Faculty Bibliography

OBJECTIVES/OBJECTIVE:Detecting and treating severe hypoglycemia promptly after birth is crucial due to its association with adverse long-term neurodevelopmental outcomes. However, limited data are available on the optimal timing of glucose screening in asymptomatic high-risk neonates prone to hypoglycemia. Risk factors associated with asymptomatic high-risk neonates include late prematurity ≥35 and <37 weeks gestation (LPT), small-for-gestational-age (SGA), large-for-gestational-age (LGA), and infant-of-a-diabetic mother (IDM). This study aims to determine the incidence and the impact of individual risk factors on early hypoglycemia (defined as blood glucose ≤25 mg/dL in the initial hour after birth) in asymptomatic high-risk neonates. METHODS:All asymptomatic high-risk neonates ≥35 weeks gestation underwent early blood glucose screening within the first hour after birth (n=1,690). A 2-year retrospective analysis was conducted to assess the incidence of early neonatal hypoglycemia in this cohort and its association with hypoglycemia risk factors. RESULTS:Out of the 9,919 births, 1,690 neonates (17 %) had risk factors for neonatal hypoglycemia, prompting screening within the first hour after birth. Incidence rates for blood glucose ≤25 mg/dL and ≤15 mg/dL were 3.1 and 0.89 %, respectively. Of concern, approximately 0.5 % of all asymptomatic at-risk neonates had a blood glucose value of ≤10 mg/dL. LPT and LGA were the risk factors significantly associated with early neonatal hypoglycemia. CONCLUSIONS:Asymptomatic high-risk neonates, particularly LPT and LGA neonates, may develop early severe neonatal hypoglycemia identified by blood glucose screening in the first hour of life. Additional investigation is necessary to establish protocols for screening and managing asymptomatic high-risk neonates.

Introduction: COVID-19, in combination with steroid treatment, is known to propagate hyperglycemia in diabetic patients. The purpose of this study was to establish a new insulin protocol for diabetic patients with COVID-19 on the dexamethasone protocol for better glycemic control. Research Design and Methods: This was a retrospective cohort study conducted at NYU Langone Long Island Hospital from 1 July 2020 to 1 July 2021. Eligible cases had to meet the following inclusion criteria: age of 18 years or greater, history of or new-onset diabetes, diagnosis of COVID-19 and receiving the 10 day dexamethasone treatment, length of stay of at least 3 days with a minimum of 48 h of glucose monitoring, and requiring basal and prandial insulin with correction during hospital stay. Data were collected using the hospital"™s electronic record system. The total basal, prandial, and daily doses of insulin on the day at which glycemic control was achieved, or if glycemic control was not achieved by the discharge date, then on the completion date of the dexamethasone treatment, were collected and assessed. Results: A total of 145 patient cases were analyzed. About 46% of patients achieved glycemic control. The average insulin dose required was 0.67 (0.61"“0.74) unit/kg. The mean total dose of insulin was 59 units. The mean total basal dose was 21 units. The mean total prandial dose was 38 units. The average prandial doses were higher than the basal doses for all participants. Conclusions: Diabetic patients with COVID-19 on dexamethasone should be initiated on at least 0.6"“0.7 u/kg of insulin to achieve glycemic control.

We assessed our institutional practice of individualized insulin dosing for patients with type 2 diabetes receiving preoperative carbohydrate loading (CHO-L) within an enhanced recovery after surgery (ERAS®) protocol. Patients enrolled in an ERAS® protocol with concomitant type 2 diabetes received rapid acting insulin (Novolog®[insulin aspart]) prior to 50 g CHO-L on the day of surgery. Following CHO-L and the administration of insulin, no hypoglycemic episodes occurred with preoperative POC glucose values between 6.8 and 12.3 mmol/L (123 and 221 mg/dL). Our experience demonstrates that administering rapid acting insulin prior to CHO-L in patients with type 2 diabetes is feasible and targets the potentially negative influence CHO-L may impose on preoperative glycemia in this population. Important considerations of this approach are highlighted and an insulin dosing algorithm designed for non-specialty providers is suggested.

Hyperlipidemia predisposes individuals to cardio-metabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apoB-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglycerides (TG) and not phospholipids (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different β-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in β2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in β1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, while negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention.

OBJECTIVE/UNASSIGNED:The ideal inpatient insulin regimen efficiently attains the target blood glucose range, effectively treats hyperglycemia, and minimizes the risk of hypoglycemia. The objective of this study was to compare glycemic targets achieved by using correctional monotherapy (CM) and basal-bolus therapy (BBT) in insulin-naive patients in the inpatient setting to determine optimal blood glucose management for these patients. DESIGN/UNASSIGNED:This was a retrospective observational cohort study of 792 patients with diabetes not on home insulin therapy who were admitted to an academic hospital over a 5.5-month period. The percentages of hyperglycemic and hypoglycemic values in each group were compared. RESULTS/UNASSIGNED:= 0.301). CONCLUSION/UNASSIGNED:Utilizing BBT in insulin-naive patients admitted to the hospital within the first 24 hours of insulin administration results in lower rates of hyperglycemia without higher rates of hypoglycemia when compared with CM.

BACKGROUND:Many patients require revascularization after an index acute coronary syndrome (ACS). Lipoprotein(a) is thought to play a pathogenic role in atherothrombosis. In ODYSSEY OUTCOMES, alirocumab reduced major adverse cardiovascular events after ACS, with greater reduction among those with higher lipoprotein(a) levels. We explored whether risk of revascularization after ACS was modified by the level of lipoprotein(a) and treatment with alirocumab or placebo. METHODS:ODYSSEY OUTCOMES compared alirocumab with placebo in 18 924 patients with ACS and elevated atherogenic lipoproteins despite optimized statin treatment. In this post hoc analysis, treatment effects are summarized by competing-risks proportional hazard models. RESULTS:<0.001). Alirocumab produced the greatest reduction of coronary revascularization in patients with baseline lipoprotein(a) in the top quartile (≥59.6 mg/dL) (HR, 0.69 [95% CI, 0.57-0.84]), but no apparent reduction in the bottom quartile (HR, 1.00 [95% CI, 0.82-1.22]). Findings were similar for the effect of alirocumab on any revascularization. CONCLUSIONS:Alirocumab reduced revascularization after ACS. The risk of revascularization and reduction in that risk with alirocumab were greatest in patients with elevated lipoprotein(a) at baseline. (ODYSSEY OUTCOMES NCT01663402).

PURPOSE/OBJECTIVE:Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. MATERIALS/METHODS/METHODS:A retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. RESULTS:A total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. CONCLUSION/CONCLUSIONS:Compared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.

OBJECTIVES/OBJECTIVE:The reported malignancy rate of highly suspicious thyroid nodules based on the ACR TI-RADS criteria (TI-RADS category 5 [TR5]) varies widely. The objective of our study was to determine the rate of malignancy of TR5 nodules at our institution. We also aimed to determine the predictive values of individual sonographic features, as well as the correlation of total points assigned to a nodule and rate of malignancy. METHODS:Our single-institution retrospective study evaluated 450 TR5 nodules that had cytology results available, in 399 patients over a 1-year period. Sonographic features and total TI-RADS points were determined by the interpreting radiologist. Statistical analyses included logistic regression models to find factors associated with increased odds of malignancy, and computing sensitivity, specificity, positive and negative predictive values of various individual sonographic features. RESULTS:Of the 450 nodules, 95 (21.1%, 95% exact confidence interval 17.4-25.2%) were malignant. Each additional TI-RADS point increased the odds of malignancy (adjusted odds ratio 1.35, 95% confidence interval 1.13-1.60, P < .001). "Very hypoechoic" was the sonographic feature with the highest specificity and positive predictive value for malignancy (95.5 and 44.8%, respectively), while "punctate echogenic foci" had the lowest positive predictive value (20.0%). CONCLUSIONS:The rate of malignancy of TR5 nodules at our institution was 21.1%, which is lower than other malignancy rates reported in the literature. The total number of points assigned on the basis of the TI-RADS criteria was positively associated with malignancy, which indicates that TR5 should be viewed as a spectrum of risk.