Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.

No abstract

No abstract

INTRODUCTION: Gastrointestinal bleeding (GIB) is a common symptom in patients with advanced cardiovascular disease. Among those at highest risk are patients with non-pulsatile left ventricular assist devices (LVADs).1 This has been attributed to multiple factors including therapeutic anticoagulation, degradation of von Willebrand factor,1 formation of angiodysplasias and advanced age.2,3 Such conditions predispose bleeding from arteriovenous malformations (AVMs) as well as other commonly occurring lesions. However, an overlooked cause of bleeding in these patients is direct injury from tunnelization of the LVAD driveline. Here we review a case of overt GIB, months after direct colonic injury from an LVAD driveline. CASE DESCRIPTION/METHODS: A 72 year old man with history of end stage heart failure underwent placement of an LVAD in January of 2019. His post-operative course was tumultuous and complicated by polymicrobial driveline infection. He recovered gradually and was discharged to medical rehabilitation in February with therapeutic warfarin and low dose aspirin. In April the patient presented to the Emergency Department after a syncopal episode and subsequent dizziness. He was found to have heme positive stool and hemoglobin of 7.8 g/dL (from 9.0 g/dL one month earlier). Other labs revealed iron deficiency with serum Iron level of 48 ug/dL and international normalized ratio (INR) elevation to 1.9 with warfarin therapy. Gastroenterology was consulted for evaluation of gastrointestinal blood loss with anemia. The patient underwent EGD and colonoscopy. EGD showed only retained gastric contents and no active bleeding. Colonoscopy revealed a linear, rigid foreign body penetrating the colonic wall and traversing the lumen (Figure 1). Review of prior CT scans confirmed the LVAD driveline had penetrated and passed through the transverse colon (Figures 2 and 3). The patient was subsequently taken to surgery for transverse colon resection with washout and exteriorization of the contaminated LVAD driveline. DISCUSSION: Gastrointestinal bleeding is common in cardiac patients following LVAD placement.1 Contributing factors include the use of anticoagulation and acquired von Willebrand disease, which most commonly causes bleeding from from AVMs.1,2 However, this case describes late bleeding after direct mucosal injury with LVAD driveline placement. Although a rare occurrence, this complication should be considered in LVAD patients, especially those with history of prior driveline infection.

No abstract