Role of Hyperbilirubinaemia as a Predictor of Complicated Appendicitis in Paediatric Population.

BACKGROUND: Acute appendicitis is a common surgical emergency amongst the paediatric population. Available diagnostic tools are focussed to make a diagnosis of acute appendicitis. A definitive predictive factor for the diagnosis of complicated appendicitis is lacking. Thus, this aims to analyse hyperbilirubinaemia as a predictor of complicated appendicitis amongst the paediatric population. MATERIALS AND METHODS: A prospective observational study was conducted in a tertiary hospital from November 2018 to October 2019. All children undergoing emergency appendectomy were included in the study. Preoperatively, patients were evaluated clinically, and routine investigations including total and direct serum bilirubin were sent. All patients were grouped as 'simple appendicitis' or 'complicated appendicitis' based on intra-operative and histological findings. Bilirubin level was compared between these groups and analysed. RESULTS: A total of 52 children fulfilling the inclusion criteria were included. The mean age was 13.2 ± 4.2 years, and the male: female ratio was 2.1:1. Thirty-four (65.4%) had simple appendicitis and 18 (34.6%) had complicated appendicitis. Total bilirubin was 23.83 ± 5.94 mmol/L in the complicated appendicitis group and 13.15 ± 3.29 mmol/L in the simple appendicitis group. Direct bilirubin was 5.28 ± 2.22 mmol/L in complicated appendicitis and 2.62 ± 0.83 mmol/L in simple one. Both total and direct bilirubin were significantly high in the complicated group (P < 0.001) compared to the simple appendicitis group. On the Receiver operating curve (ROC), the best cutoff value for total and direct bilirubin was 21 and 5.5 mmol/L, respectively. The sensitivity and specificity of total and direct bilirubin were 72.2%, 100%, and 61.1%, and 85.3%, respectively. CONCLUSION: It is concluded that hyperbilirubinaemia is a good predictor for paediatric complicated appendicitis.

Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study.

BACKGROUND: Hyperbilirubinemia is a common complication after off-pump coronary artery bypass grafting (OPCAB), but the incidence and the risk factors are unclear. This study aimed to analyze the incidence and risk factors of postoperative hyperbilirubinemia in patients undergoing OPCAB. METHODS: From December 2016 to March 2019, a total of 416 consecutive patients undergoing OPCAB were enrolled in this single-center retrospective study. Patients were divided into the normal serum total bilirubin group and the hyperbilirubinemia group based on the serum total bilirubin levels. Perioperative variables between the two groups were compared by univariate logistic regression analysis. Then, multivariate binary logistic regression analysis was used to analyze the independent risk factors of developing hyperbilirubinemia in patients underwent OPCAB. P < 0.05 was considered as statistically significant. RESULTS: Thirty two of 416 (7.7%) patients developed postoperative hyperbilirubinemia. Univariate regression analysis showed significant differences in gender (73.96% vs. 93.75%, P = 0.012), preoperative total bilirubin levels (11.92 ± 4.52 vs. 18.28 ± 7.57, P < 0.001), perioperative IABP implantation (22.66% vs. 43.75%, P = 0.008), perioperative blood transfusion (37.50% vs. 56.25%, P = 0.037) between the two groups. Multivariate logistic regression analysis revealed that elevated preoperative serum total bilirubin levels (OR = 1.225, 95% CI 1.145-1.310, P < 0.001), perioperative blood transfusion (OR = 4.488, 95% CI 1.876-10.737, P = 0.001) and perioperative IABP implantation (OR = 4.016, 95% CI 1.709-9.439, P = 0.001) were independent risk factors for hyperbilirubinemia after OPCAB. CONCLUSIONS: Hyperbilirubinemia is also a common complication after OPCAB. Elevated preoperative serum total bilirubin levels, perioperative blood transfusion, and perioperative IABP implantation were independent risk factors for patients developing hyperbilirubinemia after OPCAB. Further studies need to be conducted to confirm the risk factors of hyperbilirubinemia after OPCAB procedure.

Hyperbilirubinemia as an Indicator of Perforated Acute Appendicitis in Pediatric Population: A Prospective Study.

Background: This prospective cohort study aimed to investigate the association of hyperbilirubinemia with perforated appendicitis in the pediatric population. Patients and Methods: A total of 284 children in whom the diagnosis of acute appendicitis was established were included in this study. The patients were allocated in study groups in regard to operative findings. The first study group included patients who had perforated appendicitis (n = 64; 22.5%) whereas the patients in the second group had simple appendicitis (n = 220; 77.5%). Blood samples for serum bilirubin levels and acute inflammatory markers were taken before the patients underwent surgery. The primary outcome of the study was to investigate whether the level of serum bilirubin should be used to distinguish between simple and perforated appendicitis. Results: The median level of serum bilirubin in children with perforated appendicitis was 27 mcmol/L whereas the patients with simple appendicitis had lower median levels of serum bilirubin (10 µmol/L; p < 0.001). An area under the receiver operating characteristic (ROC) curve for total serum bilirubin was 0.876 (95% confidence interval [CI], 0.820-0.929) in the patients who had a perforated appendicitis. An ROC analysis showed the best sensitivity (92%) and specificity (77.3%) for a cutoff value of 15.5 mcmol/L for total serum bilirubin (p < 0.001). Hyperbilirubinemia at admission was found in 35 patients (54.7%) with complicated appendicitis and in 14 patients (6.4%) with non-perforated appendicitis (p < 0.001). The modeling of collected data by multivariable logistic regression identified serum bilirubin concentration (odss ratio [OR] = 1.12; 95% CI, 1.07-1.18; p < 0.001), serum sodium concentration (OR = 0.64; 95% CI, 0.51-0.81; p < 0.001), body temperature (OR = 2.48; 95% CI, 1.05-0.84; p < 0.001), and duration of symptoms (OR = 1.06; 95% CI, 1.02-1.09; p < 0.001) as risk factors for perforated appendicitis. Conclusion: Elevateds level of total serum bilirubin may be useful as an indicator of perforated appendicitis in children. Levels of bilirubin in serum is an inexpensive, simple, and available laboratory marker and should therefore be recommended in the initial evaluation for acute appendicitis in pediatric patients.

The incidence, risk factors, and prognosis of postoperative hyperbilirubinemia after cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: The purpose of the present systematic review was to evaluate the incidence, risk factors, and outcome of hyperbilirubinemia after cardiac surgery. METHODS: The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was employed to develop the search strategy, and the findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Embase, and the Cochrane Library were systematically searched for studies that provided data on the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac surgery patients from January 1960 to May 2020. Publication bias was graphically explored through funnel plots, and the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the included studies. RESULTS: Ten studies with 6,100 patients were included in our systematic review. The pooled incidence of hyperbilirubinemia was 23% [95% confidence interval (CI), 0.13-0.32]. Preoperative factors, including right atrial pressure [mean difference (MD), 4.65; 95% CI, 4.43-4.88], total bilirubin (TB) concentration (MD, 0.72; 95% CI, 0.65-0.79), alkaline phosphatase (MD, 27.38; 95% CI, 12.94-41.82), and alanine aminotransferase (MD, 12.02; 95% CI, 10.73-13.31), and intraoperative factors, including cardiopulmonary bypass (CPB) time (MD, 1.57; 95% CI, 0.52-2.63), aortic cross-clamping (ACC) time (MD, 11.82; 95% CI, 9.50-14.14), and the amount of blood transfused (MD, 3.77; 95% CI, 0.68-6.85), were the most robust risk factors for hyperbilirubinemia after cardiac surgery. Additionally, postoperative hyperbilirubinemia was associated with increased in-hospital mortality [odds ratio (OR), 9.9; 95% CI, 5.00-19.60, P<0.0001]. DISCUSSION: Hyperbilirubinemia was common and was associated with increased in-hospital mortality. Preoperative high right atrial pressure, high TB concentration, prolonged CPB and ACC time, and a large amount of blood transfused were the commonly observed risk factors for postoperative hyperbilirubinemia in cardiac surgery patients. Addressing these risk factors may be helpful to lower the occurrence of postoperative hyperbilirubinemia.

Conjugated hyperbilirubinemia among infants with hyperinsulinemic hypoglycemia.

From clinical practice, we noted that a subset of neonates with hyperinsulinism develop conjugated hyperbilirubinemia. A relationship between these two conditions has not been previously described. We aimed to assess the incidence of cholestasis in a cohort of neonates with hyperinsulinism and describe their clinical characteristics. In a retrospective cohort of 63 neonates with hyperinsulinism, 48% developed cholestasis (conjugated bilirubin > 17 µmol/L) with a median maximum conjugated bilirubin of 81 [21 to 191] µmol/L. A history of fetal distress (RR 2.3 [1.24-4.45], p < 0.01) and prematurity (RR 2.0 [1.23-3.26], p <0.01) was associated with the development of cholestasis, but not parental nutrition or other pharmacological treatments. An underlying etiology for the cholestasis was only found in 1 patient, and in all cases the cholestasis spontaneously improved.Conclusions: A significant percentage of infants with hyperinsulinism develop idiopathic, spontaneously resolving, conjugated hyperbilirubinemia. The association with a history of fetal distress potentially suggests that intrauterine factors leading to hyperinsulinism may also predispose towards conjugated hyperbilirubinemia. While the presence of neonatal cholestatic jaundice warrants timely investigations to exclude important underling etiologies, if validated, these findings may support a less invasive diagnostic workup of conjugated hyperbilirubinemia in infants with co-existent hyperinsulinism. What is Known: • Hyperinsulinism and conjugated hyperbilirubinemia are two common presentations in neonates. • A clinical association between the two conditions has not been described. What is New: • A significant proportion of infants with hyperinsulinism develop idiopathic, spontaneously resolving conjugated hyperbilirubinemia. • Increased risk for cholestasis in this patient population is associated with fetal distress and prematurity but not parental nutrition.

Risk factors and outcomes for hyperbilirubinaemia after heart surgery in children.

INTRODUCTION: Liver dysfunction, associated with morbidity and mortality, is common in patients with CHD. We investigate risk factors for and outcomes of hyperbilirubinaemia in neonates and infants after cardiac surgery. MATERIALS AND METHODS: In a retrospective analysis of neonates and infants undergoing cardiac surgery at our institution between January 2013 and December 2017, we identified those with post-operative conjugated hyperbilirubinaemia. We tested various demographic and surgical risk factors, and use of post-operative interventions, for an association with conjugated hyperbilirubinaemia. We also tested hyperbilirubinaemia for association with post-operative mortality and prolonged length of stay. RESULTS: We identified 242 post-operative admissions, of which 45 (19%) had conjugated hyperbilirubinaemia. The average conjugated bilirubin level in this group was 2.0 mg/dl versus 0.3 mg/dl for peers without hyperbilirubinaemia. The post-operative use of both extracorporeal membrane oxygenation (OR 4.97, 95% CI 1.89-13.5, p = 0.001) and total parenteral nutrition (OR 2.98, 95% CI 1.34-7.17, p = 0.010) was associated with conjugated hyperbilirubinaemia. No demographic variable analysed was found to be a risk factor. Hyperbilirubinaemia was associated with higher odds of mortality (OR 3.74, 95% CI 2.69-13.8, p = 0.005) and prolonged length of stay (OR 2.87, 95% CI 2.02-7.97, p = 0.005), which were independent of other risk factors. DISCUSSION: We identified the post-operative use of total parenteral nutrition and extracorporeal membrane oxygenation as risk factors for hyperbilirubinaemia. These patients were more likely to experience morbidity and mortality than control peers. As such, bilirubin may be marker for elevated risk of poor post-operative outcomes and should be more frequently measured after cardiac surgery.

Causative factors of liver fibrosis in HIV-infected patients. A single center study.

BACKGROUND: Liver disease is a leading cause of morbidity and mortality among Human Immunodeficiency virus (HIV) infected patients; however no consensus exists on HIV-related risk factors for it. The aim of this study was to identify risk factors for liver fibrosis/cirrhosis in a cohort of Greek HIV-infected patients. METHODS: Patients attending the HIV outpatient clinic of Pathophysiology Department at «Laiko¼ General Hospital in Athens, Greece, between December 2014 and December 2017 were eligible for inclusion. Inclusion criteria were confirmed HIV infection and age > 18 years. Exclusion criteria were Body-Mass index (BMI) > 40, liver metastases of malignant diseases and concurrent or previous chemotherapy. Liver stiffness (LS) was measured using Vibration Controlled Transient Elastography (TE) and laboratory tests were acquired in all patients. Patients were classified in 2 groups: those with mild or no fibrosis (equivalent to Metavir score F0-F2) and those with significant fibrosis (equivalent to Metavir score F3-F4). RESULTS: A total of 187 consecutive patients were included in this study. Median TE value was 5.1 kilopascals (KPa) (range 2.8-26.3), with 92.5% (173/187) of the patients having no/mild fibrosis and 7.4% (14/187) significant fibrosis. On multivariate logistic regression analysis older patient's age, abnormal serum aspartate aminotransferase (AST) value, Hepatitis C virus (HCV) infection, alcohol abuse, CD4/CD8 ratio and an increased number of liver related events (LREs) were significantly correlated with liver fibrosis/cirrhosis. CONCLUSIONS: In our cohort of HIV-infected individuals HCV/HIV co-infection, older age, alcohol abuse and CD4/CD8 ratio seem to correlate with fibrogenesis in the liver.

The prevalence and prognostic implications of pre-procedural hyperbilirubinemia in patients undergoing transcatheter aortic valve replacement.

Preoperative hyperbilirubinemia is associated with increased mortality and morbidity after cardiac surgery. However, this clinical significance is unclear with transcatheter aortic valve replacement (TAVR) procedures. The aims of this study were to determine the prevalence and prognostic implications of preoperative elevations of serum total bilirubin on TAVR outcomes. In 611 consecutive patients who underwent an elective TAVR procedure, 576 patients had recorded serum total bilirubin levels. Hyperbilirubinemia was defined as any value of serum total bilirubin ≥ 1.2 mg/dL obtained within 30-days prior to the TAVR procedure. The primary composite endpoint was post-TAVR all-cause in-hospital mortality or stroke. The overall prevalence of hyperbilirubinemia was 10% (n = 58). There were no patients with a prespecified diagnosis of liver cirrhosis. Pre-TAVR hyperbilirubinemia compared to normal bilirubin level was more common in younger (78 ± 10 vs. 82 ± 8 years old, p < 0.001) males (15 vs. 6%, p < 0.001), with history of pacemaker or ICD (33 vs. 18%, p = 0.005), congestive heart failure New York Heart Association class IV within 2 weeks from TAVR (35 vs. 14%, p < 0.001), severe tricuspid regurgitation (14 vs. 4%, p < 0.001), and atrial fibrillation or flutter (60 vs. 40%, p = 0.004, respectively). Pre-TAVR hyperbilirubinemia was independently associated with an increased post-TAVR in-hospital mortality (7 vs. 2% in normal bilirubin, p = 0.03), stroke (5 vs. 1%, p = 0.019, respectively), and a composite endpoint of death or stroke (12 vs. 3%, p < 0.001). Preoperative hyperbilirubinemia in patients undergoing TAVR is more prevalent than previously considered with multifactorial causes. Hyperbilirubinemia is independently associated with an increased post-TAVR in-hospital mortality and stroke.

Increased risk of neonatal complications or death among neonates born small for gestational age to mothers with gestational diabetes.

AIMS: To evaluate if neonatal complications or death were poorer for neonates born small for gestational age (SGA) than for those born with adequate weight or large for gestation age (LGA) to women with gestational diabetes mellitus (GDM). METHODS: Retrospective analysis of the clinical outcomes of neonates born to 3413 women with GDM. The prevalence of neonatal hypoglycaemia, hypocalcaemia, hyperbilirubinemia, polycythaemia, and death was compared among three birthweight groups: SGA, adequate, and LGA. A two-sided chi-squared or Fisher's exact test was used for between-group comparisons. A forward multiple logistic regression was performed to determine the odds ratio (OR) associated with SGA. RESULTS: Neonatal complications were more frequent in the SGA group (20.1%) than in the adequate (9.9%) or LGA (15.2%) groups. There were four deaths (1.6%) in the SGA group compared to one in the LGA (0.4%) and six in the adequate (0.2%) groups (P = 0.002). SGA was a risk factor for neonatal complications or death (OR. 2.122; 95% confidence interval, 1.552-2.899), independent of maternal age, weight gain, fasting glucose, glycaemic control, gestational hypertension, pre-eclampsia, smoking, or neonatal prematurity. CONCLUSION: SGA birthweight is an important risk factor for neonatal complications or death among neonates born to mothers with GDM.

Incidence and predictors of treatment-related conjugated hyperbilirubinemia during early treatment phases for children with acute lymphoblastic leukemia.

Conjugated hyperbilirubinemia (CHB) and liver transaminase elevation are known complications of acute lymphoblastic leukemia (ALL) therapy, but host risk factors are poorly understood. Among 373 children diagnosed with ALL between 2011 and 2016, clinically significant CHB and transaminase elevation were observed in 15 (4.0%) and 12 (3.2%) children, respectively, during induction and consolidation. Body mass index ≥95th percentile (odds ratio 9.20, 95% confidence interval 2.56-32.96) was the only host factor independently associated with CHB, and no host factors were associated with transaminase elevation. Obese patients warrant closer monitoring of hepatic function to facilitate early intervention prior to the development of severe, adverse hepatic events.

Hyperbilirubinaemia after cardiac surgery: the point of no return.

AIMS: The occurrence of hyperbilirubinaemia after heart surgery using cardiopulmonary bypass or post-operative heart failure is fairly common. We investigated the incidence, predictive value, and post-operative outcome of hyperbilirubinaemia after cardiac surgery in an effort to identify potential risk factors and significance on clinical outcome. METHODS AND RESULTS: Between 2006 and 2016, 1272 (10.1%) out of 12 556 patients developed hyperbilirubinaemia, defined as bilirubin concentration >3 mg/dL, during post-operative course at our institution. All patients who were operated using cardiopulmonary bypass were included. Hepatic dysfunction was diagnosed preoperatively in 200 patients (15.7%), whereas mean model of end-stage liver disease score was 11.22 ± 4.99. Early mortality was 17.4% with age [hazard ratio (HR) 1.019, 95% confidence interval (CI) 1.008-1.029; P = 0.001], diabetes (HR 1.115, CI 1.020-1.220; P = 0.017), and emergent procedures (HR 1.315, CI 1.012-1.710) as multivariate predictors. Post-operative predictors were low-output syndrome (HR 3.193, 95% CI 2.495-4.086; P < 0.001), blood transfusion (HR 1.0, CI 1.0-1.0; P < 0.001), and time to peak bilirubin (HR 1.1, CI 1.0-1.1; P < 0.001). We found an increased correlation with mortality at 3.5 post-operative day as well as an optimal cut-off value for bilirubin of 5.35 mg/dL. A maximum bilirubin of 25.5 mg/dL was associated with 99% mortality. Survival analysis showed significantly decreased survival for patients who developed late, rather than early, hyperbilirubinaemia. CONCLUSIONS: Post-operative hyperbilirubinaemia is a prevalent threat after cardiopulmonary bypass, associated with high early mortality. The timing and amount of peak bilirubin concentration are linked to the underlying pathology and are predictors of post-operative outcome. Patients with late development of steep hyperbilirubinaemia warrant meticulous post-operative care optimizing cardiac and end organ functions before reaching the point of no return.

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia.

BACKGROUND/AIMS: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. PATIENTS AND METHODS: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). RESULTS: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012). CONCLUSIONS: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.

Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.

BACKGROUND: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. METHODS: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into "progression group" (n = 7) that required any therapy and "spontaneous resolution group" (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-ß1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. RESULTS: Three patients developed leukemia during the study period (median, 1147 days; range, 33-3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = -0.46, p = 0.02). CONCLUSION: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.

A safe and efficacious preventive strategy in the high-risk surgical neonate: cycled total parenteral nutrition.

INTRODUCTION: Hepatic dysfunction in patients reliant on total parenteral nutrition (TPN) may benefit from cycled TPN. A concern for neonatal hypoglycemia has limited the use of cycled TPN in neonates less than 1 week of age. We sought to determine both the safety and efficacy of cycled TPN in surgical neonates less than 1 week of age. METHODS: A retrospective chart review was conducted on surgical neonates placed on prophylactic and therapeutic cycled TPN from January 2013 to March 2016. Specific emphasis was placed on identifying incidence of direct hyperbilirubinemia and hypoglycemic episodes. RESULTS: Fourteen neonates were placed on cycled TPN; 8 were prophylactically cycled and 6 were therapeutically cycled. Median gestational age was 36 weeks (34, 37). Sixty-four percent (n = 9) had gastroschisis. There was no difference between the prophylactic and therapeutic groups in incidence of hyperbilirubinemia > 2 mg/dL (3 (37%) vs 5 (83%), p = 0.08) or the length of time to development of hyperbilirubinemia [24 days (4, 26) vs 27 days (25, 67), p = 0.17]. Time on cycling was similar though patients who were prophylactically cycled had a shorter overall time on TPN. Three (21%) infants had documented hypoglycemia, but only one infant became clinically symptomatic. CONCLUSION: Prophylactic TPN cycling is a safe and efficacious nutritional management strategy in surgical neonates less than 1 week of age with low rates of hypoglycemia and a shorter total course of TPN; however, hepatic dysfunction did not appear to be improved compared to therapeutic cycling.

Antecedentes maternos prenatales y riesgo de complicaciones neonatales en productos de término de bajo peso para edad gestacional / Maternal prenatal history and neonatal risk complications for low-weight for gestacional age term newborns

Resumen Introducción: El bajo peso neonatal (< 2.5 kg o < percentil 10) se atribuye a causas constitucionales (pequeño para la edad gestacional [PEG]) o a la restricción en el crecimiento intrauterino (RCIU), con riesgos posnatales diferentes. En ausencia de una valoración fetal-placentaria prenatal adecuada, resulta difícil establecerlo. El conocer los antecedentes maternos de enfermedades gestacionales (AMEG): hipertensión arterial (HTA), hipotiroidismo, Diabetes Mellitus (DM) gestacional y otra; pudiera orientar a la diferenciación y el manejo. El objetivo de este trabajo fue determinar si la presencia de AMEG se asocia a complicaciones neonatales en productos de bajo peso neonatal. Métodos: Se realizó un estudio de cohorte retrospectivo en un grupo de 349 recién nacidos vivos de término (≥ 37 semanas de edad gestacional [SEG]), PEG, en cunero fisiológico y agrupados según los AMEG. Se determinó la frecuencia de dificultad respiratoria (DR), hipoglucemia (HG) e hiperbilirrubinemia (HBr). Resultados: El 16.6% (58/349) presentó AMEG (58.6% HTA y 41.3% hipotiroidismo, solos o combinados). Los neonatos con AMEG fueron más limítrofes (37 SEG, 55.2% vs. 35.1%; p = 0.037). Los de 37 SEG con menor peso (diferencia de ≈100 g; p = 0.028), más riesgo de HG (13.6%; intervalo de confianza al 95% [IC 95%]: −4.08-31.2) pero menos DR (diferencia de −4.7%; IC 95%: −20.6-11.05). La HG en los de 39 SEG solo se presentó en neonatos sin AMEG (diferencia 12.7%; IC 95%: 3.9 a 31.5) igual que la HBr (tres casos). Conclusiones: Indagar sobre los AMEG en un producto PEG parece ser útil en la inferencia de RCIU. Sin embargo, es insuficiente, por lo que en conjunto con otras herramientas nos ayuda a estimar posibles complicaciones y acciones preventivas.

Abstract Background: Low-birth-weight (LWB < 2.5 kg or <10 percentile) could be caused by constitutional matters or by intrauterine growth restriction (IUGR), both with different neonatal complications. Without an adequate prenatal evaluation is hard to stablish those conditions. Knowing the maternal history for gestational diseases (MHGD) such as hypertension (HTA), hypothyroidism or diabetes, among others could help clarify that difference. The aim of this work was to determine if having a MHGD is associated to neonatal complications in newborns with LWB. Methods: Retrospective cohort study, which included 349 with LWB at term (≥ 37 weeks of gestation [WG]) grouped into those with or without MHGD at a hospital nursery. The frequency of respiratory distress, hypoglycemia, and hyperbilirubinemia was determined. Results: 16.6% (58/349) had MHGD (58.6% for HTA and 41.3% hypothyroidism alone or combined). The neonate with MHGD were more borderline term (37 WGA, 55.2% vs. 35.1%; p = 0.037), and had lower weight (difference of ≈100 g; p = 0.028), had more cases with hypoglycemia (13.6%; CI 95%: −4.08 to 31.2%) but developed less respiratory distress (RD) (difference of −4.7%; CI 95%: −20.6 to 11.05%). Hypoglycemia in 39 WGA was only seen among neonates without MHGD (difference 12.7%; CI95%: 3.9 to 31.5%) just as for the hyperbilirubinemia cases (three). Conclusions: Inquiring about the MHGD on LBW term babies could be useful in the inference of IUGR, although we need other tools so that altogether can help to predict possible complications and to plan preventive actions.

Evaluation of vitamin D status bone mineral density and dental health in children with cholestasis.

BACKGROUND: Hepatic osteodystrophy caused by vitamin D and calcium malabsorption is thought to develop in children with cholestatic liver disease leading to secondary hyperparathyroidism and rickets or osteomalacia. The aim of this study was to evaluate the dental and bone mineral densities and the serum level of vitamin D in cholestatic infants and children and to correlate this process with clinical and laboratory parameters. METHODS: This is a cross-sectional study that include 50 patients presenting with cholestasis. Thirty age and sex matched controls recruited not complaining of liver disease. All cases were subjected to full history taking, clinical and dental examination, 25(OH)D level, ALT, AST, bilirubin, albumin, GGT, alkaline phosphatase, PT, INR, calcium, corrected calcium, phosphorus and DXA scan to those above 5 years old. Controls were subjected to measuring the serum levels of 25(OH)D, total bilirubin, direct bilirubin, ALT, GGT, AST, PT, INR, alkaline phosphatase, albumin, calcium and phosphorus. RESULTS: Out of the 50 cases; 23 were females (46%), with a mean age of 6.17±3.9 years ranging from 1.1 to 17 years. Twenty-eight of the cases had signs of rickets (56%), 6 of them had bone fracture (12%) and 42.8% had milky teeth caries. The level of 25(OH) vitamin D was below normal range in around half of the patients. There was significant difference between cases and controls in calcium and phosphorus levels, ALT and alkaline phosphatase. Low bone mineral density (BMD) was present in 50% and 5 cases (17.9%) were diagnosed as having osteoporosis. There was a negative correlation between the Z-score, BMD of total body, BMD and bone mineral content (BMC) of spine and total and direct bilirubin. There was a positive correlation between (BMD of total body, spine and BMC of spine) and serum phosphorus, alkaline phosphatase and albumin. There was a positive correlation between the Z-score of total body and serum calcium. CONCLUSION: Decreased level of 25-OH vitamin D is present in more than half of cholestatic patients, and is correlated positively to serum calcium. Decreased BMD was present in more than half of studied cholestatic patients correlated to the low serum calcium rather than the vitamin D level. The decreased BMD and the dental affection in cholestatic children is related to the level of hyperbilirubinemia.

Defining Eligibility of FOLFIRINOX for First-Line Metastatic Pancreatic Adenocarcinoma (MPC) in the Province of British Columbia: A Population-based Retrospective Study.

BACKGROUND: FOLFIRINOX is a first-line treatment option for patients with metastatic pancreatic cancer (MPC) and is associated with improved survival yet significantly more toxicities than standard gemcitabine. Our aim was to determine the proportion of patients with MPC who would be eligible for FOLFIRINOX based upon the pivotal ACCORD study criteria. METHODS: Patients with confirmed MPC at the time of referral to the BC Cancer Agency between 2004 and 2007 were identified from the Gastrointestinal Cancers Outcomes Unit Database (GICOU). Proportion of patients that met the ACCORD study eligibility criteria was determined by chart review. Criteria for FOLFIRINOX exclusion were assessed using descriptive statistics. RESULTS: A total of 100 consecutive patients with complete chart records and MPC were identified. Fifty-two (52%) were male and the median age was 68 years (range, 42 to 98 y). The most common sites of metastases were liver (63%) and peritoneum (22%). Only 26 patients fulfilled the ACCORD study eligibility criteria. The most common reasons for FOLIFIRINOX exclusion per ACCORD were poor Eastern Cooperative Oncology Group score of ≥2 (64%), age of 76 years or greater (22%), elevated bilirubin (22%), and inadequate renal function (6%). CONCLUSIONS: Despite the proven survival benefit of FOLFIRINOX, only approximately one quarter of patients in the real-world setting with MPC would have been considered eligible for such therapy based upon the ACCORD eligibility criteria. Careful patient selection and more tolerable therapies are required.

Gestational Diabetes Screening: The International Association of the Diabetes and Pregnancy Study Groups Compared With Carpenter-Coustan Screening.

OBJECTIVE: To evaluate whether one-step gestational diabetes screening recommended by The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) is associated with better maternal, perinatal, or neonatal outcomes than the two-step Carpenter-Coustan screening. METHODS: In this before-after retrospective cohort study conducted between July 1, 2010, and December 31, 2013, we compared Carpenter-Coustan and IADPSG screening in patients with singleton pregnancies. All patients diagnosed with gestational diabetes received intensive teaching, home glucose monitoring, and medications as indicated. The primary outcome was the rate of large-for-gestational-age neonates. Secondary outcome measures were macrosomia (greater than 4,000 g), primary cesarean delivery, neonatal intensive care unit admission, preterm delivery, preeclampsia, and hyperbilirubinemia. We determined that a sample size of 2,782 per group was sufficient to detect a 2% difference in the primary outcome between groups with 80% power assuming a 10% incidence in the before group. The groups were compared using Fisher exact test for proportions and a χ test for odds ratios. RESULTS: In the before (Carpenter-Coustan) group, 513 (17%) of the 2,972 patients were diagnosed with gestational diabetes, and in the after (IADPSG) group, 847 (27%) of the 3,094 patients were so diagnosed (P<.001). There was no significant difference in rates of large for gestational age, 10% and 9%, respectively (P=.25). The IADPSG group had a significantly higher primary cesarean delivery rate-16% compared with 20% (P<.001), but there were no significant differences in any other pregnancy outcomes. CONCLUSION: Although one-step screening was associated with more patients being treated for gestational diabetes, it was not associated with a decrease in large-for-gestational-age or macrosomic neonates but was associated with an increased rate of primary cesarean delivery. Our results did not support the IADPSG-recommended screening protocol.

The Effect of Soy Intake on Metabolic Profiles of Women With Gestational Diabetes Mellitus.

CONTEXT: To our knowledge, no study has examined the effects of soy intake on metabolic status of women with gestational diabetes mellitus (GDM). OBJECTIVE: This study was designed to assess the effects of soy intake on metabolic status of GDM women. METHODS: A randomized clinical trial was performed among 68 women with GDM. Women were randomly assigned to receive either a control diet containing 0.8-g/kg protein (70% animal and 30% plant proteins) (n = 34) or a soy diet containing the same amount of protein with 35% animal protein, 35% soy protein, and 30% other plant proteins (n = 34) for 6 weeks. RESULTS: Compared with soy protein consumption, the control group significantly increased fasting plasma glucose (+1.4 ± 11.6 vs -12.7 ± 13.2 mg/dL, P < .001), serum insulin levels (+5.0 ± 11.6 vs -0.9 ± 10.0 µIU/mL, P = .02), homeostasis model of assessment-insulin resistance (+1.2 ± 2.7 vs -0.8 ± 2.2, P = .002), and decreased quantitative insulin sensitivity check index (-0.007 ± 0.02 vs +0.01 ± 0.03, P = .004). Administration of the control diet resulted in a significant difference in serum triglycerides changes (+31.3 ± 38.0 vs +8.9 ± 46.1 mg/dL, P = .03) compared with soy protein. There were a significant decrease in total antioxidant capacity (-35.0 ± 136.2 vs +81.8 ± 188.8 mmol/L, P = .005) and glutathione (-41.3 ± 145.7 vs +53.3 ± 117.3 µmol/L, P = .004) by the control diet intake compared with soy protein. The control diet group had a higher incidence of newborn hyperbilirubinemia (32.4% vs 8.8%, P = .01) and newborn hospitalization (20.6% vs 2.9%, P = .02) compared with soy protein. CONCLUSION: Soy protein consumption in women with GDM significantly improved the glucose homeostasis parameters, triglycerides, and biomarkers of oxidative stress, as well as reductions in the incidence of newborn hyperbilirubinemia and hospitalizations.

Byler disease: early natural history.

OBJECTIVES: Byler disease, originally described in Amish kindred, results from mutations in ATPase Class I Type 8b Member 1 (ATP8b1). Specific clinical reports of Amish Byler disease were last published 40 years ago. These investigations were directed at the present detailed clinical understanding of the early course of hepatic manifestations of Byler disease. METHODS: This study analyzed routine clinical practice and outcomes of children with Byler disease (defined by homozygous c.923G>T mutation in ATP8b1), who initially presented to Children's Hospital of Pittsburgh of UPMC between January 2007 and October 2014. Data were analyzed to the earlier of 24 months of age or partial external biliary diversion. RESULTS: Six children presented between 1 and 135 days of life: 2 presented with newborn direct hyperbilirubinemia, 2 had complications of coagulopathy, 1 had failure to thrive and rickets, and 1 sibling was identified by newborn genetic testing. Intensive fat-soluble vitamin supplementation was required to prevent insufficiencies in vitamins D, E, and K. Hyperbilirubinemia was variable both over time and between children. Serum bile acid levels were elevated, whereas γ-glutamyltranspeptidase levels were low normal. Scratching behavior (pruritus) was intractable in 4 of 6 children with onset between 6 and 12 months of age. Features of portal hypertension were not observed. Partial external biliary diversion was used during the second year of life in 4 children. CONCLUSIONS: Detailed analysis of Byler disease revealed varied disease presentation and course. Nutritional issues and pruritus dominated the clinical picture in the first 2 years of life.