Clinical significance of iron deficiency among candidates for metabolic surgery.

BACKGROUND: Iron deficiency (ID), a known complication after metabolic surgery, is common among preoperative patients in the presence of inflammation. Evidence is now accumulating that preoperative ID may adversely affect perioperative outcomes. OBJECTIVES: To investigate the relationship between preoperative iron status and the risk of postoperative severe anemia. In addition, this study investigates the relationship between preoperative iron status and length of surgical stay SETTING: A large regional tertiary health system. METHODS: Among patients who underwent metabolic surgery between 2004 and 2020, 5171 patients had a full iron nutritional assessment prior to surgery. Study patients were divided into multiple smaller groups (10 female groups and 7 male groups) on the basis of levels of serum ferritin and Transferrin Saturation (T Sat) < or ≥20%. Study patients were followed after surgery and the time to the development of severe anemia (hemoglobin < 8 gm/dL) was recorded. Hospital length of stay (LOS) was analyzed in relation to preoperative iron status. RESULTS: Lower ferritin levels were associated with older age in males (P = .0001) and younger age in females (P < .0001). For males, after adjustment for age, body mass index (BMI), and year of surgery, surgical LOS was prolonged in those with T Sat <20% (P = .0041). For females the time until the development of severe anemia was associated with baseline iron status (P < .0001). CONCLUSIONS: Male preoperative patients for metabolic surgery with T Sat <20% are at risk for increased surgical LOS. Females with low ferritin levels consistent with ID are at increased risk for the development of postoperative severe anemia.

Prior metabolic surgery reduced COVID-19 severity: Systematic analysis from year one of the COVID-19 pandemic.

Background: Obesity is a risk factor for COVID-19 severity. Recent studies suggest that prior metabolic surgery (MS) modifies the risk of COVID-19 severity. Methods: COVID-19 outcomes were compared between patients with MS (n = 287) and a matched cohort of unoperated patients (n = 861). Multiple logistic regression was used to identify predictors of hospitalization. A systematic literature review and pooled analysis was conducted to provide overall evidence of the influence of prior metabolic surgery on COVID-19 outcomes. Results: COVID-19 patients with MS had less hospitalization (9.8% versus 14.3%, p = 0.049). Age 70+, higher BMI, and low weight regain after MS were associated with more hospitalization after COVID-19. A systematic review of 7 studies confirmed that MS reduced the risk of post-COVID-19 hospitalization (OR = 0.71, 95%CI = [0.61-0.83], p < 0.0001) and death (OR = 0.44, 95%CI = [0.30-0.65], p < 0.0001). Conclusion: MS favorably modifies the risks of severe COVID-19 infection. Older age and higher BMI are major risk factors for severity of COVID-19 infection.

"Bioelectrical impedance analysis in managing sarcopenic obesity in NAFLD".

INTRODUCTION: Sarcopenic obesity and its association with nonalcoholic fatty liver disease (NAFLD) is under-recognized by many healthcare providers in Western medicine due to the lack of awareness and diagnostic guidelines. The result is delayed recognition and treatment, which leads to further health deterioration and increased healthcare costs. Sarcopenic obesity is characterized by the presence of increased fat mass in combination with muscle catabolism related to chronic inflammation and/or inactivity. Previous research has recommended evaluating body composition and physical function performance to adequately diagnose sarcopenic obesity. Body composition analysis can be performed by imaging applications through magnetic resonance imaging, computed tomography, and dual-energy x-ray absorptiometry. Due to the cost of each device and radiation exposure for patients as evidenced in all three modalities, bioelectrical impedance analysis offers a noninvasive approach capable of providing quick and reliable estimates of lean body and fat mass. METHODS AND RESULTS: This review analyzes the current evidence-based literature, indicating a lower skeletal muscle mass and increased visceral adipose tissue correlation to the advancement of fibrosis in fatty liver disease. CONCLUSION: Given the substantial promising research conducted in predominantly Asian populations regarding body tissue distribution and NAFLD, additional prospective research is needed to extend these findings in Western populations.

Iron deficiency is highly prevalent among candidates for metabolic surgery and may affect perioperative outcomes.

BACKGROUND: The presence of chronic low-grade inflammation, commonly identified in patients with severe obesity, alters iron homeostasis and indicators of iron status, fostering the development of updated guidelines for the diagnosis of iron deficiency (ID). Current recommended diagnostic thresholds for ID in obesity derived from expert opinion include a ferritin level of <30 ng/mL and/or transferrin saturation (TSAT) < 20%. Earlier studies of ID among candidates for metabolic surgery using low levels of ferritin or iron as diagnostic thresholds demonstrated a prevalence of 5%-20%. OBJECTIVES: Using the current recommended diagnostic thresholds for ID, this study measures the prevalence of ID in a large cohort of surgical candidates and its relationship to surgical outcomes. SETTING: Geisinger Medical Center, Danville, Pennsylvania. METHODS: The study cohort included 3,723 patients who underwent pre- operative nutritional assessment which included markers of iron nutrition over the period 2004-2018. RESULTS: The cohort included 2,988 women (80.3%) and 735 men (19.7%); body mass index: 49.4 ± 9 kg/m2. The diagnosis of ID was based on ferritin level <30 ng/mL (true ID) and/or TSAT < 20% representing a combination of true ID and inflammation (serum ferritin ≥ 30 ng/mL and TSAT < 20%). A total of 399 patients (10.8%) were anemic. A serum ferritin level of < 30 ng/mL was found in 488 patients (13%; 481 women and 7 men). Of these, 122 patients (25.2%) were also anemic. An additional 1,204 had serum ferritin ≥ 30 ng/mL and TSAT < 20%. Overall, 1,692 patients (45.4%) in this cohort had laboratory evidence of ID by current criteria that adjusts for the very high prevalence of inflammation. Men with serum ferritin levels ≥30 ng/mL with TSAT < 20% had an increased surgical length of stay. CONCLUSION: The prevalence of ID among surgical candidates (45.4%) is more than twice that identified as ID in earlier studies. ID was commonly identified in the absence of anemia. The most severe ID was found in those with a serum ferritin level <30 ng/mL and TSAT < 20%. ID in the presence of inflammation is often unrecognized and has implications regarding surgical outcomes after metabolic surgery.

The relationship between specialized pro-resolving lipid mediators, morbid obesity and weight loss after bariatric surgery.

Obesity and diabetes are associated with chronic inflammation. Specialized pro-resolving lipid mediators (SPMs)-resolvins (Rv), protectins (PD) and maresins (MaR)-actively resolve inflammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinflammatory eicosanoid levels using liquid chromatography-tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs-RvD3, RvD4 and PD1-and white blood cells (WBC) and platelets. Post-surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued inflammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had significant reductions in WBC and platelet counts whereas five non-remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14-HDHA, a maresin pathway marker; non-remitters had an 875.7% increase in 14-HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17-HDHA, are markers of leukocyte activation and inflammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained inflammation in the latter. Lack of diabetes remission after surgically-induced weight loss may be associated with reduced ability to produce MaR1 and sustained inflammation.

New concepts in the diagnosis and management approach to iron deficiency in candidates for metabolic surgery: should we change our practice?

The near universal presence of chronic low-grade systemic inflammation among patients with severe obesity disrupts iron homeostasis and underlies the association between obesity and iron deficiency. Immune activation and inflammation result in a reduction in circulating iron and diminished iron bioavailability for erythropoiesis. Inflammation also alters blood levels of commonly measured markers of iron nutrition status, which makes the diagnosis of iron deficiency difficult and has led to new recommendations regarding laboratory markers for the diagnosis. Recent evidence using these newly recommended laboratory markers, which include levels of ferritin, C-reactive protein, and transferrin saturation, suggests that the actual prevalence of iron deficiency among candidates for metabolic surgery may be double or triple the prevalence identified by low levels of ferritin alone. Thus large numbers of surgical candidates have iron deficiency that has been heretofore largely unrecognized and inadequately treated. The assessment of iron status using the currently recommended markers in the presence of chronic inflammatory diseases and repletion of depleted stores for surgical candidates with deficiency during the preoperative period present an important opportunity for mitigating this condition in postoperative patients.

Metabolic surgery and iron homeostasis.

Iron deficiency and anaemia after metabolic surgery, potentially modifiable nutritional complications, are becoming an increasing cause for concern as prevalence increases with time and there is limited evidence supporting the effectiveness of the current guidelines for prophylactic oral iron supplementation and treatment for deficiency. Abnormalities in iron nutrition predisposing to deficiency are common in severely obese patients, and the low-grade systemic inflammation, also common to these patients, reduces the effectiveness of oral iron supplementation. The surgical procedures result in alterations of foregut anatomy and physiology, which limit iron absorptive capacity and daily food intake. These alterations and the limited effects of oral iron supplementation explain the high prevalence of postoperative iron deficiency and anaemia. This review outlines current mechanisms concerning the pathogenesis of disordered iron nutrition in patients with severe obesity, current gaps in knowledge, and opportunities for quality improvement.

Demographic, clinical, and behavioral determinants of 7-year weight change trajectories in Roux-en-Y gastric bypass patients.

BACKGROUND: Weight change trajectories after weight-loss surgery may vary significantly. OBJECTIVES: This study evaluated the weight trajectories of Roux-en-Y gastric bypass (RYGB) patients and identified the distinct clinical, behavioral, and demographic features of patients by trajectory. SETTING: Data from 2918 RYGB patients from a comprehensive medical center between January 2004 and November 2016 were included. METHODS: This retrospective, observational study used data for RYGB patients up to year 7 postsurgery. Group-based trajectory models were fitted for percentage weight change. Variables evaluated by trajectory included age, sex, diagnoses, medications, smoking, presurgical body mass index, preoperative weight loss, and early postoperative weight loss. RESULTS: Of 3215 possible patients, 2918 (90.8%) were included (mean age = 46.2 ± 11.2 yr, body mass index = 46.9 ± 7.9 kg/m2 at the time of surgery). Three weight change trajectories were identified (above average, average, and below average). Mean percentage weight change at the nadir for the above average group was -42.85% ± 5.7% compared with -31.57% ± 5.0% in the average group and -22.74% ± 5.7% in the below average group. Compared with the above average group, the below average group was more likely to be male (odds ratio [OR] = 2.40, P < .0001) and have diabetes (noninsulin users, OR = 2.08, P < .0001), but less likely to have a smoking history (OR = .62, P = .0007) or take sleep medications (OR = .50, P = .005). Below average group patients had a lower BMI at the time of surgery (OR = .91, P < .0001). Lower initial weight loss postsurgery was associated with a greater chance of a poorer weight outcomes (OR = 1.64, P < .0001). CONCLUSION: Select clinical, demographic, and behavioral factors may increase or decrease the chance for better weight loss after RYGB.

Clinical Characteristics of Roux-en-Y Gastric Bypass Patients with Death from Accidental Overdose or Intentional Self-Harm: a Descriptive Study.

PURPOSE: The objective of this descriptive study was to identify clinical characteristics of Roux-en-Y gastric bypass (RYGB) patients who died from intentional self-harm or accidental overdose postoperatively. MATERIALS AND METHODS: This retrospective, descriptive study included RYGB patients from a large rural medical center that completed surgery between January 2004 and December 2014 and died from intentional self-harm or accidental overdose through December 2015. Specific causes of death were obtained from the National Death Index and clinical data from electronic health records. Clinical characteristics explored were age, sex, time to surgery, weight loss expectations, postoperative weight loss, medication, diagnoses, psychiatric histories (diagnoses, self-harm, suicidal ideation and behaviors, medications, substance use, preoperative Beck Depression Inventory-II scores), pain, social support, and reported life stressors. RESULTS: Overall, 22 patients of 146 total deceased patients died from intention self-harm (n = 6) or accidental overdose (n = 16) over the study period (77.3% female, mean age at time of surgery = 38.4 ± 9.1 years). Younger age (< 40 years), history of self-harm or depression, preoperative pain, and use of opioids at the time of surgery emerged as common characteristics in weight loss surgery patients who died from intentional self-harm or accidental overdose. No trends regarding social support, life stressors, or actual or expected weight loss were identified. CONCLUSION: Certain weight loss surgery patients may be at risk for death from self-harm or overdose and may benefit from greater surveillance postoperatively.

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes.

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.

Surgical weight-loss to improve functional status trajectories following total knee arthroplasty: SWIFT trial: Rationale, design, and methods.

Total Knee Arthroplasty (TKA, also known as total knee replacement) is a highly effective surgical intervention for the restoration of physical function and improving quality of life in patients with disabling knee osteoarthritis. Recent data suggest that obesity is a major risk factor in the pathogenesis and progression of knee osteoarthritis, with increases in body mass index (BMI, kg/m2) directly correlating with the prevalence of knee osteoarthritis. However, recent data also suggest that there are increased risks associated with TKAs when performed in patients with morbid obesity (BMI > 40 kg/m2). Patients with morbid obesity are routinely referred for weight management prior to surgery. Many of these patients fail to meet the recommended weight loss goals prior to TKA, potentially making them ineligible for surgery or placing them at increased risk for sub-optimal outcomes. Thus, the purpose of this study is to examine the potential therapeutic impact and long-term outcomes of surgically induced weight loss on TKA outcomes. Specifically, these outcomes will include measures of physical function, mobility, and indices of joint function at 1 and 2 years post-TKA compared between extremely obese patients who undergo TKA (Control group, n = 150) and those with TKA performed ~1 year after bariatric surgery (Test group, n = 150). An additional primary endpoint will be the percent of bariatric patients that negate or delay the need for TKA. Secondary endpoints include perioperative outcomes after TKA.

All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes.

OBJECTIVE: This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS: RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS: Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS: All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

BACKGROUND: Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events. METHODS AND RESULTS: A cohort of Roux-en-Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated-measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan-Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events (P=0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42-0.82). Improvements of cardiovascular risk factors (eg, 10-year cardiovascular risk score, total cholesterol, high-density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. CONCLUSIONS: Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure.

Evaluation of the Association Between Preoperative Clinical Factors and Long-term Weight Loss After Roux-en-Y Gastric Bypass.

Importance: Weight loss after bariatric surgery varies, yet preoperative clinical factors associated with long-term suboptimal outcomes are not well understood. Objective: To evaluate the association between preoperative clinical factors and long-term weight loss after Roux-en-Y gastric bypass (RYGB). Design, Setting, and Participants: From June 2001 to September 2007, this retrospective cohort study followed up RYGB patients before surgery to 7 to 12 years after surgery. The setting was a large rural integrated health system. Of 1033 eligible RYGB patients who consented to participate in longitudinal research and completed surgery before October 2007, a total of 726 (70.3%) had a weight entered in the electronic medical record 7 or more years after surgery and were included in the analyses after exclusions for pregnancy and mortality. Date of the long-term weight measurement was recorded between August 2010 and January 2016. Main Outcomes and Measures: The primary outcome was percentage weight loss (%WL) at 7 to 12 years after surgery. Preoperative clinical factors (>200) extracted from the electronic medical record included medications, comorbidities, laboratory test results, and demographics, among others. Results: Among the 726 study participants, 83.1% (n = 603) were female and 97.4% (n = 707) were of white race, with a mean (SD) preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) of 47.5 (7.4). From the time of surgery to long-term follow-up (median, 9.3 postoperative years), the mean (SD) %WL was 22.5% (13.1%). Preoperative insulin use, history of smoking, and use of 12 or more medications before surgery were associated with greater long-term postoperative %WL (6.8%, 2.8%, and 3.1%, respectively). Preoperative hyperlipidemia, older age, and higher body mass index were associated with poorer long-term postoperative %WL (-2.8%, -8.8%, and -4.1%, respectively). Conclusions and Relevance: Few preoperative clinical factors associated with long-term weight loss after RYGB were identified. Preoperative insulin use was strongly associated with better long-term %WL, while preoperative hyperlipidemia, higher body mass index, and older age were associated with poorer %WL. Our findings provide additional insight into preoperative identification of RYGB patients at higher risk for long-term suboptimal outcomes.

Bariatric Surgery Patients and Their Families: Health, Physical Activity, and Social Support.

BACKGROUND: This study evaluated the social environment of bariatric surgery patients in the preoperative period. METHODS: Forty bariatric surgery patients (mean = 46.2 ± 11.2 years), 35 adult cohabitating family members (mean = 45.2 ± 12.7 years), and 15 cohabitating children (mean = 11.5 ± 3.6 years) were recruited from a large rural medical center. Adult participants (patients and family members) completed height, weight, body composition, blood draws, and physical activity assessments (accelerometry), as well as eating behavior and social support inventories before the patient underwent bariatric surgery. Child participants completed demographic, height, and weight assessment only. RESULTS: Over 90 % of adult family members were overweight or obese (body mass index (BMI) ≥ 25 kg/m2, as were 50 % of children (BMI percentile ≥ 85 %). More than one third (37.1 %) of family members met the criteria for moderate to severe insulin resistance. Physical activity measured by accelerometry was moderately correlated between the patient and adult family members (r = 0.46, p = 0.023). Bariatric surgery patients reported high levels of social support from their family members on multiple social support measures. CONCLUSIONS: Many family members of bariatric surgery patients also lived with obesity and related comorbidities, and demonstrate high sedentary behavior. However, patients reported high levels of support from family members, including support in following a healthy diet and engaging in physical activity. Engaging families in behavior change may help bariatric surgery patients and their families to become healthier.