Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

BACKGROUND: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. METHODS: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U-13C3]glycerol (50 mg/kg) prior to surgery and liver tissue (0.2-0.7g) was obtained during surgery. Glutathione, amino acids, and other water-soluble metabolites were extracted from the liver tissue and isotopomers were quantified with nuclear magnetic resonance spectroscopy. RESULTS: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m2 [range 41.3-63.3]). The concentrations of free glutamate, cysteine, and glycine were similar among participants, and so were the fractions of 13C-labeled glutamate and glycine derived from [U-13C3]glycerol. The signals from all component amino acids of glutathione - glutamate, cysteine and glycine - were strong and analyzed to obtain the relative concentrations of the antioxidant in the liver. The signals from glutathione containing [13C2]glycine or [13C2]glutamate derived from the [U-13C3]glycerol drink were readily detected, and 13C-labelling patterns in the moieties were consistent with the patterns in corresponding free amino acids from the de novo glutathione synthesis pathway. The newly synthesized glutathione with [U-13C3]glycerol trended to be lower in obese adolescents with liver pathology. CONCLUSIONS: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.

Third-trimester percentage predicted lung volume and percentage liver herniation as prognostic indicators in congenital diaphragmatic hernia.

BACKGROUND: Over the last two decades, fetal imaging has greatly improved, and new prenatal imaging measurements have been developed to characterize congenital diaphragmatic hernia (CDH) severity. OBJECTIVE: To determine the best prenatal imaging predictor of postnatal CDH outcomes, including use of extracorporeal membrane oxygenation (ECMO) and in-hospital mortality, with particular attention to the percentage of liver herniation (%LH) as a predictor. Additionally, we sought to guide best practices across hospital systems including improved models of prenatal risk assessment. MATERIALS AND METHODS: We conducted a retrospective review of infants with left CDH who were prenatally diagnosed. We analyzed prenatal imaging measurements including observed-to-expected (O/E) lung-to-head ratio (LHR) on US, percentage predicted lung volume (PPLV) on MRI, and O/E total fetal lung volume (TFLV) and %LH on MRI. We compared prenatal imaging characteristics for infants with (1) in-hospital postnatal mortality and (2) use of ECMO. Then we performed multivariate logistic regression to determine independent predictors of postnatal outcomes. RESULTS: We included 63 infants with a median gestation of 34 weeks at the time of prenatal MRI. Low O/E LHR (31.2 vs. 50, P < 0.0001), PPLV (14.7 vs. 22.6, P < 0.0001) and O/E TLFV (24.6 vs. 38.3, P < 0.0001) and high %LH (15.1 vs. 2.1, P = 0.0006) were associated with worse postnatal outcomes; however, only PPLV was predictive of survival and need for ECMO on multivariable analysis. PPLV survival to discharge model showed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.86, 0.99), P < 0.0001; and an odds ratio of 68.7 (95% CI: 6.5-2,302), P = 0.003. PPLV need for ECMO model showed AUC = 0.87 (95% CI: 0.78, 0.96), P < 0.0001; and odds ratio = 20.1 (95% CI: 3.1-226.3), P = 0.011. CONCLUSION: Low O/E LHR, PPLV and O/E TFLV and high %LH in the third trimester are associated with worse postnatal outcomes. PPLV most strongly predicted outcome using a logistic regression model. Percentage of liver herniation was not an independent predictor of outcomes.

Factores de riesgo de bacteriemia en niños con cáncer y neutropenia febril / Risk factors for bacteremia in children with cancer and febrile neutropenia

La bacteriemia representa una importante causa de morbimortalidad en pacientes oncológicos. Durante el episodio de neutropenia inducida por quimioterapia, un 15%­25% de los pacientes tendrá bacteriemia. Objetivo: identificar factores de riesgo asociados con bacteriemia en pacientes oncológicos pediátricos con neutropenia y fiebre. Material y métodos: estudio de cohorte prospectivo. Se incluyeron pacientes con enfermedades hematooncológicas y neutropenia febril, internados en un hospital pediátrico de alta complejidad entre julio de 2018 y mayo de 2019. Se excluyeron receptores de trasplante de médula ósea. Se compararon las características clínicas según se documentara bacteriemia (B) o no. Resultados: Se incluyeron 160 pacientes (p). Eran varones 93 (58%). La mediana de edad fue 81,5 meses (RIC 36-127,5). La enfermedad de base (EB) más frecuente fue: leucemia linfoblástica aguda (LLA) 88 (55%). Se identificaron 20 (12,5%) pacientes con bacteriemia (B). En el análisis univariado hubo asociación entre B y LMA (p=0,003) y la internación en UCI (p=0,0001). En el modelo multivariado, ajustado por el resto de las variables, se identificaron la LMA (OR 8,24, IC95% 2,5-26,4; p<0,001) y la tiflitis (OR 5,86, IC95% 1,2-27,3; p=0,02) como factores relacionados con bacteriemia. Los principales microorganismos identificados fueron: estreptococos del grupo viridans 6 (30%), Escherichia coli 4 (20%) y estafilococos coagulasa negativos 3 (15%). Quince (75%) fueron bacteriemias secundarias a un foco clínico. El foco más frecuente fue el mucocutáneo (n=7, 35%). En esta cohorte de niños con cáncer y neutropenia febril, los factores asociados con bacteriemia fueron: la LMA, la tiflitis y la internación en UCI (AU)

Bacteremia is an important cause of morbidity and mortality in oncology patients. During an episode of chemotherapy-induced neutropenia, 15%-25% of patients will develop bacteremia. Objective: to identify risk factors associated with bacteremia in pediatric oncology patients with neutropenia and fever. Material and methods: prospective cohort study. Patients with hematology-oncology diseases and febrile neutropenia, admitted to a tertiary-care pediatric hospital between July 2018 and May 2019 were included. Bone marrow transplant recipients were excluded. Clinical characteristics were compared according to whether or not bacteremia was recorded. Results: 160 patients were included of whom 93 (58%) were male. Median age was 81.5 months (IQR 36-127.5). The most common underlying disease was acute lymphoblastic leukemia (ALL) in 88 patients (55%). Twenty (12.5%) patients with bacteremia were identified. In univariate analysis, an association was found between bacteremia and acute myeloid leukemia (AML) (p=0.003) and ICU admission (p=0.0001). In the multivariate model, adjusted for the remaining variables, AML (OR 8.24; 95%CI 2.5-26.4; p<0.001) and typhlitis (OR 5.86; 95%CI 1.2-27.3; p=0.02) were identified as factors related to bacteremia. The main microorganisms identified were viridans group streptococci in 6 (30%), Escherichia coli in 4 (20%), and coagulase negative staphylococci in 3 (15%). In 15 cases (75%), bacteremia was secondary to a clinical focus. The most frequent focus was mucocutaneous (n=7, 35%). In this cohort of children with cancer and febrile neutropenia, the factors associated with bacteremia were AML, typhlitis, and ICU admission (AU)

Ultrasound-guided erector spinae plane block versus thoracic epidural analgesia: Postoperative pain management after Nuss repair for pectus excavatum.

AIM OF THE STUDY: Postoperative pain management is a significant challenge in patients undergoing Nuss repair for pectus excavatum chest wall deformity. Therapeutic anesthetic options primarily include patient-controlled intravenous analgesia, thoracic epidural analgesia (TEA), and cryoanalgesia. However, TEA is limited to inpatient use and both TEA and cryoanalgesia can result in neurologic injury. The novel technique of ultrasound-guided erector spinae plane regional analgesia has been used recently in our patients undergoing the Nuss repair and has shown impressive pain relief, but without the potential complications of other modalities. Erector spinae plane block (ESPB) postoperative pain management outcomes were studied as compared to TEA. METHODS: Thirty consecutive patients with severe pectus excavatum undergoing Nuss repair and placement of ultrasound-guided ESPB were each paired to a historical cohort control patient with TEA postoperative pain management. The cohort patient match was defined by age (± 2 years), gender, and CT pectus index (± 15%). Study variables included hospital length of stay (LOS), pain scores, and pain medication usage. RESULTS: Pain scores as measured by area under the curve per hour (Day 1: 2.72 (SD = 1.37) vs. 3.90 (SD = 1.81), P = 0.006; Day 2: 2.83 (SD = 1.32) vs. 3.97 (SD = 1.82), P = 0.007) and oral morphine equivalent (OME) pain medication usage (Day 1: 11.9 (SD = 4.9) vs 56.0 (SD = 32.2), P < 0.001; Day 2: 14.7 (SD = 7.1) vs. 38.0 (SD = 21.7), P < 0.001) were higher for the first two postoperative days in the ESPB group. However, mean hospital LOS was nearly one day shorter for ESPB patients (3.78 (SD = 0.82) vs. 2.90 (SD = 0.87), P < 0.001) who were discharged home with the catheter in place until removal, typically at 5-7 days postoperatively. CONCLUSION: Ultrasound-guided ESPB is thus a feasible, safe, and effective alternative to TEA in postoperative pain management after Nuss repair and results in decreased hospital stay. LEVEL OF EVIDENCE: III.

Magnetic properties of the Ising-like rare earth pyrosilicate: D-Er2Si2O7.

Ising-like spin-1/2 magnetic materials are of interest for their ready connection to theory, particularly in the context of quantum critical behavior. In this work we report detailed studies of the magnetic properties of a member of the rare earth pyrosilicate family, D-Er2Si2O7, which is known to display a highly anisotropic Ising-likeg-tensor and effective spin-1/2 magnetic moments. We used powder neutron diffraction, powder inelastic neutron spectroscopy (INS), and single crystal AC susceptibility to characterize its magnetic properties. Neutron diffraction enabled us to determine the magnetic structure below the known transition temperature (TN= 1.9 K) in zero field, confirming that the magnetic state is a four-sublattice antiferromagnetic structure with two non-collinear Ising axes, as was previously hypothesized. Our powder INS data revealed a gapped excitation at zero field, consistent with anisotropic (possibly Ising) exchange. An applied field of 1 T produces a mode softening, which is consistent with a field-induced second order phase transition. To assess the relevance of D-Er2Si2O7to the transverse field Ising model, we performed AC susceptibility measurements on a single crystal with the magnetic field oriented in the direction transverse to the Ising axes. This revealed a transition at 2.65 T at 0.1 K, a field significantly higher than the mode-softening field observed by powder INS, showing that the field-induced phase transitions are highly field-direction dependent as expected. These measurements suggest that D-Er2Si2O7may be a candidate for further exploration related to the transverse field Ising model.

The role of preoperative upper endoscopy in adolescents undergoing laparoscopic vertical sleeve gastrectomy.

BACKGROUND: Vertical sleeve gastrectomy (VSG) has been associated with gastroesophageal reflux symptoms and, in adults, with a development of Barrett's esophagus. Adults with Barrett's esophagus identified at baseline before bariatric operation are generally advised against VSG operations. The role of preoperative esophagogastroduodenoscopy (EGD) in adolescents preparing for bariatric surgery is not clearly defined. OBJECTIVE: The goal of this study was to report the frequency of abnormalities identified on EGD performed at baseline in adolescents undergoing VSG for severe obesity. SETTING: Free-standing academic children's hospital. United States. METHODS: A retrospective chart review was conducted to describe findings of EGD performed just before VSG in a cohort of 40 adolescents and young adults (age range 14-25 yr) immediately before VSG. Review of findings from gross and histopathological evaluation of the esophagus, resected stomach, and duodenum was performed. RESULTS: Five individuals reported preoperative symptoms of gastroesophageal reflux. Anatomic findings at EGD were normal in 98% of individuals. Histopathology of the esophagus, stomach, and duodenum was normal in 88%, 70%, and 95%, respectively. Abnormal findings of gastritis (18%), esophagitis (13%), and/or Helicobacter pylori (10%) infection were most common. Those with evidence of H. pylori in gastric resection specimens were treated appropriately with eradication therapy postoperatively. With the exception of 2 patients with incidentally detected esophageal mucosal eosinophilia, EGD findings did not lead to additional changes in medical or surgical management. There were no complications of the EGD procedure. CONCLUSIONS: Routine EGD at the time of VSG was safe but resulted in low yield of abnormal findings requiring a change in clinical management.

Bacteriemia por Pseudomonas aeruginosa (PAE) en niños / Pseudomonas aeruginosa-associated bacteremia en children

Introducción. La bacteriemia por Pseudomonas aeruginosa (PAE) en niños es infrecuente. Objetivo.Describir las características epidemiológicas, clínicas, microbiológicas y evolutivas en niños con bacteriemia por PAE. Métodos. Estudio de cohorte retrospectivo. Resultados. Se incluyeron 100 pacientes (p). La mediana de edad fue de 27 meses (RIC 6-88).Tenían enfermedad de base: 93 p (93%) y 36 de ellos estaban neutropénicos. Ochenta y cinco p (85%) habían recibido antibióticos en el último mes, 60 (60%) tuvieron procedimientos invasivos previos y 81 (81%) tuvieron internaciones previas. Ingresaron con shock séptico 42 p (42%), 56 p (56%) fueron admitidos en unidad de cuidados intensivos (UCI) y 49 (49%) requirieron ventilación mecánica (VM). La bacteriemia fue primaria en 17 p (17%); asociada a catéter en 15 p (15%) y secundaria en 68 p (68%). El foco más frecuente fue mucocutáneo, 21 p, seguido por el pulmonar, 20 p. El tratamiento empírico fue adecuado en 84 p (84%). La resistencia a uno o más grupos de antibióticos se dio en el 38% de los casos, 11% fueron multirresistentes y 15% fueron resistentes sólo a carbapenemes. Fallecieron 31 p (31%). Pseudomonas aeruginosa resistente a carbapenemes en forma exclusiva o combinada con otros antibióticos se relacionó en esta serie a exposición previa a antibióticos, (p≤0,03), tratamiento empírico inicial inadecuado (p≤0,006) y mayor mortalidad (p≤0,01), prolongación de la internación y del tiempo de tratamiento (p≤0,001)

Introduction. Pseudomonas aeruginosa (PAE) associated bacteremia is uncommon in children. Objective. To describe the epidemiological, clinical, and microbiological features and outcome in children with PAE-associated bacteremia. Methods. A retrospective cohort study. Results. 100 patients (p) were included. Median age was 27 months (IQR 6-88). Overall 93 p (93%) had an underlying disease, 36 of whom had neutropenia. Eighty-five p (85%) had received antibiotics over the previous month, 60 (60%) had undergone previous invasive procedures, and 81 (81%) had been previously admitted. Forty-two p (42%) were admitted because of septic shock, 56 p (56%) were admitted to the intensive care unit (ICU), and 49 (49%) required mechanical ventilation (MV). Seventeen p (17%) had primary bacteremia, 15 p (15%) had catheter-related bacteremia, and 68 p (68%) had secondary bacteremia. The most common focus was mucocutaneous (21 p), followed by pulmonary (20 p). Emperical treatment was adequate in 84 p (84%). Resistance to one or more groups of antibiotics was observed in 38% of the cases; 11% were multiresistant and 15% were only resistant to carbapenems. Thirty-one p (31%) died. In our series, Pseudomonas aeruginosa resistant to carbapenems only or combined with other antibiotics was associated with previous exposition to antibiotics (p≤0.03), inadequate initial emperical treatment (p≤0.006), and higher mortality (p≤0.01), and longer hospital stay and treatment duration (p≤0.001)

Candidemia en un hospital pediátrico de alta complejidad / Candidemia in a tertiary-care pediatric hospital

Introducción: La frecuencia de las candidemias ha aumentado en los últimos años asociada principalmente a internación prolongada, antibióticos de amplio espectro y enfermedades de base. Se produjo también un cambio en la distribución y un aumento en la resistencia a los antifúngicos de las distintas especies de Candida spp., todo esto asociado a una elevada morbimortalidad. En este trabajo realizado durante un año en un hospital de alta complejidad, se incluyeron 33 pacientes con candidemia. La mediana de la edad fue de 22 meses y un 60% de los afectados fueron varones. El 97% de los niños tenían enfermedad de base con predominio de la patología oncohematológica. Un 88% presentó algún procedimiento o condición predisponente para la infección, principalmente portación de catéter venoso central y cirugía previa. En un 59% de los aislamientos predominaron especies de Candida diferentes de Candida albicans. Anfotericina B desoxicolato fue el tratamiento empírico de elección. La mediana de tratamiento fue de 21 días y la de internación de 66 días. La mortalidad fue del 12% y se asoció a ingreso a UCI, presencia de fiebre al momento del diagnóstico y requerimiento de ARM (AU)

The incidence of candidemia has increased over the past years mainly associated with prolonged hospital stay, wide-spectrum antibiotics, and underlying diseases. At the same time there has been a change in the distribution and an increase in the resistance to antifungals in different Candida spp, associated with a high morbidity and mortality. In this study, conducted during one year at a tertiary hospital, 33 patients with candidemia were included. Median age was 22 months and 60% of the patients were boys. Overall, 97% of the children had an underlying hematology-oncology disease. Of the patients, 88% underwent a procedure or had a condition that predisposed to infection, mainly the placement of a central venous catheter and previous surgery. In 59% the isolated Candida species were Candida albicans. Amphotericin B deoxycholate was the empirical treatment of choice. Median time of treatment was 21 days and median hospital stay was 66 days. Mortality was 12% and was associated with ICU admission, presence of fever at the time of diagnosis, and requirement of mechanical ventilation (AU)

Anidulafungina en niños: Experiencia en niños con trasplante de médula ósea / Anidulafungin in children: experience in children undergoing bone marrow transplantation

Introducción: Las infecciones fúngicas invasoras (IFI) son un problema de salud cada vez mayor, y se asocian con una alta morbilidad y mortalidad. Las nuevas opciones terapéuticas, tales como las equinocandinas y entre estos anidulafungina, se han utilizado en la población adulta, pero en pacientes pediátricos con trasplante de médula ósea la experiencia es escasa. Objetivo: El objetivo de este estudio descriptivo es presentar nuestra experiencia con el uso de la anidulafungina como profilaxis o tratamiento en pacientes con trasplante de médula ósea. Material y métodos: Entre enero hasta junio 2016, 29 pacientes trasplantados de médula ósea recibieron anidulafungina como profilaxis o tratamiento de infecciones fúngicas invasivas (IFI) probadas, probables o posibles. En todos los casos se monitorizó el valor de transaminasas, bilirrubina, creatinina y el recuento de glóbulos blancos al inicio y al final del tratamiento. Resultados: La anidulafungina se administró por vía intravenosa en una dosis de carga de 3 mg/kg/día, seguida de 1,5 mg/kg/día durante una mediana (Md) de 16 días (intervalo intercuartílico: 2-65 d). La Md de la edad de los pacientes fue de 97 meses (rango: 6-211m). La anidulafungina fue indicada como tratamiento en 7 casos (24%) y como profilaxis primaria o secundaria,en 22 (76%). En un paciente se confirmó microbiológicamente una IFI, por Candida albicans. Las Md de los parámetros bioquímicos en el inicio del tratamiento y al final, fueron: transaminasas GOT 29,5 U/l y 32 U/l (p 0,44); bilirrubina 0,35 y 0,30 mg/dL (p: 0,20); creatinina, 0,52 y 0,60 mg/dl (p:0,67). El recuento de glóbulos blancos mostró una gran variabilidad debido a la enfermedad subyacente, pero la diferencia de su valor entre el inicio y al final de la administración del fármaco, no fue significativo: Md 2810 células/mm3 y 5160 células/mm3, respectivamente (p: 0,07). Ninguno de los pacientes tuvo eventos adversos o murieron por causas relacionadas con anidulafungina. En el seguimiento a 30 días no se registró recaída de la infección o mortalidad relacionada a la droga. Conclusiones: Los resultados de nuestra serie sugieren que la anidulafungina podría ser una opción para la profilaxis o el tratamiento de las IFI en los niños con trasplante de médula ósea. Se requieren más estudios para confirmar estas observaciones (AU)

Introduction: Invasive fungal infections (IFI) are an increasing health problem associated with high morbidity and mortality. New treatment options, such as echinocandins and among these anidulafungin, have been used in the adult population, but experience in children undergoing bone marrow transplantation is scarce. Aim: The aim of this descriptive study is to present our experience with the use of anidulafungine as prophylaxis or treatment in patients undergoing bone marrow transplantation. Material and methods: Between January and June 2016, 29 patients who underwent bone marrow transplantation received anidulafungin as prophylaxis against or treatment for confirmed, probable, or possible (IFI). In all cases transaminase, bilirubin, and creatinine levels as well as total white blood cell count were monitored at treatment initiation and completion. Results: Anidulafungine is administered intravenously in a loading dose of 3 mg/kg/day, followed by 1.5 mg/kg/day for a mean of 16 days (interquartile range: 2-65 d). Mean age of the patients was 97 months (range: 6-211m). Anidulafungine was used as treatment in 7 cases (24%) and as primary or secondary prophylaxis in 22 (76%). IFI was microbiologically confirmed to be Candida albicans in one patient. Mean biochemical parameters at treatment onset and completion were: transaminases AST 29.5 U/l and 32 U/l (p 0.44); bilirubin 0.35 and 0.30 mg/dL (p 0.20); creatinine, 0.52 and 0.60 mg/dl (p : 0.67). White blood cell count was highly variable due to the underlying disease; however, the difference between values at treatment initiation and completion were not significant: Mean 2810 cells/mm3 and 5160 cells/mm3, respectively (p: 0.07). None of the patients had adverse effects or died because of anidulafungin-related causes. At 30 days of follow-up no relapse of infection or drug-related mortality was observed. Conclusions: The results in our series suggest that anidulafungin is an option for the prophylaxis against or treatment of IFI in children undergoing bone marrow transplantation. Further studies are necessary to confirm these findings (AU)

Programa de prevención de las bacteriemias asociadas a catéteres venosos centrales / Program for prevention of central venous catheter-related bacteremia

Introducción: Las infecciones son las complicaciones más importantes asociadas al uso de los Catéteres Venosos Centrales (CVC), representan un riesgo 20 veces mayor de bacteriemias que los catéteres venosos periféricos. El objetivo de este estudio fue evaluar el efecto de la implementación de un paquete de medidas o "bundle" en las infecciones asociadas a catéteres venosos centrales (BACT- CVC) en la Unidad de Cuidados Intensivos del Hospital Garrahan (UCI). Métodos: El Programa de Intervención para disminuir las bacteriemias asociadas a catéteres venosos centrales requirió de la aplicación de cuatro paquetes de medidas y un subprograma para aumentar la adherencia a la higiene de manos. Se aplicó en todas las UCI, pero en el presente estudio se presenta como modelo de referencia el que se llevó a cabo en una de ellas. Período del estudio: se compararon 2 períodos: basal (1º Agosto de 2008 - 31 de Diciembre de 2009) y intervención (1º de Enero 2010 al 31 de Diciembre de 2011). La tasa de BACT - CVC se calculó en concordancia con los protocolos utilizados por el sistema NHSN - CDC de los Estados Unidos y el sistema nacional VIHDA. La base de datos utilizada para el estudio fue el software provisto por el programa VIHDA. Se compararon las tasas de BACT - CVC en el período previo y posterior a las intervenciones realizadas. Para el análisis estadístico se utilizó el programa EPIINFO. Se consideró estadísticamente significativo un valor de p < 0.05. Resultados: en el primer período (Agosto 2008 - Diciembre 2009) se produjeron un total de 44 BACT - CVC, con una tasa promedio de 9.64 BACT-CVC por 1000 días-catéter versus 17 BACT - CVC, tasa promedio de 4.41 BACT-CVC por 1000 días-catéter en el período en que se desarrolla el programa de intervención. Esta disminución resulta estadísticamente significativa (Chi cuadrado; valor P= 0,0048; RR 0,46; IC 95%: 0,26 - 0,80). Conclusiones: La aplicación de los combos y el subprograma para mejorar la adherencia a la higiene de manos según orientación de la OMS y aplicando Estrategias Multimodales, resultaron en una mejora significativa en la tasa de BACT- CVC (AU)

Introduction: Infections are the main complication associated with the use of central venous catheters (CVC), accounting for an infection risk about 20 times that of peripheral venous catheters. The aim of this study was to assess the effect of the implementation of sets of measures or "bundle" for the prevention of CVC-associated bacteremia (CVC-BACT) in the ICU. Methods: The intervention program for the reduction of CVC-BACT consisted of four sets of measures and a sub-program to increase adherence to hand hygiene. Bundle use was started in all PICUs, however, in this study implementation of the program in one of them was used as a reference model. Study period: Two periods were compared: Baseline (August 1, 2008 ­ December 31, 2009) and intervention (January 1, 2010 ­ December 31, 2011). The CVC-BACT rate was calculated according to the NHSN-CDC protocols of the United States and the Argentine VIHDA system. For the data base of the study software provided by the VIHDA program was used. CVC-BACT rates before and after the intervention period were calculated. For statistical analysis the EPIINFO program was used. A p < 0.05 was considered significant. Results: In the first period (August 2008 - December 2009) 44 CVC-BACT occurred, with a mean CVC-BACT rate of 9.64 per 1000 catheter days versus 17 CVC-BACT, mean CVC-BACT rate of 4.41 per 1000 catheter days, in the intervention period. This decrease was statistically significant (Chi square 7.94; p = 0.0048; RR 0.46; 95% CI: 0.26 ­ 0.80). Conclusions: Bundle use and the subprogram for better adherence to hand hygiene, according to WHO guidelines and applying multimodal strategies, resulted in a significantly lower CVC-BACT rate (AU)

Infecciones asociadas a dispositivos de soporte circulatorio mecánico / Ventricular assist device-related infections

El dispositivo de asistencia ventricular asistida (DAV) se utiliza como terapéutica final o puente al trasplante cardíaco. La tasa de complicaciones infecciosas asociada a este dispositivo es elevada. La experiencia con este tipo de complicación en pediatría es escasa. Objetivo: conocer las características clínicas, microbiológicas y de evolución de pacientes con DAV. Material y métodos: pacientes internados en el Hospital Garrahan desde marzo del 2006 a marzo 2014 con DAV. Estudio retrospectivo, descriptivo. Se analizaron: edad, sexo, tipo de enfermedad de base, características clínicas, microbiológicas y de evolución de los pacientes con DAV. Resultados: se incluyeron 33 pacientes. La mediana de edad fue 79 meses (rango:13-133). La indicación de colocación del DAV fue miocardiopatía dilatada en el 81.8% (27). Los días acumulados de uso del DAV fue de 4.638 días. Diecisiete pacientes (51.5%) presentaron 23 episodios de infección. La infección pericánula se presentó 10 casos (43.4%), bacteriemias primarias en 4 (17.4%), bacteriemia asociada a catéter de corta permanencia 5 (21.7%), mediastinitis 3 (13%) y un caso de sepsis (4.3%). Los microorganismos prevalentes fueron los cocos gram positivos. Fallecieron 12 pacientes en DAV a la espera del trasplante, uno de ellos con sepsis y mediastinitis por S. aureus meticilino sensible. Conclusiones: La infección asociada a DAV fue frecuente en nuestros pacientes y dentro de ellas la infección pericánula fue la más común. Los cocos gran positivos fueron los microorganismos predominantes. Los pacientes con mayor tiempo de permanencia del DAV presentaron varios episodios de infección. Las infecciones asociadas al DAV no impidieron el éxito del trasplante cardíaco (AU)

Endospanin 1 silencing in the hypothalamic arcuate nucleus contributes to sustained weight loss of high fat diet obese mice.

Leptin targets specific receptors (OB-R) expressed in the hypothalamus to regulate energy balance. Leptin decreases food intake in normal weight individuals, but this effect is blunted in obese subjects who are characterized by a state of leptin resistance. The prevention of leptin resistance is one of the major goals of obesity research. Recently, we identified endospanin 1 as a negative regulator of OB-R, which by interacting with OB-R retains the receptor inside the cell. We show here that in obese mice endospanin 1 is upregulated in the hypothalamic arcuate nucleus (ARC), the major brain structure involved in body weight regulation, suggesting that endospanin 1 is implicated in obesity development and/or the installation of leptin resistance. In contrast, silencing of endospanin 1 with lentiviral vectors in the ARC of obese mice fully restores leptin responsiveness when combined with a switch to ad libitum fed chow diet. The recovery of central leptin sensitivity is accompanied by sustained body weight loss and amelioration of blood lipid parameters and steatosis. Collectively, our results define endospanin 1 as a novel therapeutic target against obesity.

Cystic biliary atresia: a wolf in sheep's clothing.

Neonatal obstructive jaundice is frequently explained by biliary atresia (BA) or the presence of a choledochal cyst (CC). Cystic biliary atresia (CBA) has been a proposed as a subtype of BA with projected improved outcomes. We aimed to characterize these lesions further. We conducted an Institutional Review Board-approved review of all patients treated for obstructive jaundice at our tertiary children's hospital over 10 years. Over the decade we evaluated 91 children with obstructive jaundice: 13 CBA, 52 BA, and 26 CC. Patients with isolated CBA and BA were diagnosed significantly earlier than those with CC (15.9, 54, and 281 days, respectively; P = 0.0001). There was a significant delay between diagnosis and surgical intervention for patients with CBA compared with BA: 17 days versus 5.7 days (P = 0.004). There was no difference in rate of transplant between CBA and BA (31 vs. 50%; P = 0.35). The time from surgery until transplant was 13.9 and 18.6 months for CBA and BA, respectively (P = 0.62). Although radiographically similar to CC, CBA behaves similarly to isolated BA. Delay in recognition and surgical treatment may affect outcomes and lead to an increased incidence of liver failure. The presence of a cystic biliary malformation in the setting of neonatal jaundice should be regarded as CBA until proven otherwise.