Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study.

OBJECTIVE: Type 1 diabetes is associated with compositional differences in gut microbiota. To date, no microbiome studies have been performed in maturity-onset diabetes of the young 2 (MODY2), a monogenic cause of diabetes. Gut microbiota of type 1 diabetes, MODY2, and healthy control subjects was compared. RESEARCH DESIGN AND METHODS: This was a case-control study in 15 children with type 1 diabetes, 15 children with MODY2, and 13 healthy children. Metabolic control and potential factors modifying gut microbiota were controlled. Microbiome composition was determined by 16S rRNA pyrosequencing. RESULTS: Compared with healthy control subjects, type 1 diabetes was associated with a significantly lower microbiota diversity, a significantly higher relative abundance of Bacteroides, Ruminococcus, Veillonella, Blautia, and Streptococcus genera, and a lower relative abundance of Bifidobacterium, Roseburia, Faecalibacterium, and Lachnospira. Children with MODY2 showed a significantly higher Prevotella abundance and a lower Ruminococcus and Bacteroides abundance. Proinflammatory cytokines and lipopolysaccharides were increased in type 1 diabetes, and gut permeability (determined by zonulin levels) was significantly increased in type 1 diabetes and MODY2. The PICRUSt analysis found an increment of genes related to lipid and amino acid metabolism, ABC transport, lipopolysaccharide biosynthesis, arachidonic acid metabolism, antigen processing and presentation, and chemokine signaling pathways in type 1 diabetes. CONCLUSIONS: Gut microbiota in type 1 diabetes differs at taxonomic and functional levels not only in comparison with healthy subjects but fundamentally with regard to a model of nonautoimmune diabetes. Future longitudinal studies should be aimed at evaluating if the modulation of gut microbiota in patients with a high risk of type 1 diabetes could modify the natural history of this autoimmune disease.

[Apnoea in infants with bronchiolitis: Incidence and risk factors for a prediction model]. / Apneas en lactantes con bronquiolitis: incidencia y factores de riesgo para un modelo de predicción.

INTRODUCTION: The presence of apnoea in acute bronchiolitis (AB) varies between 1.2% and 28.8%, depending on the series, and is one of its most fearsome complications. The aim of this study is to determine the incidence of apnoea in hospitalised patients diagnosed with AB, and to define their associated risk factors in order to construct a prediction model. PATIENTS AND METHOD: A retrospective observational study of patients admitted to a tertiary hospital in the last 5 years with a diagnosis of AB, according to the classic criteria. Data was collected on the frequency of apnoea and related clinical variables to find risk factors in a binary logistic regression model for the prediction of apnoea. A ROC curve was developed with the model. RESULTS: Apnoea was recorded during the admission of 53 (4.4%) patients out of a total 1,197 cases found. The risk factors included in the equation were: Female (OR 0.6, 95% CI: 0.27-1.37), Caesarean delivery (OR: 3.44, 95% CI: 1.5-7.7), Postmenstrual age ≤43 weeks (OR: 6.62, 95% CI: 2.38-18.7), Fever (OR: 0.33, 95% CI: 0.09-1.97), Low birth weight (OR: 5.93, 95% CI: 2.23-7.67), Apnoea observed by caregivers before admission (OR: 5.93, 95% CI: 2.64-13.3), and severe bacterial infection (OR: 3.98, 95% CI: 1.68-9.46). The optimal sensitivity and specificity of the model in the ROC curve was 0.842 and 0.846, respectively (P<.001). CONCLUSIONS: The incidence of apnoea during admission was 4.4 per 100 admissions of AB and year. The estimated prediction model equation may be of help to the clinician in order to classify patients with increased risk of apnoea during admission due to AB.

[Lower lymphocyte response in severe cases of acute bronchiolitis due to respiratory syncytial virus]. / Menor respuesta linfocitaria en casos graves de bronquiolitis aguda por virus respiratorio sincitial.

INTRODUCTION: Acute bronchiolitis (AB) of the infant has a serious outcome in 6-16% of the hospital admitted cases. Its pathogenesis and evolution is related to the response of the T lymphocytes. The objective of the present study is to determine if the lower systemic lymphocytic response is related to a worse outcome of AB in hospitalised infants. PATIENTS AND METHOD: Retrospective observational-analytical study of cases-controls nested in a cohort of patients admitted due to RSV-AB between the period from October 2010 to March 2015. Those with a full blood count in the first 48hours of respiratory distress were included. Infants with underlying disease, bacterial superinfection, and premature infants <32 weeks of gestation were excluded. The main dichotomous variable was PICU admission. Other variables were: gender, age, post-menstrual age, gestational and post-natal tobacco exposure, admission month, type of lactation, and days of onset of respiratory distress. Lymphocyte counts were categorised by quartiles. Bivariate analysis was performed with the main variable and then by logistic regression to analyse confounding factors. RESULTS: The study included 252 infants, of whom 6.6% (17) required PICU admission. The difference in mean±SD of lymphocytes for patients admitted to and not admitted to PICU was 4,044±1755 and 5,035±1786, respectively (Student-t test, P<.05). An association was found between PICU admission and lymphocyte count <3700/ml (Chi-squared, P=.019; OR: 3.2) and it was found to be maintained in the logistic regression, regardless of age and all other studied factors (Wald 4.191 P=.041, OR: 3.8). CONCLUSIONS: A relationship was found between lymphocytosis <3700/ml in the first days of respiratory distress and a worse outcome in previously healthy infants <12 months and gestational age greater than 32 weeks with RSV-AB.

[Validation study of an acute bronchiolitis severity scale to determine admission to a Paediatric Intensive Care Unit]. / Estudio de validez de una escala de gravedad de la bronquiolitis aguda para orientar el ingreso en UCIP.

INTRODUCTION: At present, there are few validated scoring tests for assessing acute bronchiolitis (AB) severity, and limited information on their test power. The aim of the present study is to evaluate the validity of an acute bronchiolitis severity score (ABSS) to help in deciding PICU admission. PATIENTS AND METHOD: Prospective, descriptive, observational study of previously healthy infants under 1 year of age with AB, where the ABSS was used to compare severity as regards the need for PICU admission. The sample size was estimated as at least 175 patients. The research team was trained in the use of ABSS. All patients in the study were evaluated with ABSS daily, as well as in the case of clinical deterioration. The initial and maximum ABSS scores were contrasted to the need for PICU admission. A receiver operative curve was constructed, and the area under the curve was calculated, and the optimum point of sensitivity / specificity was estimated. RESULTS: The study included a total of 190 patients (male / female: 58% / 42%). PICU was required in 11 (6%). The mean± SD ABSS-maximal score for patients who required and did not require PICU was 10.55± 1.12 and 6.35± 2.3, respectively (P<.001). The AUC for ABSS-maximal was 0.94 (P<.001, 95% CI: 0.90-0.98). The optimal cut-off point was set at ≥10 points for a sensitivity of 82% and a specificity of 91%. CONCLUSIONS: ABSS estimates the severity of AB regarding the need for PICU admission, with a sensitivity and specificity of clinical usefulness.

Recurrent multifocal osteomyelitis in children: Experience in a tertiary care center. / Osteomielitis multifocal recurrente en niños: experiencia de un centro de tercer nivel.

INTRODUCTION: Chronic recurrent multifocal osteomyelitis is a rare aseptic bone inflammation that affects pediatric patients. Its management and treatment have not yet been standardized. METHODS: Retrospective, descriptive study of patients under 14 years of age diagnosed with chronic nonbacterial osteomyelitis (CNBO) in a tertiary hospital. We included patients diagnosed over the last 6 years (2010-2015) who met the Jansson criteria. The clinical and radiological characteristics of CNBO were analyzed, as was the outcome after different therapeutic options. RESULTS: We report 12 patients, with a mean age of 11 years (±1.6 standard deviation [SD]) and female predominance (10:2). The mean number of foci was 3.5 (±2.2 SD). The most common locations were ankle (58%), clavicle (50%), sternum (33%) and hip (25%). The mean disease duration was 10.5 months (±10.3 SD), and the median time to diagnosis was 2.38 months (range 0.17-16). Bone scintigraphy detected asymptomatic foci in 33% and we detected lytic lesions in 50% through magnetic resonance imaging. Biopsy was performed in 60%; 2/12 (16%) were associated with inflammatory disease and 1/12 (8.3%) later developed lymphoma. In all, 58% received antibiotic therapy with little response, 100% anti-inflammatory agents, 50% systemic corticosteroids, 41.6% methotrexate/pamidronate and 16% anti-tumor necrosis factor (TNF) α. The mean duration of treatment was 14.8 months (±12.4 SD) and 66% had recurrences. Currently, 83% are in clinical remission without treatment. CONCLUSIONS: When CNBO is refractory to treatment with anti-inflammatory drugs, intravenous pamidronate can be an alternative. Anti-TNF drugs can be considered in patients who fail with pamidronate, as can agents associated with other autoimmune conditions.

[Low bone mineral density in juvenile idiopathic arthritis: Prevalence and related factors]. / Baja densidad mineral ósea en artritis idiopática juvenil: prevalencia y factores relacionados.

INTRODUCTION: Height adjustment is currently recommended for Z-score bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. At present there are no studies that evaluate the prevalence of low BMD in paediatric patients with Juvenile Idiopathic Arthritis (JIA) in Spain following current recommendations. OBJECTIVES: To evaluate low BMD in JIA in paediatric patients with JIA in Spain following the latest recommendations, as well as to assess associated factors. METHODS: Observational cross-sectional study of Spanish JIA patients from 5 to 16 years-old, followed-up in a Paediatric Rheumatology Unit between July 2014 and July 2015. Anthropometric, clinical and treatment data were recorded. Dual energy X-ray absorptiometry, and bone metabolism parameters were collected, and a completed diet and exercise questionnaire was obtained. RESULTS: A total of 92 children participated. The population prevalence estimation of low BMD was less than 5% (95% CI). A significant positive correlation was found in the multiple linear regression analysis between the body mass index percentile (B: 0.021; P<.001) and lean mass index (B: 0.0002; P=.012), and BMD Z-score adjusted for height (Z-SAH). A significant negative correlation was found between fat mass index (B: -0.0001; P=.018) and serum type I collagen N-propeptide (B: -0,0006; P=.036) and Z-SAH. CONCLUSIONS: Low BMD prevalence in JIA patients in our population is low. An adequate nutritional status and the prevalence of lean over fat mass seem to promote the acquisition of bone mass. Those JIA patients with lower BMD could be subjected to an increase of bone turnover.

[Prediction of Severe Course in Infants with RSV Bronchiolitis under 6 Months. Spain]. / Predicción de la evolución de la bronquiolitis por virus respiratorio sincitial en lactantes menores de 6 meses.

OBJECTIVE: The need for mechanical ventilation (MV) in acute bronchiolitis (AB) by respiratory syncytial virus (RSV) varies depending on the series (6-18%). Our goal is to determine the admissions to PICU for MV in patients under 6 months with AB and define the risk factors for building a prediction model. METHODS: Retrospective study of patients younger than 6 months admitted by BA-VRS between the periods April 1, 2010 and March 31, 2015 was made. The primary variable was the admission to PICU for MV. Related addition, to find risk factors in a model of binary logistic regression clinical variables were collected. A ROC curve model was developed and optimal cutoff point was identified. RESULTS: In 695 cases, the need of MV in the PICU (Y) was 56 (8.1%). Risk factors (Xi) included in the equation were: 1. male sex (OR 4.27) 2. postmenstrual age (OR: 0.76) 3. Weight income less than p3 (OR: 5.53) 4. intake lees than 50% (OR: 12.4) 5. Severity by scale (OR: 1.58) 6. apneas before admission (OR: 25.5) 7. bacterial superinfection (OR 5.03) and 8. gestational age more than 37 weeks OR (0.32). The area under the curve, sensitivity and specificity were 0.943, 0.84 and 0.93 respectively. CONCLUSIONS: The PICU admission for MV was 8.1 in every 100 healthy infants hospitalized for AB and year. The prediction model equation can help to predict patients at increased risk of severe evolution.

OBJETIVO: La necesidad de ventilación mecánica (VM) en la bronquiolitis aguda por el virus respiratorio sincitial (VRS) varía según las series entre el 6 y el 18 %. Nuestro objetivo fue conocer los ingresos en la unidad de cuidados intensivos para VM de pacientes con bronquiolitis aguda menores de 6 meses y definir los factores de riesgo con el fin de construir un modelo de predicción. METODOS: Estudio retrospectivo de pacientes menores de 6 meses ingresados por bronquiolitis aguda por VRS entre los periodos 1 de abril de 2010 y 31 de marzo de 2015. La variable principal fue el ingreso en la unidad de cuidados intensivos pediátricos para ventilación mecánica. Además, se recogieron variables clínicas relacionadas para hallar factores de riesgo en un modelo de regresión logística binaria. Con el modelo se elaboró una curva ROC y se identificó un punto óptimo de corte. RESULTADOS: De 695 casos, precisaron VM 56 (8,1%). Los factores de riesgo (Xi) incluidos en la ecuación fueron: 1. Sexo varón (OR: 4,27) 2. Edad postmenstrual (OR:0,76) 3. Peso al ingreso inferior a p3(OR: 5,53) 4. Ingesta inferior a 50% (OR:12,4), 5. Gravedad por escala (OR:1,58), 6. Apneas antes del ingreso (OR:25,5) 7. Sobreinfección bacteriana (OR: 5,03) y 8. Edad gestacional superior a 37 semanas OR (0,32). El área bajo la curva, sensibilidad y especificidad fueron 0,943; 0,84 y 0,93 respectivamente. CONCLUSIONES: Los ingresos en UCIP para VM fueron 8,1 por cada 100 lactantes sanos hospitalizados por BA y año. La ecuación elaborada del modelo de predicción puede ser de ayuda para predecir los pacientes con mayor riesgo de evolución grave.

[Renal scarring in children under 36 months hospitalised for acute pyelonephritis]. / Cicatrices renales en menores de 36 meses ingresados por pielonefritis aguda.

INTRODUCTION: Acute pyelonephritis (APN) is one of the most common causes of serious bacterial infection in infants. Renal scarring is the most prevalent long-term complication. OBJECTIVES: To review the incidence of renal scarring within 6 months after an episode of APN in children under 36 months and its relationship with imaging studies, clinical settings, and bacteriology. METHOD: A retrospective study of previously healthy patients aged one to 36 months, admitted for a first episode of APN, with a minimum follow-up of 6 months. Demographic and clinical variables were collected along with bacteriology, renal and bladder ultrasound scan, voiding cystourethrography, DMSA-scintigraphy, and re-infection events. RESULTS: A total of 125 patients were included in the study, of which 60% were male, the large majority (92%) febrile, and due to E. coli (74.6%). There was a history of prenatal ultrasound scan changes in 15.4%. Ultrasound scan found dilation of the urinary tract in 22.1%. Voiding cystourethrography was performed on 70 patients: 54.3% no abnormalities, 12.8% vesicoureteral reflux (VUR) grade i-iii, and 32.9% iv-v grade VUR. Six patients had iv-v grade VUR with a normal ultrasound scan. Adherence to DMSA-scintigraphy at 6 months was only 61% of that indicated. Renal scarring was found in 44.3% of those in which it was performed (60 cases). CONCLUSIONS: Almost half (44%) DMSA-scintigraphy in children aged one to 36 months hospitalised for APN show renal scarring at 6 months, which was found to be associated with the re-infection events and the iv-v grade VUR. There was no relationship between scarring and the bacteriology or the elevations of inflammatory biochemical markers.

[Epidemiology of patients hospitalised due to bronchiolitis in the south of Europe: Analysis of the epidemics, 2010-2015]. / Epidemiología de los ingresos por bronquiolitis en el sur de Europa: análisis de las epidemias 2010-2015.

INTRODUCTION: The renewal of clinical practice guidelines on acute bronchiolitis (AB) requires the re-assessment of the consequences of their implementation. An update is presented on the main clinical and epidemiological variables in patients hospitalised due to AB in Southern Europe and an analysis made of the causes associated with longer hospital stay. PATIENTS AND METHOD: A retrospective study was conducted on patients admitted to hospital due to AB during 5 epidemics (2010-2015), with an analysis of the major clinical and epidemiological variables. A logistic regression analysis was performed on the factors associated with a longer hospital stay. RESULTS: The beginning of the epidemic occurred between the 4th week of September and the 3rd week of October. Of those children under 2 years (42,530), 15.21% (6,468 patients) attended paediatric emergency department due to having AB, and 2.36% (1,006 patients) were admitted. Of these, 18.5% of were premature, 12.2% had a birth weight <2,300g, 21.1% were younger than 1 month, 10.8% consulted for associated apnoea, 31.1% had an intake <50%, and 13.1% had bacterial superinfection. These factors were independently associated with prolonged stay. The median length of stay was 5 days, and 8.5% of cases were admitted to a paediatric intensive care unit (PICU). CONCLUSIONS: The beginning of the bronchiolitis epidemic showed a variability of up to 4 weeks in this region. Five years after implementing the new guidelines, the incidence of admissions was approximately 2.3%, and appeared stable compared to previous studies. The mean age of the patients decreased to 2.4 months, although with a similar proportion of PICU admissions of 8.5%. Independent factors associated with prolonged stay were: low birth weight, age less than one month, apnoea prior-to-admission, intake of less than 50%, and severe bacterial superinfection. Respiratory bacterial infection exceeded the prevalence of urinary tract infection.

Paradoxical reaction in immunocompetent children with tuberculosis.

BACKGROUND: A paradoxical reaction (PR) during anti-tuberculosis treatment is a phenomenon that is poorly studied in immunocompetent children. It is defined as a clinical or radiological worsening of pre-existing tuberculosis (TB) disease. METHODS: A retrospective descriptive study of children younger than 14 years of age was performed; these children developed PR during the years 2009 to 2014, following a diagnosis of TB. Demographic characteristics, microbiological results, treatment and outcome data were collected. RESULTS: Of 51 children diagnosed with TB, five (9.8%) developed a PR; four of these children had pulmonary TB and the remaining patient had miliary TB with central nervous system involvement. The PR occurred at a median of 42 days (range 23-53 days) after initiating therapy. Corticosteroids were started when PR was suspected, at a median dose of 1mg/kg/day. Clinical and radiological improvement was noted in all cases, with a median clinical regression time of 10.5 days (range 3-15 days) and a median radiological regression time of 45 days (range 26-105 days). No sequelae were described in any patient. CONCLUSIONS: PR in immunocompetent children during anti-tuberculosis treatment is not such an unusual reaction. Treatment with corticosteroids may be useful for the resolution of PR.

[Incidence and severity of pertussis in infants with a respiratory syncytial virus infection]. / Incidencia y gravedad de la tosferina en lactantes coinfectados por el virus respiratorio sincitial.

INTRODUCTION: Pertussis is a re-emerging disease that mostly affects infants. At this age, the severity can be affected by intercurrent infections such as respiratory syncytial virus (RSV). OBJECTIVES: To estimate the incidence of RSV infection during an epidemic period in patients hospitalized due to pertussis. The impact on the severity was also observed during hospitalization. PATIENTS AND METHOD: A descriptive study of cases diagnosed with pertussis admitted to a tertiary hospital over a 3year period, where the presence of co-infection with RSV was analyzed. The estimate of severity was estimated using the incidence of complications and the level of care required. RESULTS: From a total of 73 infants with pertussis, 34 occurred in a bronchiolitis season epidemic. A co-infection due to RSV was detected in 17 patients. The mean age was not significantly different compared to the non co-infected. The mean stay and the need for intensive care was similar in both groups. The need for oxygen therapy care and nutritional support was higher in the coinfected patients. CONCLUSIONS: Coinfection with RSV in infants hospitalized with pertussis occurred in ono in 2 patients during a RSV epidemic season, in infants of similar age. Severity in terms of stay, presence of apnea and admission to intensive care was similar, but more need for respiratory care and nutritional support was found.