Mortality and Cardiovascular Outcomes in Adult Non-Liver Solid Organ Transplant Patients With Nonalcoholic Steatohepatitis.

BACKGROUND: The effect of nonalcoholic steatohepatitis (NASH) on mortality or major adverse cardiovascular events (MACE) in non-liver solid organ transplant recipients (NL-SOT) is unknown. METHODS: Using a retrospective design, adult NL-SOT recipients who had biopsy-proven NASH were compared NL-SOT recipients with normal liver function tests and imaging; propensity matched at a 1:10 ratio on the following: age, sex, race, transplant year, transplant organ, smoking status, and diabetes status. Both deceased and living donor recipients were included; heart and liver transplant patients were excluded. Primary outcome was incidence of all-cause mortality and MACE (a composite outcome of coronary artery disease, ischemic stroke, and peripheral arterial disease). RESULTS: Seven patients (3 kidney and 4 lung transplants) had biopsy-proven NASH and 70 patients without NASH, both groups were predominantly male (53%-57%), White (86%-91%), and overweight (mean body mass index ∼ 26). The majority of patients were on calcineurin inhibitors (≥85%), antimetabolites (≥97%), and prednisone (≥50%). Survival analysis showed that NASH patients had a higher risk of death (hazard ratio [HR], 3.24; 95% confidence interval [CI], 1.26-8.33, P = 0.02). NASH did not affect the risk of death-censored graft failure (HR, 1.08; 95% CI, 0.14-8.67; P = .94) or the risk of MACE (HR, 1.03; 95% CI, 0.23-4.62; P = .97). CONCLUSIONS: In NL-SOT recipients, NASH is significantly associated with mortality but not with MACE.

Impact of Gastroenterology Consultation on the Clinical Outcomes of Patients Admitted With Hepatic Encephalopathy.

Introduction Hepatic encephalopathy (HE) is a common complication of cirrhosis and a common reason for hospital admission. We aimed to determine whether expert consultation from gastroenterology (GI) leads to better clinical outcomes for inpatients with HE. Methods A retrospective review was performed of all adult patients (age ≥ 18) admitted with HE to a tertiary care hospital between January 2013 and April 2018. Patients who received a GI consult were compared to patients who did not receive a GI consult (No consult group). The primary outcome was hospital length of stay (LOS); secondary outcomes were rates of 30-day hospital readmission and 90-day mortality. Multivariate analysis was conducted to adjust for known confounders.  Results Four hundred and twenty-five patients (814 encounters) were included in the study; of these, 236 patients had received a GI consultation for HE. Patients in the GI consult group were younger (mean age 55 vs 58 years, p= 0.02) and had higher Model For End-Stage Liver Disease-sodium (MELD-Na) score (mean MELD-Na 23.5 vs 17.5, p<0.01) compared to patients who did not receive GI consultation. The precipitants of HE were significantly different between the groups: there was more spontaneous bacterial peritonitis (SBP) and GI bleeding (GIB) in the GI consult group and more lactulose non-adherence in the no consult group. There was no difference in the etiology of liver disease between the two groups. Median LOS for the GI consult group was six days vs three days in the no consult group (p<0.01); the incidence rate ratio was 1.79 (95%CI 1.59-2.02, p<0.01) on multivariate analysis. There was no difference in 30-day readmission or 90-day mortality between the two groups.  Conclusion GI consultation for patients with HE admitted to a hospital medicine service may be associated with longer LOS. In selected patients admitted with HE, GI consultation may not be necessary to achieve good clinical outcomes.

Prediction of thirty-day morbidity and mortality after duodenal switch using an artificial neural network.

BACKGROUND: Understanding factors that increase risk of both mortality and specific measures of morbidity after duodenal switch (DS) is important in deciding to offer this weight loss operation. Artificial neural networks (ANN) are computational deep learning approaches that model complex interactions among input factors to optimally predict an outcome. Here, a comprehensive national database is examined for patient factors associated with poor outcomes, while comparing the performance of multivariate logistic regression and ANN models in predicting these outcomes. METHODS: 2907 DS patients from the 2019 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database were assessed for patient factors associated with the previously validated composite endpoint of 30-day postoperative reintervention, reoperation, readmission, or mortality using bivariate analysis. Variables associated (P ≤ 0.05) with the endpoint were imputed in a multivariate logistic regression model and a three-node ANN with 20% holdback for validation. Goodness-of-fit was assessed using area under receiver operating curves (AUROC). RESULTS: There were 229 DS patients with the composite endpoint (7.9%), and 12 mortalities (0.4%). Associated patient factors on bivariate analysis included advanced age, non-white race, cardiac history, hypertension requiring 3 + medications (HTN), previous foregut/obesity surgery, obstructive sleep apnea (OSA), and higher creatinine (P ≤ 0.05). Upon multivariate analysis, independently associated factors were non-white race (odds ratio 1.40; P = 0.075), HTN (1.55; P = 0.038), previous foregut/bariatric surgery (1.43; P = 0.041), and OSA (1.46; P = 0.018). The nominal logistic regression multivariate analysis (n = 2330; R2 = 0.02, P < 0.001) and ANN (R2 = 0.06; n = 1863 [training set], n = 467 [validation]) models generated AUROCs of 0.619, 0.656 (training set) and 0.685 (validation set), respectively. CONCLUSION: Readily obtainable patient factors were identified that confer increased risk of the 30-day composite endpoint after DS. Moreover, use of an ANN to model these factors may optimize prediction of this outcome. This information provides useful guidance to bariatricians and surgical candidates alike.

Metabolic surgery may protect against admission for COVID-19 in persons with nonalcoholic fatty liver disease.

BACKGROUND: SARS-CoV-2 (COVID-19) disease causes significant morbidity and mortality through increased inflammation and thrombosis. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are states of chronic inflammation and indicate advanced metabolic disease. OBJECTIVE: The purpose of this observational study was to characterize the risk of hospitalization for COVID-19 in patients with NAFLD/NASH and evaluate the mitigating effect of various metabolic treatments. SETTING: Retrospective analysis of electronic medical record data of 26,896 adults from a 12-hospital Midwest healthcare system with a positive COVID-19 polymerase chain reaction (PCR) test from March 1, 2020, to January 26, 2021. METHODS: Variable selection was guided by the least absolute shrinkage and selection operator (LASSO) method, and multiple imputation was used to account for missing data. Multivariable logistic regression and competing risk models were used to assess the odds of being hospitalized within 45 days of a COVID-19 diagnosis. Analysis assessed the risk of hospitalization among patients with a prescription for metformin and statin use within the 3 months prior to the COVID-19 PCR result, history of home glucagon-like peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by sex and race. RESULTS: A history of NAFLD/NASH was associated with increased odds of admission for COVID-19 (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.57-2.26; P < .001) and mortality (OR, 1.96; 95% CI, 1.45-2.67; P < .001). Each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for COVID-19 (OR, 1.24; 95% CI, 1.14-1.35; P < .001). NAFLD/NASH increased the risk of hospitalization in men, but not women, and increased the risk of hospitalization in all multiracial/multiethnic subgroups. Medication treatments for metabolic syndrome were associated with significantly reduced risk of admission (OR, .81; 95% CI, .67-.99; P < .001 for home metformin use; OR, .71; 95% CI, .65-.83; P < .001 for home statin use). MBS was associated with a significant decreased risk of admission (OR, .48; 95% CI, .33-.69; P < .001). CONCLUSIONS: NAFLD/NASH is a significant risk factor for hospitalization for COVID-19 and appears to account for risk attributed to obesity. Other significant risks include factors associated with socioeconomic status and other co-morbidities, such as history of venous thromboembolism. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm the risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.

We Should Do More to Offer Evidence-Based Treatment for an Important Modifiable Risk Factor for COVID-19: Obesity.

Observational studies, from multiple countries, repeatedly demonstrate an association between obesity and severe COVID-19, which is defined as need for hospitalization, intensive care unit admission, invasive mechanical ventilation (IMV) or death. Meta-analysis of studies from China, USA, and France show odds ratio (OR) of 2.31 (95% CI 1.3-4.1) for obesity and severe COVID-19. Other studies show OR of 12.1 (95% CI 3.25-45.1) for mortality and OR of 7.36 (95% CI 1.63-33.14) for need for IMV for patients with body mass index (BMI) ≥ 35 kg/m2. Obesity is the only modifiable risk factor that is not routinely treated but treatment can lead to improvement in visceral adiposity, insulin sensitivity, and mortality risk. Increasing the awareness of the association between obesity and COVID-19 risk in the general population and medical community may serve as the impetus to make obesity identification and management a higher priority.

Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19.

Background: Covid-19 disease causes significant morbidity and mortality through increase inflammation and thrombosis. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are states of chronic inflammation and indicate advanced metabolic disease. We sought to understand the risk of hospitalization for Covid-19 associated with NAFLD/NASH. Methods: Retrospective analysis of electronic medical record data of 6,700 adults with a positive SARS-CoV-2 PCR from March 1, 2020 to Aug 25, 2020. Logistic regression and competing risk were used to assess odds of being hospitalized. Additional adjustment was added to assess risk of hospitalization among patients with a prescription for metformin use within the 3 months prior to the SARS-CoV-2 PCR result, history of home glucagon-like-peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by gender and race. Results: A history of NAFLD/NASH was associated with increased odds of admission for Covid-19: logistic regression OR 2.04 (1.55, 2.96, p<0.01), competing risks OR 1.43 (1.09-1.88, p<0.01); and each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for Covid-19, OR 1.86 (1.43-2.42, p<0.01). After controlling for NAFLD/NASH, persons with obesity had decreased odds of hospitalization for Covid-19, OR 0.41 (0.34-0.49, p<0.01). NAFLD/NASH increased risk of hospitalization in men and women, and in all racial/ethnic subgroups. Mediation treatments for metabolic syndrome were associated with non-significant reduced risk of admission: OR 0.42 (0.18-1.01, p=0.05) for home metformin use and OR 0.40 (0.14-1.17, p=0.10) for home GLP-1RA use. MBS was associated with a significant decreased risk of admission: OR 0.22 (0.05-0.98, p<0.05). Conclusions: NAFLD/NASH is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.

One-year follow-up of a sit-stand workstation intervention to decrease sedentary time in office workers.

BACKGROUND: Prolonged sedentary time is associated with adverse health outcomes, after controlling for the role of moderate-to-vigorous physical activity. We previously reported on a four-week randomized trial using a sit-stand desk (SSD) intervention that decreased sedentary time at work without changing activity level during non-work hours. PURPOSE: The purpose of this study was to measure the impact of the SSD on sitting time and activity level one year after the original intervention. METHODS: A pre-post design was used where the control period from the original study was regarded as "pre" and the measurements made in the follow-up study as "post." The follow-up study was conducted in the same office workers over a two-week period in June 2013. RESULTS: Fifteen out of the 23 participants took part in the follow-up study. Self-reported sitting time during work-hours was decreased by 22% (95% CI: 15% to 29%; p < 0.001), replaced almost entirely by standing. Activity measured by Gruve accelerometer during work-hours were significantly higher in the one-year follow-up period compared to baseline (+24,748 AU/h; 95% CI: 7150 to 42,347; p < 0.01). Sedentary time during work-hours was decreased by 0.77 min per work-hour (95% CI: -1.88 to 0.33 min/h; p = 0.17). Qualitative findings through focus group sessions suggested the workers had overall favorable experiences with the SSDs without negatively impacting productivity. CONCLUSION: One year following the original intervention, participants continue to have increased activity and decreased sedentary time at work with the use of SSDs.

Experience of switching from a traditional sitting workstation to a sit-stand workstation in sedentary office workers.

Prolonged sedentary time (ST) is associated with adverse health outcomes, while decreasing ST improves health outcomes. The use of sit-stand desks (SSDs) in workplaces has been proposed as a means of reducing ST. The purpose of this study was to gain knowledge about participants' experience and perceptions of a workplace intervention involving the introduction of SSDs. Focus groups and interviews were conducted with 28 study participants who used SSDs for 4 weeks. Data were analyzed using a grounded theory approach. Participants reported a high level of satisfaction with the SSDs and 96% chose to use them permanently. Participants experienced greater energy and alertness at work and reported increased face-to-face interaction with coworkers. Lack of work-surface space was the most significant problem with the use of SSDs. There was no perception of decreased productivity or reduced workplace privacy among participants.

Effects of Active Video Games on Energy Expenditure in Adults: A Systematic Literature Review.

BACKGROUND: The objective of this study was to estimate the mean difference in energy expenditure (EE) in healthy adults between playing active video games (AVGs) compared with traditional video games (TVGs) or rest. METHODS: A systematic search was conducted on Ovid MEDLINE, Web of Knowledge, and Academic Search Premier between 1998 and April 2012 for relevant keywords, yielding 15 studies. EE and heart rate (HR) data were extracted, and random effects meta-analysis was performed. RESULTS: EE during AVG play was 1.81 (95% CI, 1.29-2.34; I² = 94.2%) kcal/kg/hr higher, or about 108 kcal higher per hour for a 60-kg person, compared with TVG play. Mean HR was 21 (95% CI, 13.7-28.3; I² = 93.4%) beats higher per minute during AVG play compared with TVG play. There was wide variation in the EE and HR estimates across studies because different games were evaluated. Overall metabolic equivalent associated with AVG play was 2.62 (95% CI, 2.25-3.00; I² = 99.2%), equivalent to a light activity level. Most studies had low risk of bias due to proper study design and use of indirect calorimetry to measure EE. CONCLUSION: AVGs may be used to replace sedentary screen time (eg, television watching or TVG play) with light activity in healthy adults.

Using sit-stand workstations to decrease sedentary time in office workers: a randomized crossover trial.

OBJECTIVE: This study was conducted to determine whether installation of sit-stand desks (SSDs) could lead to decreased sitting time during the workday among sedentary office workers. METHODS: A randomized cross-over trial was conducted from January to April, 2012 at a business in Minneapolis. 28 (nine men, 26 full-time) sedentary office workers took part in a 4 week intervention period which included the use of SSDs to gradually replace 50% of sitting time with standing during the workday. Physical activity was the primary outcome. Mood, energy level, fatigue, appetite, dietary intake, and productivity were explored as secondary outcomes. RESULTS: The intervention reduced sitting time at work by 21% (95% CI 18%-25%) and sedentary time by 4.8 min/work-hr (95% CI 4.1-5.4 min/work-hr). For a 40 h work-week, this translates into replacement of 8 h of sitting time with standing and sedentary time being reduced by 3.2 h. Activity level during non-work hours did not change. The intervention also increased overall sense of well-being, energy, decreased fatigue, had no impact on productivity, and reduced appetite and dietary intake. The workstations were popular with the participants. CONCLUSION: The SSD intervention was successful in increasing work-time activity level, without changing activity level during non-work hours.

Carbon monoxide reverses diabetic gastroparesis in NOD mice.

Diabetic gastroparesis is associated with increased oxidative stress attributable to loss of upregulation of heme oxygenase-1 (HO1), with resultant damage to interstitial cells of Cajal and delayed gastric emptying. These changes can be reversed by induction of HO1. HO1 catalyzes the breakdown of heme into iron, biliverdin and, carbon monoxide (CO). The aim of this study was to determine whether inhalation of CO can mimic the protective effects of HO1. Nonobese diabetic (NOD) mice with delayed gastric emptying were treated with CO inhalation. Serum malondialdehyde was measured as a marker of oxidative stress. Gastric emptying of solids was measured using a [(13)C]octanoic acid breath test. Kit expression levels were determined in immunoblots of protein extracted from the external muscle layers of the gastric body and antrum. The effect of CO on oxidative stress and gastric emptying was also determined in the presence of HO activity inhibitor chromium mesoporphyrin. CO inhalation reduced oxidative stress, restored Kit expression and reversed delayed gastric emptying in diabetic NOD mice with delayed gastric emptying. CO inhalation maintained this effect in the presence of the HO activity inhibitor, chromium mesoporphyrin, also resulting in restoration of the delay in gastric emptying. CO inhalation mimics the protective effect of upregulation of HO1 and decreased oxidative stress, increased Kit expression, and restored delay in gastric emptying. This effect of CO was independent of HO activity, suggesting that its effects were downstream of HO1. CO represents a potential therapeutic option for treatment of diabetic gastroparesis.

CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice.

BACKGROUND & AIMS: Gastroparesis is a well-recognized complication of diabetes. In diabetics, up-regulation of heme oxygenase-1 (HO1) in gastric macrophages protects against oxidative stress-induced damage. Loss of up-regulation of HO1, the subsequent increase in oxidative stress, and loss of Kit delays gastric emptying; this effect is reversed by induction of HO1. Macrophages have pro- and anti-inflammatory activities, depending on their phenotype. We investigated the number and phenotype of gastric macrophages in NOD/ShiLtJ (nonobese diabetic [NOD]) mice after onset of diabetes, when delayed gastric emptying develops, and after induction of HO1 to reverse delay. METHODS: Four groups of NOD and db/db mice were studied: nondiabetic, diabetic with normal emptying, diabetic with delayed gastric emptying, and diabetic with delayed gastric emptying reversed by the HO1 inducer hemin. Whole mount samples from stomach were labeled in triplicate with antisera against F4/80, HO1, and CD206, and macrophages were quantified in stacked confocal images. Markers for macrophage subtypes were measured by quantitative polymerase chain reaction. RESULTS: Development of diabetes was associated with an increased number of macrophages and up-regulation of HO1 in CD206(+) M2 macrophages. Onset of delayed gastric emptying did not alter the total number of macrophages, but there was a selective loss of CD206(+)/HO1(+) M2 macrophages. Normalization of gastric emptying was associated with repopulation of CD206(+)/HO1(+) M2 macrophages. CONCLUSIONS: CD206(+) M2 macrophages that express HO1 appear to be required for prevention of diabetes-induced delayed gastric emptying. Induction of HO1 in macrophages might be a therapeutic option for patients with diabetic gastroparesis.