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.

Lifestyle modification for weight loss: Effects on cardiorespiratory capacity in patients with class II and class III obesity.

BACKGROUND: The prevalence of obesity has increased worldwide. Obesity affects the lungs and airways, limits peak oxygen uptake, and hampers physical performance; however, objective data are scarce. Does lifestyle modification for weight loss (LM) have an impact on cardiorespiratory capacity (CRC) in patients with class II and class III obesity? METHOD: This was a single-center prospective 2-year follow-up pilot study. Four separated stays in the inpatient specialized medical center Muritunet with an integrated approach to LM, including an individual plan on diet and physical activity (PA) goals. Furthermore, it included lectures and counseling on human anatomy and physiology, nutrition, physical exercise, and motivation, as well as daily PA. Cardiopulmonary and blood chemistry tests were conducted. RESULTS: Seventy-seven participants were included; however, 47% (n = 36) dropped out during follow-up. Forty-one participants completed the study. At baseline (BL), the mean age was 45.4 (SD 10.2, range 23-62) years, with a mean body mass index (BMI) of 41.3 (SD 5.4) kg/m2, and 85% (n = 35) had one or more comorbidities, such as obstructive pulmonary disease (n = 15, 37%), obstructive sleep apnea (n = 19, 46%), type 2 diabetes (n = 20, 49%), and hypertension (n = 17, 41%). The mean functional residual capacity increased, significantly the second year (p = 0,037). CRC increased significantly the first year (p = 0.032). Weight and BMI declined, reaching statistical significance at 2 years for both males and females (p = 0.033 and p = 0.003, respectively). At BL, the participants reported lower health-related quality of life compared to the general Norwegian population. Across time the physical component summary score (quality of life) for both males and females (p = 0.011 and p = 0.049, respectively) increased significantly. CONCLUSION: Lifestyle modification for weight loss improves CRC in patients with class II and class III obesity.

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.

Cardiopulmonary resuscitation retention training for hospital nurses by a self-learner skill station or the traditional instructor led course: A randomised controlled trial.

INTRODUCTION: Intrahospital cardiac arrest has a steep mortality and high-quality cardiopulmonary resuscitation (CPR) is essential for favourable outcome. Instructor led (IL) CPR training is resource demanding and instructor free, feedback providing CPR skill stations (SS) could provide a means to enable the needed frequent retraining. The main objective of this study was to test the hypothesis that there was no difference between IL and SS training. METHODS: A total of 129 hospital nurses were randomised to CPR retraining in three groups; skill station with retraining at 2 months (SS-R), skill station without retraining (SS) and instructor led training (IL). Participants were tested at baseline, 2 and 8 months. The skill station groups were combined (c-SS) for analysis at baseline and 2 months when comparing to IL. RESULTS: Baseline characteristics for the three groups differed significantly, however c-SS and IL groups performed equally at baseline and testing at 2 months. At 8 months the SS group performed 71% correct ventilations compared to 54% in the IL group (p = 0.04), but CPR quality was otherwise equal. Longitudinal analysis showed SS-R performed 3.4 mm deeper compressions at final evaluation compared to baseline (p = 0.02) and 2.8 mm deeper compared to 2-month test (p = 0.02). No effects of retraining at 2 months could be detected at final comparison of SS-R and SS groups. CONCLUSION: CPR training using a skill station led to equal performance at 2 and 8 months compared to instructor led training. Feedback-providing skill stations could be a feasible tool for required frequent retraining.

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.

Supplementation with Low Doses of a Cod Protein Hydrolysate on Glucose Regulation and Lipid Metabolism in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study.

The risk of cardiovascular diseases and type 2 diabetes mellitus are increased in subjects with metabolic syndrome (MetS), and hydrolyzed fish protein may have favorable effects on metabolic health. Here, we investigated the effect of 8 weeks supplementation with 4 g of cod protein hydrolysate (CPH) on glucose metabolism, lipid profile and body composition in individuals with MetS in a double-blind, randomized intervention study with a parallel-group design. Subjects received a daily supplement of CPH (n = 15) or placebo (n = 15). Primary outcomes were serum fasting and postprandial glucose levels. Secondary outcomes were fasting and postprandial insulin and glucagon-like peptide 1 (GLP-1), fasting lipid concentrations and body composition. No difference was observed between CPH and placebo for insulin, glucose or GLP-1 after 8 weeks intervention. Fasting triacylglycerol decreased in both the CPH group and placebo group, with no change between groups. Fasting total cholesterol and low-density lipoprotein cholesterol decreased significantly within both groups from baseline to study end, but no difference was observed between the two groups. In conclusion, supplementing with a low dose of CPH in subjects with MetS for 8 weeks had no effect on fasting or postprandial levels of insulin, glucose or GLP-1, lipid profile or body composition.

Acute effect of a cod protein hydrolysate on postprandial acylated ghrelin concentration and sensations associated with appetite in healthy subjects: a double-blind crossover trial.

BACKGROUND: Fish protein hydrolysates are suggested to contain bioactive sequences capable of affecting metabolic pathways involved in the regulation of glucose metabolism and body weight when consumed in low doses. Modulation of the appetite-regulating hormone ghrelin may explain suppression of insulin secretion and weight loss observed in previous studies with fish protein hydrolysates. OBJECTIVE: This study aimed to assess the effect of a single, low dose of cod protein hydrolysate (CPH) before a breakfast meal on postprandial acylated ghrelin concentration and sensations associated with appetite in healthy subjects. DESIGN: In this explorative trial with a crossover design, 41 healthy individuals (15 males and 26 females, age 51 ± 6 years) completed 2 study days separated by 4-7 days of washout. On both study days, a test drink containing 20 mg CPH or casein (control) per kg body weight was given immediately before a standardized breakfast meal. Acylated ghrelin concentrations were measured before test drink/breakfast (baseline) and at time 0, 20, 40, 80, and 180 min postprandially. Sensations associated with appetite were measured by a Visual Analog Scale (100 mm) at baseline and 0, 20, 40, and 180 min postprandially. RESULTS: Statistically, no difference was observed between CPH and control for postprandial acylated ghrelin concentrations (mean difference geometric mean: 1.05 pg/mL, 95% confidence interval [CI]: 0.97-1.13, P = 0.266), or between the total area under the curve (tAUC) for acylated ghrelin after CPH (tAUC = 17518 pg/mL × min, 95% CI: 0-47941) and control (tAUC = 17272 pg/mL × min, 95% CI: 0-48048, P = 0.991). No differences were found between CPH and control for sensation of appetite, according to tAUC of postprandial scores for satiety (P = 0.794) and the feeling of fullness (P = 0.996). CONCLUSION: We did not find an effect of a single dose of CPH on postprandial concentrations of acylated ghrelin or sensations related to feeling of hunger, compared to control. Further studies should aim to evaluate the effect of a supplement with CPH given daily over a period of time.

Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome.

Peptides from fish may beneficially affect several metabolic outcomes, including gut health and inflammation. The effect of fish peptides in subjects with irritable bowel syndrome (IBS) has not previously been investigated, hence this study aimed to evaluate the effect of a cod protein hydrolysate (CPH) supplement on symptom severity, gut integrity markers and fecal fermentation in IBS-patients. A double-blind, randomized parallel-intervention with six weeks of supplementation with 2.5 g CPH (n = 13) or placebo (n = 15) was conducted. The outcomes were evaluated at baseline and the end of the study. The primary outcomes were symptom severity evaluated by the IBS severity scoring system (IBS-SSS) and quality of life. The secondary outcomes included gut integrity markers and pro-inflammatory cytokines in serum, fecal fermentation measured by concentration of short-chain fatty acids (SCFAs) and fecal calprotectin. The groups were comparable at baseline. The total IBS-SSS-scores were reduced in both the CPH-group (298 ± 69 to 236 ± 106, p = 0.081) and the placebo-group (295 ± 107 to 202 ± 103, p = 0.005), but the end of study-scores did not differ (p = 0.395). The concentrations of serum markers and SCFAs did not change for any of the groups. The baseline measures for the whole group showed that the total SCFA concentrations were inversely correlated with the total IBS-SSS-score (r = -0.527, p = 0.004). Our study showed that a low dose of CPH taken daily by IBS-patients for six weeks did not affect symptom severity, gut integrity markers or fecal fermentation when compared to the placebo group.

Erratum: Effect of a cod protein hydrolysate on postprandial glucose metabolism in healthy subjects: a double-blind cross-over trial - CORRIGENDUM.

[This corrects the article DOI: 10.1017/jns.2018.23.].

Esophageal multimodal stimulation and sensation.

Esophageal mechanosensation describes the relationship between a mechanical stimulation of the esophageal wall, such as bag distension, and the reaction to the stimulation perceived or unperceived. When studying mechanosensation in esophageal disease, it is important to recognize that symptoms might be due to alterations at different levels of the neuromuscular system, such as alterations at the mechanoreceptor level or in the afferent mechanosensory pathways, or irregularities in the homeostatic state. One might ask if it is possible to provoke, record, and describe the multidimensional responses behind a mechanosensory experience? It is a complex system and, at a minimum, a multidisciplinary approach is needed to avoid erroneous conclusions. The multimodal study design, taking the mode, location, and parameters of stimulation into consideration, together with controlled recording of assessment parameters, is an approach that seems rational and valid. Gastrointestinal (GI) physicians of the 21th century need to have knowledge of advances in the evaluation of GI mechanical function and what provokes symptoms. Hereby, it is possible to fully appreciate the slowly emerging awareness of how GI pain symptoms should be explored and explained to patients.

Pharmacological and other treatment modalities for esophageal pain.

Treatment of esophageal pain remains a major challenge for the clinician. Although many patients have heartburn and may respond to proton pump inhibitors, there in an unmet need for other treatment modalities in patients where there are no obvious pathological findings. Although analgesics are the mainstay in esophageal pain treatment, many patients are nonresponders to these drugs. The current concise review focuses on other systems affecting pain processing, where better understanding may serve as a framework for therapy. These are the parasympathetic nervous system, exercise, and personality profiles. Finally, treatment with analgesics for functional chest pain remains a challenge, and an overview of treatment with antidepressive drugs is provided.

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.

Mechanosensation and mucosal blood perfusion in the esophagus of healthy volunteers studied with a multimodal device incorporating laser Doppler flowmetry and endosonography.

Both mechanical and ischemic mechanisms can cause gastrointestinal pain. We investigated whether discomfort and pain caused by bag distension in the esophagus of healthy subjects correlated best with mechanical forces (stress), deformation (strain), or mucosal perfusion. Twenty-nine subjects underwent ramp bag distension using a novel catheter design incorporating high-frequency intraluminal ultrasound, laser Doppler flowmetry, and manometry. Perfusion, pressure, and geometric data were analyzed at visual analog scale (VAS) levels 1-7 in 19 subjects. The circumferential stress increased exponentially as a function of volume, whereas strain showed a linear increase. The perfusion showed a modest decline, on average 15% from baseline to VAS = 7. A significant association was found between the sensory response and stress and strain (P < 0.05). No significant association was found between the sensory response and perfusion. In conclusion, the discomfort and pain response to bag distension in the esophagus is likely to be caused by mechanical rather than ischemic mechanisms.