Accuracy of NGAL as a Biomarker for Urinary Tract Infection in Young Febrile Children: An Individual Patient Data Meta-Analysis.

OBJECTIVE: To compare the accuracy of urine neutrophil gelatinase-associated lipocalin (NGAL) and leukocyte esterase (LE) for the diagnosis of urinary tract infection (UTI) in children. STUDY DESIGN: We performed a systematic review and individual patient data meta-analysis of studies that examined urine NGAL as a marker of UTI in children <18 years of age. We created a standardized definition of UTI and applied it to all included children. We compared sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of NGAL with LE. RESULTS: We included individual patient data from 3 studies for a total of 845 children. Included children had a mean age of 0.9 years (SD, 0.6 years). Using a cutoff of 32.7 ng/mL, NGAL had a sensitivity of 90.3% (95% CI: 83.2%-95.0%) and specificity of 93.7% (95% CI: 91.7%-95.4%) for the diagnosis of UTI. LE, using a cutoff of ≧ trace had a sensitivity of 81.1% (95% CI: 72.5%-87.9%) and specificity of 97.0% (95% CI: 95.4%-98.1%). The AUC for NGAL was 0.95 (95% CI: 0.92-0.98). The AUC for LE was 0.90 (95% CI: 0.86-0.93). CONCLUSION: In young, febrile children, urinary NGAL is more sensitive for the diagnosis of UTI than LE but is slightly less specific.

Biomarkers for febrile urinary tract infection in children.

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. METHODS: This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. RESULTS: We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. CONCLUSIONS: NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

Hemolysis and Neurologic Impairment in PAMI Syndrome: Novel Characteristics of an Elusive Disease.

PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare early-onset autoinflammatory disease associated with various hematologic findings, including chronic neutropenia and pancytopenia. We report a unique case of PAMI syndrome in a toddler with transfusion-dependent hemolytic anemia, hepatosplenomegaly, failure to thrive, developmental delay, and multiple malformations. Because of acute inflammatory-driven decompensation, anakinra was started with dramatic improvement of both the hematologic and neurologic involvement. A customized next-generation sequencing panel later identified a de novo pathogenic variant in the PSTPIP1 gene, confirming the diagnosis. Our case illustrates the broad spectrum of phenotypes associated with PAMI syndrome, which should be considered in any case of unexplained cytopenias associated with autoinflammatory stigmata. It is also one of the few reports of neurologic involvement in PSTPIP1-associated inflammatory diseases. Increased awareness of this rare disease and early performance of genetic testing can correctly diagnose PAMI syndrome and prevent disease complications.

Preoperative urine nitrite versus urine culture for predicting postoperative fever following flexible ureteroscopic lithotripsy: a propensity score matching analysis.

PURPOSE: Multiple studies have reported that preoperative positive urine culture is an independent risk factor for postoperative fever (POF) after ureteroscopy (URS). Urine nitrite is associated urinary tract infections (UTIs). However, none of studies has explored the role of urine nitrite in the prediction of POF after flexible URS (fURS). METHODS: Patients who underwent fURS by the same surgeon between 2009 and 2019 were screened. Sensitivity and specificity of urine culture and urine nitrite were calculated. Propensity score (PS) matching was performed to get a baseline-balanced retrospective cohort to avoid potential bias. Receiver operating characteristic-area under the curve (ROC-AUC) calculated was used to determine the predictive power of models. Decision curve analysis (DCA) was plotted to obtain the clinical benefit of the models. RESULTS: Poseoperative fever (POF) is defined as the temperature of the patient higher than 38 ℃ within 72 h after operation, with no sign of infection in other systems. 31(2.8%) of 1095 cases had POF after fURL. Urine nitrite had a better specificity than urine culture for POF diagnosis (P < 0.001). After the PS matching, a well-balanced cohort of 24 POF group and 96 no-POF group was produced. The mean AUC from the bootstrap resampling method for urine nitrite model (AUC: 0.8736; 95% CI: 0.8731-0.8743) was significantly increased than that of the urine culture model (AUC: 0.8385; 95% CI: 0.8378-0.8392). The application of two kinds of POF predicting models could bring clinical net benefit when the probability is < 35%. However, urine nitrite model showed a better clinical net benefit acquirement compared to the urine culture model. CONCLUSION: Preoperative positive urine nitrite may play a pivotal role in the prediction of POF after fURS and needs to be validated by future evidence.

Influence of a high-temperature programme on serum, urinary and sweat levels of selenium and zinc.

INTRODUCTION: The effect of hyperthermia on the antioxidant system in the human organism is well known. AIM: The objective of this study was to observe the effects of heat on the concentration of Se and Zn, elements related to antioxidant systems. METHODS: Twenty-nine subjects voluntarily participated in this study. They were divided into a control group (CG; n = 14) and an experimental group (EG; n = 15). All of them underwent two incremental tests until exhaustion in normothermia (22 °C, 20-40%RH) and hyperthermia (42 °C, 20-40%RH). EG experienced nine sessions of repeated heat exposure at high temperatures (100 °C, 20%RH) for three weeks (HEHT). After the intervention, the initial measurements were repeated. Urine and blood samples were collected before and after each test. Additionally, sweat samples were collected after tests in hyperthermia. RESULTS: There were no significant changes in serum. An increase in the elimination of Zn and Se in EG was observed in urine after HEHT (p < .05). The elimination of Zn by sweating decreased after HEHT in EG (p < .05). CONCLUSIONS: Exposure to heat at high temperatures increases the urinary excretion of Se and Zn.

Serum and urine metabolomics based on UPLC-Q-TOF/MS reveals the antipyretic mechanism of Reduning injection in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDN), a patented traditional Chinese medicine, has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear. AIM OF THE STUDY: To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper. MATERIALS AND METHODS: Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1ß, IL-6, TNF-α, PGE2 and cAMP. RESULTS: The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine, leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine, all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance. CONCLUSIONS: RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine.

Urine dipstick low sensitivity for UTI diagnosis in febrile infants *.

Background: Urine cultures are usually obtained from 0- to 2-month-old febrile infants, while in older children they are obtained more selectively. In 3- to 23-month-old children, urinary tract infection (UTI) diagnosis requires both positive culture and dipstick, but data are scarce regarding 0- to 2-month-old infants. We assessed dipstick performance for UTI diagnosis in 0-2 vs. 3- to 23-month-old children. Methods: A case-control study, conducted between 2015 and 2016, in southern Israel. Sensitivity and specificity of urine dipstick for diagnosing UTI were assessed. We compared dipstick false-negative (FN) and true-positive (TP) groups; high FN rate indicates low sensitivity. Results: Overall, 434 positive and 571 sterile urine culture episodes were included. Dipstick sensitivity was 63% in 0-2 month old children; 93% for supra-pubic aspiration (SPA), and ∼50% for non-SPA sampling method. However, sensitivity was >90% for 3-5 and 6- to 23-month-old children. In univariate analysis, younger age, hospitalization, lower temperature, short fever duration, lower leukocyte blood levels, neutrophils, stabs and C-reactive protein, and absent future UTI within <1 year were associated with FN compared with TP. In multivariate analysis, among positive culture episodes, age 0-2 months (odds ratio, OR = 6.60) and non-SPA sampling method (OR = 8.39) were associated with FN episodes. Conclusions: Dipstick lower sensitivity for diagnosing UTI in febrile infants 0-2 months old vs. their older counterparts, was associated with non-SPA sampling method, lower inflammatory markers, lower temperature and low risk for future UTI. This suggests that positive culture in negative dipstick episodes may not reflect a true UTI.

High prevalence of hypohydration in occupations with heat stress-Perspectives for performance in combined cognitive and motor tasks.

PURPOSE: To evaluate the prevalence of dehydration in occupational settings and contextualize findings to effects on performance in cognitively dominated tasks, simple and complex motor tasks during moderate and high heat stress. METHODS: The study included an occupational part with hydration assessed in five industries across Europe with urine samples collected from 139 workers and analyzed for urine specific gravity. In addition, laboratory experiments included eight male participants completing mild-intensity exercise once with full fluid replacement to maintain euhydration, and once with restricted water intake until the dehydration level corresponded to 2% bodyweight deficit. Following familiarization, euhydration and dehydration sessions were completed on separate days in random order (cross-over design) with assessment of simple motor (target pinch), complex motor (visuo-motor tracking), cognitive (math addition) and combined motor-cognitive (math and pinch) performance at baseline, at 1°C (MOD) and 2°C (HYPER) delta increase in body core temperature. RESULTS: The field studies revealed that 70% of all workers had urine specific gravity values ≥1.020 corresponding to the urine specific gravity (1.020±0.001) at the end of the laboratory dehydration session. At this hydration level, HYPER was associated with reductions in simple motor task performance by 4±1%, math task by 4±1%, math and pinch by 9±3% and visuo-motor tracking by 16±4% (all P<0.05 compared to baseline), whereas no significant changes were observed when the heat stress was MOD (P>0.05). In the euhydration session, HYPER reduced complex (tracking) motor performance by 10±3% and simple pinch by 3±1% (both P<0.05, compared to baseline), while performance in the two cognitively dominated tasks were unaffected when dehydration was prevented (P>0.05). CONCLUSION: Dehydration at levels commonly observed across a range of occupational settings with environmental heat stress aggravates the impact of hyperthermia on performance in tasks relying on combinations of cognitive function and motor response accuracy.

Antimicrobial prophylaxis for transurethral resection of bladder tumor: A retrospective comparison of preoperative single-dose administration of piperacillin and tazobactam/piperacillin.

We aimed to clarify prophylactic antimicrobial effects of single-dose piperacillin (PIPC) for perioperative infections in the transurethral resection of bladder tumor (TURBT) in comparison with those of single-dose tazobactam/piperacillin (TAZ/PIPC) through a retrospective analysis. We analyzed data from 192 TURBT patients treated with single-dose (4 g) intravenous PIPC (P group) between April 2015 and April 2017. For comparison, we analyzed data from 50 TURBT patients treated with single-dose (4.5 g) intravenous TAZ/PIPC (T/P group) between June 2013 and April 2014. We compared the perioperative incidences of fever (≥38 °C) and bacteriuria in the two groups. The number of febrile patients was four (2.1%) in the P group and one (2.0%) in the T/P group, without significant difference (p = 0.970). Among these febrile patients, urine and blood samples of two patients in the P group tested positive for bacterial cultures of Citrobacter koseri and Enterococcus faecalis, respectively. None of the patients in the T/P group tested positive for urine culture, postoperatively. However, 22 patients (18.2%) in the P group tested positive for urine culture, and Staphylococcus epidermidis (six patients), E. faecalis (three patients), Escherichia coli (three patients), Streptococcus agalactiae (two patients), Staphylococcus aureus (two patients), and C. koseri (one patient) were isolated. There was no significant difference in the incidence of bacteriuria in these two groups (p = 0.055). Based on these results, single-dose PIPC administration for the prevention of perioperative infections in TURBT was as effective as TAZ/PIPC.

Urinary C-megalin for screening of renal scarring in children after febrile urinary tract infection.

BackgroundFebrile urinary tract infection (fUTI) in children may cause renal scarring. This study aimed to investigate the usefulness of urinary biomarkers for diagnosing renal scarring after fUTI.MethodsThirty-seven children (median age: 1.36 years, range: 0.52-12.17 years, 25 boys) with a history of fUTI, who underwent renal scintigraphy for 4 months or longer after the last episode of fUTI, were analyzed. A spot urine sample was obtained on the day of renal scintigraphy to measure levels of total protein, N-acetyl-ß-D-glucosaminidase (NAG), ß2-microglobulin (BMG), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and C-megalin (full-length megalin). Results were corrected for urinary creatinine (Cr) and compared between the group with renal scarring (n=23) and that without scarring (n=14). Urinary levels of C-megalin were also measured in healthy control subjects.ResultsNo significant differences in total protein, NGAL, L-FABP, NAG, and BMG levels were found between the groups. However, C-megalin levels were significantly higher in the renal scarring group than in the non-renal scarring group and healthy controls (P<0.001). A cutoff value of 6.5 pmol/nmol of urinary C-megalin/Cr yielded 73.9% of specificity and 92.9% of sensitivity.ConclusionUrinary C-megalin is useful for diagnosing renal scarring caused by fUTI.

Urine Cultures in Hospitalized Geriatric Patients Presenting With Fever.

INTRODUCTION: Urine cultures are commonly ordered in geriatric patients presenting with fever in the emergency department, but it is unclear if indiscriminate urine culture testing is warranted. MATERIALS AND METHODS: We selected 708 consecutive geriatric patients with a chief complaint of fever to determine the clinical usage (changes in antibiotic therapy according to culture results) and the costs of culturing the urine that included the need for catheterization to obtain a sample for culture and complications from catheterization. We divided the patients into those with and without an extraurinary tract source for fever on admission. RESULTS: Urine cultures were performed in 74.9% (233/312) of the patients with a source for the fever outside the urinary tract and required urinary catheterization to obtain a sample in 36.8% (95/233) of those patients. Cultures were positive for bacteria 29.6% of the time (69/233), but did not result in the change of antibiotic treatment in any of the patients. Urine cultures were performed in 92.6% (326/352) of the patients without an extraurinary tract source for the fever, required catheterization in 49.7% (162/326) of the patients and 58.3% (190/326) of the cultures were positive for bacteria. Urine culture sensitivities changed antibiotic therapy in 24.2% (46/190) of the patients. There were no patients in either group with complications from urinary catheterization, but indwelling catheter rates increased inappropriately in both the groups. CONCLUSIONS: We conclude that urine culture testing is unnecessary in hospitalized geriatric patients who on admission have an extraurinary tract source for their fever, but it has clinical usage when the source for the fever on admission is unclear.

Afebrile Infants Evaluated in the Emergency Department for Serious Bacterial Infection.

OBJECTIVES: Afebrile infants 0 to 60 days of age are sometimes evaluated for serious bacterial infection (SBI). Our objective was to describe the clinical and laboratory findings in this population and compare them to their febrile counterparts. METHODS: We performed a retrospective observational study comparing afebrile infants undergoing an SBI evaluation to those evaluated for fever. RESULTS: We included infants who were admitted to the hospital and had at least 2 of 3 following bacterial cultures: blood, urine, or cerebrospinal fluid. Of the 1184 infants presenting to the emergency department with chief complaints that may prompt an SBI evaluation, 579 patients met our inclusion criteria with 362 in the fever group and 217 in the afebrile group. The most common chief complaints in the afebrile group were respiratory symptoms (27%), seizure (22%), vomiting/diarrhea (21%), and apparent life-threatening event (11%). Rates of true-positive blood, urine, and cerebrospinal fluid cultures were 2%, 2.4%, and 0.9% respectively. All cases of bacterial meningitis were in the fever group antibiotics (P = 0.16). Infants with fever were more likely to receive antibiotics (P < 0.001), although there were no statistical differences between the 2 groups in the rates of positive blood or urine cultures. CONCLUSIONS: Afebrile infants make up a significant percentage of SBI evaluations in the emergency department. Respiratory symptoms, vomiting, and seizure-like activity are common presentations. Although rates of bacteremia and urinary tract infection are higher in the febrile group, this did not reach statistical significance, and therefore afebrile infants should still be considered at risk for SBI.

Undernutrition, Vitamin A and Iron Deficiency Are Associated with Impaired Intestinal Mucosal Permeability in Young Bangladeshi Children Assessed by Lactulose/Mannitol Test.

BACKGROUND: Lactulose/mannitol (L:M) test has been used as a non-invasive marker of intestinal mucosal -integrity and -permeability (enteropathy). We investigated the association of enteropathy with anthropometrics, micronutrient- status, and morbidity in children. METHODS: The urine and blood samples were collected from 925 children aged 6-24 months residing in Mirpur slum of Dhaka, Bangladesh during November 2009 to April 2013. L:M test and micronutrient status were assessed in the laboratory of International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b) following standard procedure. RESULTS: Mean±SD age of the children was 13.2±5.2 months and 47.8% were female. Urinary- lactulose recovery was 0.264±0.236, mannitol recovery was 3.423±3.952, and L:M was 0.109±0.158. An overall negative correlation (Spearman's-rho) of L:M was found with age (rs = -0.087; p = 0.004), weight-for-age (rs = -0.077; p = 0.010), weight-for-length (rs = -0.060; p = 0.034), mid-upper-arm-circumference (rs = -0.098; p = 0.001) and plasma-retinol (rs = -0.105; p = 0.002); and a positive correlation with plasma α-1-acid glycoprotein (rs = 0.066; p = 0.027). However, most of the correlations were not very strong. Approximately 44% of children had enteropathy as reflected by L:M of ≥0.09. Logistic regression analysis revealed that younger age (infancy) (adjusted odds ratio (AOR) = 1.35; p = 0.027), diarrhea (AOR = 4.00; p = 0.039) or fever (AOR = 2.18; p = 0.003) within previous three days of L:M test were the risk factors of enteropathy (L:M of ≥0.09). CONCLUSIONS: Enteropathy (high L:M) is associated with younger age, undernutrition, low vitamin A and iron status, and infection particularly diarrhea and fever.

Importance of Urine Dipstick in Evaluation of Young Febrile Infants With Positive Urine Culture: A Spanish Pediatric Emergency Research Group Study.

BACKGROUND AND OBJECTIVES: Guidelines from the American Academy of Pediatrics define urinary tract infection (UTI) as the growth of greater than 50,000 ufc/mL of a single bacterium in a urine culture with a positive urine dipstick or with a urinalysis associated. Our objective was to evaluate the adequacy of this cutoff point for the diagnosis of UTI in young febrile infants. METHODS: Subanalysis of a prospective multicenter study developed in RISeuP-SPERG Network between October 11 and September 13. To carry out the study, it was performed a comparison of analytical and microbiological characteristics of patients younger than 90 days with fever without focus, taking into account the results of urine dipstick and urine culture. RESULTS: Of a total of 3333 infants younger than 90 days with fever without focus which were included in the study, 538 were classified as UTI in accordance with American Academy of Pediatrics' guidelines. These patients were similar to those who had a positive urine dipstick and a urine culture yielding of 10,000 to 50,000 ufc/mL, and they were different from those who had a normal urine dipstick and a urine culture >50,000 ufc/mL, being focused on the isolated bacteria and blood biomarkers values. Forty-five invasive bacterial infections were diagnosed (5.9% of the 756 with a urine culture >10,000 ufc/mL). Half of the infants with a normal urine dipstick diagnosed with invasive bacterial infections were younger than 15 days. CONCLUSIONS: It might be inadequate to use a threshold of 50,000 cfu/mL to consider a urine culture as positive in young febrile infants given the fact that it would misdiagnose several UTIs.

Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL).

BACKGROUND: Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis. METHODS: In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA). RESULTS: uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, p<0.001). A receiver operating characteristic curve comparison was done for tested parameters and encouraging results were obtained for uNGAL (AUC=0.952). A cut-off value of 29.4 ng/mL had 92.5% sensitivity and 90.7% specificity. We showed that uNGAL can also serve in differentiating acute pyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL). CONCLUSIONS: uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.

Assessing the Utility of Urine Testing in Febrile Infants Aged 2 to 12 Months With Bronchiolitis.

OBJECTIVES: The aims of the study were to investigate whether the prevalence of urinary tract infections (UTIs) in febrile infants aged 2 to 12 months with bronchiolitis is higher than the presumed prevalence of asymptomatic bacteriuria (1%) in similarly aged patients and thus to determine whether UTI testing is necessary for these patients. METHODS: This was a prospective cohort study in which we enrolled a convenience sample of febrile infants aged 2 to 12 months with a clinical diagnosis of bronchiolitis. All patients were seen in the emergency department at a large children's hospital between November 1, 2011 and April 15, 2012, had reported or documented fever higher than 38°C, and had urine collected for determination of the presence of UTI. After the conclusion of enrollment, a chart review was conducted to assess missed cases. RESULTS: Positive urine cultures were found in 6/90 (6.7%) patients (confidence interval, 2.5%-13.9%). The positive urine cultures and urinalysis results were found in 4/90 (4.5%) patients (confidence interval, 1.2%-11%). CONCLUSIONS: In our patient population, a significant proportion of infants aged 2 to 12 months who present with bronchiolitis and fever have a concurrent UTI. Obtaining a urine specimen for UTI testing should be considered in infants aged 2 to 12 months with bronchiolitis and fever. A larger multicenter study is needed to further assess the risk factors for UTIs in this patient population.

Urinary proteins, vitamin D and genetic polymorphisms as risk factors for febrile urinary tract infection and relation with bacteremia: a case control study.

OBJECTIVE/PURPOSE: Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia. METHODS: A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, ß-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF. RESULTS: IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher ß-defensin 2 production. CONCLUSION: Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype.

Evaluation of urinary prostaglandin E2 metabolite as a biomarker in infants with fever due to viral infection.

We have investigated the clinical feasibility of the major urinary metabolite of prostaglandin (PG) E2, tetranor-PGEM, as a biomarker of inflammation in infants with fever. We tested two different and clinically relevant sampling methods, using self-adhesive urinary bags or gauze pads, with respect to stability of tetranor-PGEM and ease of sampling from infants. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis was used to quantify tetranor-PGEM in urine, and different normalization parameters, i.e., urinary creatinine and body surface area, were investigated. To study inflammation, infants (1 month-1 year) that were hospitalized with fever of unknown origin at admittance (n=14) were compared to age-matched healthy controls (n=14). Levels of urinary tetranor-PGEM in infants with viral induced fever were increased compared to controls (102.4±56.2 vs. 37.0±21.6pmol/ml/m(2) body surface area, p<0.001). We conclude that urinary tetranor-PGEM is a potential non-invasive biomarker of inflammation in infants.

Aetiology of acute febrile episodes in children attending Korogwe District Hospital in north-eastern Tanzania.

INTRODUCTION: Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH). METHODS: A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was performed in selected cases to test for bacterial infection and a chest radiograph was requested if pneumonia was suspected. Diagnosis was based on both clinical and laboratory investigations. RESULTS: A total of 867 patients with a median age of 15.1 months (Interquartile range 8.6-29.9) were enrolled from January 2013 to October 2013. Respiratory tract infections were the leading clinical diagnosis with 406/867 (46.8%) of patients diagnosed with upper respiratory tract infection and 130/867 (15.0%) with pneumonia. Gastroenteritis was diagnosed in 184/867 (21.2%) of patients. Malaria infection was confirmed in 72/867 (8.3%) of patients. Bacterial infection in blood and urine accounted for 26/808 (3.2%) infections in the former, and 66/373 (17.7%) infections in the latter. HIV infection was confirmed in 10/824 (1.2%) of patients. Respiratory tract infections and gastroenteritis were frequent in patients under 36 months of age (87.3% and 91.3% respectively). Co-infections were seen in 221/867 (25.5%) of patients. The cause of fever was not identified in 65/867 (7.5%) of these patients. CONCLUSIONS: The different proportions of infections found among febrile children reflect the causes of fever in the study area. These findings indicate the need to optimise patient management by developing malaria and non-malaria febrile illnesses management protocols.