Infant Vitamin B12 Status and its Predictors – Cross-Sectional Baseline Results from an Ongoing Randomized Controlled Trial

Background: Vitamin B12 is a crucial micronutrient for infant growth and development. Objective: The objective of this study was to describe vitamin B12 status in Norwegian infants aged 6-15 wk using multiple biomarkers and cut-off approaches, and to identify its predictors. Methods: From November 2021 through August 2024, infants aged 6-15 wk and their mothers were recruited from public health clinics in Innlandet County, Norway, as part of an ongoing randomized controlled trial. Plasma cobalamin and methylmalonic acid (MMA) concentrations were analyzed among all infants in the cohort (n = 644), and total homocysteine (tHcy) concentrations were analyzed in a subgroup (n = 358). The combined indicator for vitamin B12 status (cB12) was calculated by Fedosov's equation. Low status was defined using multiple cut-off approaches. Potential predictors of infant vitamin B12 status were evaluated using regression models. Results: Mean (standard deviation [SD]) infant age was 9.1 (1.8) wk. The median (interquartile range) concentrations were: cobalamin 242 (192, 322) pmol/L, tHcy 7.4 (6.2, 9.4) μmol/L, and MMA 0.34 (0.21, 0.77) μmol/L. The mean (SD) cB12 was -0.5 (0.7). Eight percent had cobalamin 6.5 μmol/L, 19% >10 μmol/L, and 4% >13 μmol/L. Sixty-four percent had MMA>0.26 μmol/L. Exclusively breastfed infants had 40% lower cobalamin and 30% higher tHcy compared with nonbreastfed infants. Partially breastfed infants had 21% lower cobalamin and 12% higher tHcy compared with nonbreastfed infants. Conclusion: A substantial proportion of Norwegian infants have biochemical signs of low vitamin B12 status, given that the cut-offs were established in adults. Lower status was observed in partially and exclusively breastfed infants, compared with nonbreastfed infants. However, it is unclear whether these biomarker patterns have clinical significance. Further research is needed to determine consequences of low vitamin B12 biomarker concentrations in early infancy. This trial was registered as NCT05005897.This work was supported by South-Eastern Norway Regional Health Authority (grant no. 2020096) (to TAS), by Norwegian Regional Research Fund (grant no. 332775) (to KSB) and by Innlandet Hospital Trust (grant no. 150455 and grant no. 150473) (to TAS).publishedVersio

Predictive Clinical Factors of Pain-Related Quality of Recovery Following Elective Gastrointestinal and Hepato-Pancreato-Biliary Surgery: An Observational Study in Norway

Purpose: This observational cohort study aimed to identify predictive factors associated with pain-related quality of recovery among patients undergoing elective gastrointestinal and hepato-pancreato-biliary surgery. Patients and methods: This study involved a secondary analysis of the data collected from five hospitals across all healthcare regions in Norway to validate the Norwegian version of the Quality of Recovery-15 (QoR-15NO). The sample consisted of 268 adult patients who underwent elective gastrointestinal and hepato-pancreato-biliary surgery between September 2021 and May 2022. Data were collected using QoR-15NO upon admission for surgery and on the first postoperative day, and surgery severity was classified using the Surgical Outcome Risk Tool. A linear mixed model and multivariate linear regression were used to investigate associations between postoperative scores and possible predictive clinically relevant factors. Results: The results of this study showed that postoperative pain was significantly associated with age, gender, severity of surgery, and changes from pre- to postoperative status. Younger patients, compared to older patients (b=0.23, 95% CI: [0.03, 0.41]), female patients (b=-0.61, 95% CI: [-1.19, -0.04]), patients undergoing minor and intermediate surgeries compared to major surgeries (b=0.96, 95% CI: [0.00, 1.92]) all reported higher levels of postoperative pain. There was a significant decline in QoR post-surgery due to increased pain severity (b=-1.91, 95% CI: [-2.33, -1.50]; p <0.001). No clinically significant associations were found between ASA physical status, surgery duration, and pain-related QoR. Conclusion: This study identified age, gender, and surgery severity as key predictors of postoperative pain. Younger and female patients and those undergoing minor surgeries are at higher risk for severe postoperative pain. Proactive approaches for minor surgeries and tailored pain management for younger patients and females might enhance recovery and postoperative pain outcomes. Thus, future research should focus on the long-term effects of individualized pain management and additional strategies for high-risk patient groups.publishedVersio

A 12-Week Strict Low FODMAP Diet Reduces the Severity Levels of Fatigue, Depression, Anxiety, and Inattention in Patients with Irritable Bowel Syndrome

Background: The low FODMAP diet (LFD) has been shown to alleviate gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). However, the impact of the LFD on coexisting symptoms of fatigue, anxiety, depression, and cognitive functions remains unclear. Objectives: This study aims to investigate the effects of a 12-wk strict LFD on symptoms of fatigue, depression, anxiety, and inattention in patients with moderate-to-severe IBS-D (diarrhea-predominant), and IBS-M (mixed diarrhea and constipation). Methods: Participants with IBS were included in an open-label, single-center, 12-wk dietary intervention conducted at Haukeland University Hospital in Bergen, Norway. They followed a strict LFD guided by a registered dietitian and completed questionnaires assessing fatigue [Chalder Fatigue Scale (CFQ-11)] and anxiety and depression [Hospital Anxiety and Depression Scale (HADS)] and performed a test of attention [the third edition of the Connors' continuous performance test (CPT-3)] at baseline and 12-wk follow-up. Data were analyzed using Wilcoxon signed-rank tests to evaluate changes from baseline to post intervention. Results: Thirty-six participants completed the intervention. Statistically significant reductions were observed in symptoms of fatigue (CFQ-11, P < 0.013) and symptoms of anxiety (HADS-A, P < 0.006). Most of the patients were defined as noncases of fatigue and anxiety following the intervention. Performance on the CPT-3 revealed improvements in measures of inattention. Conclusions: A 12-wk strict LFD intervention significantly alleviated coexisting symptoms of fatigue, anxiety, and depression, and improved performance on a psychometric test of attention. These findings suggest that dietary management plays a crucial role in improving both physical and mental health in patients with IBS.This study was registered at clinical trial as NCT04296552 (https://clinicaltrials.gov/study/NCT04296552?term=NCT04296552&rank=1).This research was funded by the Research Council of Norway (grant ID FRIMED-BIO276010) and Helse Vest’s Research Funding (grant ID HV912243) and by the Trond Mohn Research Foundation, grant number BFS2018TMT0, and from , project number 294594.publishedVersio

International Delphi Study on Wound Closure and Incision Management in Joint Arthroplasty Part 2: Total Hip Arthroplasty

Background: This modified Delphi study aimed to develop a consensus on optimal wound closure and incision management strategies for total hip arthroplasty (THA). Given the critical nature of wound care and incision management in influencing patient outcomes, this study sought to synthesize evidence-based best practices for wound care in THA procedures. Methods: An international panel of 20 orthopedic surgeons from Europe, Canada, and the United States evaluated a targeted literature review of 18 statements (14 specific to THA and 4 related to both THA and total knee arthroplasty). There were 3 rounds of anonymous voting per topic using a modified 5-point Likert scale with a predetermined consensus threshold of ≥ 75% agreement necessary for a statement to be accepted. Results: After 3 rounds of voting, consensus was achieved for all 18 statements. Notable recommendations for THA wound management included (1) the use of barbed sutures over non-barbed sutures (shorter closing times and overall cost savings); (2) the use of subcuticular sutures over skin staples (lower risk of superficial infections and higher patient preferences, but longer closing times); (3) the use of mesh-adhesives over silver-impregnated dressings (lower rate of wound complications); (4) for at-risk patients, the use of negative pressure wound therapy over other dressings (lower wound complications and reoperations, as well as fewer dressing changes); and (5) the use of triclosan-coated sutures (lower risk of surgical site infection) over standard sutures. Conclusions: Through a structured modified Delphi approach, a panel of 20 orthopedic surgeons reached consensus on all 18 statements pertaining to wound closure and incision management in THA. This study provides a foundational framework for establishing evidence-based best practices, aiming to reduce variability in patient outcomes and to enhance the overall quality of care in THA procedures.publishedVersio

Biotin: a scoping review for Nordic Nutrition Recommendations 2023

Biotin is a water-soluble B-vitamin with key roles in metabolism and are found in most foods at low concentrations. Symptomatic biotin deficiency is rare, and few studies have investigated biotin requirements in relation to health outcomes. Data to support the setting of dietary reference values for biotin are limited. Keywords: biotin; carboxylation; nutrition recommendations; vitamin B7.publishedVersio

Prevalence and Characteristics of Female and Male Esports Players among Norwegian Youth: A General Population Study

Electronic sports (esports) have evolved into a major cultural phenomenon in the 21st century, mirroring traditional sports with organized, competitive play. This study investigates the prevalence of esports participation and characteristics of esports players among Norwegian adolescents. Using data from the Ungdata survey, a comprehensive web-based survey of Norwegian adolescents that includes questions on demographics, health, physical activity, social relations, and leisure activities such as gaming and esports, we analyzed responses from 70,695 students aged 16–18 years collected during 2021–2023. We conclude that about one out of twenty in the age group of 16–18 years actively engage in esports. The figure conceals significant gender differences: only 0.7% of girls, compared to 8.8% of boys, actively participate in esports. While female esports players differ noticeably from non-players on almost all indicators included in our analyses, the picture among boys reflects more similarities between esports players and other boys, than differences. Among the esports players, females almost consistently reported more negative experiences than males, including less physical socialization, lower self-rated health, higher rates of loneliness and sleeping problems, and a greater difficulty fitting in at school. Despite these negative aspects, esports players maintain close friendships similar to their non-playing peers.Prevalence and Characteristics of Female and Male Esports Players among Norwegian Youth: A General Population StudyThis research was funded by the Norwegian Ministry of Culture and Equality, and by Innlandet Hospital Trust, project 150631.publishedVersio

Mental Health Dynamics between Mothers and Siblings of Children with Disabilities

When a child has a disability, their families face significant challenges that also impact parents' and siblings' mental health and adjustment. We examined the potential bidirectional relationships between parental mental health and sibling mental health and adjustment in families of children with a disability. Methods. We utilized baseline and 12month follow-up data from a randomized controlled trial of a brief intervention designed to enhance parent-sibling communication in families of children with a disability. The sample comprised 214 siblings aged 8-16 years and their parents (N = 203 mothers, N = 124 fathers).We estimated bivariate latent change score models to examine the longitudinal cross-domain associations between changes in parental mental health and changes in sibling mental health, and changes in parental mental health and sibling adjustment. Results. The results showed that changes in maternal mental health and sibling adjustment over the 12-month period were correlated (r = .22). The cross-domain associations between changes in maternal mental health and sibling mental health and adjustment were not statistically significant in any of the two models. However, baseline sibling mental health had nearly doubled impact on changes in maternal mental health (Β = 0.232, p = 0.061) compared to maternal health's impact on sibling mental health (Β = -0.134, p = 0.289). Models with paternal mental health data unfortunately did not run due to low paternal response rate at 12-months. Discussion. The findings suggest that whereas maternal mental health and sibling adjustment changes are correlated over time, the relationship between maternal and sibling measures does not necessarily operate bidirectionally. Future studies on family mental health dynamics should include data from fathers that may contribute to a broader understanding of these complex relationships.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Norwegian Women’s Public Health Organization [grant number 40404] and the Norwegian Research Council [grant number 321027].publishedVersio

MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - a Nordic Lymphoma Group study

The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement N 754299, Cancer fonden (2016/465, 19 0309Pj and 21 1561 Pj), Mats Paulssons Stiftelse för forskning, innovation och samhällsbyggande, Stiftelsen Stefan Paulssons cancerfond, and CREATE Health. All financial support was granted to SE.publishedVersio

Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle fatigability and weakness. Heterozygous parents do not show any conserved clinical pathology but report multiple incidences of intra-uterine fetal death, which were also observed in an eighth family included in this study. In vivo studies of abcc9 loss-of-function in zebrafish revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility. Our findings define an ABCC9 loss-of-function-related phenotype, expanding the genotypic and phenotypic spectrum of AIMS and reveal novel human pathologies arising from KATP channel dysfunction.publishedVersio

Mental Health, Psychosocial Functioning, and Quality of Life in Adolescents With Hirschsprung Disease

Background: Studies of mental health in adolescents with Hirschsprung disease (HD) are scarce. This cross-sectional study investigates mental health, psychosocial functioning and quality of life in HD adolescents. Methods: Adolescents (12-18 years) treated at the Department of pediatric surgery at Oslo University Hospital were invited for participation. Mental health was assessed by interview; Child Assessment Schedule (CAS) and questionnaires; parental Child Behavior Checklist (CBCL) and adolescent Youth Self-Report (YSR). Psychosocial functioning was rated by Child Global Assessment Scale (cGAS). Adolescent Quality of Life was assessed by Pediatric Quality of Life inventory (PedsQL) and chronic family difficulties (CFD) by interview. Medical records were reviewed for somatic history. Results: Thirty-seven adolescents, 28 males, median age 14.3 years, participated. By CAS interview, 8 of 37 (44% of females and 14% of males) fulfilled criteria for psychiatric diagnosis all within emotional and related disorders. Twenty-seven percent had CBCL internalizing scores and 16% had YSR internalizing scores in clinical range indicating emotional problems. By interviewer rated cGAS, 27% were scored in clinical range. By PedsQL 16% reported reduced psychosocial health score. Increased CFD, lower psychosocial functioning and reduced QoL as well as less paternal education were significantly associated with psychiatric diagnosis. Twice as many (4/8) adolescents who either had a stoma or bowel management had a psychiatric diagnosis compared to those who had neither stoma nor bowel management (7/28). Conclusion: Nearly one in four adolescents with HD fulfilled criteria for psychiatric diagnosis. Mental health problems were associated with reduced psychosocial function and reduced QoL. Level of evidence: III.The study has financial support from the Norwegian DAM foundation (2019/FO249474).publishedVersio