Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-κB pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-κB signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-κB pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.

General principles of uncomplicated cystitis therapy during pregnancy

Urinary tract infections during pregnancy are associated with severe complications. Earlier initiation of antibiotic treatment for acute uncomplicated cystitis, reduces the various complications.Objective. To assess the effectiveness of fosfomycin in the treatment of acute uncomplicated cystitis during II and III trimester of pregnancy.Material and methods. The study included 74 pregnant women who had acute uncomplicated cystitis in II or III trimesters. All patients received fosfomycin trometamol 3.754 g (equivalent to 3 g fosfomycin) as antimicrobial therapy for acute uncomplicated cystitis. The drug was prescribed to 24 pregnant women in the II, and 50 in the III trimester of pregnancy.Results. After treatment with fosfomycin signs of acute cystitis gone in all patients. At the same time, regression of clinical symptoms was noted during the next days after therapy in 95.9% (n = 71) of cases. Repeated microbiological test of the middle portion of urine was performed 7 days after the end of antibiotic therapy. In 94.6% (n = 70) cases, total elimination of the pathogen was achieved. In 5.4% (n = 4) cases, there was a significant decrease of colonization Follow-up for three months showed the absence of recurrence of acute cystitis in all pregnant women who were included in the study.Conclusion. Fosfomycin is a highly effective drug in the treatment of uncomplicated cystitis during pregnancy.

Clinical Validation of the Greek Version of the Acute Cystitis Symptom Score (ACSS)—Part II

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) is the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different points in time after the start of treatment was demonstrated as well. The age (mean ± SD) of the 53 patients (44.7 ± 17.0 years) and 39 controls (49.3 ± 15.9 years) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p < 0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patients’ self-diagnosis of AC and as a PRO measure tool.

Clinical Validation of the Greek Version of the Acute Cystitis Symptom Score (ACSS). Part II

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) was the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed after ethical approval by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different time points after the start of treatment was demonstrated as well. The age (mean&plusmn;SD) of the 53 patients (44.7&plusmn;17.0) and 39 controls (49.3&plusmn;15.9) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p&amp;lt;0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patient&rsquo;s self-diagnosis of AC and as a PRO measure tool.

Retrospective Review on the Safety and Efficacy of Nitrofurantoin for the Treatment of Cystitis in the Veteran Population With or Without Renal Insufficiency

Background The emergence of antimicrobial resistance in uropathogens has generated interest in the use of nitrofurantoin in controversial populations, such as in males and those with renal dysfunction. The purpose of this study was to compare the efficacy and safety of nitrofurantoin for the treatment of cystitis in males and females with variable degrees of renal dysfunction. Methods A retrospective chart review was conducted in adult patients who received nitrofurantoin for acute cystitis in the outpatient setting. The primary outcome was clinical cure compared between males and females and across various renal function groups (creatinine clearances [CrCl] &gt;60 mL/min, 30–60 mL/min, and &lt;30 mL/min) following nitrofurantoin treatment. The secondary outcome was adverse events. Results A total of 446 patients were included, with 278 females and 168 males. The overall clinical cure rate was 86.5% (95% CI, 83.0%–89.4%; n = 386). The clinical cure rate did not vary between genders (odds ratio [OR], 0.6; 95% CI 0.35–1.04; P = .085) or between patients with a CrCl &gt;60 mL/min compared with those with CrCl 30–60 mL/min (OR, 1.01; 95% CI, 0.40–2.44; P = 1). The 1 patient with a CrCl &lt;30 mL/min was not included in the analysis. A history of benign prostatic hyperplasia (OR, 0.5; 95% CI, 0.26–0.99; P = .045) or cirrhosis (OR, 0.21; 95% CI, 0.06–0.82; P = .025) was associated with decreased odds of clinical cure. Adverse events occurred in 2% (n = 9) of patients. Conclusions There was no statistically significant difference in clinical cure with nitrofurantoin between genders or various renal functions.

Catheterization Does Not Improve Course of Disease in Female Patients with Acute Cystitis or Pyelonephritis: Retrospective Analysis of >300 In-Hospital Treated Patients

<b><i>Purpose:</i></b> Females with in-hospital treatment for acute cystitis (AC) or pyelonephritis may benefit from catheterization at admission. <b><i>Methods:</i></b> All female patients with AC or pyelonephritis requiring in-hospital treatment at University Hospital Frankfurt (2004–2019) were retrospectively analyzed. Logistic regression models were used to predict the catheter value. <b><i>Results:</i></b> Of 310 female patients, 40% harbored AC versus 60% pyelonephritis, of whom 62% and 74% received a catheter at admission: C-reactive protein (CRP) and white blood count (WBC) were significantly elevated in AC and pyelonephritis catheter versus no catheter patients (both <i>p</i> &#x3c; 0.05). Time to CRP and WBC nadir did not differ between the AC catheter versus no catheter group (both <i>p</i> &#x3e; 0.05). Conversely, time to CRP nadir was prolonged in pyelonephritis catheter patients. AC and pyelonephritis catheter patients exhibited a prolonged antibiotic treatment and length of stay (LOS, both <i>p</i> &#x3c; 0.05). In multivariable analyses, CRP &#x3e;5 ng/mL was a predictor for receiving a catheter in all patients. In AC, a positive urine culture and fever predicted, respectively, prolonged LOS or antibiotic treatment (all <i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> Risk factors exist with regard to receiving a catheter and prolonged antibiotic treatment or LOS in females with AC or pyelonephritis. A catheter may not accelerate recovery or WBC nadir.

A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection

ABSTRACT In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract.