP (n = 19) or adenomectomy (n = 5) were analysed. Repeated TURP was carried out in three patients, with a median time between surgery and SBRT of 54 months. Genitourinary toxicity was assessed using the Common Terminology Criteria for Adverse Events v4.0 grading scale. With a median follow-up of 45 months, 10 of 24 (42%) patients experienced at least one episode of transient haematuria. One patient (4%) with three previous TURP presented a grade 3 acute non-infective cystitis. Late grade 2 and 3 genitourinary toxicities were observed in eight (33%) and four patients (17%) (two treated with adenomectomy, one with multiple TURP and one with a 140 cm3 prostate size), respectively, with no grade ≥4 adverse events. A complete recovery of grade 3 genitourinary toxicities was observed for all patients after hyperbaric oxygen therapy. Prostate SBRT is feasible and well-tolerated in patients with a medical history of surgical treatments of benign hyperplasia. Patients with prior adenomectomy or multiple TURP are at higher risk of developing severe genitourinary toxicity and should be carefully evaluated before SBRT treatments. • Prostate SBRT is feasible and safe in patients with a previous TURP or adenomectomy. • Increased genitourinary toxicity is observed in patients with multiple TURP. • Intraprostatic postsurgical cavity volume is correlated with genitourinary toxicity rate. • HBOT allows significant recovery of genitourinary symptoms after prostate SBRT. [ABSTRACT FROM AUTHOR]

Thymoquinone (TQ), the most prominent constituent of Nigella sativa seeds, essential oil, is reported to possess an organ protective effect via Nrf2 expression and activation of Phase-II antioxidant enzymes. Haemorrhagic cystitis is the sudden onset of haematuria combined with bladder pain and irritable bladder symptoms are the known toxic effects of cyclophosphamide (CYP) chemotherapy. The objective of the present study was to investigate and compare the protective effect of thymoquinone (TQ) and thymoquinone nanoparticles (TQ-NP) in the kidney against CYP-induced haemorrhagic cystitis. Primarily, TQ-NP was fabricated by synthesis of N -acetylated chitosan and nanoparticle preparation by the ionic gelation technique. They were characterized by particle size, polydispersive index (PDI), zeta potential, entrapment efficiency (EE), SEM, and dynamic scattering calorimetry (DSC). Moreover, fluorescein isothiocyanate (FITC) labeled NPs were prepared for biodistribution studies. The protective mechanisms of TQ-NP included its anti-inflammatory activity, inhibitory effects on cytokine levels, and protection against the DNA damage in the bladder epithelium. The cystitis was induced in rats by orally administering 200 mg/kg of CYP. The dose-dependent protective effect of the TQ-NP was determined by intravenously administering 1, 2, and 5 mg/kg of the TQ-NP to CYP-treated rats. The present study revealed that the TQ-NP prepared by ionic gelation method provides kidney targeted delivery of TQ as compared to TQ solution. The mean particle size, PDI, and %EE of TQ-NP were 272.6 nm, 0.216, 70.81 ± 0.12% respectively. The zeta potential of thymoquinone-loaded nanoparticles was found to be −20.7 mV and − 22.6 mV respectively before and after lyophilization. SEM study also confirmed the small size and spherical shape. Pharmacokinetic studies revealed the improvement in half-life and prolonged action of the TQ-NP as compared to the TQ solution. Also, TQ-NP administration showed more protection against the characteristic histological alterations in the bladder in comparison to TQ solution. The present study indicates that TQ-NP exerts potent anti-oxidant, DNA protective and cytokine inhibitory activity at considerably lower concentrations as compared to plain TQ solution. The nano formulation of TQ using N -acetylated chitosan provides effective kidney targeted delivery of TQ, which in turn improves its retention and protective efficacy against CYP-induced haemorrhagic cystitis. [ABSTRACT FROM AUTHOR]

Radiation cystitis, a long-term bladder defect due to pelvic radiation therapy, results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. The goal of this study was to identify alterations to the mechanical behavior of the urinary bladder extracellular matrix of a murine model of radiation cystitis, at 3 and 6 months after radiation exposure. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls. These findings coincided with functional bladder changes, including increased number of voids and decreased voided volume. Both mechanical and functional changes were apparent at 3 months post-irradiation and were statistically significant at 6 months, demonstrating the progressive nature of radiation cystitis. Overall, the results of this study indicate that irradiation exposure changes both the mechanical and physiological properties of the bladder. In humans, radiation cystitis results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. This pathology can significantly affect recovery and quality of life for cancer survivors. Gaining knowledge about how alterations to the mechanical behavior of the urinary bladder extracellular matrix can affect urinary function will have a significant impact on this population. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls, in a mouse model of radiation cystitis. These findings were accompanied by functional voiding changes, including increased number of voids and decreased voided volume. The results of this study uncovered that irradiation exposure changes the mechanical and physiological properties of the bladder. [Display omitted] [ABSTRACT FROM AUTHOR]

Abelmoschus manihot (L.) Medik. (A. manihot) is a traditional Chinese herbal medicine with a variety of pharmacological properties. It was first recorded in Jiayou Materia Medica dating back to the Song dynasty to eliminate urinary tract irritation by clearing away heat and diuretic effect. However, its pharmacological action on urinary tract infections has not been investigated. The present study aims to evaluate the anti-inflammatory activity of A. manihot on a mouse model of lipopolysaccharide (LPS)-induced cystitis. The results showed that A. manihot decreased white blood cell (WBC) count in urine sediments of the cystitis mice, alleviated bladder congestion, edema, as well as histopathological damage, reduced the expression levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β simultaneously. Moreover, A. manihot administration significantly downregulated the expression levels of TLR4, MYD88, IκBα, p-IκBα, NF-κB p65, and p-NF-κB p65 in LPS-induced cystitis mice. These findings demonstrated the protective effect of A. manihot against LPS-induced cystitis, which is attributed to its anti-inflammatory profile by suppressing TLR4/MYD88/NF-κB pathways. Our results suggest that A. manihot could be a potential candidate for cystitis treatment. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder inflammation characterized by the main symptoms of urinary frequency, urgency, and pelvic pain. The hypersensitivity of bladder afferent neurons is considered a significant pathophysiologic mechanism in IC/PBS. Serotonin (5-HT, 5-hydroxytryptamine) receptors are known to be involved in the regulation of the micturition reflex and hyperalgesia, but the effect of 5-HT receptors on cystitis remains unknown. In this study, a rat model of interstitial cystitis induced by intraperitoneal injection of cyclophosphamide (CYP) was used to investigate the role of 5-HT receptors on cystitis. The histology and urodynamics exhibited chronic cystitis and overactive bladder in CYP-treated rats. Notably, among 5-HT1A, 5-HT2A and 5-HT7 receptors, the expression of 5-HT2A receptor was significantly increased in bladder afferent neurons in CYP-treated rats. Intrathecal administration of the 5-HT2A receptor antagonist M100907 could alleviate bladder overactivity and hyperalgesia in CYP-induced cystitis rats. Neuronal calcium imaging of bladder afferent neurons revealed increased calcium influx induced by the 5-HT2A receptor agonist or capsaicin in cystitis rats, which could be inhibited by M100907. Moreover, RNA sequencing indicated that differentially expressed genes were enriched in inflammation-related pathways and cellular calcium homeostasis. These findings suggest that the 5-HT2A receptor is involved in the hypersensitivity of bladder afferent neurons in CYP-induced cystitis, and M100907 could alleviate bladder overactivity and hyperalgesia in CYP-induced cystitis by inhibiting neuronal hypersensitivity in the afferent pathways. The 5-HT2A receptor may be a potential therapeutic target for the treatment of IC/BPS. • The expression of the 5-HT2A receptor was significantly upregulated in L6-S1 DRG in CYP-induced cystitis rats. • 5-HT2A receptor antagonist M100907 could alleviate bladder overactivity and hyperalgesia in cystitis rats. • M100907 inhibited calcium influx induced by capsaicin or the 5-HT2A receptor agonist in bladder afferent neurons. • RNA sequencing indicated that DEGs were enriched in inflammatory-related pathways and intracellular calcium homeostasis. [ABSTRACT FROM AUTHOR]

• Revealing that IGFBP1 and Umod are characteristic genes of cystitis; • Clarified the new mechanism by which IGFBP1 stabilizes Umod expression through m6A modification; • Overexpression of Umod and IGFBP1 genes could suppress cell apoptosis; • As confirmed, IGFBP1 inhibits the generation of pro-inflammatory factors by suppressing the NF-κB and ERK signaling pathways; • Established a rat cystitis model for in vivo mechanism verification. Cystitis is a common disease closely associated with urinary tract infections, and the specific mechanisms underlying its occurrence and development remain largely unknown. In this study, we discovered that IGFBP1 suppresses the occurrence and development of cystitis by stabilizing the expression of Umod through m6A modification, inhibiting the NF-κB and ERK signaling pathways. Initially, we obtained a bladder cystitis-related transcriptome dataset from the GEO database and identified the characteristic genes Umod and IGFBP1. Further exploration revealed that IGFBP1 in primary cells of cystitis can stabilize the expression of Umod through m6A modification. Overexpression of both IGFBP1 and Umod significantly inhibited cell apoptosis and the NF-κB and ERK signaling pathways, ultimately suppressing the production of pro-inflammatory factors. Finally, using a rat model of cystitis, we demonstrated that overexpression of IGFBP1 stabilizes the expression of Umod, inhibits the NF-κB and ERK signaling pathways, reduces the production of pro-inflammatory factors, and thus prevents the occurrence and development of cystitis. Our study elucidates the crucial role of IGFBP1 and Umod in cystitis and reveals the molecular mechanisms that inhibit the occurrence and development of cystitis. This research holds promise for offering new insights into the treatment of cystitis in the future. [ABSTRACT FROM AUTHOR]

Background: The Proteeae group (i.e., Proteus species, Morganella morganii, and Providencia species) frequently causes urinary tract infections (UTIs) and is generally resistant to nitrofurantoin. Proteeae species can produce urease, which can increase urine pH.Objective: Our aim was to determine whether higher urine pH in the emergency department is associated with nitrofurantoin resistance.Methods: A single health system database of emergency department patients aged 18 years and older who received urinalysis between April 18, 2014, and March 7, 2017, was examined using χ2 test and multivariable regression analysis.Results: Of 67,271 urine samples analyzed, 13,456 samples grew a single bacterial species. Urine cultures growing the Proteeae group were associated with significantly more alkaline urine than other bacteriuria cultures (odds ratio [OR] 2.20, 95% confidence interval [CI] 2.06-2.36; p < 0.001). The Proteeae species represented 4.4% of urine samples at pH 5-7, 24.4% at pH 8-9, and 40.0% at pH 9. At urine pH 5-7, 80.4% of urine samples were sensitive to nitrofurantoin; however, this percentage decreased to 66.1% for urine pH 8-9 and 54.6% for urine pH 9. Nitrofurantoin had the highest OR (2.10, 95% CI 1.85-2.39) among cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole for bacteriuria sensitive to those antibiotics at urine pH 5-7. At urine pH 8-9 and 9, nitrofurantoin had the lowest OR among the antibiotics: 0.48 (95% CI 0.42-0.54) and 0.31 (95% CI 0.24-0.40), respectively (p < 0.001 for both).Conclusions: Urine pH of 8 or higher is associated with high rates of nitrofurantoin resistance. [ABSTRACT FROM AUTHOR]

To compare the effectiveness of 5 versus 7 days of nitrofurantoin treatment for urinary tract infection (UTI) in women with diabetes. Data were collected retrospectively from Dutch general practitioners between 2013 and 2020. Nitrofurantoin prescriptions with a duration of 5 days (5DN) or 7 days (7DN) in women with diabetes were included. Inverse propensity weighting was performed to calculate adjusted risk differences (RD) for treatment failure within 28 days. Secondary outcomes were 14-day treatment failure, severe treatment failure and 28-day treatment failure in defined risk groups. Nitrofurantoin was prescribed in 6866 episodes, 3247 (47.3%) episodes with 5DN and 3619 (52.7%) episodes with 7DN. Patients in the 7DN group had more co-morbidities, more diabetes-related complications and were more insulin-dependent. There were 517/3247 (15.9%) failures in the 5DN group versus 520/3619 (14.4%) in the 7DN group. The adjusted RD for failure within 28 days was 1.4% (95% CI –0.6 to 3.4). We found no clinically significant difference in treatment failure in women with diabetes with UTI treated with either 5DN or 7DN within 28 days. A 5-day treatment should be considered to reduce cumulative nitrofurantoin exposure in DM patients. [ABSTRACT FROM AUTHOR]

• Urinary tract infections (UTIs) have not been previously characterized in cystic fibrosis (CF) patients. • Diabetes, distal intestinal obstruction syndrome, and nephrolithiasis were all associated with increased risk of UTIs. • UTIs in CF patients were less likely to be caused by Gram-negative rods and more likely to be caused by Enterococcus faecalis. Improved understanding of non-respiratory infections in cystic fibrosis (CF) patients will be vital to sustaining the increased life span of these patients. To date, there has not been a published report of urinary tract infections (UTIs) in CF patients. We performed a retrospective chart review at a major academic medical center during 2010-2020 to determine the features of UTIs in 826 CF patients. We identified 108 UTI episodes during this period. Diabetes, distal intestinal obstruction syndrome (DIOS), and nephrolithiasis were correlated with increased risk of UTIs. UTIs in CF patients were less likely to be caused by Gram-negative rods compared to non-CF patients and more likely to be caused by Enterococcus faecalis. The unique features of UTIs in CF patients highlight the importance of investigating non-respiratory infections to ensure appropriate treatment. [ABSTRACT FROM AUTHOR]

Most old, intact male dogs usually have prostate disorders, especially benign prostatic hypertrophy and prostatitis with or without abscesses, and concurrent cystitis. The successful treatment of dogs with prostatitis concurrent with cystitis has relied on choosing an appropriate antimicrobial drug based on a bacterial culture and drug sensitivity testing. The objective of the study was to compare the prevalence of bacterial species and results of drug susceptibility testing of bacteria that were isolated from the prostatic fluids and urine samples that were collected from dogs with both prostatitis and cystitis. One hundred and sixty intact male dogs, who presented with both diseases, were recruited for the study. The disease diagnoses were based on clinical history notes, physical examinations, abdominal ultrasonography, prostatic fluid cytology, urinalysis and bacterial cultures from both prostatic fluid and urine samples. The bacterial culture results demonstrated that the major species that were detected in either the prostatic fluid or urine samples were Staphylococcus spp., Escherichia coli , Pseudomonas spp., Streptococcus spp., Proteus mirabilis and Klebsiella pneumoniae. Staphylococcus spp. (26.5 %, 43/162) and Escherichia coli (26.1 %, 12/46) were the most prevalent species from the prostatic fluid and urine samples, respectively. Statistical tests revealed that there were no significantly different prevalence levels among the isolated bacteria between the prostatic fluid and urine samples. Imipenem and gentamicin were the most potent antimicrobial drugs tested against the bacterial isolates in the present study. However, the administration of imipenem to treat prostatitis and cystitis in dogs was of concern. Interestingly, there were no significant differences in the antimicrobial drug susceptibility trends between the prostatic fluid and urine samples. Based on these results, a urine sample might be considered as an optional sample for bacterial cultures and antimicrobial drug susceptibility testing when it is not possible to collect a prostatic fluid sample. • Bacterial prevalence and antimicrobial drug susceptibility profiles of the urine and prostatic fluid samples of the dog affected by prostatitis and concurrent cystitis were similar. • The urine sample collected from the dog showing concurrent bacterial prostatitis and cystitis could be used for bacterial culture and antimicrobial susceptibility test instead of prostatic fluid sample. • The important causes of bacterial prostatitis and concurrent cystitis in dogs were Staphylococcus spp. and Escherichia coli. [ABSTRACT FROM AUTHOR]

The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data. We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method. A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus , the susceptibility to β-lactams including carbapenems was 40–60%. The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains. [ABSTRACT FROM AUTHOR]

Background: Interstitial cystitis or painful bladder syndrome is a chronic disorder that presents an unknown etiology, with no generally accepted treatment. Although there is no gold standard treatment, transcranial direct current stimulation (tDCS) has shown efficacy in several chronic pain syndromes with decrease in pain, and improved functionality and mood. tDCS could be a safe, ease to use, and low-cost complementary intervention for patients with interstitial cystitis.Aim: This study will investigate the effects of a tDCS protocol on pain, functionality, and mood in patients with interstitial cystitis.Methods: A randomized controlled clinical trial with two arms. Women will be randomized into two groups: active or sham. Anodal tDCS over the primary motor cortex will be performed for 5 consecutive days with an intensity of 2 mA for 20 min. Participants will be evaluated five times: 1 week before intervention; on the 5th day of tDCS; and 1, 6, and 12 months after the last day of tDCS. The outcomes will be assessed using the numeric rating scale, McGill pain questionnaire, positive and negative affect scale, international consultation on incontinence questionnaire for female lower urinary tract symptoms, Hamilton anxiety scale, six-minute walk test, patient global impression of change, and voiding diary.Discussion: Only the active group will be expected to show decreased pain. The results of this trial will be the first step in the use of neuromodulation in interstitial cystitis and will provide additional data to support new studies with tDCS. [ABSTRACT FROM AUTHOR]

Objective: To identify the incidence of radiation-induced urologic complication requiring procedural intervention following high-dose radiotherapy for cervical carcinoma, and to identify predictors of complication occurrence.Materials and Methods: We performed a retrospective chart review of cervical cancer patients undergoing radiotherapy with primary focus on procedural complications (Clavien-Dindo ≥ III). Clinical data were collected including radiation dose, procedure performed, timing of complication, and need for additional procedures. Univariate and multivariate logistic regression modeling was performed to assess predictive value of demographic and clinical variables.Results: A total of 126 patients with FIGO stage 1A2-4B cervical cancer were included in study analysis, with 18 patients experiencing procedural complication (14.3%). A total of 22 complications were identified, representing an average of 1.2 complications per patient with complication. The most common complications were ureteral stricture and radiation cystitis. The most common nononcologic procedures performed in the treatment of these complications were ureteral stenting, percutaneous nephrostomy tube placement, and cystoscopy. Notably, a total of 259 procedures were performed in the treatment of urologic complications, representing 14.4 procedures per patient and 24.6 procedures per patient with ureteral stricture. Logistic regression demonstrated active smoking at the time of diagnosis to be a predictor of procedural complication.Conclusion: Radiotherapy in the treatment of cervical cancer is associated with a high rate of urologic procedural complication. These complications often require numerous procedures and long-term management given their complexity. These findings suggest a need for awareness and plans for multidisciplinary management of urologic complications in this patient population. [ABSTRACT FROM AUTHOR]

• Urinary morbidity after treatment of locally advanced cervical cancer is prevalent. • Bladder dose constraints based on a high level clinical evidence are not available. • EMBRACE I provides prospective morbidity data for analysis in a large cohort. • Individual physician and patient reported urinary endpoints were analysed in EMBRACE I. • Bladder fistula, bleeding and cystitis showed dose–effect with bladder D 2cm3. To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) ≥ 3 cystitis, for G ≥ 2 fistula, bleeding and cystitis, and for EORTC "very much" and "quite a bit" or worse. Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3–120] months. Crude incidence rates for G ≥ 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for "quite a bit" or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D 2cm3 correlated with G ≥ 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain "quite a bit" or worse. An increase from 75 Gy to 80 Gy in bladder D 2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G ≥ 2 cystitis. Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose–effect was established with bladder D 2cm3 , reinforcing the importance of continued optimization during individualized IGABT planning. [ABSTRACT FROM AUTHOR]

Bladder pain syndrome (BPS) is a debilitating disease in humans, particularly women, with patients experiencing chronic, intractable, lower urinary and pelvic pain. Although rodent models have been used, feline idiopathic cystitis (FIC) is a naturally occurring bladder disease of cats that is frequently considered to be the preferred model for BPS. Histologically, FIC is most similar to the non-Hunner BPS subtype. Histology is unnecessary for the clinical diagnosis of FIC but is of great value in elucidating the pathogenesis of this disease so that prevention and therapeutic interventions can be optimized. Further study of the histological features of FIC and BPS is required to determine the significance of Von Brunn's nests, which are invaginations of hyperplastic urothelium that have been associated with irritative bladder stimuli in animals and have been observed in FIC. We review the possible pathogenesis, histopathological similarities and differences between FIC and BPS, and highlight the potential of FIC as a model of BPS. [Display omitted] [ABSTRACT FROM AUTHOR]

Radiotherapy plays a crucial role in the multidisciplinary treatment for malignant pelvic tumors; however, it can unavoidably be delivered to the bladder leading to urothelial inflammation, hypoxia, and formation of secondary bladder wall fibrosis. As a result, chronic radiation cystitis (CRC) can develop characterized by urinary frequency, urgency, bladder pain, and nocturia.; Disruption of the urothelial barrier is closely associated with CRC. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in CRC. The therapeutic potential of AM in-part is thought to be due to its composition of extracellular matrix components that have been shown to be important for modulating inflammation and tissue regeneration in the wound healing process.; Herein, we evaluated ABT in the management of bladder storage dysfunction and female sexual dysfunction in CRC patients. This retrospective study was approved by the local institutional review board committee.; Included patients had CRC that developed >6 months after radiotherapy, were confirmed to be in cancer remission for at least 5 years and were recalcitrant to previous CRC treatments. All patients received ABT comprised of intra-detrusor injection of commercially available 100mg micronized AM (Clarix Flo) diluted in 10ml 0.9% preservative-free sodium chloride.; Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, Female Sexual Function Index (FSFI), visual analog scale (VAS) and SF-12 Health Survey) were assessed at baseline and repeated at 2, 4, 8, 12, 16 and 20 weeks.; Cystoscopy and uroflow were done pre-injection and at 20 weeks. Five consecutive female patients were included with an average age of 64.4 ± 20.1 years and median CRC disease duration of 10 years that was recalcitrant to multiple therapies including anticholinergics (n=5), beta-3 adrenergic agonist (n=5), and botulinum toxin injection (n=5). After ABT, the voiding symptoms as measured by the ICSI, ICPI, BPIC-SS, and OAB scores improved as early as 2 weeks and were maintained up to 20 weeks (Table 1). Voiding volumes improved from 124 ± 21.6 to 330 ± 45.2 at 5 months (Table 2). This corresponded to an improvement in their overall quality of life as measured by the SF-12, improvement in sexual function based on FSFI total score, and improvement in intercourse associated pain based on VAS score (Table 1).; One patient had a urinary tract infection two weeks post injection and was treated with oral antibiotics. No other adverse events related to injections were observed. Multiple therapeutic modalities have been extensively applied for CRC, however there is still a lack of an effective therapeutic method for this disease entity.; Most therapies aim to provide symptomatic relief while not addressing the pathologic process.; The bladder wall experiences inflammation and undergoes remodeling and fibrosis after radiation; hence it is important to provide CRC patients with new therapeutic solutions that will act simultaneously and progressively on multiple different mechanisms to reduce inflammation and bladder fibrosis as well as ameliorate urothelial and vascular damage.; Previous ocular and orthopedic studies have shown AM is able to simultaneously provide a multi-modality effect including reducing inflammation, reverting scar formation, and promoting epithelialization.; In this investigative pilot study, we report improvement in our CRC patients with predominantly bladder storage symptoms and female sexual dysfunction. Future studies would be needed to better clarify the potential role and durability of ABT in the treatment CRC. [ABSTRACT FROM AUTHOR]

The American Cancer Society predicts there will be more than 84,000 new cases of Bladder cancer (BCa) in 2023 in the United States. Many epidemiological and scientific studies have shown that ingesting arsenic through drinking water can be a causative factor for urogenital cancers, especially bladder cancer. Multiple studies have demonstrated an astounding 50-fold increased risk of BCa in patients exposed to arsenic. While studies in animal and cell culture models support that arsenic is a carcinogen, the mechanism of action is not fully understood. Hence, the study aims to investigate the underlying molecular mechanism by which arsenic causes malignant transformation of mice models using a physiological dose of arsenic in BCa patients. Six-week-old male and female C57BL/6 mice were grouped into three groups, and mice were exposed to drinking water containing 0, 30mg/L (mean concentration of arsenic in BCa patients), or 60mg/L of sodium arsenite for six months. A board-certified veterinary pathologist evaluated the lung, liver, bladder, colon, kidneys, and prostate sections for histopathological and molecular analysis. No significant histological differences in the liver, colon, kidney, and prostate of control and arsenic-exposed (30, -60mg/L) mice were seen. However, we observed multifocal areas of moderate type II pneumocyte hyperplasia in the lungs of arsenic-exposed (male and female) mice. More interestingly, bladder hyperplasia and inflammation were seen in arsenic-exposed mice, which was more prominent in female-treated mice than in male or control mice. In our in vitro arsenic-induced bladder cancer model, we observed that induction of MTF1, FOXA2, and ALDH1A1 signaling was responsible for the malignant transformation of normal bladder epithelial cells, and similar results were observed in arsenic-exposed sections of the mice bladder. MTF1, FOXA2, and ALDH1 expression was also observed in the BCa patient cohort exposed to high levels of arsenic compared to the low or unexposed patient cohort. Our preclinical and clinical studies demonstrate that arsenic is a potent carcinogen for bladder carcinogenesis, and the expression of molecular markers differs among arsenic-exposed and low or non-exposed BCa patients. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC), also called painful bladder syndrome (PBS), is 2 to 5 times more common in women than in men, yet its cause and pathogenesis remain unclear. In our study using the cyclophosphamide (CYP)-induced mouse model of cystitis, histological evaluation of the urinary bladder (UB) lamina propria (LP) showed immune cell infiltrations, indicating moderate to severe inflammation. In this study, we noticed a differential expression of a subset of microRNAs (miRs) in the UB cells (UBs) of CYP-induced cystitis as compared to the control. UB inflammatory scores and inflammatory signaling were also elevated in CYP-induced cystitis as compared to control. We identified eight UBs miRs that exhibited altered expression after CYP induction and are predicted to have a role in inflammation and smooth muscle function (miRs-34c-5p, −34b-3p, −212-3p, −449a-5p, −21a-3p, −376b-3p, −376b-5p and − 409-5p). Further analysis using ELISA for inflammatory markers and real-time PCR (RT-PCR) for differentially enriched miRs identified miR-34c as a potential target for the suppression of UB inflammation in cystitis. Blocking miR-34c by antagomir ex vivo reduced STAT3, TGF-β1, and VEGF expression in the UBs, which was induced during cystitis as compared to control. Interestingly, miR-34c inhibition also downregulated ROCK2 but elevated ROCK1 expression in bladder and detrusor cells. Thus, the present study shows that targeting miR-34c can mitigate the STAT3, TGF-β, and VEGF, inflammatory signaling in UB, and suppress ROCK2 expression in UBs to effectively suppress the inflammatory response in cystitis. This study highlights miR-34c as a potential biomarker and/or serves as the basis for new therapies for the treatment of cystitis. [Display omitted] [ABSTRACT FROM AUTHOR]

Corynebacterium species, typically considered contaminants in urine culture, can cause encrusted cystitis (EC), a form of chronic urinary tract infection causing pain, bladder necrosis, renal failure, and death. Delayed diagnosis is common due to its rarity and the fastidious nature of Corynebacterium urealyticum. Reported mostly in elderly and immunocompromised patients, EC is rare in pediatric patients. A female adolescent on high dose steroids developed persistent dysuria after urinary catheterization. Abnormal bladder ultrasound and characteristic cystoscopy led to the diagnosis of EC. Appropriate treatment instituted 4 months from onset of dysuria led to an excellent response. [ABSTRACT FROM AUTHOR]

T lymphocytes play important roles in the skin and mucosal surfaces such as the gut and lung. Until recently the contributions of T cells to mammalian bladder immunity were largely unknown. With newer techniques, including single-cell RNA sequencing and reporter mice, an understanding is emerging of T cell roles in bladder diseases (bacterial infections, bladder cancer, chronic inflammation). In these pathologies, many bladder T cell responses can be harmful to the host through suboptimal clearance of bacteria or cancer cells, or by modulating autoinflammation. Recent findings suggest that T cell behavior might be influenced by resident T cell interactions with the bladder microbiota and other immunostimulants. Thus, regulating bladder T cell functions could emerge as a putative immunotherapy to treat some bladder diseases. During bacterial bladder infections in mammals, the local type 2 T helper (Th2) cell response (important for epithelial repair) can be enhanced. This response can negatively impact on Th1 responses that are important for bacterial clearance. Consequently, bladder infections are not completely cleared and recur. In bladder cancer, a diverse T cell population is recruited into the bladder, including proinflammatory cytotoxic T cells (presumably beneficial) and anti-inflammatory regulatory T cells (presumably detrimental). Immunotherapies directed at either promoting antitumor T cells or depleting immune inhibitory cells or signals are under intensive study. T cells are central to promoting bladder inflammation in interstitial cystitis in patients, as well as in animal models that replicate this bladder disorder. Strategies that aim to Inhibit T cell activity and recruitment to the bladder may be a promising treatment for interstitial cystitis. [ABSTRACT FROM AUTHOR]