Manganese is associated with increased plasma interleukin-1β during pregnancy,within a mixtures analysis framework of urinary trace metals

Exposure to trace metals may impact reproductive health outcomes through perturbations in maternal immune signaling molecules. We conducted a cross-sectional study of 390 pregnant women from the LIFECODES birth cohort and investigated the associations between 17 urinary metals and five immune biomarkers measured in the 3rd trimester (median 26 weeks gestation). We used linear regression to estimate pair-wise associations and applied elastic net and Bayesian kernel machine regression to identify important contributing exposures analytes as well as non-linear effects. Maternal urinary manganese, nickel, and barium were positively associated with maternal plasma interleukin-1β (IL-1β). Elastic net and Bayesian kernel machine regression identified manganese as the dominant trace metal in association with IL-1β. An interquartile range difference in manganese (0.6 μg/L) was associated with a 29 % increase in IL-1β (95 % CI: 12.4–48.2). In conclusion, trace metal exposures were associated with biomarkers of immune perturbations, and this warrants further investigation.     

Bupropion Overdose Complicated by Cardiogenic Shock Requiring Vasopressor Support and Lipid Emulsion Therapy

BackgroundBupropion overdose is a commonly encountered presentation in the emergency department (ED). While the majority of cases resolve with supportive care, serious adverse effects, including seizures, cardiogenic shock, and death, can occur. Intravenous lipid emulsion (ILE) therapy has been utilized for a multitude of poisonings with varying levels of success. Although a number of cases suggest the value of ILE therapy in cases of bupropion overdose, more recent data propose that its role may be overstated.Case ReportA young woman presented to the ED with altered mental status complicated by seizure after bupropion overdose. She subsequently developed cardiogenic shock requiring vasopressor support. Bedside echocardiogram revealed a decreased left ventricular ejection fraction (LVEF). She received ILE therapy with significant improvement in both hemodynamic status and LVEF by bedside ultrasound.Why Should an Emergency Physician Be Aware of This?Although the majority of patients presenting with bupropion overdose improve with supportive care, life-threatening sequelae are possible. ILE therapy has shown promise in a variety of different overdose situations, although the evidence in cases of bupropion poisoning has been varied, and it has traditionally been utilized as a last-line rescue modality. Based on hemodynamic parameters and bedside ultrasound, this case suggests that early initiation of ILE therapy should be considered in these cases, as the potential benefits likely outweigh the theoretical risks.     

IKZF1 Deletion Subtyping and Outcome Analysis in BCR–ABL1-Negative Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single-Institution Experience from North India

BackgroundIKZF1 deletions are associated with adverse outcomes in B-cell acute lymphoblastic leukemia (B-ALL). We assessed the prevalence and clinical impact of functional subtypes of IKZF1 deletions in pediatric BCR–ABL1-negative B-ALL. Patients andMethodsThis retrospective study of IKZF1 deletions was done in cases of pediatric BCR–ABL1-negative B-ALL. The genomic DNA of cases, over a 53-month period, was analyzed using multiplex ligation-dependent probe amplification and multiplex fluorescent polymerase chain reaction. The deletions were divided into functional subgroups: (1) loss-of-function/haploinsufficiency, (2) dominant-negative, and (3) a combination of both types of deletion. The post-induction remission status, event-free survival (EFS), and overall survival (OS) were noted.ResultsOut of 320 cases, 47 (14.7%) had IKZF1 deletions. Thirty-six of the 47 (77%) had loss-of-function deletions, 10 (21%) had dominant-negative deletions, and one (2%) had a combination of both types. The post-induction remission rates in cases with loss-of-function deletions (22/30, 73%; P = .060) and dominant-negative deletions (4/5, 80%; P = .517) were lower compared with those without deletions (215/248, 86.7%). These cases also had worse median EFS: 21.1 months (P = .006) for loss-of-function and 15.4 months (P = .156) for dominant-negative deletions, compared with 46.4 months in cases without IKZF1 deletions. They also had worse median OS: 23.4 months (P = .012) for loss-of-function deletions and 15.7 months (P = .233) for dominant-negative deletions, compared with median not reached in cases without IKZF1 deletions.ConclusionThe IKZF1 deletions were seen in 14.7% of BCR–ABL1-negative pediatric B-ALL. Most of these deletions (77%) were loss-of-function type. The cases with loss-of-function deletions had lower remission rates and poor EFS and OS compared with cases without IKZF1 deletions. A similar trend of poor outcome was seen in the few cases with dominant-negative IKZF1 deletions.     

International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer

BackgroundThe objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer.MethodsWe included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement.ResultsOverall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64–0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001).ConclusionsThis large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.