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Aim of the study: To evaluate the efficacy of a nutraceutical compound containing Uticlin® (D-mannose, cranberry, bearberry, Olea europaea), inulin, Orthosiphon and Lactobacillus acidophilus, in preventing recurrent urinary tract infections (UTIs) in menopausal women. Material and methods: This was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS). Results: At 6 months of therapy, the reduction in the number of patients with ≥ 2 UTIs was statistically significant (p < 0.05) compared to baseline only in group 1. At 12 months, the number of patients who were disease-free was significantly higher (p < 0.05) in group 1 compared to group 2. Moreover, the improvement of related symptoms was statistically significant (p < 0.05) in group 1, as shown by the reduction in the VAS scale value. Conclusions: In menopausal women, the combination of D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus SGL 11 per os represents a useful therapy for recurrent UTIs in women wanting a natural approach.

Objective: To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens. Summary: The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. Key Messages: Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed.

Background: Non-celiac wheat sensitivity (NCWS) most frequently presents clinically with irritable bowel syndrome (IBS)-like symptoms, although many extra-intestinal manifestations have also been attributed to it. No studies to date have evaluated the presence and frequency of gynecological symptoms in NCWS. Aim: To evaluate the frequency of gynecological disorders in patients with NCWS. Patients and Methods: Sixty-eight women with NCWS were included in the study. A questionnaire investigating gynecological symptoms and recurrent cystitis was administered, and patients reporting symptoms were then examined by specialists. Three control groups were selected: 52 patients with IBS not related to NCWS, 56 patients with celiac disease (CD), and 71 healthy controls. Results: 59% of the patients with NCWS showed gynecological symptoms, a higher frequency than in healthy controls (P = 0.04), IBS controls (P = 0.01) and CD controls (P = 0.02). Menstrual cycle alterations were more frequent in patients with NCWS than in healthy controls (26.5% vs 11.3%; P = 0.03); the patients with NCWS suffered from recurrent vaginitis (16%) and dyspareunia (6%) significantly more frequently than healthy controls. Twenty-nine percent of patients with NCWS reported recurrent cystitis, a finding higher than in the control groups (vs healthy P = 0.0001, vs IBS P = 0.001, vs CD controls P = 0.04). Microbiological examinations were negative in most of the patients with NCWS and recurrent vaginitis or cystitis. During the 1-year follow-up, 46% of patients with menstrual disorders and 36% with recurrent vaginitis reported resolution of symptoms on a wheat-free diet. Conclusions: Patients with NCWS showed a significantly higher frequency of gynecological symptoms and recurrent cystitis than patients with IBS.

A new strategy that takes advantage of the synergism between NMR and LC-HRMS (SYNHMET), and that allows to obtain a unique list of the absolute concentrations of 164 metabolites in urine, is presented. Metabolite identification and quantification by this method in one of the most difficult biofluids to characterize, due to complexity and variability, is more accurate than what can be obtained using the two techniques separately. This result is achieved without the need for chemical reactions to cross-check the data between the two types of spectra, nor the use of analytical standards and calibration curves. The fact that the absolute rather than relative concentration is obtained allows the final dataset to be used to determine a patient's personalized profile. The number of quantifiable metabolites by the application of this method can be expanded in the future with further analysis. We will illustrate the use of SYNHMET in the study of urine samples from healthy subjects, patients with chronic cystitis and bladder cancer.

Contains fulltext : 190548.pdf (Publisher’s version ) (Closed access) Objectives: To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Methods: Review of English literature and evidence-based recommendations by expert consensus. Results: BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. Conclusions: BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials.

Objective: We investigated the efficacy of intravesical instillations of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in patients with bacillus Calmette-Guérin (BCG)-induced chemical cystitis unresponsive to first-line therapies. Patients and methods: We retrospectively reviewed the clinical records of patients with grade 2 BCG-induced chemical cystitis unresponsive to first line therapeutic options performed according to the International Bladder Cancer Group guidelines who underwent intravesical instillations of HA/CS. Bladder pain, urinary urgency, voiding volume and number of voids/24 hours recorded prior to treatment, at the end of the treatment, at six months and at one-year follow-up were recorded and analyzed. Results: The records of 20 patients were identified. All patients underwent eight weekly instillations of HA/CS. Mean baseline visual analogue scale (VAS) scores ± Standard Deviation (SD) for urinary urgency and bladder pain were 7.8 ± 0.5 and 7.2 ± 1.0, respectively. Mean number of voids/24 hours ± SD was 15.4 ± 2.3 and mean urine volume per void ± SD was 85.8 ± 21.0 mL. At the end of the treatment, mean VAS scores ± SD for urgency and pain significantly decreased to 4.7 ± 1.1 and 4.2 ± 0.9, respectively (p < 0.05 in both cases). Mean number of voids/24 hours ± SD decreased to 9.6 ± 1.4 (p < 0.05) and mean urine volume per void ± SD significantly increased to 194.1 ± 59.5 mL (p < 0.05). At six months and one-year followup, all outcome measures remained stable. Conclusions: Bladder instillations of HA/CS provide significant and durable improvement of bladder pain, urinary urgency, urinary volume per void and urinary frequency in patients with refractory BCG-induced chemical cystitis.

Background Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. Methods We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. Results Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II–IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II–IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). Conclusion The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

Objective Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. Materials and methods This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1 st month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. Results Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. Conclusion The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis.

Components of the so-called endocannabinoid system, i.e., cannabinoid receptors, endocannabinoids, as well as enzymes involved in endocannabinoid synthesis and degradation, have been identified both in the gastrointestinal and in the urinary tract. Evidence suggests that the endocannabinoid system is implicated in many gastrointestinal and urinary physiological and pathophysiological processes, including epithelial cell growth, inflammation, analgesia, and motor function. A pharmacological modulation of the endocannabinoid system might be beneficial for widespread diseases such as gastrointestinal reflux disease, irritable bowel syndrome, inflammatory bowel disease, colon cancer, cystitis, and hyperactive bladder. Drugs that inhibit endocannabinoid degradation and raise the level of endocannabinoids, non-psychotropic cannabinoids (notably cannabidiol), and palmitoylethanolamide, an acylethanolamide co-released with the endocannabinoid anandamide, are promising candidates for gastrointestinal and urinary diseases.

We used immunohistochemical detection of the Fos protein to study the neuronal activation in the brain of methoxyfluorane-anesthetized rats after noxious deep somatic or visceral stimulation. The anesthesia was effective in triggering gene induction in many brain regions. Nevertheless, Fos appeared de novo in several brain nuclei following noxious stimulation in anesthetized animals. This could be of clinical relevance, as it suggests that the gas anesthetic does not suppress noxious stimulus-evoked reactivity in brain neurons. Two types of visceronociceptive stimuli were used to compare the effects of a diffuse visceral inflammation (peritoneal inflammation) with those of a more restricted inflammation (urinary bladder inflammation). In the same supraspinal areas, there were very few immunostained neurons in unstimulated controls, whereas Fos-positive cells were slightly more numerous in anesthetized controls and significantly more numerous after noxious stimulation. The peritoneal inflammation induced more Fos-labeled neurons than the restricted visceral stimulation. Labeled cells were found in these cases mainly in the ventrolateral medulla, parabrachial complex, dorsal raphe nucleus, periaqueductal gray, several hypothalamic and thalamic nuclei, amygdaloid complex, and cortex. Altogether these findings indicated that somatic and visceral inputs generally activate the same neuronal groups. However, a separation between the activation of somatic and visceral pathways was found in some brain nuclei, such as the parabrachial complex, hypothalamic, and thalamic nuclei.

Attributable risks (ARs) for bladder cancer were computed in relationship to cigarette smoking, coffee consumption, low intake of vegetables, history of cystitis, and occupation using data from a case-control study conducted in northern Italy between 1985 and 1993. Cases were 431 patients with histologically confirmed bladder cancer, and controls were 491 patients admitted to the same network of hospitals for acute, nonneoplastic, and non-urinary-tract diseases. Overall, the AR estimates were 49% for cigarette smoking, 23% for coffee consumption, 16% for low intake of vegetables, 12% for history of cystitis, and 4% for occupation. These five factors together explained more than 70% of bladder cancer cases in this population. The AR for cigarette smoking was significantly higher among men (56%) than women (17%), whereas coffee consumption, low vegetable intake, and cystitis were more important (but not significantly so) among women. These results suggest that more than 2500 of the 5400 deaths due to bladder cancer in Italy in 1990 could have been prevented by the elimination of cigarette smoking. With some appropriate dietary modification and intervention to prevent urinary tract infections and occupational exposures, this figure could approach 4000 avoidable deaths. Thus, bladder cancer could become a rare cause of death in this population.

BACKGROUND: Urinary tract infection is the most common health problem affecting millions of people each year, mainly caused by a large genetically heterogeneous group of Escherichia coli called uropathogenic E. coli This study investigates the genotypic analysis of E. coli strains isolated from patients with cystitis and pyelonephritis. METHODS: During 2008-2009, 90 E. coli strains were analyzed, consisting of 48 isolates causing pyelonephritis in children and 42 isolates causing cystitis. Having identified the strains by standard methods, they were subtyped by pulsed field gel electrophoresis (PFGE) and their corresponding patterns were compared using dendrogram. RESULTS: Sixty five PFGE profiles were obtained from the genome of E. coli strains by this genotyping method. Thirty six and thirty three patterns were obtained for pyelonephritis and cystitis, respectively. Most strains exhi-bited twelve and thirteen bands and the patterns with eight or nineteen bands had the lowest rate. Genome sizes of the strains were between 1610-4170 kbp. CONCLUSION: With due attention to these results, genetic patterns showed that the strains had different clonalities and it could be suggested in some cases that the strains causing pyelonephritis or cystitis have common patterns and different diseases could be explained by different gene factors.