Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis : A Randomized Controlled Trial.

BACKGROUND: Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. OBJECTIVE: To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis. DESIGN: Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tønsberg]). (ClinicalTrials.gov: NCT01778738). SETTING: Tertiary care obesity center in Norway. PARTICIPANTS: 100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM). INTERVENTION: From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB. MEASUREMENTS: The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes. RESULTS: Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. LIMITATIONS: Single-center study, short follow-up time, and lack of power for secondary outcomes. CONCLUSION: With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted. PRIMARY FUNDING SOURCE: Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.

Hematology reference intervals in 6-12-year-old children: the health-oriented pedagogical project (HOPP).

Reference intervals are essential for correct interpretation of laboratory test results, supporting clinicians in distinguishing between healthy and sick individuals. The present study aims to establish pediatric reference intervals for hematological parameters based on a large population of healthy schoolchildren. Blood samples were obtained from 1351 children 6-12 years of age participating in the Health-Oriented Pedagogical Project (HOPP). Reference intervals for hematological parameters were estimated by the nonparametric method following the CLSI C28-A3 guidelines. Reference intervals were estimated as 2.5th and 97.5th percentiles with corresponding 90% confidence intervals. While hematocrit and MCV required age and sex partitioning, hemoglobin and erythrocytes were partitioned for age. The remaining parameters, MCH, MCHC, platelets and white blood cell counts did not require partitioning. While red blood cell parameters exhibited an increasing trend with age, there was a slight decrease in leukocytes, lymphocytes, basophils and platelets with age. The remaining parameters were stable across our age span.

Lower iron stores were associated with suboptimal gross motor scores in infants at 3-7 months.

AIM: To investigate associations between iron status and gross motor scores in infants aged 3-7 months. METHODS: In a prospective study, 252 infants aged 3-7 months were examined using the age-standardised Alberta Infant Motor Scale (AIMS) prior to analysing iron status in 250 infants. Combined AIMS and ferritin results were assessed in 226 infants, whereas AIMS and reticulocyte haemoglobin (ret-Hb) results were obtained for 61 infants. We used logistic regressions and receiver operator characteristics to analyse our data. RESULTS: With AIMS z-score <10th percentile as outcome measure, optimal cut-off value for ferritin was 51 µg/L (sensitivity 86%, specificity 81%) and 28 pg for ret-Hb (sensitivity 86%, specificity 85%). The area under the curve for ferritin and ret-Hb was 0.886 and 0.896, respectively (n = 61). Ferritin <51 µg/L predicted an AIMS z-score <10th percentile in a logistic regression (OR 3.3, 95% CI 1.4-7.5, p = 0.006, n = 226). Six of 14 (43%) infants with ret-Hb <28 pg scored <10th percentile on AIMS compared to 1/47 (2.1%) infants with ret-Hb ≥28 µg/L (Exact, p < 0.001). CONCLUSION: Reticulocyte haemoglobin of <28 pg and ferritin <51 µg/L were associated with suboptimal gross motor scores in infants 3-7 months.

Nitrous oxide in labour predicted newborn screening total homocysteine and is a potential risk factor for infant vitamin B12 deficiency.

AIM: Risk factors for vitamin B12 deficiency in infants are not fully understood. The aim of the study was to assess predictors of total homocysteine and methylmalonic acid analysed in newborn screening dried blood spots. METHODS: In a Norwegian case control study, we analysed total homocysteine and methylmalonic acid in newborn screening dried blood spots of 86 infants clinically diagnosed with vitamin B12 deficiency during 2012-2018. Results were compared to 252 healthy infants and 400 dried blood spot controls. Medical records were reviewed, and mothers completed questionnaires. RESULTS: Both total homocysteine and methylmalonic acid were significantly higher on newborn screening dried blood spots in infants later clinically diagnosed with vitamin B12 deficiency than controls. Multiple regression analysis showed that the dose of nitrous oxide during labour was the strongest predictor for total homocysteine level in newborn screening dried blood spots for all infants, with larger effect in infants later clinically diagnosed with vitamin B12 deficiency than controls. CONCLUSION: Nitrous oxide dose during labour was a predictor for total homocysteine and may impact the interpretation of total homocysteine analysis in newborn screening. Nitrous oxide is suggested as a contributing risk factor for infants prone to develop vitamin B12 deficiency.

Falsely markedly elevated 25-hydroxyvitamin D in patients with monoclonal gammopathies.

OBJECTIVES: Monoclonal immunoglobulins can cause interference in many laboratory analyses. During a 4 month period we observed seven patients with monoclonal disease and falsely extremely elevated 25-hydroxyvitamin D (25(OH)D) results above 160 ng/mL (>400 nmol/L) measured using an immunoassay from Abbott Diagnostics. Based on these findings, we studied the occurrence of falsely elevated 25(OH)D in samples with paraproteins and investigated possible mechanisms of the observed interference. METHODS: 25(OH)D was analyzed using the Architect i2000 platform from Abbott Diagnostics and a higher order method, liquid chromatography-mass spectrometry (LC-MS/MS), in serum samples from 50 patients with known monoclonal disease. Patients with falsely elevated 25(OH)D were included in further studies to elucidate the cause of interference. Spuriously elevated results were in addition analyzed on two alternative platforms (Siemens and Roche). RESULTS: Falsely elevated 25(OH)D levels were present in eight patients on the Abbott analyzer and one on the Siemens platform. Results from Roche were comparable with LC-MS/MS. Additional investigations excluded elevated concentrations of rheumatoid factor and heterophilic antibodies as the cause of interference in the Abbott assay. CONCLUSIONS: Laboratories should be aware of the risk of falsely elevated 25(OH)D in samples run on the Architect analyzer from patients with monoclonal disease. Highly elevated vitamin D results should be diluted and if the dilution is non-linear, rerun by a different method, preferably LC-MS/MS. In patients with spuriously elevated 25(OH)D without known monoclonal disease, the laboratory should consider requesting protein electrophoresis to exclude paraprotein interference.

Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms.

BACKGROUND: There is evidence of increased low grade inflammation (LGI) in schizophrenia patients. However, the inter-individual variation is large and the association with demographic, somatic and psychiatric factors remains unclear. Our aim was to explore whether levels of the novel LGI marker soluble urokinase plasminogen activator receptor (suPAR) were associated with clinical factors in schizophrenia and if such associations were sex-dependent. METHOD: In this observational study a total of 187 participants with schizophrenia (108 males, 79 females) underwent physical examination and assessment with clinical interviews (Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Alcohol Use Disorder Identification Test (AUDIT), and Drug Use Disorder Identification Test (DUDIT)). Blood levels of suPAR, glucose, lipids, and high sensitivity C-reactive protein (hsCRP) were determined and body mass index (BMI) calculated. Multivariable linear regression analyses were used adjusting for confounders, and sex interaction tested in significant variables. RESULTS: Adjusting for sex, age, current tobacco smoking and BMI, we found that levels of hsCRP and depressive symptoms (CDSS) were positively associated with levels of suPAR (p < 0.001). The association between suPAR and CDSS score was significant in females (p < 0.001) but not in males. Immune activation measured by hsCRP was not associated with depressive symptoms after adjusting for BMI. CONCLUSION: Our findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup. Our results warrant further studies, including longitudinal follow-up of suPAR levels in schizophrenia and experimental studies of mechanisms.

Distribution of creatinine and estimated glomerular filtration rate in healthy schoolchildren: The Health Oriented Pedagogical Project (HOPP).

Glomerular filtration rate (GFR) measured by urinary clearance of inulin is considered the gold standard for assessment of kidney function in both adults and children. Because the procedure is cumbersome, GFR is estimated (eGFR) using algorithms based on the observed relationship between measured GFR (mGFR) and more accessible biomarkers such as creatinine and cystatin C. In children, most of the data on this relationship is retrieved from patients with reduced kidney function. Nonetheless, eGFR equations are widely in use in healthy children to evaluate kidney status and diagnose kidney disease. The aim of the present study was to compare the distribution of eGFR using two established pediatric eGFR equations incorporating age, height and serum creatinine (Schwartz-Lyon and Full Age Spectrum-height) and two recently published equations restricted to age and serum creatinine (Lund-Malmö Revised 18 and European Kidney Function Consortium equation) in 1200 healthy schoolchildren age 6-12 years. In addition, we present 2.5th, median and 97.5th percentiles for serum creatinine stratified by age and gender. Depending on the equation used, mean eGFR ranged from 101.6 to 115.4 mL/min/1.73 m2. The lower 2.5th percentile ranged from 83.3 to 89.0 mL/min/1.73 m2 and the fraction of children with eGFR < 90 mL/min/1.73 m2 ranged from 2.9% to 9.8%. In conclusion, expected values of eGFR in healthy children are significantly dependent on the equation used. When decision limits for diagnosis or classification are applied to eGFR results, the related equation should be clearly stated.

Population-based reference intervals for ferritin, iron, transferrin and transferrin saturation and prevalence of iron deficiency in 6-12-year-old children: the Health Oriented Pedagogical Project (HOPP).

Appropriate reference intervals are important for correct interpretation of laboratory test results. The primary objective of the present study was to establish pediatric reference intervals for biochemical markers essential in the assessment of iron status. As a secondary objective we calculated the prevalence of iron deficiency according to WHO recommendations. Blood samples were obtained from 1355 healthy children 6-12 years of age participating in the Health Oriented Pedagogical Project (HOPP). For our primary objective, data from 1333 children were used to establish reference intervals for ferritin, iron, transferrin and transferrin saturation. Following the CLSI C28-A3 guidelines, the 2.5th and 97.5th percentiles with corresponding 90% confidence intervals, were estimated by the nonparametric method. None of the measured analytes required partitioning for age or sex. The prevalence of iron deficiency was 8.2%, which is higher than reported in other populations.

Reference values for osmolal gap in healthy subjects and in medical inpatients.

Methanol and ethylene glycol poisonings are associated with high morbidity and mortality rates if treatment is not initiated early. Since few hospitals measure these toxic alcohols on a 24/7 basis, calculation of the osmolal gap (OG) is an important diagnostic tool. The reference value for the OG lacks consensus. We, therefore, wanted to update the reference value for OG in presumed healthy subjects and study OG values in internal medicine patients. The OG was calculated in 285 patients at the Medical Clinic at Oslo University Hospital, and in 118 healthy blood donors at Vestfold Hospital Trust. OG was calculated by the formula: OG = Measured osmolality - calculated osmolality ((1.86 × s-sodium + s-glucose + s-urea)/0.93) mOsm/kg H2O. In the patients, median OG was 0 mOsm/kg H2O (interquartile range -3 to 3 mOsm/kg H2O, range -16 to103 mOsm/kg H2O). When corrected for one outlier, the central 95% interval for OG was -10 to 20. The healthy blood donors had a median OG of -1 mOsm/kg H2O (interquartile range -3 to1 mOsm/kg H2O, range -13 to 8 mOsm/kg H2O). When corrected for outliers, the reference range was -6 to 5 mOsm/kg H2O. Based on results from a healthy population, we suggest a reference value for the OG of ≤5 mOsm/kg H2O, but also recommend, based on our results from medical inpatients, to keep today's practice for suspecting poisoning with toxic alcohols at an elevated OG of ≥20 mOsm/kg H2O.

Laparoscopic gastric bypass versus lifestyle intervention for adolescents with morbid obesity. / Laparoskopisk gastrisk bypassoperasjon versus livsstilsbehandling av unge med sykelig overvekt.

BACKGROUND: There is limited evidence for the effectiveness of bariatric surgery in adolescents, and the associated complications. The main objective of the 4XL study was to clarify whether laparoscopic Roux-en-Y gastric bypass (LGBP) combined with lifestyle intervention is a safe and effective treatment method. MATERIAL AND METHOD: Data were retrieved from an ongoing non-randomised intervention study of adolescents with morbid obesity that is comparing the effects of gastric bypass combined with lifestyle intervention versus lifestyle intervention alone. RESULTS: Altogether 39 patients (64 % girls) treated with a gastric bypass, and 96 patients (57 % girls) treated with lifestyle intervention were examined prior to the start of treatment and one year later. The average age at inclusion (SD) was 16.7 (1.0) years vs. 15.6 (1.3) years, and average BMI was 45.6 (4.4) vs. 43.3 (4.1) kg/m2 in the two groups. Average (95 % CI) percentage weight loss was 30 % (27 %-33 %) after surgery versus weight gain of 1 % (-1 % to 3 %) in the control group. The difference between the groups was 31 % (95 % CI 27 %-34 %, p<0.001). Cardiometabolic risk factors improved only after surgery. After gastric bypass, two early (<6 weeks) minor complications were recorded. One year after surgery, 4 (10 %), 8 (21 %) and 4 (10 %) of patients had anaemia, iron deficiency or low vitamin B12 levels respectively, and 20 of 33 patients (61 %) had low two-hour blood glucose (<2.8 mmol/l) after oral glucose tolerance testing. INTERPRETATION: The results support previous studies showing that gastric bypass is associated with significant weight loss in adolescent patients with morbid obesity. The 4XL study is currently too small and the follow-up time too short to allow the risk of long-term complications to be assessed.

Week-to-week biological variation of methylmalonic acid and homocysteine in healthy women.

Metylmalonic acid (MMA) and homocysteine (HCY) are important biomarkers in the assessment of cobalamin and folate metabolism. Correct interpretation of patient results benefit from knowledge of biological variation. The aim of the present study was to determine within-subject (CVI) and between-subject (CVG) biological variations of serum MMA and HCY in healthy women. We collected blood samples from 12 healthy volunteers (33-61 years) on the same weekday for 10 consecutive weeks. Samples were stored at -80 °C until analysis in duplicate in a single analytical run in random order. The CVI and CVG biological variations were estimated by CV-ANOVA after the data were first subjected to outlier and homogeneity analysis. The CVI (95% CI) for MMA and HCY were 7.2% (6.1-8.5) and 7.4% (6.5-8.5), respectively. The corresponding CVG were 21.1% (14.0-32.2) and 24.2% (16.2-36.8). The index of individuality (II) was 0.34 for MMA and 0.31 for HCY and the reference change value (RCV) was -17.7; 21.0 (% decrease; increase) for MMA and -16.2; 19.4 for HCY. We provide within- and between-subject biological variation estimates for MMA and HCY in healthy women using an updated protocol. The results will contribute to a better clinical interpretation of these biomarkers and be of aid when setting analytical performance specifications.

Reference intervals for serum lipids and prevalence of dyslipidaemia in 6-12-year-old children: The Health Oriented Pedagogical Project (HOPP).

AIMS: Elevated serum lipid concentrations in childhood are thought to be risk factors for the development of cardiovascular disease later in life. The present study aims to provide age- and gender-related reference intervals for total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol in healthy school children. We also investigated the prevalence of dyslipidaemia using the published criteria for these biomarkers. METHODS: Venous blood and anthropometric data were collected from 1340 children in the HOPP study, aged between 6 and 12 years. Age- and gender-related reference intervals (2.5th and 97.5th percentiles) were established according to the IFCC recommendations, using the software RefVal 4.10. RESULTS: Gender differences were observed for total cholesterol and non-HDL cholesterol, but not for HDL cholesterol. Age differences were observed for total cholesterol. The reference intervals were in the range of 3.1-5.9 mmol/L for total cholesterol, 1.0-2.4 mmol/L for HDL cholesterol and 1.4-4.2 mmol/L for non-HDL cholesterol. Dyslipidaemia prevalence was as follows: increased TC 9.6%, decreased HDL 1.6%, and increased non-HDL 5.6%. CONCLUSIONS: Age- and gender-related reference intervals in a Norwegian population are similar to those reported in other countries. The prevalence of dyslipidaemia among Norwegian children is significant, emphasising the importance of appropriate reference intervals in clinical practice.

Handgrip strength in 6-12-year-old children: The Health Oriented Pedagogical Project (HOPP).

AIMS: The aim of the study was to describe the natural course of handgrip strength development in primary school children and to establish a reference material to be used in future screening studies. In addition, the study aims to investigate a possible association between handgrip strength and cardiovascular risk factors. METHODS: Anthropometric measures along with results for handgrip strength, endurance tests, blood pressure and cholesterol were measured on 2272 children of both sexes. An ROC analysis was used to estimate the suitability of handgrip strength as a predictor for known cardiometabolic risk factors. RESULTS: A reference material for handgrip strength is presented for boys and girls aged 6-12 years. The results indicate that handgrip strength is unsuitable as a predictor for cardiometabolic risk factors in children. CONCLUSIONS: The results may be used as reference values for handgrip strength in 6-12-year-old children of both sexes. Handgrip strength may not be used as a screening tool for cardiometabolic risk factors in pre-pubertal children.

Cardiovascular risk factors in a child population: The Health Oriented Pedagogical Project (HOPP).

AIMS: The main aim of the present study was to investigate the clustering of risk factors for cardiovascular diseases and metabolic syndrome in a large, healthy representative Norwegian child population. METHODS: From a population of 2817, parents of 2297 children agreed to participate. Values of waist circumference (WC), total cholesterol (TC), high-density lipoprotein (HDL), systolic blood pressure (sysBP), haemoglobin-A1c (HbA1c) and Andersen aerobic fitness test were used to test clustering of cardiometabolic risk factors in this sample. Expected distributions of probability for zero to five risk factors are, respectively, 23.7%, 39.6%, 26.4%, 8.8%, 1.5% and 0.1%. A cardiometabolic risk score from zero to five for each individual was derived by adding the number of variables in the least desirable quartile (highest for WC, sysBP, TC and HbA1c; lowest for aerobic fitness and HDL). RESULTS: A risk ratio of 5.8 (95% confidence interval 0.7-46.9) was found for five risk factors, though the small sample size rendered the results non-significant. An explorative analysis combining children with four and five risk factors did not reveal any significant clustering either. CONCLUSIONS: No clustering of risk factors was found among Norwegian children aged 6-12 years.

Factors affecting running performance in 6-12-year-olds: The Health Oriented Pedagogical Project (HOPP).

AIMS: The purpose of this study was to examine factors affecting running performance in children. METHOD: A cross-sectional study exploring the relationships between height, weight, waist circumference, muscle mass, body fat percentage, relevant biomarkers, and the Andersen intermittent running test in 2272 children aged 6 to 12 years. Parental education level was used as a non-physiological explanatory variable. RESULTS: Mean values (SD) and percentiles are presented as reference values. Height (ß = 6.4, p < .0001), high values of haemoglobin (ß = 18, p = .013) and low percentage of body fat (ß = -7.5, p < .0001) showed an association with results from the running test. In addition, high parental education level showed a positive association with the running test. CONCLUSION: Boys display better running performance than girls at all age ages, except 7 years old, probably because of additional muscle mass and less fatty tissue. Height and increased level of haemoglobin positively affected running performance. Lower body fat percentage and high parental education level correlated with better running performance.

Association of Bariatric Surgery vs Medical Obesity Treatment With Long-term Medical Complications and Obesity-Related Comorbidities.

Importance: The association of bariatric surgery and specialized medical obesity treatment with beneficial and detrimental outcomes remains uncertain. Objective: To compare changes in obesity-related comorbidities in patients with severe obesity (body mass index ≥40 or ≥35 and at least 1 comorbidity) undergoing bariatric surgery or specialized medical treatment. Design, Setting, and Participants: Cohort study with baseline data of exposures from November 2005 through July 2010 and follow-up data from 2006 until death or through December 2015 at a tertiary care outpatient center, Vestfold Hospital Trust, Norway. Consecutive treatment-seeking adult patients (n = 2109) with severe obesity assessed (221 patients excluded and 1888 patients included). Exposures: Bariatric surgery (n = 932, 92% gastric bypass) or specialized medical treatment (n = 956) including individual or group-based lifestyle intervention programs. Main Outcomes and Measures: Primary outcomes included remission and new onset of hypertension based on drugs dispensed according to the Norwegian Prescription Database. Prespecified secondary outcomes included changes in comorbidities. Adverse events included complications retrieved from the Norwegian Patient Registry and a local laboratory database. Results: Among 1888 patients included in the study, the mean (SD) age was 43.5 (12.3) years (1249 women [66%]; mean [SD] baseline BMI, 44.2 [6.1]; 100% completed follow-up at a median of 6.5 years [range, 0.2-10.1]). Surgically treated patients had a greater likelihood of remission and lesser likelihood for new onset of hypertension (remission: absolute risk [AR], 31.9% vs 12.4%); risk difference [RD], 19.5% [95% CI, 15.8%-23.2%], relative risk [RR], 2.1 [95% CI, 2.0-2.2]; new onset: AR, 3.5% vs 12.2%, RD, 8.7% [95% CI, 6.7%-10.7%], RR, 0.4 [95% CI, 0.3-0.5]; greater likelihood of diabetes remission: AR, 57.5% vs 14.8%; RD, 42.7% [95% CI, 35.8%-49.7%], RR, 3.9 [95% CI, 2.8-5.4]; greater risk of new-onset depression: AR, 8.9% vs 6.5%; RD, 2.4% [95% CI, 1.3%-3.5%], RR, 1.5 [95% CI, 1.4-1.7]; and treatment with opioids: AR, 19.4% vs 15.8%, RD, 3.6% [95% CI, 2.3%-4.9%], RR, 1.3 [95% CI, 1.2-1.4]). Surgical patients had a greater risk for undergoing at least 1 additional gastrointestinal surgical procedure (AR, 31.3% vs 15.5%; RD, 15.8% [95% CI, 13.1%-18.5%]; RR, 2.0 [95% CI, 1.7-2.4]). The proportion of patients with low ferritin levels was significantly greater in the surgical group (26% vs 12%, P < .001). Conclusions and Relevance: Among patients with severe obesity followed up for a median of 6.5 years, bariatric surgery compared with medical treatment was associated with a clinically important increased risk for complications, as well as lower risks of obesity-related comorbidities. The risk for complications should be considered in the decision-making process.

Biological variation of holotranscobalamin and cobalamin in healthy individuals.

Data on biological variation for cobalamin and holotranscobalamin (holoTC) are limited. The aim of this study was to determine within-subject (CVI) and between-subject (CVG) biological variations for these analytes in a healthy population. We collected blood samples from 15 healthy volunteers (12 women and three men, 22-66 years) on the same weekday for 10 consecutive weeks. Serum samples were stored at -80 °C until analysis in duplicate in a single analytical run. The CVI and CVG were estimated by nested ANOVA. The CVI (95% CI) for cobalamin and holoTC was 6.7% (5.7-7.7) and 13.0% (11.5-15.0), respectively. The corresponding CVG was 24.1% (16.4-36.0) and 24.6% (16.3-37.7). The analytical variation (CVA) (95% CI) was 3.5% (3.2-4.0) for cobalamin and 2.4% (2.1-2.6) for holoTC. The index of individuality (II) was low (<0.6) for both cobalamin and holoTC and the reference change value (RCV) was 20.1% for cobalamin and 36.6% for holoTC. Our study describes the components of biological variation of cobalamin and holoTC in a healthy population, contributing to a better clinical interpretation of these biomarkers.

Long-term tracking of plasma phospholipid fatty acid concentrations and their correlation with the dietary intake of marine foods in newly diagnosed diabetic patients: results from a follow-up of the HUNT Study, Norway.

Analysis of long-chain n-3 and n-6 fatty acid (FA) concentrations is used to evaluate their potential health effects in epidemiological studies, and, recently, also to counsel patients with a suboptimal intake of n-3 FA. Data on the method's ability to track and detect differences within and between individuals in appropriate populations are, however, lacking. The present study provides such data for twenty-nine plasma phospholipid (PL) FA concentrations and indices measured in 214 newly diagnosed type 2 diabetic patients at baseline and after 3 years. 20 : 3n-6 and the 20 : 4n-6:20 : 3n-6 ratio showed the highest tracking coefficients (Spearman's r 0.68), while DHA, EPA and PLN3-index (EPA+DHA) coefficients were 0.60, 0.47 and 0.55, respectively. Fish consumption measured simultaneously with EPA, DHA, sum n-3 and PLN3 index showed Spearman's correlation coefficients of 0.47, 0.44, 0.48 and 0.49, respectively, decreasing to 0.20, 0.19, 0.22 and 0.21 when measured 3 years apart. The within-subject CV of EPA, DHA and PLN3 index were 39.9, 14.3 and 18.0 %, respectively. The corresponding between-subject CV were 33.6, 16.5 and 18.7 %, while the reference change values were 112, 41 and 52 %. In conclusion, PL n-3 FA concentrations showed a significant long-term tracking and were positively correlated with marine food intake. Analytical precision, biological variability, reference change value and the index of individuality of EPA, DHA and PLN3 index are similar to commonly used clinical biomarkers, supporting their validity as dietary markers in clinical and epidemiological work.

Single-centre, non-randomised clinical trial at a tertiary care centre to investigate 1-year changes in social experiences and biomarkers of well-being after bariatric surgery in individuals with severe obesity: protocol for the Bariatric Surgery and Social Experiences (BaSES) study.

INTRODUCTION: Obesity is linked to increased loneliness and less enjoyment of social interactions. While bariatric surgery is the most effective treatment targeting severe obesity, there is limited understanding as to whether patients experience social interactions differently after surgery. The Bariatric Surgery and Social Experiences study is designed to assess potential changes in how much patients enjoy and engage in daily social interactions 1 year after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). METHODS AND ANALYSIS: Single-centre, non-randomised clinical trial carried out at the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust, Norway. Eligible patients (N=113) will undergo either RYGB, SG or single anastomosis sleeve ileal (SASI) bypass. The primary outcome measure is change in the social experience score (assessed with a questionnaire) from a presurgery to a follow-up assessment 1 year after RYGB and SG. The respective changes after SASI bypass will be assessed and considered exploratory. ETHICS AND DISSEMINATION: The most recent protocol version of this study was reviewed and approved by the Regional Committee for Medical Research Ethics South East Norway (REK sør-øst A) on 29 August 2022 (ref: 238406). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05207917.

Delirium, neurofilament light chain, and progressive cognitive impairment: analysis of a prospective Norwegian population-based cohort.

BACKGROUND: Previous population-based, longitudinal studies have shown that delirium is associated with an increased risk of dementia and cognitive decline. However, the underlying biological mechanisms are largely unknown. We aimed to assess the effects of delirium on both cognitive trajectories and any neuronal injury, measured via neurofilament light chain (NfL). METHODS: In this analysis of a prospective, 2-year follow-up, cohort study of participants aged 65 years or older living in Sandefjord municipality, Norway, we included cohort participants who were receiving domiciliary care services at least once per week between May 12, 2015, and July 8, 2016. Individuals with a life expectancy of less than 1 week, with Lewy body dementia, with psychiatric illness (except dementia), or for whom substance misuse was the principal indication for domiciliary services were excluded. Participants had a comprehensive assessment at 6-month intervals for 2 years, which included the Montreal Cognitive Assessment (MoCA) and a blood sample for NfL to measure neuronal injury. All information on clinical diagnoses and medications were cross-referenced with medical records. During any acute change in mental status or hospitalisation (ie, admission to hospital), participants were assessed once per day for delirium with Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. We also measured NfL from blood samples taken from participants who were acutely hospitalised. FINDINGS: Between May 12, 2015, and July 8, 2016, 210 participants were eligible for inclusion and assessed at baseline (138 [66%] of whom were female and 72 [34%] of whom were male), 203 completed cognitive assessment, and 141 were followed up for 2 years. 160 (76%) of 210 had moderate or severe frailty and 112 (53%) were living with dementia. During the 2-year follow-up, 89 (42%) of 210 participants were diagnosed with one or more episodes of delirium. Incident delirium was independently associated with a decrease in MoCA score at the next 6-month follow-up, even after adjustment for age, sex, education, previous MoCA score, and frailty (adjusted mean difference -1·5, 95% CI -2·9 to -0·1). We found an interaction between previous MoCA score and delirium (ß -0·254, 95% CI -0·441 to -0·066, p=0·010), with the largest decline being observed in people with better baseline cognition. Participants with delirium and good previous cognitive function and participants with a high peak concentration of NfL during any hospitalisation had increased NfL at the next 6-month follow-up. Mediation analyses showed independent pathways from previous MoCA score to follow-up MoCA score with contributions from incident delirium (-1·7, 95% CI -2·8 to -0·6) and from previous NfL to follow-up MoCA score with contributions from acute NfL concentrations (-1·8, -2·5 to -1·1). Delirium was directly linked with a predicted value of 1·2 pg/mL (95% CI 1·02 to 1·40, p=0·029) increase in NfL. INTERPRETATION: In people aged 65 years or older, an episode of delirium was associated with a decline in MoCA score. Greater neuronal injury during acute illness and delirium, measured by NfL, was associated with greater cognitive decline. For clinicians, our finding of delirium associated with both signs of acute neuronal injury, measured via NfL, and cognitive decline is important regarding the risk of long-term cognitive deterioration and to acknowledge that delirium is harmful for the brain. FUNDING: South-Eastern Norway Health Authorities, Old Age Psychiatry Research Network, Telemark Hospital Trust, Vestfold Hospital Trust, and Norwegian National Centre for Ageing and Health. TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.