Validation of a fibrinogen γ' enzyme-linked immunosorbent assay using a new monoclonal antibody: effects of bariatric surgery.

Background: Fibrinogen γ' is a naturally occurring 20-amino-acid splice variant of the fibrinogen γ chain. Animal studies link variations in fibrinogen to obesity, but it is unknown how fibrinogen γ' is associated with obesity in humans. Objectives: To develop and validate an enzyme-linked immunosorbent assay (ELISA) for fibrinogen γ' quantification in human plasma and analyze fibrinogen γ' before and after bariatric surgery. Methods: We generated C-terminal fibrinogen γ' specific mouse monoclonal antibodies and developed a γ' ELISA. Validation included measures of accuracy, sensitivity, and precision. Fibrinogen γ' and total fibrinogen were measured in 60 individuals before and 6 months after bariatric surgery and in 19 normal-weight controls and 120 blood donors. Results: Highly specific fibrinogen γ' monoclonal antibodies were produced and successfully used in the ELISA. Recovery was 88%, and limits of detection and quantification were 0.003 mg/mL and 0.014 mg/mL, respectively. Coefficients of variation were 3% for repeatability and 7% for within-laboratory variation. The fibrinogen γ' reference interval was 0.25 to 0.80 mg/mL. Fibrinogen γ' concentrations were reduced after bariatric surgery and were higher in individuals with obesity than in those with normal weight. The fibrinogen γ'/total fibrinogen ratio was unchanged after surgery but was higher than the ratio in normal-weight individuals. Conclusion: We developed a precise and sensitive ELISA for fibrinogen γ'. Levels of fibrinogen γ', but not the fibrinogen γ'/fibrinogen ratio, were reduced 6 months after bariatric surgery. Absolute and relative levels of fibrinogen γ' were increased in individuals with obesity compared to normal-weight individuals.

Are Nonalcoholic Fatty Liver Disease and Bone Mineral Density Associated? - A Cross-Sectional Study Using Liver Biopsy and Dual-Energy X-Ray Absorptiometry.

There is controversy regarding the association between nonalcoholic fatty liver disease (NAFLD) and osteoporosis. Our study aim was to assess bone mineral density (BMD) in patients with biopsy-proven NAFLD and examine if the severity of NAFLD affects BMD. A total of 147 adult women (n = 108) and men (n = 39) aged 18-76 years (mean ± standard deviation [SD] age 45.3 ± 12.5) were recruited in this cross-sectional study and underwent a liver biopsy and dual-energy X-ray absorptiometry (DXA). NAFLD activity score (NAS) based on the degree of steatosis, lobular inflammation and hepatocellular ballooning was used to assess NAFLD severity. The majority of subjects, 53%, had steatosis, 25% had nonalcoholic steatohepatitis (NASH) whereas 23% served as control subjects with no evidence of NAFLD. There were no significant differences in the lumbar spine (1.09 ± 0.12, 1.11 ± 0.18, and 1.12 ± 0.15 g/cm2, p = 0.69, in controls, steatosis, and NASH, respectively) or hip BMD (1.10 ± 0.15, 1.12 ± 0.13, and 1.09 ± 0.13 g/cm2, p = 0.48, in controls, steatosis, and NASH, respectively) between the groups. Adjusting for age, gender, body mass index, and diabetes in multiple regression models did not alter the results. There was no correlation between NAS and neither lumbar spine BMD (r = 0.06, p = 0.471), nor hip BMD (r = -0.03, p = 0.716). In conclusion, BMD was similar across the spectrum of NAFLD in both genders and not related to the severity of the underlying histological lesions, suggesting that neither steatosis nor NASH exerts a detrimental effect on BMD in these relatively young patients. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Zoledronic Acid for prevention of bone and muscle loss after BAriatric Surgery (ZABAS)-a study protocol for a randomized controlled trial.

BACKGROUND: Bariatric surgery has adverse effects on the muscular-skeletal system with loss of bone mass and muscle mass and an increase in the risk of fracture. Zoledronic acid is widely used in osteoporosis and prevents bone loss and fracture. Bisphosphonates may also have positive effects on skeletal muscle. The aim of this study is to investigate the effects of zoledronic acid for the prevention of bone and muscle loss after bariatric surgery.  METHODS/DESIGN: This is a randomized double-blind placebo-controlled study. Sixty women and men with obesity aged 35 years or older will complete baseline assessments before randomization to either zoledronic acid (5 mg in 100 ml isotonic saline) or placebo (100 ml isotonic saline only) 3 weeks before surgery with Roux-en-Y-gastric bypass (RYGB) or sleeve gastrectomy (SG). Follow-up assessments are performed 12 and 24 months after surgery. The primary outcome is changes in lumbar spine volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT). Secondary bone outcomes are changes in proximal femur vBMD assessed by QCT. Changes in cortical and trabecular bone microarchitecture and estimated bone strength will be assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical material bone strength at the mid-tibia diaphysis will be assessed using microindentation and fasting blood samples will be obtained to assess biochemical markers of bone turnover and calcium metabolism.  Secondary muscle outcomes include whole body lean mass assessed using dual-energy X-ray absorptiometry. Dynamometers will be used to assess handgrip, shoulder, ankle, and knee muscle strength. Short Physical Performance Battery, 7.6-m walking tests, 2-min walking test, and a stair climb test will be assessed as biomarkers of physical function. Self-reported physical activity level is assessed using International Physical Activity Questionnaire (IPAQ). DISCUSSION: Results from this study will be instrumental for the evidence-based care of patients undergoing bariatric surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04742010. Registered on 5 February 2021.

Effect of bariatric surgery on employment status-a 7 years controlled nationwide registry study.

BACKGROUND: Severe obesity is associated with a reduced ability to work. Bariatric surgery is the most effective method to achieve a sustained weight loss. Previous studies have reported conflicting results regarding the effect of bariatric surgery on employment status. To address this, we investigated the effect of bariatric surgery on employment status in the Danish population. METHODS: In this nationwide study, we identified 5450 subjects who underwent bariatric surgery and 10 900 control subjects matched for age, sex and municipality. From accessible registries, we extracted data regarding employment, absenteeism, sick leave and pension. Using a multistate model, we compared time in occupational states and transitions between these states to determine the effect of bariatric surgery on employment status. FINDINGS: Before surgery, cases had an absolute risk increase (95% CI)(ARI (CI)) and a relative risk (RR (CI)) of being in full-time employment of -0.12 (-0.14 to -0.10) and 0.84 (0.82 to 0.86) and were more often unemployed or in a subsidised job than the background population. Taking into account the employment status before surgery, the bariatric surgery group increased their probability of being in full-time employment 1-3 years after bariatric surgery. However, this positive effect was not present with a longer duration of follow-up. Being male, above 50 years of age, or employed as a craftsman or office worker were associated with a sustained positive effect of being in full-time employment (ARI (CI) and RR (CI) 0.05 (0.04 to 0.05) and 1.05 (1.04 to 1.06), 0.06 (0.06 to 0.07) and 1.08 (1.07 to 1.09) and 0.05 (0.05 to 0.06) and 1.05 (1.05 to 1.06), respectively). INTERPRETATION: Compared with a matched control group, those undergoing bariatric surgery did not improve their employment status in the long term. Certain subgroups had a more sustained positive effect.

Effects of Obesity Surgery on Blood Coagulation and Fibrinolysis: A Literature Review.

OBJECTIVE: Obesity is characterized by a disturbed hemostatic balance with increased coagulation and impaired fibrinolysis. This increases the risk of thrombosis, and the risk is lowered after obesity surgery. Over the past 25 years, several studies have contributed to understand the mechanisms behind the antithrombotic effect of obesity surgery, and this literature review summarizes the results of these studies. METHODS: A detailed literature search on the effects of obesity surgery on the hemostatic balance was conducted. RESULTS: The 25 relevant studies reviewed demonstrated that obesity surgery has favorable effects on many biomarkers of coagulation and fibrinolysis. The evidence is substantial for fibrinogen and plasminogen activator inhibitor type 1 with average reductions from 1 to 24 months after obesity surgery of 17 and 48%, respectively. For most other biomarkers, the evidence is moderate or weak with average effect sizes varying from 2% for fiber mass length ratio to 70% for prothrombin fragment 1 + 2 and with a large variation between studies. Many studies are small and of short duration, and the surgical techniques differ. Also, studies are confounded by changes in medication, comorbidity, diet, and exercise. It is unknown whether the hemostatic changes are mediated by weight loss alone or by the accompanying metabolic improvements. CONCLUSION: Despite issues of confounding, this review suggests that obesity surgery shifts the hemostatic balance in the antithrombotic direction, thereby reducing the thrombotic potential of people with obesity, but more studies are needed for most of the biomarkers.

Development of the BODY-Q Chest Module Evaluating Outcomes following Chest Contouring Surgery.

BACKGROUND: Plastic surgery to improve chest appearance is becoming increasingly popular. The BODY-Q is a patient-reported outcome instrument designed for weight loss and/or body contouring. In this article, the authors describe the development of a new module for masculinizing chest contouring surgery. METHODS: Qualitative methods were used to develop the BODY-Q Chest Module, which was subsequently field-tested in Canada, the United States, The Netherlands, and Denmark between June of 2016 and June of 2017. Participants were aged 16 years or older and seen for gynecomastia, weight loss, or transman chest surgery. Data were collected using either a Web-based application or paper questionnaire. Rasch measurement theory analysis was performed. RESULTS: The sample included 739 participants (i.e., 174 gynecomastia, 224 weight loss, and 341 gender-affirming). Rasch measurement theory analysis refined a 10-item chest scale and a five-item nipple scale. All items had ordered thresholds and good item fit, and scales evidenced reliability [i.e., person separation index and Cronbach alpha values were 0.95 and 0.98 (chest scale) and 0.87 and 0.94 (nipple scale), respectively]. Scores for both scales correlated more strongly with similar (satisfaction with the body) versus dissimilar (psychological and social function) BODY-Q scales. The mean scores for the chest and nipple scales were significantly higher (p < 0.001 on independent samples t tests) in participants who were postoperative compared with preoperative. CONCLUSION: This new BODY-Q Chest Module is a clinically meaningful and scientifically sound patient-reported outcome instrument that can be used to measure outcomes for masculinizing chest contouring surgery.

Physical training following gastric bypass: effects on physical activity and quality of life-a randomized controlled trial.

BACKGROUND: Obesity is associated with physical inactivity and impaired health-related quality of life (HRQoL). We aim to test the hypothesis that Roux-en-Y gastric bypass (RYGB) followed by supervised physical training improves physical activity (PA) levels and HRQoL. METHODS: Sixty patients, qualified for RYGB, were at 6 months post-surgery randomized to 26 weeks of a supervised physical training intervention (INT) or to a control (CON) group. PA was assessed by accelerometry and using the questionnaire RPAQ. HRQoL was measured by the SF-36 questionnaire. All assessments were performed pre-surgery and 6, 12, and 24 months post-surgery. RESULTS: RYGB did not improve objectively or self-reported PA, but improved all domains of SF-36 (all p < 0.01). Objectively measured light PA, moderate to vigorous PA, and step counts tended to increase in INT compared to CON 12 months after RYGB (0.05 < p < 0.09), but the effects failed to persist. The SF-36 domain "general health" increased in INT compared to CON 24 months after RYGB (p = 0.041). CONCLUSION: RYGB improves HRQoL, but does not increase PA. Supervised physical training intervention improves general health 24 months after RYGB and tends to improve certain domains of PA right after the intervention period, but fails to increase the patients' overall PA level over time. Clinical Trial Registration Registered at ClinicalTrials.gov-no. NCT01690728.

Effects of gastric bypass followed by a randomized study of physical training on markers of coagulation activation, fibrin clot properties, and fibrinolysis.

BACKGROUND: The risk of cardiovascular disease is reduced by bariatric surgery, but it is unknown if exercise after bariatric surgery reduces this risk even further. OBJECTIVE: To investigate if Roux-en-Y-gastric bypass (RYGB) and supervised physical training after RYGB improve cardiovascular disease risk markers within coagulation activation, fibrin clot properties, and fibrinolysis. SETTING: Bariatric center, Hospital of Southwest Jutland, Denmark. METHODS: Sixty obese patients underwent RYGB and 6 months after RYGB were randomized to 26 weeks of physical training or a control group. Biomarkers within coagulation activation, fibrin clot properties, and fibrinolysis were measured presurgery, and 6, 12, and 24 months postsurgery. RESULTS: Six months after RYGB, the endogenous thrombin potential decreased from 1744 (1603-2003) to 1416 (1276-1582) nM × min (P<.001). Alterations in fibrin clot properties resulted in an increased clot lysis from 23.8% (16.1%-38.9%) to 40.3% (28.5%-59.35; P<.0001). Furthermore, fibrinogen was reduced from 12.6 (11.1-14.7) to 11.5 (9.90-13.3) µM (P<.001), and plasminogen activator inhibitor antigen was reduced from 40.5 (28.4-49.4) to 24.4 (15.4-32.7) ng/mL (P<.0001). Physical training after RYGB increased fibrinolytic activity from 58.0 (36.0-75.5) to 88.0 (66.0-132.0) IU/mL compared with 52.5 (30.0-80.0) to 64.0 (49.0-100.0) IU/mL in controls (P<.01) and reduced plasminogen activator inhibitor antigen from 23.5 (16.7-35.4) to 18.1 (14.3-25.4) ng/mL compared with 24.4 (13.9-28.7) to 24.2 (14.1-29.6) ng/mL in controls (P<.05). No effects of physical training were observed on markers of coagulation activation and fibrin clot properties. CONCLUSION: We observed favorable long-term reductions in markers of thrombin generation, improved fibrin clot properties, and increases in fibrinolysis after RYGB. Supervised physical training after RYGB further increased fibrinolysis.

Effects of gastric bypass surgery followed by supervised physical training on inflammation and endothelial function: A randomized controlled trial.

BACKGROUND AND AIMS: Obesity and physical inactivity are both associated with low-grade inflammation and endothelial dysfunction. Bariatric surgery improves markers of inflammation and endothelial function, but it is unknown if physical training after bariatric surgery can improve these markers even further. Therefore, we aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) followed by physical training on markers of low-grade inflammation and endothelial function. METHODS: Sixty patients approved for RYGB underwent examinations pre-surgery, 6, 12, and 24 months post-surgery. Six months post-surgery, they were randomized 1:1 to an intervention group or a control group. The interventions consisted of two weekly sessions of supervised moderate intensity physical training for a period of 26 weeks. Fasting blood samples were analyzed for concentrations of interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), tissue-type plasminogen activator antigen (t-PA:Ag) and von Willebrand factor (vWF). RESULTS: RYGB markedly improved markers of inflammation (IL-6, CRP) (p < 0.001) and endothelial function (ICAM-1, t-PA:Ag, vWF) (p < 0.05), and the improvements were sustained 24 months post-surgery (p < 0.01), except for the effects on vWF. We found no correlations between the changes in weight or BMI and the changes in markers of inflammation and endothelial function, except that the change in vWF was found to be inversely correlated with the changes in weight and BMI. We observed no effects of supervised physical training on markers on inflammation or endothelial function (p>0.1 for all). CONCLUSIONS: RYGB causes substantial and sustained favorable effects on markers of inflammation and endothelial function. Supervised physical training after RYGB did not cause additional improvements.

Supervised Physical Training Improves Weight Loss After Roux-en-Y Gastric Bypass Surgery: A Randomized Controlled Trial.

OBJECTIVE: Bariatric surgery results in significant weight loss and reduces cardiovascular morbidity. However, a large variation in postsurgery weight loss is seen. Physical activity promotes weight loss in nonsurgically treated subjects with obesity. The aim of this study was to investigate the effects of 6 months of supervised physical training following Roux-en-Y gastric bypass surgery (RYGB) on body weight and cardiovascular risk markers. METHODS: Sixty participants eligible for RYGB were included. Six months post surgery, the participants were randomly assigned to either twice-weekly supervised physical training sessions in a fitness center (INT) or a control group (CON) for 26 weeks. Before surgery and 6, 12, and 24 months after surgery, the participants underwent an examination program that included anthropometric measurements, blood pressure, heart rate, blood samples, and an abdominal computed tomography scan. RESULTS: RYGB significantly reduced body weight and improved cardiovascular risk markers (all P < 0.01). The supervised physical training intervention resulted in a 4.2-kg (CI: -0.2 to -8.3 kg) lower body weight in INT compared with CON at the study end (P = 0.042). The high-density lipoprotein concentration was significantly higher in INT than in CON at the termination of the intervention, but this was not maintained at the 24-months examination. CONCLUSIONS: Physical training following RYGB improves weight loss and cardiovascular health.

The BODY-Q Stretch Marks Scale: A Development and Validation Study.

BACKGROUND: Stretch marks are common permanent dermal lesions that can cause psychosocial distress. A number of treatment modalities are available, with the majority targeted towards collagen production. OBJECTIVES: To develop and field test a new BODY-Q scale to measure appearance of stretch marks in order to provide a means to incorporate the patient perspective into future treatment studies. METHODS: We previously described the development of the BODY-Q conceptual framework, which involved a literature review, 63 patient interviews, 22 cognitive interviews and input from 9 experts, and the international field-test study that involved 403 weight loss and 331 body contouring patients. To develop the Stretch Marks scale, we reexamined appearance codes from the original interviews. The scale was field tested in an international study. Rasch measurement theory (RMT) analysis was used to refine the scale and examine measurement properties. RESULTS: The Stretch Marks scale was completed by 630 participants, who provided 774 assessments. After dropping 3 items, the data fit the Rasch model (P = 0.56). Items (eg, length, width, amount, location, up close) mapped out a well-targeted clinical hierarchy. All items had ordered thresholds and good item fit. There was no evidence of differential item functioning (bias) by gender, age group or language (English vs Danish). The scale evidenced high reliability (ie, person separation index = 0.94, Cronbach's alpha = 0.97). For construct validity, the mean score correlated with the total number of body areas with stretch marks, higher BMI before bariatric surgery, and other BODY-Q scales. CONCLUSIONS: This scale could be used to measure the impact of innovative treatments for stretch marks.

Psychometric Validation of the BODY-Q in Danish Patients Undergoing Weight Loss and Body Contouring Surgery.

BACKGROUND: A well-developed patient-reported outcome instrument is needed for use in Danish bariatric and body contouring patients. The BODY-Q is designed to measure changes in important patient outcomes over the entire patient journey, from obesity to post-body contouring surgery. The current study aims to psychometrically validate the BODY-Q for use in Danish patients. METHODS: The process consisted of 3 stages: translation and linguistic validation, field-test, and data analysis. The translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research and World Health Organization guidelines, and field-test data were collected in 4 departments in 2 different hospitals. Field-test data were analyzed using Rasch Measurement Theory. RESULTS: A total of 495 patients completed the Danish BODY-Q field-test 1-4 times, leading to a total of 681 assessments with an overall response rate at 76%. Cronbach α values were ≥ 0.90, and person separation index values were in general high. The Rasch Measurement Theory analysis provided broad support for the reliability and validity of the Danish version of the BODY-Q scales. Item fit was outside the criteria for 34 of 138 items, and of these, 21 had a significant chi-square P value after Bonferroni adjustment. Most items (128 of 138) had ordered thresholds, indicating that response options worked as intended. CONCLUSION: The Danish version of the BODY-Q is a reliable and valid patient-reported outcome instrument for use in Danish bariatric and body contouring patients.

Patient-Reported Outcomes in Weight Loss and Body Contouring Surgery: A Cross-Sectional Analysis Using the BODY-Q.

BACKGROUND: Health-related quality of life and satisfaction with appearance are important outcomes in bariatric and body contouring surgery. To investigate these outcomes, scientifically sound and clinically meaningful patient-reported outcome instruments are needed. The authors measured health-related quality of life and appearance in a cohort of Danish patients at different phases in the weight loss journey: before bariatric surgery, after bariatric surgery, before body contouring surgery, and after body contouring surgery. METHODS: From June of 2015 to June of 2016, a cross-sectional sample of 493 bariatric and body contouring patients were recruited from four different hospital departments. Patients were asked to fill out the BODY-Q, a new patient-reported outcomes instrument designed specifically to measure health-related quality of life and appearance over the entire patient journey, from obesity to the post-body contouring surgery period. Data were collected using REDCap, and analyzed using SPSS software. RESULTS: For all appearance and health-related quality-of-life scales, the mean score was significantly lower in the pre-bariatric surgery group compared with the post-body contouring group. Furthermore, the correlation between body mass index and mean scores was significant for all appearance and health-related quality-of-life scales, with higher scores associated with lower body mass index. The mean score for the group reporting no excess skin compared with the group reporting a lot of excess skin was significantly higher for five of seven appearance scales and four of five health-related quality-of-life scales. CONCLUSION: This study provides evidence to suggest that body contouring plays an important role in the weight loss patient's journey and that patients need access to treatments.