Gastrointestinal Dysmotility in Critically Ill Patients: Bridging the Gap Between Evidence and Common Misconceptions.

Disruption of normal gastrointestinal (GI) function in critical illness is linked to increased morbidity and mortality, and GI dysmotility is frequently observed in patients who are critically ill. Despite its high prevalence, the diagnosis and management of GI motility problems in the intensive care unit remain very challenging, given that critically ill patients often cannot verbalize symptoms and the general lack of understanding of underlying pathophysiology. Common clinical presentations of GI dysmotility issues among critically ill patients include: (1) high gastric residual volumes, acid reflux, and vomiting, (2) abdominal distention, and (3) diarrhea.

Feeding intolerance in critically ill patients with COVID-19.

Background & Aims: Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19.

Methods: We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11 and June 28, 2020 who received enteral nutrition.

Ceramide launches an acute anti-adhesion pro-migration cell signaling program in response to chemotherapy.

Chemotherapy has been reported to upregulate sphingomylinases and increase cellular ceramide, often linked to the induction to cell death. In this work, we show that sublethal doses of doxorubicin and vorinostat still increased cellular ceramide, which was located predominantly at the plasma membrane. To interrogate possible functions of this specific pool of ceramide, we used recombinant enzymes to mimic physiological levels of ceramide at the plasma membrane upon chemotherapy treatment.

Replacing plasma membrane outer leaflet lipids with exogenous lipid without damaging membrane integrity.

We recently introduced a MαCD-based method to efficiently replace virtually the entire population of plasma membrane outer leaflet phospholipids and sphingolipids of cultured mammalian cells with exogenous lipids (Li et al, (2016) Proc. Natl. Acad.

Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases.

Sphingolipids contribute to the regulation of cell and tissue homeostasis, and disorders of sphingolipid metabolism lead to diseases such as inflammation, stroke, diabetes, and cancer. Sphingolipid metabolic pathways involve an array of enzymes that reside in specific subcellular organelles, resulting in the formation of many diverse sphingolipids with distinct molecular species based on the diversity of the ceramide (Cer) structure. In order to probe compartment-specific metabolism of sphingolipids in this study, we analyzed the Cer and SM species preferentially produced in the inner plasma membrane (PM), Golgi apparatus, ER, mitochondria, nucleus, and cytoplasm by using compartmentally targeted bacterial SMases and ceramidases.

Visualizing bioactive ceramides.

In the last 30 years, ceramides have been found to mediate a myriad of biological processes. Ceramides have been recognized as bioactive molecules and their metabolizing enzymes are attractive targets in cancer therapy and other diseases. The molecular mechanism of action of cellular ceramides are still not fully established, with insights into roles through modification of lipid rafts, creation of ceramide platforms, ceramide channels, or through regulation of direct protein effectors such as protein phosphatases and kinases.