The management of pregnancy and delivery in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

3-hydroxy-3-methylglutaric (HMG)-CoA lyase is required for ketogenesis and leucine degradation. Patients with HMG-CoA lyase deficiency typically present with hypoketotic hypoglycemia and metabolic acidosis, which can be fatal if untreated. The patient is a 28-year-old female with HMG-CoA lyase deficiency who presented at 4 weeks gestation for prenatal care. Protein intake as well as carnitine supplementation were gradually increased to support maternal and fetal demands up to 65 g per day for protein and 80 mg/kg/day for carnitine. Fetal growth was appropriate. At 36 5/7 weeks, she presented with spontaneous rupture of membranes. Twice maintenance 10% glucose-containing intravenous fluids were initiated. During labor, vomiting and metabolic acidosis developed. Delivery was by cesarean. Preeclampsia developed postpartum. The patient recovered well and was discharged home on postpartum day 5. Stress of pregnancy and labor and delivery can lead to metabolic decompensation in HMG-CoA lyase deficiency. Patients should be monitored closely by a biochemical geneticist, dietitian, and high-risk obstetrician at a tertiary care center during their pregnancy. Fasting should be avoided. Intravenous 10% glucose-containing fluids should be provided to prevent catabolism and metabolic decompensation during labor and delivery. © 2016 Wiley Periodicals, Inc.

Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay.

Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as predictive biomarkers of immunotherapy response in metastatic melanoma patients treated with nivolumab or pembrolizumab as first-line treatment. In all, 41 patients were included in the study. The baseline plasma level of sPD-1 was significantly lower, and the sBTN2A1 was significantly higher, in long-responder patients to nivolumab or pembrolizumab (median sPD-1: 10.3 ng/ml versus 16.6 ng/ml, p = 0.001; median sBTN2A1: 4.4 ng/ml versus 3.77 ng/ml, p = 0.004). Lower levels of sPD-1 and higher levels of sBTN2A1 were also significantly associated with better overall response rate. Notably, when we further stratified the study cohort using BMI along with sPD-1, patients with BMI ⩾ 25 and sPD-1 < 11.24 ng/ml had longer time to treatment failure after PD-1 inhibitor than other subgroups of patients (p < 0.001). Circulating sPD-1 and sBTN2A1 detection, along with BMI, could give more insights into the immune-metabolic interactions underlying the benefit observed in overweight/obese patients, improving the use of dynamic, noninvasive, biomarkers for patient selection.

Compensatory increased enteral feeding goal rates: a way to achieve optimal nutrition.

BACKGROUND: Traditionally, enteral nutrition (EN) goal rates have been calculated based on an intended continuous 24-hour infusion rate. Many factors in the care of critically ill patients result in interruption of EN infusions, often for several hours daily, which may lead to significant underfeeding. The objective of this study was to evaluate the difference of daily EN volume deficits between a traditionally calculated infusion rate and a compensatory, higher calculated infusion rate in which the 24-hour volume was delivered over a 20-hour infusion period. METHODS: Data collection consisted of daily EN volume deficit (intended volume - actual volume infused), based on intensive care unit nursing flow sheets. The primary outcome was daily EN volume deficit from a standard 24-hour calculated goal rate, compared with volume deficit from delivery of the same volume over 20 hours. For the 20-hour group, the calculated daily requirement of EN was divided by 20 rather than 24 for the higher hourly rate but still delivered for 24 hours. RESULTS: One hundred ten baseline (24-hour) EN days were evaluated with a mean infusion volume deficit of (±)247 mL/d. This compared with 158 patients in the 20-hour infusion group, in which the mean volume deficit was (±)45 mL/d (P < .001). Enteral nutrition was most often held for extubation or procedures. A higher level of overfeeding was noted in the 20-hour infusion group. CONCLUSION: Calculating and prescribing higher EN infusion rates, assuming 20 hours of actual infusion daily, promoted delivery of optimal nutrient provisions and avoidance of unintended malnutrition by significantly reducing caloric deficit from frequent EN holding.