Muscle fat content and abdominal adipose tissue distribution investigated by magnetic resonance spectroscopy and imaging in obese children and youths

The degree of fat deposition in muscle and its implications for obesity-related complications in children and youths are not well understood. One hundred and fifty-nine patients (mean age: 13.3 years; range: 6–20) with a body mass index (BMI) >90th percentile for age and sex were included. Muscle fat content (MFC) was measured in the psoas muscle by proton magnetic resonance spectroscopy. The patients were assigned to two groups: MFC <5% or ≥5%. Visceral adipose tissue volume (VAT) and subcutaneous adipose tissue volume (SAT) were measured by magnetic resonance imaging. The data were analysed to detect associations between MFC and BMI standard deviation scores, VAT and SAT, blood values, pubertal stages, and physical activity scores. The mean BMI standard deviation score (SDS) was 3.04 (range 1.32–5.02). The mean MFC was 8.9% (range 0.8–46.7), and 118 (74.2%) of 159 patients had an MFC ≥5%. Children with an MFC ≥5%, compared with children with an MFC <5%, had a higher BMI SDS (P=0.03), a higher VAT (P=0.04), and elevated intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) contents (both P<0.0001). SAT, SAT/VAT ratio, blood values, pubertal stages and physical activity scores did not differ between the two groups. Severely obese children and youths tend to have a high MFC, which is associated with elevated VAT, IMCL, and EMCL contents. An increased MFC may be associated with impaired metabolic processes, which may predispose these young people to obesity-related complications

Exercise-based cardiac rehabilitation for adult patients with an implantable cardioverter defibrillator

Review question: We reviewed the benefits and harms of exercise-based cardiac rehabilitation programmes in adults who have been treated with an implantable cardioverter defibrillator from any cause. Background: An implantable cardioverter defibrillator is a very effective device that prevents sudden cardiac death. This is done by the use of either antitachycardia pacing, high-voltage shock therapy, or both. In spite of the potential mortality benefits, patients may also experience a negative impact on their health-related quality of life, increased readmission to hospital and healthcare facilities, loss of productivity and employment earnings, and increased morbidity and mortality. Exercise-based cardiac rehabilitation may benefit patients with an implantable cardioverter defibrillator. Study characteristics: We searched for randomised controlled trials (experiments in which participants are randomly allocated to an experimental intervention compared with a control intervention) that investigated exercise-based interventions compared with no exercise intervention control. We found eight trials published from 2004 to 2017 with a total of 1730 participants. Two trials did not report on funding and one trial reported funding from industry. The evidence is current to 30 August 2018. Key results: The review showed no evidence of an impact on the risk of death, harmful side effects or having antitachycardia pacing or shock therapy when comparing the exercise intervention to the control. There was also little or no evidence of a difference on health-related quality of life. However, there was an improvement in exercise capacity in favour of the exercise group. Quality of the evidence: The quality of the evidence ranged from moderate to very low for all outcomes. The number of events was low, it was possible for people in the trials to know to which intervention group they were randomised, the reporting of the results was not complete in some trials, and for some outcomes, the results varied across trials. These considerations limited our confidence in the overall results of the review. Conclusion: Further adequately powered and well-conducted randomised trials are needed to assess the impact of exercise-based cardiac rehabilitation in adults with an implantable cardioverter defibrillator

Major Cardiac Events in Patients and Relatives With Hereditary Hypertrophic Cardiomyopathy

BackgroundLittle evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families.ObjectivesThe purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes.MethodsA total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants.ResultsForty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up.ConclusionsThe disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives

Associations of gender with sexual functioning, loneliness, depression, fatigue and physical function amongst patients suffering from rheumatoid arthritis with a particular focus on methotrexate usage

There is a lack of knowledge regarding methotrexate (MTX) usage in patients with rheumatoid arthritis (RA) and its possible links with gender, disease characterization and sexual functioning, loneliness, fatigue and depression. We, therefore, investigated the associations of gender with physical function, fatigue, depression, loneliness and sexual functioning with a particular focus on MTX usage. A cross-sectional study design was used. Inclusion criteria were RA diagnosis, age above 18years and available data on MTX treatment 1year after diagnosis. Data consisted of responses from validated questionnaires regarding physical function, fatigue, depression, loneliness and sexual functioning combined with evaluations from medical records. Data were analysed with linear regression models comparing numerical outcome measures between male and female patients and between MTX users and MTX non-users. Amongst 286 patients with RA (69 men and 217 women), 67.8% were MTX users 1year after diagnosis. Comparing women and men, both overall and within subgroups of MTX usage, we found significantly more adverse outcomes for women than men in physical functioning at diagnosis and in sexual function, depression, fatigue and physical functioning at enrolment in the study. Gender differences were also present when comparing MTX users with MTX non-users divided by gender. There were only significant differences in the HAQ and loneliness scores when comparing MTX users with MTX non-users. Women with RA had more negative outcomes measured by the selected PROMs compared to men with RA, both overall and in subgroups of users and non-users of MTX. These findings call for sharpened attention to the importance of gender in the treatment and care of patients with RA, as well as in future clinical research. [Abstract copyright: © 2024. The Author(s).

Comparison of vaccine-induced antibody neutralization against SARS-CoV-2 variants of concern following primary and booster doses of COVID-19 vaccines

The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants

Greenland Geothermal Heat Flow Database and Map (Version 1)

We compile and analyze all available geothermal heat flow measurements collected in and around Greenland into a new database of 419 sites and generate an accompanying spatial map. This database includes 290 sites previously reported by the International Heat Flow Commission (IHFC), for which we now standardize measurement and metadata quality. This database also includes 129 new sites, which have not been previously reported by the IHFC. These new sites consist of 88 offshore measurements and 41 onshore measurements, of which 24 are subglacial. We employ machine learning to synthesize these in situ measurements into a gridded geothermal heat flow model that is consistent across both continental and marine areas in and around Greenland. This model has a native horizontal resolution of 55ĝ€¯km. In comparison to five existing Greenland geothermal heat flow models, our model has the lowest mean geothermal heat flow for Greenland onshore areas. Our modeled heat flow in central North Greenland is highly sensitive to whether the NGRIP (North GReenland Ice core Project) elevated heat flow anomaly is included in the training dataset. Our model's most distinctive spatial feature is pronounced low geothermal heat flow (<ĝ€¯40ĝ€¯mWĝ€¯m-2) across the North Atlantic Craton of southern Greenland. Crucially, our model does not show an area of elevated heat flow that might be interpreted as remnant from the Icelandic plume track. Finally, we discuss the substantial influence of paleoclimatic and other corrections on geothermal heat flow measurements in Greenland. The in situ measurement database and gridded heat flow model, as well as other supporting materials, are freely available from the GEUS Dataverse (10.22008/FK2/F9P03L; Colgan and Wansing, 2021).publishedVersionPeer reviewe

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81–0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999–0.93) and hot-spot methods (0.84; 95% CI: 0.77–0.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples

Evolving and evaluating the OMERACT fellows program: insights and implications from OMERACT 2023 fellows

Objective: To describe the evolution of the OMERACT Fellows Program (OM FP) and to evaluate the innovative changes implemented in the 2023 program. Methods: The OM FP, the first of its kind in global rheumatology, was developed in 2000 to mentor early career researchers in methods and processes for reaching evidence-driven consensus for outcome measures in clinical studies. The OM FP has evolved through continuing iterations of face to face and online feedback. Key new features delivered in 2023 included e-learning modules, virtual introductory pre-meetings, increased networking with Patient Research Partners (PRPs), learning opportunities to give and receive personal feedback, ongoing performance feedback during the meeting from Fellow peers, PRPs, senior OMERACTers (members of the OMERACT community) and Emerging Leader mentors, involvement in pitching promotions, two-minute Lightning Talks in a plenary session and an embedded poster tour. An online survey was distributed after the meeting to evaluate the program. Results: OM FP has included 208 fellows from 16 countries across 4 continents covering 47 different aspects of rheumatology outcomes since its inception. Over 50 % have remained engaged with OMERACT work. In 2023, 18 Fellows attended and 15 (83 %) completed the post-meeting survey. A dedicated OM FP was deemed important by all respondents, and 93 % would attend the meeting in future. The PRP/Fellow Connection Carousel and Lightning Talks were rated exceptional by 93 %. Key components to improve included clarification of expectations, overall workload, the Emerging Leaders Mentoring Program, and the content and duration of daily summary sessions. Conclusion: The innovations in the 2023 OM FP were well received by the majority of participants and supports early career rheumatology researchers to develop collaborations, skills and expertise in outcome measurement. Implementation of feedback from Fellows will enhance the program for future meetings, continuing to facilitate learning and succession planning within OMERACT