ECMO RESCUE IN A PATIENT WITH THYMOGLOBULIN-INDUCED ARDS AFTER LIVER TRANSPLANTATION

INTRODUCTION: Postoperative care after liver transplantation can be associated with significant cardiopulmonary complications. Thymoglobulin is used for prevention and treatment of acute rejection in organ transplantations. Although there are few case reports describing thymoglobulin induced acute respiratory distress syndrome in immunocompromised patients, there are limited reports to date on the mortality and outcomes for patients who receive extracorporeal membrane oxygenation therapy after liver transplant. DESCRIPTION: We present a case of a 43 year old male with decompensated alcoholic cirrhosis with ascites and hepato-renal syndrome who underwent a liver transplant. Intra-operative course was complicated by vasoplegia and coagulopathy. Post-operatively, patient was on intermittent hemodialysis, on minimal ventilator settings. However, on post-operative day 2 the patient had worsening hypoxia within few hours from receiving a dose of thymoglobulin for immunosuppression. The patient had severe ARDS, with requirement of 100% Fio2 and PEEP of 20. Later in the ICU, patient developed bi-ventricular failure with ejection fraction of 30% with need for veno-arterial extracorporeal membrane oxygenation support. His course was complicated by acute kidney injury requiring slow efficiency dialysis, critical illness induced myopathy and prolonged ICU stay. He required a tracheostomy, prolonged ventilator wean and was eventually discharged home. DISCUSSION: Our patient was diagnosed with thymoglobulin induced ARDS due to acute development of respiratory failure after thymoglobulin administration. Thymoglobulin contains cytotoxic antibodies directed against T-cell markers which can trigger immune mediated acute lung injury. The etiology of thymoglubulin-induced ARDS is not fully understood however it is regarded as a special type of transfusion-related acute lung injury characterized by acute respiratory distress during or within 6 hours after the completion of transfusion. ARDS from thymoglobulin is a rare complication however can be life-threatening. Hence it\u27s prudent that the treating physician is aware of this potential complication which facilitates appropriate management. In our case, management included continuing steroids, utilizing ECMO, renal replacement therapy and ongoing respiratory support

Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods

Background: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. Objectives: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. Design: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level–dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). Results: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. Conclusion: Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438

Link between increased gut hormones signaling satiety and reduced food reward following gastric bypass surgery for obesity

CONTEXT: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. OBJECTIVE: To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. DESIGN: These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. PATIENTS: Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. INTERVENTION: Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. MAIN OUTCOME MEASURES: Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. RESULTS: Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. CONCLUSIONS: Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food

Effect of Intubation Timing on the Outcome of Patients With Severe Respiratory Distress Secondary to COVID-19 Pneumonia.

Background: The optimal timing of intubation for critically ill patients with severe respiratory illness remains controversial among healthcare providers. The coronavirus disease 2019 (COVID-19) pandemic has raised even more questions about when to implement this life-saving therapy. While one group of providers prefers early intubation for patients with respiratory distress because these patients may deteriorate rapidly without it, other providers believe that intubation should be delayed or avoided because of its associated risks including worse outcomes. Research question: Our objective was to assess whether the timing of intubation in patients with severe COVID-19 pneumonia was associated with differences in mortality or other outcomes. Study design and methods: This was a single-center retrospective observational cohort study. We analyzed outcomes of patients who were intubated secondary to COVID-19 pneumonia between March 13, 2020, and December 12, 2020, at Henry Ford Hospital in Detroit, Michigan. Patients were categorized into two groups: early intubated (intubated within 24 hours of the onset of severe respiratory distress) and late intubated (intubated after 24 hours of the onset of severe respiratory distress). Demographics, comorbidities, respiratory rate oxygenation (ROX) index, sequential organ failure assessment (SOFA) score, and treatment received were compared between groups. The primary outcome was mortality. Secondary outcomes were ventilation time, intensive care unit stay, hospital length of stay, and discharge disposition. Post hoc and Kaplan-Meier survival analyses were performed. Results: A total of 110 patients were included: 55 early intubated and 55 late intubated. We did not observe a significant difference in overall mortality between the early intubated (43%) and the late intubated groups (53%) (p = 0.34). There was no statistically significant difference in patients\u27 baseline characteristics including SOFA scores (the early intubation group had a mean score of 7.5 compared to 6.7 in the late intubation group). Based on the ROX index, the early intubation group had significantly more patients with a reduced risk of intubation (45%) than the late group (27%) (p = 0.029). The early intubation group was treated with a high-flow nasal cannula at a significantly lower rate (47%) than the late intubation group (83%) (p \u3c 0.001). Significant differences in patient baseline characteristics, treatment received, and other outcomes were not observed. Post hoc analysis adjusting for SOFA score between 0 and 9 revealed significantly higher mortality in the late intubation group (49%) than in the early intubation group (26%) (p = 0.03). Patients in the 0 to 9 SOFA group who were intubated later had 2.7 times the odds of dying during hospital admission compared to patients who were intubated early (CI, 1.09-6.67). Interpretation: The timing of intubation for patients with severe COVID-19 pneumonia was not significantly associated with overall mortality or other patient outcomes. However, within the subgroup of patients with SOFA scores of 9 or lower at the time of intubation, patients intubated after 24 hours of the onset of respiratory distress had a higher risk of death than those who were intubated within 24 hours of respiratory distress. Thus, patients with COVID-19 pneumonia who are not at a high level of organ dysfunction may benefit from early mechanical ventilation

LEAP2 changes with body mass and food intake in humans and mice

Acyl-ghrelin administration increases food intake, body weight, and blood glucose. In contrast, mice lacking ghrelin or ghrelin receptors (GHSRs) exhibit life-threatening hypoglycemia during starvation-like conditions but do not consistently exhibit overt metabolic phenotypes when given ad libitum food access. These results, and findings of ghrelin resistance in obese states, imply nutritional state-dependence of ghrelin’s metabolic actions. Here, we hypothesized that LEAP2 (liver enriched antimicrobial peptide-2), a recently-characterized endogenous GHSR antagonist, blunts ghrelin action during obese states and post-prandially. To test this hypothesis, we determined changes in plasma LEAP2 and acyl-ghrelin due to fasting, eating, obesity, Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), oral glucose administration, and type 1 diabetes mellitus (T1DM) using humans and/or mice. Our results suggest that plasma LEAP2 is regulated by metabolic status: its levels increase with body mass and blood glucose, and decrease with fasting, RYGB, and in post-prandial states following VSG. These changes were mostly opposite to those of acyl-ghrelin. Furthermore, using electrophysiology, we showed that LEAP2 both hyperpolarizes and prevents acyl-ghrelin from activating arcuate NPY neurons. We predict that the plasma LEAP2:acyl-ghrelin molar ratio may be a key determinant modulating acyl-ghrelin activity in response to body mass, feeding status, and blood glucose

Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding

Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity. Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour