【特刊综述】雄激素对骨骼肌的作用：对乏力的发展和治疗的意义

雄激素对骨骼肌合成有明显影响,随着年龄增大,雄激素的下降常伴随肌量和肌力的下降。这种肌量和肌功能的下降,被称为少肌症或肌体老化,是老年人体质弱化（男性化减退）进展的关键事项。也是导致快速机能衰退及其不良后果的关键。雄激素水平下降对老年男性体质弱化（男性化减退）的潜在影响和对躯体功能的促进治疗作用无疑已经引起了相当的关注。本综述概述了近期关于肌肉老化、少肌症、老年体质弱化的概念、定义,并评估了关于雄激素和老年体质弱化的研究进展。近期源于观测性和介入性研究的证据强烈支持雄激素对老年男性肌量的作用,但雄激素对肌力和特有的躯体功能的效用并不明确。研究显示,雄激素治疗在老年男性中通常有良好的耐受性,而近期的研究则关注于雄激素的高剂量治疗和对于心血管风险较高人群的治疗。雄激素受体调节剂（SARMs）的初期试验研究显示传统雄激素治疗对于老年患者在肌量和肌功能方面有相同的效用。将来的重要研究方向包括利用这类雄激素治疗并结合适用于不同老年患者群体促进躯体功能的运动训练,同时将更多地关注近期关于激素水平、身体成分及躯体功能间关系的观测性（回顾性）研究。     

Longitudinal changes and seasonal variations in serum 25-hydroxyvitamin D levels in different age groups: results of the Longitudinal Aging Study Amsterdam

Summary

Vitamin D levels remained fairly stable during ageing with increasing levels in persons aged 55–65 years old and decreasing levels in persons aged 65–88 years old. The seasonal variation was larger than the longitudinal change. Our findings implicate that vitamin D supplementation becomes more important in older age groups and during wintertime.

Introduction

Longitudinal changes in serum 25-hydroxyvitamin D (25-OHD) levels during aging have not been studied extensively. Two studies showed increasing serum 25-OHD levels. One of these studies suggested that there might be decreasing levels in persons aged 65 years and older. The objectives of the current study are the following: (1) to examine longitudinal changes in serum 25-OHD levels in different age groups and (2) to describe the seasonal variation in different age groups.

Methods

Data of the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study, were used. Two different cohorts were included: (1) younger cohort: aged 55–65 years old at baseline, n?=?738, follow-up of 6 years and (2) older cohort: aged 65–88 years old at baseline, n?=?1,320, follow-up of 13 years.

Results

At baseline, average levels were 56.5 nmol/L in the younger cohort and 51.1 nmol/L in the older cohort. In the younger cohort, a longitudinal increase in the mean serum 25-OHD levels of 4 nmol/L in 6 years was observed; in the older cohort, a longitudinal decrease in the mean serum 25-OHD levels of 4 nmol/L in 13 years was observed. The seasonal variation was ±12 nmol/L in the younger cohort and ±7 nmol/L in the older cohort.

Conclusions

Long-term serum 25-OHD levels remained fairly stable during aging with slightly increasing levels in persons aged 55–65 years old and slightly decreasing levels in persons aged 65–88 years old. On average, the seasonal variation was larger than the longitudinal change. Our findings implicate that vitamin D supplementation becomes more important in older age groups and during wintertime.     

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence‐based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non‐life‐threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

Screening for coronary artery disease in early surgical treatment of acute aortic valve infective endocarditis

OBJECTIVESIn patients with unknown coronary status undergoing surgery for acute infective endocarditis (IE), the need to screen for coronary artery disease (CAD) and the risk of embolization during invasive coronary angiography (ICA) are debated. Coronary computed tomography angiography (CCTA) is a non-invasive alternative in these patients. We aimed to evaluate the safety and feasibility of ICA and CCTA to diagnose CAD, and the necessity to treat CAD to prevent CAD-related postoperative complications. Open in a separate windowMETHODSIn this single-centre retrospective cohort study, all patients with acute aortic IE between 2009 and 2019 undergoing surgery were selected. Outcomes were any clinically evident embolization after preoperative ICA, in-hospital mortality, perioperative myocardial infarction or unplanned revascularization and postoperative renal function.RESULTSOf the 159 included patients, CAD status was already known in 14. No preoperative diagnostics for CAD was done in 46/145, a CCTA was performed in 54/145 patients and an ICA in 52/145 patients. Significant CAD was found after CCTA in 22% and after ICA in 21% of patients. In 1 of the 52 (2%) patients undergoing preoperative ICA, a cerebral embolism occurred. The rate of perioperative myocardial infarction or unplanned revascularization in patients not screened for CAD was 2% (1 out of 46 patients).CONCLUSIONSAlthough the risk of embolism after preoperative ICA is low, it should be carefully weighed against the estimated risk of CAD-related perioperative complications. CCTA can serve as a gatekeeper for ICA in most patients with acute aortic IE.     

Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

Introduction

Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure.

Methods

One hundred thirty-five relapsing–remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline.

Results

A significant atrophy occurred over 6 months (PBVC?=??0.33%, SE?=?0.061, p?<?0.0001). The number of baseline T2 lesions (p?=?0.024), the on-study Gd-enhancing lesion volume (p?=?0.044), and the number of on-study PBHs (p?=?0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population.

Conclusion

Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power.     

Recent Developments in Basophil Research: Do Basophils Initiate and Perpetuate Type 2 T-Helper Cell Responses?

Basophils account for only 0.1-1% of all peripheral blood leukocytes. They were considered to be a redundant cell type for a long time. However, several findings show a non-redundant role for basophils in type 2 T-helper cell (Th2) immune responses in helminth infections, allergy and autoimmunity. Both immunoglobulin-E-dependent and -independent pathways have been described to contribute to basophil activation. In addition, several recent studies reported that basophils can function as antigen-presenting cells and are important in the initiation of Th2 immune responses. However, there are also conflicting studies that do not corroborate the importance of basophils in Th2 immune responses. This review discusses the role of basophils in Th2 immune responses in view of these recent findings.     

Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) Checklist

Background  

The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported outcomes. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114).