Type 2 diabetes complications are associated with liver fibrosis independent of hemoglobin A1c.

INTRODUCTION AND OBJECTIVES: The association between type 2 diabetes, non-alcoholic fatty liver disease, and liver fibrosis is well established, but it is unknown whether complications of type 2 diabetes influence fibrosis levels. We defined the complications of type 2 diabetes by the presence of diabetic nephropathy, retinopathy, or neuropathy and aimed to evaluate their association with the degree of liver fibrosis measured by the fibrosis-4 (FIB-4) index. MATERIALS AND METHODS: This is a cross-sectional study evaluating the association of type 2 diabetes complications with liver fibrosis. A total of 2389 participants were evaluated from a primary care practice. FIB-4 was evaluated as a continuous and categorical measure using linear and ordinal logistic regression. RESULTS: Patients with complications were older, had higher hemoglobin A1c, and a higher median FIB-4 score (1.34 vs. 1.12, P<0.001). On adjusted analysis, type 2 diabetes complications were associated with higher fibrosis by continuous FIB-4 score (Beta-coefficient: 0.23, 95% confidence interval [CI]: 0.004-1.65) and demonstrated increased odds of fibrosis by categorical FIB-4 score (odds ratio [OR]: 4.48, 95% CI: 1.7-11.8, P=0.003), independent of hemoglobin A1c level. CONCLUSIONS: The presence of type 2 diabetes complications is associated with the degree of liver fibrosis, independent of hemoglobin A1c level.

Retrospective review of accelerated daratumumab administration.

Daratumumab is an anti-CD38 monoclonal antibody approved for multiple myeloma. The initial infusion is administered over a median of 7.5 hours with subsequent infusions given over 3 to 4 hours. Studies show high incidence of infusion related reactions (IRRs) with the initial dose which decreases with subsequent infusions. Accelerated 90 minute daratumumab infusions following the second dose of standard administration are widely accepted in practice including at Beth Israel Deaconess Medical Center (BIDMC) despite limited data from small safety studies. The objective of this study is to evaluate the safety of accelerated daratumumab administration compared to standard administration. The primary outcome is the incidence of common terminology criteria for adverse events (CTCAE) version 5.0 grade 1 or higher for IRRs in accelerated and standard infusions. Secondary outcomes include non-IRR adverse events and amount of supportive care medications used pre- and post- and during accelerated and standard infusions. A total of seventy five patients received a daratumumab infusion between November 2015 and August 2019. There were a total of 420 daratumumab infusions evaluated, 317 (75.5%) were standard infusions of which 152 infusions were standard infusions that preceded an accelerated infusion. There were a total of 103 (24.5%) accelerated infusions. IRRs occurred in a total of 38 (9%) of the infusions with CTCAE grade 2 reactions occurring in total of 21 (5%) infusions and grade 1 occurring in 15 (3.6%) infusions. Overall accelerated daratumumab administration is safe and well tolerated when given following at least two standard infusions.

Weight-Based Dosing Versus a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate in Obese Patients Requiring Vitamin K Antagonist Reversal.

INTRODUCTION: Despite an increase in the use of fixed-dose protocols of 4-factor prothrombin complex concentrate (4F-PCC) for the reversal of vitamin K antagonists (VKAs), there remains a paucity of data in obese patients. In this study, we aimed to compare the proportion of patients attaining international normalized ratio (INR) goals using a weight-based dosing strategy versus a fixed-dose regimen of 4F-PCC. METHODS: This was a retrospective study conducted in patients 18 years of age or older, weighing ≥ 100 kg, who received either a weight-based dose or fixed dose of 4F-PCC (2000 units) for the reversal of VKA, and had a documented baseline and post-treatment INR. The primary outcome was the proportion of patients achieving an INR of < 2 for all indications of warfarin reversal, except in patients with intracranial hemorrhage, where the goal was an INR of < 1.5. RESULTS: A total of 44 patients met the inclusion criteria; 25 patients in the weight-based dosing group and 19 patients in the fixed-dose group. The median baseline INR was similar in both groups (weight-based dosing group 3.2 [interquartile range {IQR} 2.8-3.7] vs fixed-dose group 3.0 [IQR 2.7-4.9], p = 1). The median post-treatment INR was significantly lower in the weight-based dosing group compared to the fixed-dose group (1.3 [IQR 1.2-1.5] vs 1.6 [IQR 1.5-1.9], p < 0.01). However, there was no significant difference in the primary outcome between both groups (weight-based dosing strategy 84% vs fixed dose strategy 90%, p = 0.68). CONCLUSION: Our findings suggest that a fixed-dose regimen of 2000 units in obese patients weighing ≥ 100 kg is adequate to achieve these INR goals.