Cognitive Impairment in Patients with Diabetes Mellitus

Diabetes mellitus (DM) is a risk factor for the development of cognitive impairment, when unsatisfactory glycemic control is associated with glioma biomarkers and changes in neuronal integrity. Given some limitations in the performance of neuropsychological testing, it is important to indicate specific markers of brain damage

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Markers for the Prediction of Probably Sarcopenia in Middle-Aged Individuals

Sarcopenia is a condition that is characterized by a progressive loss of muscle mass, strength, and function, resulting in reduced quality of life. The aim of the study was to analyze the significance of pro-inflammatory markers in the prognostic diagnosis of sarcopenia. The participants were divided into two groups: the main group of 146 people and the control—75 people. The complex of examinations included neuropsychological testing (Hospital Anxiety and Depression Scale (HADS), quality-of-life questionnaire for patients with sarcopenia (SarQoL), and short health assessment form (MOS SF-36)), a 6 m walking speed test, manual dynamometry, bioimpedancemetry, and metabolic markers (nitrates, fibroblast growth factor 21, and malondialdehyde). When analyzing metabolic markers in the main group, a twofold increase in nitrates in the main group was recorded in a subsequent analysis adjusted for multiple variables, there was a negative association between the nitrate levels for weak grip strength and appendicular muscle mass. An additional analysis revealed that the complaint of pain in the lower extremities was more frequent in patients of the main group, as well as constipation and the pathology of thyroid gland, and they were more frequently diagnosed with arterial hypertension. At the same time, patients from the main group more frequently took vitamin D. When conducting body composition, the main group recorded a higher weight visceral fat content, as well as a decrease in appendicular and skeletal muscle mass; these changes were accompanied by a decrease in protein and minerals. Among the markers that differed significantly were nitrates, and it was this that was associated with decreased muscle strength and appendicular mass, which may indicate both a possible mechanism and a possible predictive marker. The results of this study can be used to develop a screening method for diagnosing sarcopenia at the outpatient stage

Clinicopathological Features and Outcomes of T- and NK-Cell Lymphomas in European Russia

With the introduction of the revised World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues in 2001, many patients had to be re-evaluated for the correct diagnosis of T- and NK-cell lymphomas. Because some T-cell malignancies are associated with poor outcome, it is important to identify subsets of patients that may benefit from novel or more intensive therapies. The purpose of this study was to determine, for the first time, the relative frequencies, pathological features and outcomes of patients with T- and NK-cell lymphomas in a predominantly Russian Slavic population. We identified 291 patients with a diagnosis of T- and NK-cell malignancies treated at our Center between 2000-2008. In applying the revised WHO classification, we confirmed the diagnosis and had complete clinical follow up and pathological information on 264 cases that were included in the analysis. We found some differences in frequency of several subsets as compared with previously published reports, including younger age of onset and relatively higher incidence of T-LGL in our patients. We also confirm that intensive treatment regimens of advanced stage PTCL and ALK—ALCL led to considerable improvement in response rates, but not in the overall survival