Blood plasma and urinary biomarkers of oxidative stress in cats with urethral obstruction.

BACKGROUND: This study aimed to investigate variations of the oxidative status in cats affected by urethral obstruction (UO) under Feline Idiopathic Cystitis (FIC) and Bacterial Cystitis (BC), in comparison with a group of healthy subjects. In both groups, the levels of several markers (either direct or indirect) indicative of the oxidative attack and of the antioxidant response were analyzed on plasma and urine samples. In particular, the plasma samples were evaluated for nitric oxide (NO), hydroperoxides derived by reactive oxygen activity (d-ROMs test), superoxide anion (O2-), glutathione peroxidase activity (GPx), superoxide dismutase activity (SOD), and ferric reducing antioxidant power (FRAP test); while on urine the levels of NO, d-ROMs, FRAP, SOD, malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured. Urine of UO patients was also subjected to urine-culture test. RESULTS: The analytical data on plasma showed that UO, independently of the FIC or BC etiology, induced the insurgence of oxidative stress conditions at the systemic level. In the urine of the UO patients, except for SOD that increased, the markers of redox status were markedly decreased due probably their compromised filtration, thus suggesting involvement of renal function (assessed also by the high levels of plasma creatinine and proteinuria) with no oxidative damage of the lower urinary tract. Moreover, the adoption of a novel oxidative stress index' (OSI) allowed to establish, by means of a numerical value, the different degrees of oxidative stress conditions for single UO patients, both in terms of oxidative attack and antioxidant response. CONCLUSIONS: Feline urethral obstruction, induced by Idiopathic Cystitis and Bacterial Cystitis, causes oxidative stress conditions at the systemic level that do not interest the lower urinary tract. Despite to the high variability of the profiles of oxidative stress indexes both in healthy and UO patients, the determination of OSI made possible the evaluation of their single degrees of oxidative stress. Possibly the results of this investigation can be compared with those of correspondent pathologies both in humans and in other animal species.

Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children.

BACKGROUND: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long-term renal sequelae. If non-invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow-up could potentially be individualized. This is an update of a review first published in 2015. OBJECTIVES: The objectives of this review were to 1) determine whether procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other. SEARCH METHODS: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews through to 17th December 2019 for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We only considered published studies that evaluated the results of an index test (PCT, CRP, ESR) against the results of an acute-phase 99Tc-dimercaptosuccinic acid (DMSA) scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture-confirmed episode of UTI. The following cut-off values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/hour for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random-effects pooled sensitivity and specificity values. MAIN RESULTS: A total of 36 studies met our inclusion criteria. Twenty-five studies provided data for the primary analysis: 12 studies (1000 children) included data on PCT, 16 studies (1895 children) included data on CRP, and eight studies (1910 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the PCT, CRP, ESR tests at the aforementioned cut-offs were 0.81 (0.67 to 0.90), 0.93 (0.86 to 0.96), and 0.83 (0.71 to 0.91), respectively. The summary specificity values for PCT, CRP, and ESR tests at these cut-offs were 0.76 (0.66 to 0.84), 0.37 (0.24 to 0.53), and 0.57 (0.41 to 0.72), respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

Host and Bacterial Markers that Differ in Children with Cystitis and Pyelonephritis.

OBJECTIVE: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis. STUDY DESIGN: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes. RESULTS: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis. CONCLUSIONS: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.

Comparison of intravenous or intravesical cidofovir in the treatment of BK polyomavirus-associated hemorrhagic cystitis following adult allogeneic stem cell transplantation-A systematic review.

INTRODUCTION: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical. METHODS: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively. RESULTS: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure. CONCLUSION: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile.

Viral-specific T-cell response in hemorrhagic cystitis after haploidentical donor stem cell transplantation.

Viral hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) can be devastating. Standard treatment modalities have not been well established, but immune reconstitution may be necessary for sustained viral clearance. We studied five pediatric patients who developed viral HC after haplo-identical HSCT. All patients developed virus-specific CD4- and CD8-positive T cells, and the emergence of these viral-specific T cells was temporally associated with successful viral clearance.

Measurements of C-reactive protein (CRP) and nerve-growth-factor (NGF) concentrations in serum and urine samples of dogs with neurologic disorders.

BACKGROUND: The purpose of this study was to prove the hypothesis that C-reactive protein (CRP) and nerve growth factor (NGF) may be potential biomarkers for lower urinary tract disorders and may be able to distinguish between micturition dysfunctions of different origin in dogs with spinal cord diseases. NGF- and CRP- concentrations were measured in serum and urine samples using specific ELISA-Kits. Results in urine were standardized by urine-creatinine levels. RESULTS: CRP in serum was detectable in 32/76 and in urine samples in 40/76 patients. NGF could be measured in all serum and in 70/76 urine samples. Urinary CRP concentrations were significantly higher in dogs with micturition dysfunction (p = 0.0009) and in dogs with different neurological diseases (p = 0.0020) compared to the control group. However, comparing dogs with spinal cord disorders with and without associated micturition dysfunction no significant difference could be detected for NGF and CRP values in urine or serum samples. Additionally, levels did not decrease significantly, when measured at the time when the dogs regained the ability to urinate properly (urinary NGF p = 0.7962; urinary CRP p = 0.078). Urine samples with bacteria and/or leukocytes had no significant increase in urinary NGF (p = 0.1112) or CRP (p = 0.0534) concentrations, but higher CRP-levels in urine from dogs with cystitis were found compared to dogs without signs of cystitis. CONCLUSIONS: From these data we conclude that neither CRP nor NGF in urine or serum can be considered as reliable biomarkers for micturition disorders in dogs with spinal cord disorders in a clinical setting, but their production might be part of the pathogenesis of such disorders. Significantly higher levels of CRP could be found in the urine of dogs with micturition dysfunctions compared to control dogs. This phenomenon could potentially be explained by unspecific extrahepatic CRP production by smooth muscle cells in the dilated bladder.

Pathogenic Features of Dysuria in Young Women with Secondary Amenorrhea Caused by Body Weight Loss.

We examined 11 women aged 19-26 years (mean age 22.5±3.5 years) with secondary amenorrhea complaining frequent urination over 1.5 years and repeatedly, but unsuccessful treated for overactive bladder and chronic cystitis. The rare cause of sustained urination disorders in young female patients of reproductive age was established: development of secondary amenorrhea caused by weight loss ("cosmetic" amenorrhea) with subsequent estrogene deficit and urogenital atrophy. Morphological examination of the bladder mucosa, an important clue to the diagnosis, helps to identify the true cause of dysuria, urogenital atrophy of the bladder mucosa, in secondary ("cosmetic") amenorrhea, and determine future course of etiopathogenic treatment of sustained dysuria in young women. The treatment is often effective in case of proper and timely diagnosis and the absence of irreversible changes.

Lupus enteritis: clinical characteristics and predictive factors for recurrence.

OBJECTIVES: To compare the clinical characteristics of lupus enteritis (LE) and non-enteric lupus (non-LE) patients and identify predictors of LE recurrence. METHODS: We retrospectively reviewed the medical records of 62 systemic lupus erythematosus (SLE) patients in a tertiary hospital who experienced enteric symptoms and underwent abdominal computed tomography scanning between January 1997 and December 2013. We compared the clinical characteristics between LE and non-LE patients and between recurrent LE and non-recurrent LE cases. RESULTS: Out of 62 SLE patients with enteric symptoms, 46 cases (74%) were compatible with LE based on computed tomography findings. The C4 level was decreased in the LE group compared with the non-LE group (9.0 ± 5.6 vs. 12.3 ± 6.2, p = 0.032). Recurrence of LE was observed in 14 patients (28%). Initial involvement at the colon (79% vs. 41%, p = 0.026) and bladder with/without the ureter was more common in the recurrent group (57% vs. 25%, p = 0.048). By multivariate analysis, the hazard ratios of variables associated with recurrence were 4.689 for colon involvement (95% confidence interval: 1.245-17.659, p = 0.0220] and 5.468 for cystitis with/without ureteritis (95% confidence interval: 1.629-18.360, p = 0.006). CONCLUSION: Colon and urinary tract involvement in LE patients may be associated with the recurrence of LE.

Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children.

BACKGROUND: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long-term renal sequelae. If non-invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow-up could potentially be individualized. OBJECTIVES: The objectives of this review were to 1) determine whether procalcitonin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other. SEARCH METHODS: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We only considered published studies that evaluated the results of an index test (procalcitonin, CRP, ESR) against the results of an acute-phase DMSA scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture-confirmed episode of UTI. The following cutoff values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/h for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random-effects pooled sensitivity and specificity values. MAIN RESULTS: A total of 24 studies met our inclusion criteria. Seventeen studies provided data for the primary analysis: six studies (434 children) included data on procalcitonin, 13 studies (1638 children) included data on CRP, and six studies (1737 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the procalcitonin, CRP, ESR tests at the aforementioned cutoffs were 0.86 (0.72 to 0.93), 0.94 (0.85 to 0.97), and 0.87 (0.77 to 0.93), respectively. The summary specificity values for procalcitonin, CRP, and ESR tests at these cutoffs were 0.74 (0.55 to 0.87), 0.39 (0.23 to 0.58), and 0.48 (0.33 to 0.64), respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

A novel nomogram based on inflammation biomarkers for predicting radiation cystitis in patients with local advanced cervical cancer.

BACKGROUNDS: Platelet-to-albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. METHODS: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms-one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. RESULTS: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune-Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five-cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. CONCLUSIONS: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.

Uroprotective effect of pentoxifylline in cyclophosphamide-induced hemorrhagic cystitis in rats.

The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide-induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxifylline (150 mg/kg/day/ip) was administered for 10 days followed by cyclophosphamide. Hemorrhagic cystitis was well characterized macroscopically, microscopically, and biochemically. Cyclophosphamide induced bladder injury including acute severe inflammation, vascular congestion, severe edema, hemorrhage, inflammatory cell infiltration in the lamina propria, and epithelial denudation; as well as it notably elevated serum inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1ß), bladder content of malondialdehyde and total nitrate, accompanied with depletion of bladder antioxidant enzymes activities (glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, and catalase). Prior administration of pentoxifylline improved all biochemical and histologic alterations induced by the cytotoxic drug cyclophosphamide. In conclusion, pentoxifylline has proven uroprotective efficacy in the cyclophosphamide-induced hemorrhagic cystitis model, possibly through modulating the release of inflammatory cytokines and nitric oxide and restoring the oxidant/antioxidant balance.

Diagnostic Values of Immature Granulocytes Detected by the Sysmex XN 9000 Hematology Analyzer in Children with Urinary Tract Infections.

Immature granulocytes (IGs) are used as markers of infection and systemic inflammation. We aimed to investigate the diagnostic value of IGs in children with urinary tract infections (UTIs). Children with their first UTIs were included in this observational study. Blood samples were obtained before antibiotic therapy. The blood analysis was repeated 2 weeks after the treatment ended. In total, 194 children (95 with febrile UTI, 58 with cystitis, and 41 controls) were included. The percentage of IGs (IG%) and IG count (IGC) measured at the time of admission were higher in the patients with febrile UTI than in the patients with cystitis and the controls (P = 0.000). The IGC and IG% after treatment were higher in patients with renal scarring than in those without scarring (P = 0.012 and P = 0.021, respectively). Cox's regression analysis showed the significant associations of renal scarring with both IGC and IG% (hazard ratio: 8.181, P = 0.002; hazard ratio: 5.106, P = 0.033, respectively). Both IGC and IG% were positively associated with severe vesicoureteral reflux (VUR) [odds ratio (OR): 22.235, P = 0.025; OR: 15.597, P = 0.038, respectively]. In conclusion, the IG% and IGC, which can be easily measured in a routine complete blood count without the need for additional effort, could be used as biomarkers for predicting febrile UTI, renal scarring, and severe VUR in children.

Association of overactive bladder and C-reactive protein levels. Results from the Boston Area Community Health (BACH) Survey.

OBJECTIVE: • To investigate the association between overactive bladder (OAB) and C-reactive protein (CRP) in a population-based sample of men and women. SUBJECTS AND METHODS: • Epidemiological survey of urological symptoms among men and women aged 30-79 years. A multi-stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels. • The International Continence Society defines OAB as 'Urgency with or without urge incontinence, usually with frequency and nocturia.' OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia. • Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression. RESULTS: • Prevalence of OAB increased with CRP levels in both men and women. • In men, adjusted ORs (95% CI) per log(10) (CRP) levels were 1.90 (1.26-2.86) with OAB defined as urgency, 1.65 (1.06-2.58) with OAB defined as urgency and frequency, and 1.92 (1.13-3.28) with OAB defined as urgency, frequency and nocturia. • The association was more modest in women with ORs (95% CI) of 1.53 (1.07-2.18) for OAB as defined urgency, 1.51 (1.02-2.23) for OAB defined as urgency and frequency, and 1.34 (0.85-2.12) for OAB defined as urgency, frequency and nocturia. CONCLUSIONS: • Results show a consistent association of increasing CRP levels and OAB among both men and women. • These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti-inflammatory agents in its treatment.

Blood, and not urine, BK viral load predicts renal outcome in children with hemorrhagic cystitis following hematopoietic stem cell transplantation.

BK virus is a significant cause of hemorrhagic cystitis after hematopoietic stem cell transplantation (HSCT). However, its role in nephropathy post-HSCT is less studied. We retrospectively evaluated clinical outcomes in pediatric HSCT patients with hemorrhagic cystitis. Although most of these patients had very high urine BK viral loads (viruria), patients with higher BK plasma loads (viremia) had significant renal dysfunction, a worse clinical course, and decreased survival. Patients with a peak plasma BK viral load of >10,000 copies/mL (high viremia) were more likely to need dialysis and aggressive treatment for hemorrhagic cystitis compared to patients with ≤ 10,000 copies/mL (low viremia). Conversely, most patients with low viremia had only transient elevations in creatinine, and less severe hemorrhagic cystitis that resolved with supportive therapy. Overall survival (OS) at 1 year post-HSCT was 89% in the low viremia group and 48% in the high viremia group. We conclude that the degree of BK viremia, and not viruria, may predict renal, urologic, and overall outcome in the post-HSCT population.

Elevation of serum c-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder.

AIMS: Chronic inflammation has been implicated in the development of overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). An elevation of C-reactive protein (CRP) has been associated with chronic inflammation and lower urinary tract symptoms. This study aims to elucidate the association between CRP and OAB or IC/BPS. METHODS: Serum CRP and urinary nerve growth factor (NGF) levels were examined in 70 patients with OAB (n=22) or IC/BPS (n=48) and compared with 33 normal controls. Data of serum CRP and urinary NGF levels were compared among the controls, IC/PBS, and OAB. The Spearmen correlation analysis test and ANOVA (Kruskal-Wallis) test were used for statistical analysis with P<0.05 considered significant. RESULTS: Serum CRP levels were significantly higher in subjects with OAB (1.83 ± 2.30 mg/L vs. 0.59 ± 0.40 mg/L, P=0.012) or IC/BPS (1.76 ± 3.56 mg/L vs. 0.59 ± 0.40 mg/L, P=0.049) than in controls. No significant difference in CRP level was noted between patients with OAB and IC/BPS (P=0.43). In a subgroup analysis, patients of OAB wet had higher serum CRP level than that of OAB dry (2.95 ± 3.08 mg/L vs. 0.90 ± 0.52 mg/L); however, the difference did not reach statistical significance (P=0.34). The CRP between OAB wet and OAB patients with medical disease was not significantly different. There was no significant correlation between serum CRP and urinary NGF levels in the controls or patients with OAB or IC/BPS, except in the OAB patients with a CRP level >3 mg/L. CONCLUSIONS: Our data support the association between chronic inflammation of the urinary bladder in patients with OAB or IC/BPS.

Clinical effects of 2 days of treatment by fosfomycin calcium for acute uncomplicated cystitis in women.

Fosfomycin calcium is a fosfomycin antimicrobial agent with a characteristic structure. After oral administration, the drug is absorbed and excreted via the kidneys in the unchanged form, without being metabolized in the body. It is, therefore, indicated for the treatment of urinary tract diseases, including cystitis and pyelonephritis. In the present study, the clinical usefulness of fosfomycin calcium (FOSMICIN® TABLETS 500) administered orally at the dosage of 1 g (two tablets) three times daily for 2 days was examined in female patients, who were at least 20 years of age, with acute uncomplicated cystitis of bacterial origin. Of the 48 patients enrolled between February 2008 and August 2008, 39 were evaluable for efficacy and safety. Overall evaluation of the cure revealed that microbiological eradication rate (microbiological outcome) and clinical efficacy rate (clinical outcome) at 5-9 days after drug administration (visit 2) were 94.9%. Determination of the microbiological and clinical outcomes for the evaluation of recurrence at 4-6 weeks after drug administration (visit 3) were 75.8 and 85.7%, respectively. Of the 48 patients, 40 (83.3%) returned to the clinic at visit 3. The causative bacterial species for cystitis was Escherichia coli in 31 (79.5%) of the 39 patients evaluable for efficacy and safety. Adverse drug reactions observed during the administration and follow-up periods included mild diarrhea and loose stools in 1 patient each, neither requiring any specific treatment. Evaluation of cure at visit 2 in patients in whom the causative bacterial species for the infection was E. coli revealed a microbiological outcome of 93.5%, and clinical outcome was 96.8%. Furthermore, evaluation for recurrence at visit 3 revealed a microbiological outcome of 74.1% and clinical outcome of 82.1%. When the patients were divided by age into an under 60 years of age group and an over 60 years of age group, the microbiological and clinical outcomes determined for evaluation of cure at visit 2 were 96.4 and 92.9%, respectively, and the corresponding rates determined for the evaluation of recurrence at visit 3 were 87.0 and 96.0%, respectively, in the under 60 years of age group. In the over 60 years of age group, the corresponding microbiological outcome and clinical outcome rates evaluated for cure were 90.9 and 100%, respectively, and those evaluated for recurrence were 50.0 and 60.0%, respectively. These results indicate the usefulness of fosfomycin calcium administered at 1 g three times daily for 2 days for acute uncomplicated cystitis.

Rare etiology of obstructive uropathy: pelvic lipomatosis.

We present a case of a 32-year-old hypertensive and obese male who had bilateral obstructive uropathy, and who was diagnosed as having pelvic lipomatosis on the basis of clinicoradiological findings. Cystoscopy and biopsy revealed cystitis cystica. He was successfully managed with bilateral extravesical modified Lich-Gregoir ureteric reimplantation by intraperitoneal approach. At 5 months follow-up, the patient had normal serum creatinine and was clinically asymptomatic.

Prospective Analysis of Hemorrhagic Cystitis and BK Viremia in Allogeneic Hematopoietic Stem Cell Transplantation

Objective: BK virus (BKV) infection has been shown to be related to hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are conflicting data regarding the association between BKV titers in plasma and clinical disease as well as the risk factors for BKV-related HC. Our aim is to study the risk factors and relationship with plasma BK viral load for development of HC in a prospective analysis. Materials and Methods: We prospectively evaluated 59 patients who received allo-HSCT between 2014 and 2016 by quantitative BK virus polymerase chain reaction (PCR) (Altona Diagnostics, Germany) from blood samples at days 0, 30, 60, and 90 after allo-HSCT. The patients were monitored for signs and symptoms of HC. Results: HC was diagnosed in 22 patients (37%) at a mean of 100 days (range: 0-367 days). In multivariate analysis, the usage of cyclophosphamide (sub-distribution hazard ratio [sdHR]: 7.82, confidence interval [CI]: 1.375-39.645, p=0.02), reactivated CMV (sdHR: 6.105, CI: 1.614-23.094, p=0.008), and positive BKV viremia (sdHR: 2.15, CI: 1.456-22.065, p=0.01) significantly increased the risk of developing HC. Patients with higher viral loads at day 30 and day 60 were diagnosed with more severe HC (p<0.001). Median BK viral loads of >101.5 copies/mL at day 0 (sensitivity 0.727, specificity 0.875), >98.5 copies/mL at day 30 (sensitivity 0.909, specificity 0.875), and >90.0 copies/mL at day 60 (sensitivity 0.909, specificity 0.875) were indicative of HC. Conclusion: Our study showed that administration of cyclophosphamide, CMV reactivation, and BK virus positivity were associated with HC. Plasma BK virus PCR titers at days 0, 30, and 60 after transplant were sensitive tools for predicting clinically proven HC.

Network analysis, and human and animal studies disclose the anticystitis glandularis effects of vitamin C.

BACKGROUND: Our present study aimed to unravel the therapeutic biotargets of vitamin C (VC) against cystitis glandularis (CG), and to elucidate the molecular mechanisms for VC treating CG. METHODS: Network pharmacology was used to predict therapeutic targets of VC against CG, and to identify molecular mechanisms. In addition, further human and animal studies were designed to validate the bioinformatic findings through biochemical tests, computerized tomography scans, and immunostaining assays. RESULTS: In bioinformatic analyses, pathogenic targets of CG and putative targets of VC were identified, respectively. An interaction network between biological target and functional protein was produced before screening and collecting the key therapeutic targets of VC against CG, biological processes, and signaling pathways. In addition, ingenuity pathway analysis with cloud platform indicated that anti-CG mechanisms of VC were achieved through modulating a cluster of molecular pathways, such as tumor necrosis factor (TNF) pathway. Meanwhile, 18 core targets of VC against CG were identified, and the most important TNF, interleukin-6 (IL6), and Jun biotargets were obtained, respectively. In further validation in human study, cellular TNF-α, IL6, and c-Jun expressions in patient's CG samples were elevated significantly, accompanied with detectable urinary tract infection. Beneficially, VC-dosed CG mice resulted in downregulated expressions of endogenous TNF-α, IL6, and c-Jun in blood and bladder samples. CONCLUSION: Collectively, these bioinformatic findings and experimentative data uncover the therapeutic targets and biological mechanisms of VC for treating CG, in which the key biomarkers of TNF-α, IL6, and c-Jun may be the potential molecules for treating CG in clinical application.