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.

Cistitis hemorrágica por infección viral en receptores de trasplante hematopoyético haploidéntico: reporte de dos casos / Hemorrhagic cystitis due to viral infection in patients who received hematopoietic haploidentical transplantation: two case reports

Introducción: Las infecciones por virus o la reactivación de virus en estado latente son frecuentes durante el estado de inmunosupresión que sigue al trasplante de progenitores hematopoyéticos, y constituyen una causa importante de complicaciones, como la cistitis hemorrágica, que se caracteriza por disuria, polaquiuria, dolor abdominal y hematuria. La aparición precoz se asocia a la administración de citostáticos como la ciclofosfamida, y el comienzo tardío a la primoinfección o reactivación de virus como citomegalovirus, los adenovirus o los poliomavirus como el BK y el JC. Objetivo: Describir las características clínicas, la evolución y el manejo de la cistitis hemorrágica postrasplante. Casos clínicos: Se presentan dos pacientes con leucemia mieloide aguda que desarrollaron cistitis hemorrágica asociada a infección viral por virus BK y citomegalovirus después del trasplante haploidéntico con ciclofosfamida postrasplante. La cistitis hemorrágica de causa viral después del trasplante hematopoyético en estos pacientes estuvo asociada a una severa inmunosupresión, por lo que constituyó una complicación potencialmente letal. Los dos pacientes presentaron cistitis hemorrágica grado IV y fallecieron a pesar del tratamiento. Conclusiones: El trasplante haploidéntico con la administración de ciclofosfamida postrasplante incrementa la posibilidad de donantes de progenitores hematopoyéticos para los pacientes sin un hermano HLA idéntico pero el mayor nivel de inmunosupresión podría aumentar la incidencia de cistitis hemorrágica de causa viral(AU)

Introduction: Viral infections or latent-virus reactivation are frequent during the immunosuppressed cincition that follows hematopoietic stem-cell transplantation, and an important cause of complications, such as hemorrhagic cystitis, characterized by dysuria, urinary frequency, abdominal pain, and hematuria. The early appearance is associated with the administration of cytostatic drugs such as cyclophosphamide, and the late onset is associated with primary infection or reactivation of viruses such as cytomegalovirus, adenoviruses, or polyomaviruses such as BK and JC. Objective: To describe the clinical characteristics, evolution and management of post-transplant hemorrhagic cystitis. Clinical cases: The cases are presented of two patients with acute myeloid leukemia who developed hemorrhagic cystitis associated with viral infection by BK virus and cytomegalovirus after haploidentical transplantation with post-transplant cyclophosphamide. Viral hemorrhagic cystitis after hematopoietic transplantation in these patients was associated with severe immunosuppression, making it a potentially lethal complication. Both patients presented grade IV hemorrhagic cystitis and died despite treatment. Conclusions: Haploidentical transplantation with the of post-transplant cyclophosphamide administration increases the possibility for donors of hematopoietic progenitor cells to patients without an identical HLA match, but the higher level of immunosuppression could increase the incidence of viral hemorrhagic cystitis(AU)

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.

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.

Distribution of extended-spectrum ß-lactam, quinolone and carbapenem resistance genes, and genetic diversity among uropathogenic Escherichia coli isolates in Tehran, Iran.

OBJECTIVES: Antimicrobial resistance among uropathogenic Escherichia coli (UPEC) is increasing. The aim of this study was to evaluate antimicrobial resistance in UPEC isolates and its correlation with virulence factors. METHODS: A total of 120 E. coli isolates were collected from patients with urinary tract infection in Tehran, Iran. Biofilm formation and antimicrobial susceptibility were determined by phenotypic tests. The combination disk diffusion test and modified Hodge test (MHT) were performed for phenotypic detection of extended-spectrum ß-lactamases (ESBLs) and carbapenemases, respectively. PCR was used for the detection of virulence genes, ESBL-encoding genes, and quinolone (qnr) and carbapenem resistance genes. Pulsed-field gel electrophoresis (PFGE) was performed to explore the genetic relatedness among isolates. RESULTS: Most isolates exhibited biofilm formation, and different frequencies of virulence genes were observed. There was a high rate of resistance, especially multidrug resistance, to most of the antimicrobial agents tested. Phenotypically, 67.5% of the isolates produced an ESBL and were resistant to different antimicrobial classes. In total, 83.3% of the isolates harboured ESBL genes, especially blaTEM and blaCTX-M, and 32.5% were positive for the quinolone resistance genes qnrS and qnrB. All isolates were negative for carbapenemases by the MHT and PCR. These results indicate the association between the presence of various virulence genes and antimicrobial susceptibility. PFGE analysis showed that there was great clonal diversity among the selected isolates, with 17 isolates divided into five clusters. CONCLUSIONS: These results indicate that the high antimicrobial resistance among UPEC isolates is alarming and requires urgent attention.

Protein and micronutrient deficiencies in patients with radiation cystitis and outcome after hyperbaric oxygen therapy.

BACKGROUND & AIMS: Haemorrhagic radiation cystitis (HRC) is a late complication of pelvic radiotherapy. Severe cases are difficult to treat due to persistent or recurrent bleeding, despite urological and hyperbaric oxygen therapy (HBOT). However, wound healing requires a good nutritional status. In this respect, we aimed at analysing the nutritional status of patients with HRC prior to the onset of HBOT and at highlighting predictive nutritional factors of outcome. METHODS: Data were retrospectively collected from a cohort of 179 patients with HRC (between 2011 and 2015). Haematuria was graded according to the Subjective, Objective, Management, Analytic scale (SOMA): grade-4 (n = 46) was compared with grade-3 (n = 56), and with grades 1 and 2 (n = 77). S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium, and essential fatty acids were evaluated before HBOT. HBOT response was measured at 3 months according to the haematuria SOMA grade. The Mann-Whitney test, Fisher's exact test and principal-component analysis were used to compare groups. RESULTS: Patients with higher haematuria grades (3 and 4) harboured significant deficiencies in S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium and essential fatty acids. Moreover, grade-4 patients without improvement after 3 months of HBOT had significant lower initial levels of S-albumin, vitamin C, selenium and linoleic acid. Vitamin C levels <2.5 mg/L were strongly associated with HBOT non-response (OR 23.14, 95% CI 3.73-143.69, p = 0.002). CONCLUSIONS: Our analyses show serious nutritional deficiencies associated with higher grades of HRC and worse prognoses. Patients with haemorrhagic cystitis might benefit from an adequate dietary supplementation to support healing of their bladder mucosa.

Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis.

BACKGROUND: Feline idiopathic cystitis (FIC) is a common lower urinary tract disorder of domestic cats that resembles interstitial cystitis/painful bladder syndrome (IC/PBS) in humans. Diagnosis of FIC is based on clinical signs and exclusion of other disorders because of a lack of specific pathologic findings or other objective biomarkers. Cytokines are potential noninvasive biomarkers to define the presence, severity, and progression of disease, and response to treatment. OBJECTIVES: The objective of this pilot study was to determine concentrations of selected cytokines in serum from healthy cats and cats with acute FIC. ANIMALS: Serum samples from 13 healthy cats and from 12 cats with nonobstructive acute FIC were utilized. METHODS: Multiplex analysis of 19 cytokines (CCL2, CCL5, CXCL1, CXCL12, CXCL8, Flt3L, GM-CSF, IFN-γ, IL-12 (p40), IL-13, IL-18, IL-1ß, IL-2, IL-4, IL-6, PDGF-BB, SCF, sFas, and TNF-α) was performed with a commercially available feline-specific multiplex bead-based assay. RESULTS: Mean serum concentrations of IL-12 (p40; P < 0.0001), CXCL12 (P = 0.002), IL-18 (P = 0.032), and Flt3L (P = 0.0024) were significantly increased in FIC cats compared to healthy cats. GM-CSF, IL-1b, IL-2, and PDGF-BB were undetectable or detected in an insufficient number of cats to allow meaningful comparisons. CONCLUSIONS AND CLINICAL IMPORTANCE: We have identified increased serum concentrations of pro-inflammatory cytokines and chemokines CXCL12, IL-12, IL-18, and Flt3L in FIC-affected cats. These findings suggest potential candidates for noninvasive biomarkers for diagnosis, staging, and therapeutic outcome monitoring of affected cats and provide additional insight into the etiopathogenesis of FIC.

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.

BRAF mutation as a novel driver of eosinophilic cystitis.

Eosinophilic cystitis is a rare manifestation of hypereosinophilia and a cause of morbidity, including dysuria and hematuria. Although some cases can be attributed to infection or allergy, most cases are assessed to be idiopathic and treated with corticosteroids. However, hypereosinophilia can also be due to actionable clonal molecular alterations in the haematopoietic cells, similar to other myeloproliferative neoplasms. Common mutations associated with eosonophilic syndromes are of platelet-derived growth factor receptor α or ß or c-kit, though other pathogenic mutations have been found by next generation sequencing. Determination of a specific mutation may therefore identify clonality and refine treatment of some cases. Here we review the molecular features of eosinophilic disorders. We also describe the use of a liquid biopsy of circulating cell-free DNA in the workup of a case of eosinophilic cystitis in which next generation sequencing of cell-free DNA showed a BRAF I463T mutation. In silico modeling supports the functional impact and potential clinical relevance of BRAF I463T.

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.

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.

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.

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.

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.