The Prevalence of Bradycardia 12 Years After Roux-en-Y Gastric Bypass for Severe Obesity.

PURPOSE: The aim was to describe the frequency of bradycardia 12 years after Roux-en-Y gastric bypass (RYGB), relations to weight loss, patient characteristics, and the clinical impact. MATERIALS AND METHODS: The BAROPS study is a prospective observational study of patients who had follow-up > 10 years after RYGB. Patients with heart rate (HR) ≤ 50 bpm were compared to patients with HR > 50 bpm. RESULTS: After a mean observation period of 12 years, 32 of 546 patients (6%) had a HR ≤ 50 with a mean HR of 47.0 (2.8) bpm. The comparator group (192 patients) had a mean HR of 66.4 (10.2) bpm (p < 0.001). A higher proportion of the bradycardic vs. non-bradycardic patients (18.8% vs. 7.8% at baseline (p = 0.05) and 18.8% vs. 5.2% at end of study (p = 0.006)) used beta-blockers. Both groups had a significant reduction in heart rate from pre-surgery to end of observation. Percent total weight loss from baseline was negatively related to heart rate (p < 0.001), and smoking was positively related to heart rate (p = 0.014). Change in BMI from pre-surgery (p < 0.001) and hypertension at pre-surgery (p = 0.006) were significant predictors of change in heart rate. The only predictor of HR ≤ 50 was the use of beta-blockers (p = 0.010). There were no difference in bradycardia-related symptoms. CONCLUSION: Six percent of patients had HR ≤ 50 bpm 12 years after RYGB, but there was no increased bradycardia-related symptoms in these patients. RYGB induced a significant reduction in HR, and heart rate and changes in heart rate 12 years after RYGB were related to the amount of weight loss.

Long-term changes in lung function after Roux-en-Y gastric bypass in patients with severe obesity.

Obesity can decrease the lung function. The proposed mechanisms of reduced lung function in persons with obesity have been altered mechanical properties in the lung and chest wall, airway narrowing and increased respiratory resistance. The aim of this current study was to analyse the long-term results after gastric bypass surgery in patients with reduced lung function. The bariatric surgery observation study invited patients to a follow up 10 years after gastric bypass surgery. We compared the spirometry results before surgery to the spirometry 10 years after surgery. Thirty percent of 198 participants had reduced lung function before surgery. There was no significant relation between body mass index before surgery and lung function. Seventy-three percent of the participants with reduced lung function had normal lung function 10 years after surgery. There was no significant relation between the degree of weight loss and the improvement in lung function. Most participants with reduced lung function had normal lung function 10 years after gastric bypass surgery. There was no significant correlation between weight loss and improvement in lung function.

The Effect of Roux-en-Y Gastric Bypass on Non-Alcoholic Fatty Liver Disease Fibrosis Assessed by FIB-4 and NFS Scores-An 11.6-Year Follow-Up Study.

Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated by RYGB in Central Norway were analysed. Variables incorporated in NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4) index and anthropometric data were collected before surgery and a mean of 11.6 years postoperatively. FIB-4 > 1.3 or NFS > 0.675 were used as cut-off values for advanced fibrosis. Proportions with advanced fibrosis decreased from 24% to 14% assessed by FIB-4 and from 8.6% to 2.3% using NFS, with resolution rates of advanced fibrosis of 42% and 73%, respectively. The shift towards lower fibrosis categories was significant (NFS p < 0.0001; FIB-4 p = 0.002). NFS decreased from −1.32 (IQR −2.33−−0.39) to −1.71 (IQR −2.49−−0.95, p < 0.001) 11.6 years after surgery, whereas FIB-4 did not change: 0.81 (IQR 0.59−1.25) to 0.89 (IQR 0.69−1.16, p = 0.556). There were weak correlations between change in fibrosis scores and weight loss. In conclusion, the majority of patients with advanced fibrosis at baseline had improvement after 11.6 years. Factors associated with reduction in fibrosis were not identified.

Iron Deficiency and Anemia 10 Years After Roux-en-Y Gastric Bypass for Severe Obesity.

Iron deficiency with or without anemia is a well-known long-term complication after Roux-en-Y, gastric bypass (RYGB) as the procedure alters the gastrointestinal absorption of iron. Iron is essential for hemoglobin synthesis and a number of cellular processes in muscles, neurons, and other organs. Ferritin is the best marker of iron status, and in a patient without inflammation, iron deficiency occurs when ferritin levels are below 15 µg/L, while iron insufficiency occurs when ferritin levels are below 50 µg/L. Lifelong regular blood tests are recommended after RYGB, but the clinical relevance of iron deficiency and iron insufficiency might be misjudged as long as the hemoglobin levels are normal. The aim of this study was to explore the frequency of iron deficiency and iron deficiency anemia one decade or more after RYGB, the use of per oral iron supplements, and the frequency of intravenous iron treatment. Nine hundred and thirty patients who underwent RYGB for severe obesity at three public hospitals in Norway in the period 2003-2009 were invited to a follow-up visit 10-15 years later. Results from blood tests and survey data on the use of oral iron supplements and intravenous iron treatment were analyzed. Ferritin and hemoglobin levels more than 10 years after RYGB were available on 530 patients [423 (79.8%) women]. Median (IQR) ferritin was 33 (16-63) µg/L, and mean (SD) hemoglobin was 13.4 (1.3) g/dl. Iron deficiency (ferritin ≤ 15 µg/L) was seen in 125 (23.6%) patients; in addition, iron insufficiency (ferritin 16-50 µg/L) occurred in 233 (44%) patients. Mean (SD) hemoglobin levels were 12.5 (1.4) g/dl in patients with iron deficiency, 13.5 (1.2) g/dl in patients with iron insufficiency, 13.8 (1.3) g/dl in the 111 (21%) patients with ferritin 51-100 µg/L, and 13.8 (1.2) g/dl in the 55 (10%) patients with ferritin >100 µg/L. Two hundred and seventy-five (56%) patients reported taking oral iron supplements, and 138 (27.5%) had received intravenous iron treatment after the RYGB procedure. Iron deficiency or iron insufficiency occurred in two-thirds of the patients 10 years after RYGB, although more than half of them reported taking oral iron supplements.

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.

Characteristics of Patients Reporting Presumed Problematic Drinking Behavior After Gastric Bypass: Exploring Long-Term Data From the BAROBS Study.

Objective: To explore patients' long-term experiences with drinking alcohol after Roux-n-Y gastric bypass (RYGB) for conceptualizing what may indicate problematic drinking behavior after bariatric surgery. Study Design: Three-center, observational study. Patients: 546 adult patients undergoing RYGB in the period 2003-2009 in Norway. Main Outcome Measures: Self-reported data on drinking behavior and experiences related to alcohol collected 10-15 years after surgery. Results: Out of the 959 patients undergoing RYGB in the period, 29 were diseased and 546 participated in this follow-up study (58.7%). Focusing on suspicious changes in drinking behavior, 8.8% reported drinking more, 11.5% consumed alcohol at least twice a week, and 10.6% consumed at a minimum of 6 units of alcohol at a frequency of at least once monthly. The nature of hangovers had changed for about a third of the patients, with 21.6% reporting these to feel weaker or absent. Repeated alcoholic blackouts were reported by 11.9%. A subgroup of the patients were categorized as displaying presumed problematic drinking behavior(PPDB). Among the PPDB-men there was a significant association to having had a fall last year (6 (100.0%) PPDB-patients vs. 30 (29.7%) non-PPDB, p<.001). Among the PPDB-women, there was a significant association to having had alcohol problems prior to surgery (7 (70.0%) PPDB-patients vs. 67 (17.7%) non-PPDB, p<.001). Less significant associations to PPDB reported for explorative purposes were lack of patient education (men) (16 (26.2%) PPDB-patients vs. 8 (61.5%) non-PPDB, p=.014); more than 3 months persistent musculoskeletal pain (women) (45 (15.3%) PPDB-patients vs. 29 (24.6%) non-PPDB, p=.026); subjective problems with memory (women) (58 (20.7%) PPDB-patients vs. 10 (9.1%) non-PPDB, p=.006); and, receiving professional help for mental problems last 12 months (women) (29 (22.7%) PPDB-patients vs. 45 (14.7%) non-PPDB, p=.043). Conclusion: A subset of patients display drinking behaviors that may be consistent with postsurgical alcohol problems. Screening instruments like AUDIT may not be sufficiently specific to capture several risk behaviors occurring after bariatric surgery.

The Effect of Supplementation with Low Doses of a Cod Protein Hydrolysate on Satiety Hormones and Inflammatory Biomarkers in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study.

Metabolic syndrome (MetS) is characterised by metabolic abnormalities that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. Altered levels of circulating ghrelin, several adipokines and inflammatory markers secreted from adipose tissue, such as leptin, adiponectin, tumor necrosis factor alpha, are observed in overweight and obese individuals. We assessed the effect of supplementation with low doses of a cod protein hydrolysate (CPH) on fasting and postprandial levels of acylated ghrelin, as well as fasting levels of adiponectin, leptin and inflammatory markers in subjects with MetS. A multicentre, double-blinded, randomized controlled trial with a parallel group design was conducted. Subjects received a daily supplement of CPH (4 g protein, n = 15) or placebo (0 g protein, n = 15). We observed no effect on fasting or postprandial levels of acylated ghrelin, fasting levels of adiponectin (p = 0.089) or leptin (p = 0.967) after supplementation with CPH, compared to placebo. Overall, our study showed that 8 weeks supplementation with a low dose of CPH in subjects with MetS had no effect on satiety hormones or most of the inflammatory markers, but the levels of high-sensitivity C-reactive protein were statistically significantly different in the CPH-group compared to placebo group. The robustness and clinical relevance of these findings should be explored in future studies with a larger sample size.

Do patients with functional chest pain have neuroplastic reorganization of the pain matrix? A diffusion tensor imaging study.

Background and aims In functional chest pain (FCP) of presumed esophageal origin central nervous system hyperexcitability is generally believed to play an important role in pain pathogenesis. However, this theory has recently been challenged. Using magnetic resonance diffusion tensor imaging, the aim was to characterize any microstructural reorganization of the pain neuromatrix in FCP patients. Methods 13 FCP patients and 20 matched healthy controls were studied in a 3T MR scanner. Inclusion criteria were relevant chest pain, normal coronary angiogram and normal upper gastrointestinal evaluation. Apparent diffusion coefficient (ADC) (i.e. mean diffusivity of water) and fractional anisotropy (FA) (i.e. directionality of water diffusion as a measure of fiber organization) values were assessed in the secondary sensory cortex, cingulate cortex, insula, prefrontal cortex, and amygdala. Results Overall, including all regions, no difference in ADC and FA values was found between the patients and controls (P = 0.79 and P = 0.23, respectively). Post-hoc tests revealed no difference in ADC and FA values of the individual regions. However, a trend of patients having increased ADC in the mid insula grey matter and increased FA in the mid insula white matter was observed (both P = 0.065). Conclusions This explorative study suggests that microstructural reorganization of the central pain neuromatrix may not be present in well-characterized FCP patients. Implications This finding, together with recent neurophysiologal evidence, challenges the theory of visceral hypersensitivity due to changes in the central nervous system in FCP patients.