Clinical impact of Wnt5a expression on persistence of acute kidney injury in patients with urosepsis.

Abnormal Wnt5a expression is associated with dysregulated inflammation and organ dysfunction. However, the effect of Wnt5a activation on the duration of organ dysfunction remains unclear. This prospective study investigated the association between Wnt5a levels and persistent acute kidney injury (AKI) in patients with urosepsis. Serum creatinine and Wnt5a levels were measured on days 1 and 5 and at discharge in 87 patients diagnosed with urosepsis. Patients with urosepsis were classified into an improving acute kidney injury (AKI) group and a persistent or worsening AKI group according to the AKI stage on days 1 and 5. AKI recovery was defined as a discharge-to-baseline serum creatinine ratio of <1.5. Twenty-eight patients with urosepsis (32.2%) had persistent or worsening AKI, and their Wnt5a levels were higher on days 1 and 5 and at discharge than those with improving AKI. The association between Wnt5a levels and persistent or worsening AKI was maintained after adjusting for age, sex, baseline serum creatinine levels, and disease severity. Moreover, elevated Wnt5a levels were associated with an increased risk of major adverse kidney events. High Wnt5a levels at discharge were associated with unrecovered AKI and participants with AKI recovery had a steeper Wnt5a slope over time than those without recovery, irrespective of age, sex, baseline serum creatinine level, or disease severity. Assessment of Wnt5a expression was helpful in predicting AKI persistence and adverse outcomes in patients with urosepsis. Therefore, Wnt5a may serve as a valuable bio-marker for identifying the risk of persistence of AKI.

Lower serum levels of vitamin D in adults with urinary tract infection.

PURPOSE: We aimed to explore the association between urinary tract infection (UTI) in adults and serum 25-hydroxyvitamin D (25OHD), which was used to access vitamin D status. METHODS: Serum levels of 25OHD were retrospectively analyzed in 234 subjects (190 females and 44 males): 120 UTI patients (females = 103) and 114 age- and sex-matched healthy controls (females = 87). Serum 25OHD concentrations were categorized as follows: (1) < 20 ng/mL, 20 to < 30 ng/mL, and ≥ 30 ng/mL; (2) < 20 ng/mL and ≥ 20 ng/mL. RESULTS: Serum 25OHD levels were lower in patients with UTI (p < 0.01). Women with UTI presented significantly lower 25OHD concentrations than those without UTI (p < 0.01). No association between serum 25OHD levels and UTI in men was found (p > 0.05). The multivariable logistic regression models showed significant associations between UTI and 25OHD, female sex, neutrophilic lymphocyte ratio and C-reactive protein (p < 0.05). CONCLUSION: Lower 25OHD concentrations associated with UTI were most prominent among women. The associations between UTI and low serum 25OHD levels as well as female sex were independent of each other.

Gender differences in acute stone admissions - should we have a lower threshold for treatment in female patients?

OBJECTIVES: To examine the gender-related differences in the presentation, management and outcomes of patients admitted with acute renal colic at our institution. PATIENTS AND METHODS: A retrospective analysis of 231 consecutive patients requiring inpatient admission for acute renal colic between October 2015 and March 2018. For each admission, data on demographics, admission blood results, stone characteristics, management and outcomes were collected. Differences between genders were compared using the chi-squared and Student's t-test. RESULTS: Gender distribution was 35% female: 65% male. There was no significant difference in age, American Society of Anesthesiologists Physical Status Classification grade or history of diabetes. Women had a higher admission C-reactive protein level (89.3 vs 32.9 mg/L, P < 0.001) and neutrophil count (10.0 vs 8.8 × 109 /L, P = 0.04) than men. They also had more positive cultures (34.1% vs 6.0%, P < 0.001) and were more likely to require percutaneous nephrostomy insertion (9.8% vs 0.7%, P = 0.005). Women had more intensive therapy unit (ITU) admissions (12.2% vs 0.6%, P < 0.001) and longer lengths of stay (4.4 vs 1.8 days, P < 0.001) than men. There was no mortality in our series. CONCLUSION: In the present study, women admitted with acute renal colic were more likely to have an associated infection than men and require rapid decompression. Although there was no difference in mortality, women experienced greater morbidity as evidenced by the higher rate of ITU admissions and longer length of stay. These differences are important to consider when assessing the suitability of conservative management for female patients.

Serum levels of immunoglobulin and complement in UTI of patients caused by Proteus mirabilis and using AgNPs as antiswarming.

The use of plant extracts represents a promising approach for the synthesis of silver nanoparticles (AgNPs). This study reports the low-cost, green synthesis of AgNPs using the extract of clove and black seeds. The biosynthesized AgNPs were confirmed and characterized by analysis of the spectroscopy profile of the UV-visible spectrophotometer. The purpose of the present study is to evaluate the inhibitory effect concentration (MIC) of AgNPs, clove, and black cumin seed extracts on the growth and swarming of P. mirabilis. Clinical isolates of P. mirabilis were isolated from patients suffering from urinary tract infections. Thirteen types of antibiotics were used in the present study to detect their ability to inhibit P. mirabilis's resistance. Immunological findings included the determination of serum levels of IgG, IgM, IgA and complement protein C3 and C4. Results showed that IgG and IgA concentrations significantly increased (1311.13 ± 72.54 and 279 ± 21.31) respectively in UTI patients in comparison to the healthy control group which was 1089.88 ± 37.33 and 117.611 ± 4.19 respectively, While IgM concentrations were increased non significantly in UTI patients (153.331 ± 6.45) in comparison to healthy control (145.2 ± 13.49). Complement components C3 showed a significant increase in UTI patients with mean values of 125.95 ± 6.22 compared to the control group with mean values of 55.191 ± 9.64, while C4 showed statically non-significant among UTI patients in comparison with the control group (35.195 ± 2.34 and 34.371 ± 1.22) respectively.

Clinical characteristics and prognosis in patients with urosepsis from intensive care unit in Shanghai, China: a retrospective bi-centre study.

BACKGROUND: The purpose of this study was to retrospectively analyze clinical characteristics and prognostic risk factors of urosepsis patients admitted to two intensive care units in Shanghai, China. METHODS: Clinical data from patients diagnosed with urosepsis were retrospectively retrieved and analyzed from ICU in two regional medical centers from January 2015 to December 2019. RESULTS: Two hundred two patients were included in the subsequent analysis eventually, with an average age of 72.02 ± 9.66 years, 79.21% of the patients were female and the mortality rate of 15.84%.The proportion of patients with chronic underlying diseases such as diabetes and hypertension was relatively high (56.44, 49.50%, respectively), and the incidence of shock was also high (41.58%) correspondingly. The most common pathogen isolated was Escherichia coli (79.20%), of which the extended-spectrumß-lactamases (ESBLs)(+) accounted for 42.57%. In multivariate analysis, the strongest predictors for death were mechanical ventilation (OR 7.260, 95% CI 2.200-23.963; P = 0.001),chronic kidney disease (CKD) (OR 5.140, 95% CI 1.596-16.550; P = 0.006), APACHE II score (OR 1.321, 95% CI 1.184-1.473; P < 0.001) and lactate (OR 1.258, 95% CI 1.037-1.527; P = 0.020). Both APACHE II score and lactate had the ideal predictive value, with the area under the ROC curve (AUC) of 0.858 and 0.805 respectively. CONCLUSION: The patients with urosepsis were characterized by a higher proportion of female, older age, more percentage of comorbidities in this region, and patients with ESBLs (+) Escherichia coli infection were more prone to shock. Mechanical ventilation, comorbidity with CKD, APACHE II score and lactate were independent risk factors for death in urosepsis patient, but lactate level and APACHE II score had better predictive value for prognosis.

α-Haemolysin production, as a single factor, causes fulminant sepsis in a model of Escherichia coli-induced bacteraemia.

α-Haemolysin (HlyA) from uropathogenic Escherichia coli has been demonstrated to be a significant virulence factor for ascending urinary tract infections. Once the E. coli reach the well-vascularised kidneys, there is a high risk of bacteraemia and a subsequent septic host response. Despite this, HlyA has the potential to accelerate the host response both directly and via its ability to facilitate adenosine triphosphate release from cells. It has not been settled whether HlyA aggravates bacteraemia into a septic state. To address this, we used an E. coli strain in a model of acute urosepsis that was either transfected with a plasmid containing the full HlyA operon or one with deletion in the HlyA gene. Here, we show that HlyA accelerates the host response to E. coli in the circulation. Mice exposed to HlyA-producing E. coli showed massively increased proinflammatory cytokines, a substantial fall in circulating thrombocytes, extensive haematuria, and intravascular haemolysis. This was not seen in mice exposed to either E. coli that do not secrete HlyA or vehicle controls. Consistent with the massive host response to the bacteria, the mice exposed to HlyA-producing E. coli died exceedingly early, whereas mice exposed to E. coli without HlyA production and vehicle controls survived the entire observation period. These data allow us to conclude that HlyA is a virulence factor that accelerates a state of bacteraemia into fulminant sepsis in a mouse model.

Biomarkers that differentiate false positive urinalyses from true urinary tract infection.

BACKGROUND: The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI). METHODS: Prospective cross-sectional study to compare inflammatory proteins in blood and urine samples collected at the time of a presumptive diagnosis of UTI. We also evaluated serum RNA expression in a subset. RESULTS: We enrolled 200 children; of these, 89 were later demonstrated not to have a UTI based on the results of the urine culture obtained. Urinary proteins that best discriminated between children with UTI and no UTI were involved in T cell response proliferation (IL-9, IL-2), chemoattractants (CXCL12, CXCL1, CXCL8), the cytokine/interferon pathway (IL-13, IL-2, INFγ), or involved in innate immunity (NGAL). The predictive power (as measured by the area under the curve) of a combination of four urinary markers (IL-2, IL-9, IL-8, and NGAL) was 0.94. Genes in the pathways related to inflammation were also upregulated in serum of children with UTI. CONCLUSIONS: Urinary proteins involved in the inflammatory response may be useful in identifying children with false positive results with current screening tests for UTI; this may reduce unnecessary treatment.

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.

Diagnostic Accuracy of the Mean Platelet Volume in the Prediction of Upper Urinary Tract Infections.

BACKGROUND: The studies have reported that mean platelet volume may be a marker in the discrimination of upper and lower urinary tract infections. We investigated whether the mean platelet volume was a reliable indicator in upper and lower urinary tract infections. METHODS: One hundred and eighty-two patients between the ages of 1 month and 14 years who were diagnosed with urinary tract infection were included in this study. The mean platelet volume values, clinical and other laboratory characteristics of the groups were compared. The discriminative ability of each biomarker for patients with UUTI was evaluated by drawing receiver operating characteristic (ROC) curves for the biomarkers. All values of p < 0.05 were considered statistically significant. RESULTS: The leukocyte count, C-reactive protein, and erythrocyte sedimentation rates of the patients with upper urinary tract infection were significantly higher than the patients with lower urinary tract infections (p < 0.001). However, there was no statistically significant difference in terms of the mean platelet volume values between patients with upper and lower urinary tract infection ([7.2 (1.3) vs. 7.2 (1.6) fL]; p = 0.79, respectively). The value of the area under the curve of MPV's p-value was > 0.05. However, p-values of CRP and ESR were significant in ROC analysis. CONCLUSIONS: Our study showed that there was no significant difference in the mean platelet volume values between patients with upper and lower urinary tract infections. The use of mean platelet volume as an indicator of upper urinary tract infection is controversial.

The role of specific biomarkers, as predictors of post-operative complications following flexible ureterorenoscopy (FURS), for the treatment of kidney stones: a single-centre observational clinical pilot-study in 37 patients.

BACKGROUND: The number of patients diagnosed and subsequently treated for kidney stones is increasing, and as such the number of post-operative complications is likely to increase. At present, little is known about the role of specific biomarkers, following flexible ureterorenoscopy (FURS) for the surgical treatment of kidney stones. The main aim of the study was to evaluate the role of kidney and infection biomarkers, in patients undergoing FURS. METHODS: Included were 37 patients (24 males, 13 females), who underwent elective FURS, for the treatment of kidney stones. Venous blood samples were collected from each patient: pre-operatively, and at 30 min, 2 and 4 h post-operatively. Changes to kidney (NGAL, Cystatin-C) and infection (MPO, PCT) biomarkers was quantified by means of ELISA, Biomerieux mini-vidas and Konelab 20 analysers. RESULTS: Four patients developed post-operative complications (3 - UTIs with urinary retention, 1 - urosepsis. NGAL concentration increased significantly following FURS (p = 0.034). Although no significant changes were seen in Cystatin C, MPO and PCT (p ≥ 0.05) some key clinical observation were noted. Limiting factors for this study were the small number of patients recruited and restriction in blood sampling beyond 4 h. CONCLUSIONS: Although not confirmative, changes seen to biomarkers such as Cystatin C, NGAL and MPO in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications which can develop following FURS.

The predictive value of procalcitonin for early detection of infection in elderly type 2 diabetes mellitus.

OBJECTIVE: Aimed to investigate the predictive value of procalcitonin (PCT) in early detection of infections in elderly patients with type 2 diabetes, and to discover the optimum cut-off points of PCT. METHODS: A retrospective study was conducted with type 2 diabetic patients (≥65 years) with lung infection (LI), urinary tract infection (UTI) or skin and soft tissue infection (SSTI). The receiver operating characteristic (ROC) curves of the 3 markers (PCT, WBC count, and CRP) were constructed and compared to assess their accuracies in diagnosing. RESULTS: Among the three different groups with LI, UTI or SSTI, the area under the ROC curve (AUC) of PCT was 0.98 (95% confidence interval (CI): 0.96-0.99, p < 0.05) for the LI group, 0.98 (95% CI: 0.96-0.99, p < 0.05) for the UTI group, and 0.97 (95% CI: 0.94-1.00, p < 0.05) for the SSTI group. The optimum cut-off point of PCT level was 0.73 ng/mL (Sn 89.7%, Sp 97.7%) for the LI group, 1.48 ng/mL (Sn 88.9%, Sp 100%) for the UTI group, and 0.73 ng/mL (Sn 85.7%, Sp 97.7%) for the SSTI group. CONCLUSION: PCT demonstrated the strongest correlation with each of the infection types, indicating significant diagnostic value. Optimum cut-off points of PCT levels in elderly diabetes were higher.

A novel predictive tool for prognosis in elderly patients with urinary tract infection: Modified PRACTICE.

PURPOSE: We evaluated whether combining the serum albumin level and the Prediction Rule for Admission policy in Complicated urinary Tract InfeCtion LEiden (PRACTICE) class could be a prognostic predictor in elderly patients with urinary tract infection (UTI). METHODS: We retrospectively included adult patients (age ≥ 65 years) with UTI who were hospitalized in the emergency department (ED) between January 1, 2014 and December 31, 2018. We graded the serum albumin level and classified the PRACTICE score; the modified PRACTICE was defined as the sum of the albumin level grade and the PRACTICE class. We comparatively assessed the predictive value for in-hospital mortality and admission to the intensive care unit (ICU) in survivor and non-survivor groups. RESULTS: In total, the study analysis included 1159 patients, and in-hospital mortality was 3.4% (n = 39). The modified PRACTICE score (4.0 [1.4] vs 6.1 [1.2], p < 0.001) was significantly increased in the non-survivor group. The area under the curve value of factors associated with in-hospital mortality were the Modified Early Warning Score (MEWS) 0.57 (95% CI 0.54-0.60), albumin 0.83 (95% CI 0.81-0.85), PRACTICE 0.71 (95% CI 0.69-0.74), and the modified PRACTICE 0.86 (95% CI 0.84-0.88). Factors associated with ICU admission were MEWS 0.65 (95% CI 0.62-0.68), albumin 0.66 (95% CI 0.64-0.69), PRACTICE 0.66 (95% CI 0.63-0.68), and the modified PRACTICE 0.72 (95% CI 0.69-0.74). CONCLUSION: The modified PRACTICE score can be a useful prognostic predictor in elderly patients with UTI.

Added value of inflammatory markers to vital signs to predict mortality in patients suspected of severe infection.

OBJECTIVE: To evaluate the added value of inflammatory markers to vital signs to predict mortality in patients suspected of severe infection. METHODS: This study was conducted at an acute care hospital (471-bed capacity). Consecutive adult patients suspected of severe infection who presented to either ambulatory care or the emergency department from April 2015 to March 2017 were retrospectively evaluated. A prognostic model for predicting 30-day in-hospital mortality based on previously established vital signs (systolic blood pressure, respiratory rate, and mental status) was compared with an extended model that also included four inflammatory markers (C-reactive protein, neutrophil-lymphocyte ratio, mean platelet volume, and red cell distribution width). Measures of interest were model fit, discrimination, and the net percentage of correctly reclassified individuals at the pre-specified threshold of 10% risk. RESULTS: Of the 1015 patients included, 66 (6.5%) died. The extended model including inflammatory markers performed significantly better than the vital sign model (likelihood ratio test: p < 0.001), and the c-index increased from 0.69 (range 0.67-0.70) to 0.76 (range 0.75-0.77) (p = 0.01). All included markers except C-reactive protein showed significant contribution to the model improvement. Among those who died, 9.1% (95% CI -2.8-21.8) were correctly reclassified by the extended model at the 10% threshold. CONCLUSIONS: The inflammatory markers except C-reactive protein showed added predictive value to vital signs. Future studies should focus on developing and validating prediction models for use in individualized predictions including both vital signs and the significant markers.

Application of the Hartford Hospital Nomogram for Plazomicin Dosing Interval Selection in Patients with Complicated Urinary Tract Infection.

Plazomicin is a new FDA-approved aminoglycoside antibiotic for complicated urinary tract infections (cUTI). In the product labeling, trough-based therapeutic drug management (TDM) is recommended for cUTI patients with renal impairment to prevent elevated trough concentrations associated with serum creatinine increases of ≥0.5 mg/dl above baseline. Herein, the utility of the Hartford nomogram to prevent plazomicin trough concentrations exceeding the TDM trough of 3 µg/ml and optimize the area under the curve (AUC) was assessed. The AUC reference range was defined as the 5th to 95th percentile AUC observed in the phase 3 cUTI trial (EPIC) (121 to 368 µg · h/ml). Observed 10-h plazomicin concentrations from patients in EPIC (n = 281) were plotted on the nomogram to determine an eligible dosing interval (every 24 h [q24h], q36h, q48h). Based on creatinine clearance (CLcr), a 15- or 10-mg/kg of body weight dose was simulated with the nomogram-derived interval. The nomogram recommended an extended interval (q36h and q48h) in 31% of patients. Compared with the 15 mg/kg q24h regimen received by patients with CLcr of ≥60 ml/min in EPIC, the nomogram-derived interval reduced the proportion of patients with troughs of ≥3 µg/ml (q36h, 27% versus 0%, P = 0.021; q48h, 57% versus 0%, P = 0.002) while significantly increasing the number of patients within the AUC range. Compared with the 8 to 12 mg/kg q24h regimen (received by patients with CLcr of >30 to 59 ml/min in EPIC), the nomogram-derived interval significantly reduced the proportion of troughs of ≥3µg/ml in the q48h cohort (72% versus 0%, P < 0.001) while maintaining a similar proportion of patients in the AUC range. Simulated application of the Hartford nomogram optimized plazomicin exposures in patients with cUTI while reducing troughs to <3 µg/ml.

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.

Serum soluble ST2 as a marker of renal scar in pediatric upper urinary tract infection.

BACKGROUND AND OBJECTIVES: Upper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars. RESULTS: Serum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-ß between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively. CONCLUSION: These results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection.

Is there a place for indwelling transurethral catheterization in women with febrile urinary tract infection? A prospective randomized trial.

PURPOSE: To assess the common practice to transiently place an indwelling transurethral catheter in case of hospitalization of women with febrile urinary tract infections. So far, this intervention has not been scientifically investigated. METHODS: Inclusion criteria were female gender, a leucocyte esterase-positive urine dipstick analysis (≥ 250) from urine obtained with a catheter and fever > 38 °C. Patients were randomized 1:1 to either receive an indwelling catheter French 16 or not. The catheter was removed after 24 h without fever (< 37.5 °C). Principal exclusion criteria were a post void residual volume exceeding 50 mL or abnormalities of the urinary tract. Hospital stay and fever in days, the amount of analgetic medication needed and the laboratory parameters WBC and CRP-measured on the day of admission and in predefined intervals thereafter-were study endpoints. RESULTS: 75 patients were included in the final analysis, 36 in the catheter group and 39 in the no-catheter group. Mean age was 39.4 ± 17.7 years and 39.8 ± 15.5 years, respectively (p > 0.05). The mean length of catheterisation was 3.6 ± 1.6 days in the catheter group. There were no differences between the two groups regarding duration of hospitalization and fever, or the amount of analgetic medication needed (all p > 0.05). Additionally, there was no difference in time to WBC < 10 G/L or CRP < 100 mg/L (all p > 0.05). CONCLUSIONS: This prospective, randomized trial provides no evidence to support routine insertion of an indwelling catheter in women with febrile urinary tract infection requiring hospital admission.

Procalcitonin, mid-regional proadrenomedullin and C-reactive protein in predicting treatment outcome in community-acquired febrile urinary tract infection.

BACKGROUND: A reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, those of older age or with comorbidities. Biomarkers have the potential to objectively identify the optimal moment for cessation of therapy. METHODS: A secondary analysis of a randomized placebo-controlled trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days. Patients indicated to receive antimicrobial treatment for more than 14 days were excluded from randomization. The biomarkers procalcitonin (PCT), mid-regional proadrenomedullin (MR-proADM), and C-reactive protein (CRP) were compared in their ability to predict clinical cure or failure through the 10-18 day post-treatment visit. RESULTS: Biomarker concentrations were measured in 249 patients, with a clinical cure rate of 94% in the 165 randomized and 88% in the 84 non-randomized patients. PCT, MR-proADM and CRP concentrations did not differ between patients with clinical cure and treatment failure, and did not predict treatment outcome, irrespective of 7 or 14 day treatment duration (ROCAUC 0.521; 0.515; 0.512, respectively). PCT concentrations at presentation were positively correlated with bacteraemia (τ = 0.33, p < 0.001) and presence of shaking chills (τ = 0.25, p < 0.001), and MR-proADM levels with length of hospital stay (τ = 0.40, p < 0.001), bacteraemia (τ = 0.33, p < 0.001), initial intravenous treatment (τ = 0.22, p < 0.001) and time to defervescence (τ = 0.21, p < 0.001). CRP did not display any correlation to relevant clinical parameters. CONCLUSIONS: Although the biomarkers PCT and MR-proADM were correlated to clinical parameters indicating disease severity, they did not predict treatment outcome in patients with community acquired febrile urinary tract infection who were treated for either 7 or 14 days. CRP had no added value in the management of patients with fUTI. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].

Predictors of grade 3-5 vesicoureteral reflux in infants ≤ 2 months of age with pyelonephritis.

BACKGROUND: This study aimed to assess predictors for grade 3-5 vesicoureteral reflux (VUR) in infants ≤ 2 months of age admitted for first urinary tract infection (UTI). METHODS: Retrospective cohort study of 195 infants ≤ 2 months admitted to a pediatric ward for first UTI between 2006 and 2017. Clinical, laboratory, and imaging data were collected from electronic medical charts. We examined associations between grade 3-5 VUR and different patient characteristics. RESULTS: Twenty infants (10%) were diagnosed with grade 3-5 VUR; all had fever. Infants with grade 3-5 VUR had higher blood neutrophil percentage (BNP) (65% vs. 46%, P < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (2.6 vs. 1.3, P < 0.001), more renal ultrasound abnormalities (prenatal 26% vs. 5%, P = 0.007; postnatal 84% vs. 55%, P = 0.015), and Pseudomonas UTI (15% vs. 1%, respectively, P < 0.001). NLR > 1.65 showed sensitivity 100% and specificity 61% for detecting grade 3-5 VUR. BNP > 53% showed sensitivity 100% and specificity 60% for detecting grade 3-5 VUR. BNP was the best single marker for grade 3-5 VUR with area under the curve (AUC) of 0.82 (95% CI 0.75-0.89). In a multivariate model, AUC for combination of BNP and hydronephrosis was 0.86 (95% CI 0.79-0.93, P = 0.007). CONCLUSIONS: Infants ≤ 2 months of age admitted for a first UTI are at risk for grade 3-5 VUR and thus should undergo a voiding cystourethrography (VCUG) if their renal ultrasound is abnormal or if they have Pseudomonas UTI. Avoiding VCUG can be considered in afebrile infants and in infants with BNP < 53% or NLR < 1.65.

Risk factors and outcomes of urosepsis in patients with calculous pyonephrosis receiving surgical intervention: a single-center retrospective study.

BACKGROUND: Urosepsis is a catastrophic complication, which can easily develop into septic shock and lead to death if not diagnosed early and effectively treated in time. However, there is a lack of evidence on the risk factors and outcomes in calculous pyonephrosis patients. Therefore, this study was conducted to identify risk factors and outcomes of intra- and postoperative urosepsis in this particular population. METHODS: Clinical data of 287 patients with calculous pyonephrosis were collected. In the univariate and multivariate analysis, all patients were divided into urosepsis group and non-urosepsis group. The diagnosis of urosepsis was mainly on the basis of the criteria of American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Patient characteristics and outcomes data were analyzed, and risk factors were assessed by binary logistic regression analysis. RESULTS: Of 287 patients, 41 (14.3%) acquired urosepsis. Univariate analysis showed that white blood cell (WBC > 10*10^9/L) before surgery (P = 0.027), surgery types (P = 0.009), hypotension during surgery (P < 0.001) and urgent surgery (P < 0.001) were associated with intra- and postoperative urosepsis for calculous pyonephrosis patients. In multivariate analysis, hypotension during surgery and urgent surgery were closely related to intra- and postoperative urosepsis. Outcome analysis suggested that patients developing urosepsis had a longer intensive care unit (ICU) stay and postoperative hospital stay and higher mortality. CONCLUSIONS: Hypotension during surgery and urgent surgery were risk factors of intra- and postoperative urosepsis for calculous pyonephrosis patients, which may lead to a prolonged ICU stay, postoperative hospital stay and higher mortality.