MBSAQIP risk calculator use in bariatric surgery is associated with a reduction in serious complications: a retrospective analysis of 210,710 patients.

BACKGROUND: The Metabolic and Bariatric Accreditation and Quality Improvement Program (MBSAQIP) Bariatric Surgical Risk/Benefit Calculator was developed to provide patient-specific information to assist surgical decision-making. To date, no study has characterized which patients are being evaluated with this tool. OBJECTIVE: We sought to characterize the use and impact of the MBSAQIP calculator. SETTING: MBSAQIP collects data from 955 centers in North America. METHODS: The 2021 MBSAQIP database was evaluated for the use of the calculator on preoperative counseling for patients undergoing bariatric surgery. Patient characteristics, operative techniques, and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including use of the calculator independently associated with serious complications and mortality. RESULTS: Our study included 210,710 patients, 35,158 (16.7%) of whom were evaluated using the calculator. Patients with whom the calculator was used preoperatively were older (43.8 ± 11.6 yr versus 43.6 ± 11.7 yr; P < .001) and were more likely to have insulin-dependent diabetes, hypertension, gastroesophageal reflux disease, renal insufficiency, and sleep apnea. More patients underwent Roux-en-Y gastric bypass in the calculator cohort compared with the cohort that did not use the calculator (29.6% versus 28.6%; P < .003). The rate of serious complication was significantly less in the calculator cohort (3.1% versus 3.4%; P < .030). Multivariable modeling evaluating serious complications showed that use of the calculator was independently associated with reduced risk of serious complications (odds ratio .87, CI .82-.93, P < .001) but was not associated with mortality. CONCLUSION: The use of the risk calculator may help to reduce the incidence of complications by opening a dialogue between healthcare professionals and patients, setting realistic expectations, and identifying modifiable risk factors.

Desmond Beall - a Canadian's contribution to understanding rhabdomyolysis.

A pioneer in multiple areas of biochemical research, Desmond Beall made important contributions to Canadian medical history. His legacy laid the foundation for several modern scientific advances, extending from his doctoral work in Toronto on equine estrogen (which led to the development of conjugated estrogens) to landmark work on rhabdomyolysis during World War II. Though some theoretical understanding of the pathophysiology of traumatic rhabdomyolysis existed previously, Beall and his colleague Eric Bywaters substantially advanced this field of study with their publications on patients treated during the 1940 Blitz bombings. After the war, Beall shifted to working in industry and was able to translate his scientific advances into products affecting the lives of patients worldwide. Drawing from published works and personal communications with family members, this article is a memorial to a remarkable yet relatively unknown scientist.

Liver trauma in the intensive care unit.

PURPOSE OF REVIEW: To review the surgical and critical care management of liver trauma; one of the most common abdominal injuries sustained due to its size and location. RECENT FINDINGS: Hepatic injuries range from negligible to life threatening: in the acute phase, the most common cause of morbidity and mortality is hemorrhage; however, severe traumatic hepatic injuries can also lead to biochemical abnormalities, altered coagulation, and ultimately liver failure. This brief review will review the classification of traumatic liver injuries by mechanism, grade, and severity. Most Grades I-III injuries can be managed nonoperatively, whereas the majority of Grades IV-VI injuries require operative management. Therapeutic strategies for traumatic liver injury including nonoperative, operative, radiologic will be described. The primary goal of liver trauma management in the acute setting is hemorrhage control, then the management of secondary factors such as bile leaks. The rapid restoration of homeostasis may prevent further damage to the liver and allow for deferred nonoperative management, which has been shown to be associated with good clinical outcomes. SUMMARY: A multidisciplinary approach to the care of these patients at an experienced liver surgery center is warranted.

The marine compound and elongation factor 1A1 inhibitor, didemnin B, provides benefit in western diet-induced non-alcoholic fatty liver disease.

Inhibition of eukaryotic elongation factor 1A1 (EEF1A1) with the marine compound didemnin B decreases lipotoxic HepG2 cell death in vitro and improves early stage non-alcoholic fatty liver disease (NAFLD) in young genetically obese mice. However, the effects of didemnin B on NAFLD in a model of long-term diet-induced obesity are not known. We investigated the effects of didemnin B on NAFLD severity and metabolic parameters in western diet-induced obese mice, and on the cell types that contribute to liver inflammation and fibrosis in vitro. Male 129S6 mice were fed either standard chow or western diet for 26 weeks, followed by intervention with didemnin B (50 µg/kg) or vehicle by intraperitoneal (i.p.) injection once every 3 days for 14 days. Didemnin B decreased liver and plasma triglycerides, improved oral glucose tolerance, and decreased NAFLD severity. Moreover, didemnin B moderately increased hepatic expression of genes involved in ER stress response (Perk, Chop), and fatty acid oxidation (Fgf21, Cpt1a). In vitro, didemnin B decreased THP-1 monocyte proliferation, disrupted THP-1 monocyte-macrophage differentiation, decreased THP-1 macrophage IL-1ß secretion, and decreased hepatic stellate cell (HSteC) proliferation and collagen secretion under both basal and lipotoxic (high fatty acid) conditions. Thus, didemnin B improves hepatic steatosis, glucose tolerance, and blood lipids in obesity, in association with moderate, possibly hormetic, upregulation of pathways involved in cell stress response and energy balance in the liver. Furthermore, it decreases the activity of the cell types implicated in liver inflammation and fibrosis in vitro. These findings highlight the therapeutic potential of partial protein synthesis inhibition in the treatment of NAFLD.

Factors associated with organ donation by trauma patients in Nova Scotia.

BACKGROUND: Trauma patients represent a significant pool of potential organ donors (PODs), and previous research suggests that this population is underutilized for organ donation (OD). Our objective was to assess factors associated with OD in the trauma population. METHODS: We retrospectively analyzed OD in Nova Scotia over a 7-year period (2009-2016) using data from the Nova Scotia Trauma Registry and Nova Scotia Legacy of Life Donor Registry. All trauma patients who died in the hospital were included. Multiple logistic regression was used to assess factors associated with donation. We also evaluated characteristics, donation types, and reasons for nondonation among trauma PODs. RESULTS: There were 689 trauma-related deaths in all hospitals in NS during the study period, of which 39.8% (274 of 689) met the Nova Scotia Trauma Registry definition of a POD. Data on OD were available for 108 of these patients who were referred to the Legacy of Life Program. The conversion rate was 84%. Compared with nondonors, organ donors were significantly younger, had a higher Abbreviated Injury Scale head score and a lower scene Glasgow Coma Scale score, were more likely to suffer ischemia from drowning or asphyxia and to require air transport, and were less likely to have comorbidities. Regression analysis showed that donation was associated with younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95-0.99) and lower Glasgow Coma Scale score at the scene (OR, 0.76; 95% CI, 0.66-0.88). Odds of donation were increased with air transport compared with land ambulance (OR, 8.27; 95% CI, 2.07-33.08) and injury within Halifax Regional Municipality compared with injury outside Halifax Regional Municipality (OR, 4.64; 95% CI, 1.42-15.10). Among the 60 referred PODs who did not donate, family refusal of consent was the most common reason (28 [46.7%] of 60). CONCLUSION: Younger age, greater severity of injury, and shorter time to tertiary care were associated with OD in trauma patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological, Level III.

Organ donation by patients with and without trauma in a Canadian province: a retrospective cohort analysis.

BACKGROUND: People who experience trauma represent a large pool of potential organ donors. Our objective was to describe organ donation by patients with and without trauma in Nova Scotia. METHODS: We performed a retrospective cohort study of all patients with trauma in the Nova Scotia Trauma Registry who were injured between Apr. 1, 2009, and Mar. 31, 2016, and died in hospital, as well as all potential organ donors captured in the Nova Scotia Legacy of Life Donor Registry over the same period. We compared characteristics of the 2 groups with respect to organ donation and identified reasons for nondonation. RESULTS: Overall, 940 patients were included in the analysis, of whom 689 (73.3%) had experienced trauma. Patients with trauma accounted for 37.2% (48/129) of donors. A total of 274 (39.8%) of the patients with trauma were identified as potential organ donors, and 48 (7.0%) donated organs. Only 108 (39.4%) of the 274 were referred to the Legacy of Life Program. The conversion rate (proportion of potential donors who went on to donate an organ) was 84.2% (48/57) among patients with trauma and 83.5% (81/97) among those without trauma. Donation after circulatory death occurred in 8 patients (17%) with trauma and 13 (16%) of those without trauma. Family refusal (28/60 [47%]) and medical unsuitability (16/60 [27%]) were the most common reasons for nondonation among patients with trauma. INTERPRETATION: In Nova Scotia, 40% of patients with trauma who died in hospital were potential organ donors, yet only 39% of these patients were referred for donation. More work is required to improve organ donation within the trauma population.

Organ donation in trauma victims: A systematic review and meta-analysis.

BACKGROUND: Although trauma patients represent a large pool of potential organ donors (PODs), the donor conversion rates (DCRs) in this population are unclear. Our primary objective was to synthesize published evidence on DCRs in trauma patients. As a secondary objective, we investigated factors that affect organ donation (OD) in the trauma population. METHODS: We searched four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) and gray literature for articles on OD in trauma patients (PROSPERO 2017: CRD42017070388). Articles were excluded if it was not possible to calculate the DCR (actual organ donors divided by PODs). We pooled DCRs and performed subgroups analysis by trauma subpopulation, patients' age, and study publication date. RESULTS: We identified 27 articles with a total of 123,142 participants. Cohorts ranged in size from 28 to 120,512 patients (median, 132), with most studies performed in the United States. Conversion rates among individual studies ranged from 14.0% to 75.2% (median, 49.3%). All 27 studies were included in the meta-analysis. We found a pooled DCR of 48.1% using the random effects model. There was a high level of heterogeneity between studies (I = 97.4%). Upon subgroup analysis, we found DCRs were higher in head trauma patients compared with traumatic cardiac arrest patients (45.3% vs 20.9%, p < 0.001), in pediatric patients compared with adults (61.0% vs 38.0%, p = 0.018), and in studies published after 2007 compared with those published before (50.8% vs 43.9%, p < 0.001). Few studies assessed for factors associated with OD in trauma patients. CONCLUSIONS: We found variation in DCRs among trauma patients (range, 14.0-75.2%) and estimated a pooled DCR of 48.1%. Our results are limited by heterogeneity across studies, which may be attributable to differences in study design and population, definitions of a POD, and in the institutional criteria and processes regarding OD. LEVEL OF EVIDENCE: Systematic reviews and meta-analyses level III.

Microarray data and pathway analyses for primary human activated hepatic stellate cells compared to HepG2 human hepatoma cells.

As nonalcoholic fatty liver disease progresses to end-stage diseases, including fibrosis, cirrhosis and hepatocellular carcinoma, fibrotic activated hepatic stellate cells and cancerous epithelial cells can become abundant, changing the cellular composition of this organ. Despite potentially residing within the same diseased tissue, direct comparisons of global gene expression between activated hepatic stellate cells and hepatocellular carcinoma cells are lacking. Here we provide data collected using Affymetrix GeneChip microarrays to identify differential gene expression in cultured primary human activated hepatic stellate cells compared to HepG2 human hepatoma cells. The dataset includes many genes involved in intermediary metabolism which were investigated in greater depth in our associated article (A.M. Hetherington, C.G. Sawyez, E. Zilberman, A.M. Stoianov, D.L. Robson, J.M. Hughes-Large, et al., 2016) [1]. Pathway analyses of known protein coding genes down-regulated or up-regulated by greater than 2.0-fold are also provided.

Differential Lipotoxic Effects of Palmitate and Oleate in Activated Human Hepatic Stellate Cells and Epithelial Hepatoma Cells.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved. METHODS: Primary activated hepatic stellate cells and HepG2 cells were exposed to pathophysiological concentrations of fatty acids and comparative studies of lipid metabolic and stress response pathways were performed. RESULTS: Both cell types remained proliferative during exposure to a combination of palmitate plus oleate reflective of the general saturated versus unsaturated fatty acid composition of western diets. However, exposure to either high palmitate or high oleate alone induced cytotoxicity in activated stellate cells, while only palmitate caused cytotoxicity in HepG2 cells. mRNA microarray and biochemical comparisons revealed that stellate cells stored markedly less fatty acids as neutral lipids, and had reduced capacity for beta-oxidation. Similar to previous observations in HepG2 cells, palmitate, but not oleate, induced ER stress and actin stress fiber formation in activated stellate cells. In contrast, oleate, but not palmitate, induced the inflammatory signal TXNIP, decreased cytoskeleton proteins, and decreased cell polarity preceding cell death in activated stellate cells. CONCLUSIONS: Palmitate-induced lipotoxicity was associated with ER stress pathways in both primary activated hepatic stellate cells and epithelial hepatoma cells, whereas high oleate caused lipotoxicity only in activated stellate cells, possibly through a distinct mechanism involving disruption of cytoskeleton components. This may have implications for optimal dietary fatty acid compositions during various stages of NAFLD.

Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice.

Eukaryotic elongation factor EEF1A1 is induced by oxidative and ER stress, and contributes to subsequent cell death in many cell types, including hepatocytes. We recently showed that blocking the protein synthesis activity of EEF1A1 with the peptide inhibitor, didemnin B, decreases saturated fatty acid overload-induced cell death in HepG2 cells. In light of this and other recent work suggesting that limiting protein synthesis may be beneficial in treating ER stress-related disease, we hypothesized that acute intervention with didemnin B would decrease hepatic ER stress and lipotoxicity in obese mice with nonalcoholic fatty liver disease (NAFLD). Hyperphagic male ob/ob mice were fed semipurified diet for 4 weeks, and during week 5 received i.p. injections of didemnin B or vehicle on days 1, 4, and 7. Interestingly, we observed that administration of this compound modestly decreased food intake without evidence of illness or distress, and thus included an additional control group matched for food consumption with didemnin B-treated animals. Treatment with didemnin B improved several characteristics of hepatic lipotoxicity to a greater extent than the effects of caloric restriction alone, including hepatic steatosis, and some hepatic markers of ER stress and inflammation (GRP78, Xbp1s, and Mcp1). Plasma lipid and lipoprotein profiles and histopathological measures of NAFLD, including lobular inflammation, and total NAFLD activity score were also improved by didemnin B. These data indicate that acute intervention with the EEF1A inhibitor, didemnin B, improves hepatic lipotoxicity in obese mice with NAFLD through mechanisms not entirely dependent on decreased food intake, suggesting a potential therapeutic strategy for this ER stress-related disease.

Elongation Factor 1A-1 Is a Mediator of Hepatocyte Lipotoxicity Partly through Its Canonical Function in Protein Synthesis.

Elongation factor 1A-1 (eEF1A-1) has non-canonical functions in regulation of the actin cytoskeleton and apoptosis. It was previously identified through a promoter-trap screen as a mediator of fatty acid-induced cell death (lipotoxicity), and was found to participate in this process downstream of ER stress. Since ER stress is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), we investigated the mechanism of action of eEF1A-1 in hepatocyte lipotoxicity. HepG2 cells were exposed to excess fatty acids, followed by assessments of ER stress, subcellular localization of eEF1A-1, and cell death. A specific inhibitor of eEF1A-1 elongation activity, didemnin B, was used to determine whether its function in protein synthesis is involved in lipotoxicity. Within 6 h, eEF1A-1 protein was modestly induced by high palmitate, and partially re-localized from its predominant location at the ER to polymerized actin at the cell periphery. This early induction and subcellular redistribution of eEF1A-1 coincided with the onset of ER stress, and was later followed by cell death. Didemnin B did not prevent the initiation of ER stress by high palmitate, as indicated by eIF2α phosphorylation. However, consistent with sustained inhibition of eEF1A-1-dependent elongation activity, didemnin B prevented the recovery of protein synthesis and increase in GRP78 protein that are normally associated with later phases of the response to ongoing ER stress. This resulted in decreased palmitate-induced cell death. Our data implicate eEF1A-1, and its function in protein synthesis, in hepatocyte lipotoxicity.