Maria Bitsori

Urine Interleukin-8 as a Marker of Vesicoureteral Reflux in Infants

OBJECTIVE. Vesicoureteral reflux (VUR) is a common finding in children presenting with urinary tract infection (UTI) and prenatally diagnosed urinary tract dilatation and in relatives of index patients. Children with VUR are at risk for ongoing renal damage with subsequent infections. Detecting VUR and renal scarring currently depends on imaging modalities with associated problems of radiation, invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis and would also help in identifying relatives of index cases who should be screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract in response to inflammatory stimuli and has been shown to increase during acute UTI. The objective of this study was to assess the urine levels of IL-8 as a noninvasive marker of VUR in infants in the absence of a recent UTI episode. METHODS. We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to 2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8 evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR (24 infants aged 0.15–1.95 years, median 0.43); group B, subjects with a history of UTI but negative investigation for VUR (14 infants aged 0.32–1.95 years, median 0.57); and group C, subjects without any history of acute or chronic condition that might impair renal function (21 infants aged 0.08–1.92 years, median 0.33). IL-8 concentrations were determined by a commercially available quantitative enzyme-linked immunosorbent assay. To avoid dilution effects, urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary creatinine. RESULTS. Results were presented as medians and ranges. The Kruskal-Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order correlation test were performed for the univariate analysis. Two-tailed P values were calculated and the conventional level of significance P < .05 was applied in all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52 weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively, before IL-8 determination. No significant difference was noted in the length of the UTI-free period between groups A and B (P = .469). Urine creatinine concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and 1.15 μmol/mL, respectively; P = .080). The median urine IL-8/creatinine concentrations (pg/μmol) were 40.5 (range, 2.04–3874) in group A, 1.91 (range, 0.001–386) in group B, and 2.47 (range, 0.002–55.6) in group C. Urine IL-8/creatinine concentrations were significantly higher in group A than both in group B (P = .0003) and in group C (P < .0001). No significant difference was observed between groups B and C (P = .749). In group A, no significant correlation was shown between IL-8/creatinine concentrations and the presence of renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P = .155). A receiver-operator characteristic curve was constructed by plotting the sensitivity versus the specificity for different cutoff concentrations of IL-8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5 pg/μmol, the sensitivity of this marker in diagnosing VUR was 88%, the specificity 69%, the positive prognostic value 66%, and the negative prognostic value 89%. In higher cutoff concentrations, specificity of the marker increased but sensitivity rapidly decreased. CONCLUSIONS. We present evidence that urine IL-8 concentrations remain elevated in infants with VUR even in the absence of UTI and that a cutoff of 5 pg/μmol IL-8/creatinine is of high sensitivity and adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and renal scarring have already been reported; however, the present study is, to our knowledge, the first to confirm significant differences between infants with VUR and infants with a history of UTI alone and healthy controls, and to suggest a reliable cutoff concentration for diagnosing VUR. Our findings additionally suggest that inflammatory process in VUR is ongoing even after UTI has resolved, pointing against the currently held belief that sterile reflux cannot harm kidneys. The chronic inflammatory cell infiltrate associated with reflux nephropathy rather than VUR itself might offer an explanation for the secretion of IL-8, which may well be independent of reflux grade. Using urine IL-8 for diagnosing VUR is not free of limitations, because IL-8 may be elevated as a result of urinary tract manipulation or undetected UTI. In addition, this study focused on infants and not in older children with longstanding VUR. Increased urine IL-8 concentrations after UTI has resolved is a promising noninvasive marker for an initial screening for VUR in infancy with high sensitivity and adequate specificity.

Waist circumference as a screening tool for the identification of adolescents with the metabolic syndrome phenotype

OBJECTIVES Most published definitions of the metabolic syndrome (MetS) in children and adolescents include increased waist circumference (WC) in their criteria. To assess the clinical relevance of WC in identifying adolescents with the MetS phenotype and adverse fitness patterns, we divided a cohort of 15-year-old schoolchildren in quartiles for WC, and compared the subjects of the extreme quartiles for the presence of cardiovascular (CVD) risk factors, their clustering, insulin resistance and body fitness. POPULATION AND METHODS From the original cohort of 635 adolescents investigated for childhood CVD risk, anthropometric parameters, blood pressure, fitness indexes, and serum fasting glucose, insulin and lipids were analyzed in 105 adolescents of the highest (> or =75th percentile) and 102 of the lowest (< or =25th percentile) WC quartile. RESULTS Adolescents with WC > or =75th percentile presented with significantly higher fasting insulin (17+/-0.9 vs. 9.1+/-1.0 microIU/mL), triglycerides (78.0+/-3.4 vs. 62.3+/-3.3 mg/dL), LDL-cholesterol (106.8+/-2.8 vs. 96.1+/-2.8 mg/dL), homeostasis model assessment index (HOMA-IR) (3.29+/-1.8 vs. 1.81+/-0.2), systolic blood pressure (125.6+/-1.1 vs. 116.0+/-1.1 mm Hg), and diastolic blood pressure (78.0+/-0.9 vs. 71.5+/-0.9 mm Hg) and significantly lower HDL-cholesterol (46.2+/-1.2 vs. 53.4+/-1.1 mg/dL) and physical fitness as compared with their peers with WC < or =25th percentile. Clustering of three CVD factors pointing to a full MetS phenotype was found for 13.5% of the 15 year olds with WC>75th percentile. CONCLUSIONS Our findings suggest that WC > or =75th percentile is associated with the MetS phenotype and reduced activity in adolescence, and confirm the clinical relevance of WC as a tool for the identification of adolescents with increased CVD risk.

Pseudomonas aeruginosa urinary tract infection in children: risk factors and outcomes.

PURPOSE Pseudomonas aeruginosa is an unusual uropathogen that is mostly responsible for nosocomial or catheter associated urinary tract infections in adults. Data about P. aeruginosa urinary tract infections in children are scarce. We investigated P. aeruginosa urinary tract infections in children in a well-defined area. MATERIALS AND METHODS Clinical, laboratory and radiological characteristics of all children with P. aeruginosa urinary tract infections were compared to those of gender matched children with community acquired Escherichia coli urinary tract infections during a 12-year period. RESULTS A total of 35 children with 43 P. aeruginosa urinary tract infection episodes representing 6.7% of total urinary tract infection cases during the study period were compared to 70 children with E. coli urinary tract infections. Children with P. aeruginosa more often presented with a history of at least 1 previous urinary tract infection episode (p <0.0001), hospitalization (p = 0.0001), use of antibiotics (p = 0.0001), malformations predisposing to urinary tract infections (p = 0.004), vesicoureteral reflux (p <0.0001), abnormal dimercapto-succinic acid scan (p = 0.0003), longer hospitalization and surgery. Use of antibiotics either as prophylaxis or as treatment within the preceding 2 months was demonstrated by multivariate logistic regression analysis as the single independent risk factor for P. aeruginosa urinary tract infections (odds ratio 21.6, 95% CI 4.65-100, p = 0.0001). P. aeruginosa isolates were often resistant to gentamicin (27.9%) and ceftazidime (13.9%) but remained sensitive to carbapenems and ciprofloxacin. CONCLUSIONS P. aeruginosa urinary tract infection is associated with distinct risk factors and outcomes, and should be considered in predisposed children with symptoms of urinary tract infection who are on prophylaxis or have a history of a recent course of antibiotics.

Insulin‐induced oedema in children and adolescents

Abstract:  Oedema is an uncommon complication of insulin therapy, which has only rarely been reported in childhood. We describe a case of a 12‐year‐old girl with newly diagnosed type 1 diabetes, who presented with oedema of the lower extremities and periorbitally, one day after the initiation of insulin treatment. Other causes of oedema were excluded. Following administration of frusemide, oedema resolved within ten days. An extended review of the literature revealed only nine cases of insulin‐induced oedema in children and adolescents aged ≤16 years. In conclusion, insulin‐induced oedema should be considered during the introduction of insulin therapy in children and adolescents with newly diagnosed type 1 diabetes. Loop diuretics and ephedrine may be beneficial when spontaneous resolution does not occur.

Deep venous thrombosis in a child associated with an abnormal inferior vena cava.

Congenital anomalies of the inferior vena cava (IVC), such as absence or atresia, although well documented, are uncommon and result from aberrant development during embryogenesis. Absence or atresia of the IVC is usually discovered accidentally. Patients are typically asymptomatic of the condition itself. Many concurrent cardiovascular‐associated abnormalities have been described. We report a 10‐y‐old boy admitted to the emergency room with painful swelling of his right lower limb without previous trauma or surgery. After 3 d, swelling also involved the left lower limb. A Doppler ultrasound of the lower limbs revealed bilateral thrombosis of the vena iliaca communis, vena iliaca externa, femoral vein communis and superficial extending to the IVC. Magnetic resonance imaging (MRI) of the abdomen was performed. On MRI, we demonstrated a hypoplastic IVC. The results of blood coagulation studies, including levels of antiphospholipid antibodies, proteins C and S, and antithrombin III, were normal. The patient was treated with intravenous heparin for 8 d and discharged with oral warfarin therapy, which has been recommended for life.

Vaccination coverage among adolescents in certain provinces of Greece

AIM To estimate the vaccination coverage in a sample of adolescents in Greece. METHODS Vaccination status was estimated in 483 adolescents aged 15-19 y in four prefectures. The criteria for full vaccination were based on the recommendations of the Greek National Vaccination Schedule. RESULTS The participation rate in the study was 78.7% (380/483 adolescents). The rates of full vaccination were 94.2% for poliomyelitis, 78.4% for hepatitis B, 77.4% for BCG, 65.0% for tetanus and 54.4% for diphtheria. The rates of full vaccination for measles, rubella and mumps were 65.0%, 57.6%, and 56.0%, respectively. For pertussis, the full vaccination rate was only 36.0%, and 7.1% of the study population was totally unvaccinated. The most missed dose for all vaccines was the final booster dose, which is usually administered in older children or adolescents. CONCLUSION Adolescent vaccination coverage was not satisfactory in this study, mainly due to non-compliance to the final booster dose. Completion of missing vaccines at this age represents the last opportunity for massive intervention and would be of essential value for individual and community protection against common preventable diseases.

Ochrobactrum anthropi bacteraemia in immunocompetent children.

Ochrobactrum anthropi is an emerging pathogen in immunocompromised patients but infections with the bacterium have very rarely been documented in normal hosts. We report the characteristics of O. anthropi bacteraemia in 11 immunocompetent children, aged 2 months to 7 y, hospitalized in a general hospital during a 5-y period. Children commonly presented with fever, non-specific respiratory or gastrointestinal manifestations, leukocytosis and neutrophilia and had a rapid recovery, even when they did not receive a specific treatment. In 10 cases positive blood cultures were obtained on admission and in all cases subsequent cultures were sterile. In conclusion, O. anthropi may cause bacteraemia in immunocompetent hosts, although further studies are required to clarify whether these isolates represent pseudobacteraemia or whether O. anthropi is a potential pathogen of low virulence.

Pediatric urinary tract infections: diagnosis and treatment

Urinary tract infection (UTI) is the most common serious bacterial infection in childhood. Prompt diagnosis and treatment are required for the optimal clinical outcome and the prevention of long-term morbidity and sequelae. Diagnosis and treatment of UTI may seem to be easy tasks, but they remain among the most controversial issues in pediatrics. Consequently, children suspected for UTIs are investigated and treated differently in different settings. The absence of typical clinical presentation and the uncertainties in setting the index of suspicion, collecting appropriate urine samples and interpreting results, combined with different antibiotic policies in the face of increasing resistance of uropathogens, contribute to the controversy. Recently issued guidelines have attempted to settle several thorny aspects in diagnosis and treatment, but quite a few issues still remain controversial. In this review, the authors explore the current situation on diagnosis and treatment of childhood UTI in better understanding their pathogenesis and prevalence in different child populations, discuss recently evaluated diagnostic tests and thenew management guidelines.

Siesta and sleep patterns in a sample of adolescents in Greece

Background: Sleep behaviors and disturbances in adolescence are being increasingly investigated. The aim of the present study was to investigate the sleep habits of adolescents living in provincial Greece.

Rickettsia typhi infection in childhood

Rickettsia typhi infection (murine typhus) is generally underdiagnosed in childhood, as clinical presentations are often non‐specific. We present the manifestations in nine children hospitalized in the Department of Paediatrics of the University Hospital, Heraklion, Crete, over a 3‐y period from 1998 to 2000. Titres >1:400 for IgM and >1:960 for IgG and/or a fourfold increase in a second sample were considered strongly suggestive of acute infection. Children presented with prolonged fever, hepatosplenomegaly and lymphadenopathy. Five children presented with a rash. Unusual manifestations included aseptic meningitis and Kawasaki‐like presentation. Laboratory findings included anaemia, leucopenia, and thrombocytopenia. Three children were treated with appropriate antibiotic regimens and all nine had a complete recovery.