Validation of SCORE2 on a sample from the Russian population and adaptation for the very high cardiovascular disease risk region.

SCORE2 (Systematic COronary Risk Evaluation 2) is a risk assessment scale for cardiovascular events, presented in 2021 by the European Society of Cardiology. Both for training and validation of the SCORE2 model, representative samples from the Russian population were not used. Therefore, we aimed to validate SCORE2 on a such sample. For this purpose, we used a sample from the ESSE-RF epidemiological study consisting of 7251 participants aged 40-69 years without history of CVDs. We performed the validation by comparing SCORE2 risk estimates for ESSE-RF participants with the observed incidence of cardiovascular events in the study, adjusted for event information losses. The validation demonstrated that SCORE2 risk estimates were accurate for Russian men and inaccurate for Russian women. Together with the quantitative assessment of risk, SCORE2 offers its interpretation in terms of 10-year CVD risk group: low-moderate, high, and very high. For Russian men we considered the original interpretation of the SCORE2 estimates to be questionable because almost none of the men would be categorized as having "low-to-moderate" 10-year CVD risk. This problem would be typical for all countries of the very high CVD risk region. Therefore, we proposed a new interpretation of the SCORE2 risk estimates for men from the very high risk region. According to the proposed interpretation, the fraction of men in ESSE-RF in "low-to-moderate" 10-year CVD risk increased from 2% to 18% and the fraction of men in "very high" CVD risk decreased from 63% to 20% as compared to the original interpretation. The proposed interpretation would allow a more personalized approach to CVD treatment and optimize the burden on primary healthcare in the very high risk region countries.

Heat Shock Proteins (HSPs) and Cardiovascular Complications of Obesity: Searching for Potential Biomarkers.

Heat shock proteins (HSPs), a family of proteins that support cellular proteostasis and perform a protective function under various stress conditions, such as high temperature, intoxication, inflammation, or tissue hypoxia, constitute a promising group of possible biochemical markers for obesity and cardiovascular diseases. HSP27 is involved in essential cellular processes occurring in conditions of obesity and its cardiometabolic complications; it has protective properties, and its secretion may indicate a cellular response to stress. HSP40 plays a controversial role in the pathogenesis of obesity. HSP60 is involved in various pathological processes of the cardiovascular, immune, excretory, and nervous systems and is associated with obesity and concomitant diseases. The hypersecretion of HSP60 is associated with poor prognosis; hence, this protein may become a target for further research on obesity and its cardiovascular complications. According to most studies, intracellular HSP70 is an obesity-promoting factor, whereas extracellular HSP70 exhibited inconsistent dynamics across different patient groups and diagnoses. HSPs are involved in the pathogenesis of cardiovascular pathology. However, in the context of cardiovascular and metabolic pathology, these proteins require further investigation.

Translating and adapting the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation: A multicentre pilot study to inform validation procedures.

Aims: The Alcohol Use Disorders Identification Test (AUDIT) is one of the most widely used screening instruments worldwide. Although it was translated into many languages, not many country-specific adaptations exist, and a formal validation procedure of the Russian version has been carried out only recently. The present contribution documents the different steps taken to formally translate and adapt a Russian-specific version of the AUDIT (RUS-AUDIT). Methods: The AUDIT was translated into Russian following an established protocol, revised and adapted to the country context using an expert panel, and field-tested in an iterative approach, in line with WHO rules on instrument translation and adaptation A total of three pilot phases were carried out on 134 patients from primary healthcare (PHC) and 33 patients from specialised alcohol treatment facilities (narcology), guided by a specially established advisory board. Changes in each version were informed by the findings of the previous pilot phase and a thorough panel discussion. Results: Based on the findings of three different pilot phases, the RUS-AUDIT was developed as a paper-and-pencil interview for PHC professionals. Since various issues with representation and counting of standard drinks for the second test item arose, a special show card was developed to support the assessment. Preliminary AUDIT-C scores indicated that more than one-third of the screened women (34.2%) and about half of the screened men (50.9%) from PHC facilities have exceeded risk thresholds. Conclusions: The RUS-AUDIT was constructed as a feasible assessment tool for interviewers and patients. The large number of PHC patients who exceed the risk threshold has corroborated the need for formal validation and Russia-specific cut-off scores, considering the specific drinking patterns.

Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods.

Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.

Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically based lipid disorder with an underestimated actual prevalence. In recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. The practical applicability of FD diagnostic criteria and the prevalence of FD in Russia have not been previously assessed. We demonstrated that the diagnostic algorithms of FD, including the diagnostic apoB levels, require correction, taking into account the distribution of apoB levels in the population. At the same time, a triglycerides cutoff ≥ 1.5 mmol/L may be a useful tool in identifying subjects with FD. In this study, a high prevalence of FD was detected: 0.67% (one in 150) based on the ε2ε2 haplotype and triglycerides levels ≥ 1.5 mmol/L. We also analyzed the presence and pathogenicity of APOE variants associated with autosomal dominant FD in a large research sample.

Which Comes First, Nonalcoholic Fatty Liver Disease or Arterial Hypertension?

Non-alcoholic fatty liver disease (NAFLD) and arterial hypertension (AH) are widespread noncommunicable diseases in the global population. Since hypertension and NAFLD are diseases associated with metabolic syndrome, they are often comorbid. In fact, many contemporary published studies confirm the association of these diseases with each other, regardless of whether other metabolic factors, such as obesity, dyslipidemia, and type 2 diabetes mellites, are present. This narrative review considers the features of the association between NAFLD and AH, as well as possible pathophysiological mechanisms.

Lipoprotein(a) in an adult sample from the Russian population: distribution and association with atherosclerotic cardiovascular diseases.

Introduction: Lipoprotein(a) (Lp(a)) is recognized as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to estimate the distribution of Lp(a) levels in working age adults from the Russian population and to assess its association with ischemic heart disease (IHD), myocardial infarction (MI), stroke, diabetes mellitus (DM), and arterial hypertension (AH). Material and methods: This substudy of the population-based study "Epidemiology of Cardiovascular Diseases and their Risk Factors in Some Regions of the Russian Federation" (ESSE-RF) included 8461 subjects aged 25-64 years (63.7% women) without lipid-lowering drugs. Atherosclerotic cardiovascular disease was self-reported. Lp(a), apolipoproteins AI and B, and lipid and glucose levels in blood serum were determined. Results: The prevalence of Lp(a) ≥ 30 mg/dl was 20.5% and 23.0%, and prevalence of Lp(a) ≥ 50 mg/dl was 13.3% and 15.2%, in men and women, respectively. An association of Lp(a) with IHD, MI, and AH, but not with stroke and DM, was shown. A cut-off level of Lp(a) of 9 mg/dl was determined, above which there was increased frequency of MI (by 59.2%, p = 0.02), IHD (by 33.4%, p < 0.001), and AH (by 11.6%, p < 0.001). In the multivariate analysis only the association of Lp(a) with IHD (1.19 (1.01-1.41), p = 0.038) and MI (1.57 (1.06-2.38), p = 0.028) remained significant. Conclusions: Lipoprotein(a) level ≥ 30 mg/dl was detected in every fifth adult aged 25-64 years. Increased risk of MI and IHD starts at an Lp(a) serum level above 9 mg/dl.

Clinically Meaningful Fatigue and Depression Are Associated with Sarcopenia in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Sarcopenia is thought to be related to an increased risk of non-alcoholic steatohepatitis and advanced liver fibrosis. Our cross-sectional single-center study was designed to analyze the prevalence of sarcopenia in patients with NAFLD and possible influencing factors. METHODS: A survey on the presence of sarcopenia, fatigue, anxiety, and depression, along with a quality-of-life (QoL) assessment, was forwarded by email to 189 outpatients. Demographics, anthropometric and clinical data (laboratory test results and abdomen complete ultrasound protocol), performed within 2-4 weeks prior to the enrollment, were obtained. RESULTS: Sarcopenia (defined as SARC-F score ≥ 4) was identified in 17 (15.7%) patients, all of them (100%) females, with median age (interquartile range) 56 (51-64) years. These patients had a poorer metabolic state (greater values of waist and hip circumferences, body mass index, and HOMA-IR) and significantly poorer QoL, specifically, regarding the physical component of health, compared with NAFLD patients without sarcopenia. Multivariate analysis showed that depression (OR = 1.25, 95% CI: 1.02-1.53, p = 0.035) and clinically meaningful fatigue (OR = 1.14, 95% CI: 1.04-1.26, p = 0.008) were the factors independently associated with sarcopenia in patients with NAFLD. CONCLUSION: Sarcopenia is associated with depression and fatigue rather than with the severity of liver disease alone and may negatively affect QoL in patients with NAFLD.

Possible Mechanisms Linking Obesity, Steroidogenesis, and Skeletal Muscle Dysfunction.

Increasing evidence suggests that skeletal muscles may play a role in the pathogenesis of obesity and associated conditions due to their impact on insulin resistance and systemic inflammation. Skeletal muscles, as well as adipose tissue, are largely recognized as endocrine organs, producing biologically active substances, such as myokines and adipokines. They may have either beneficial or harmful effects on the organism and its functions, acting through the endocrine, paracrine, and autocrine pathways. Moreover, the collocation of adipose tissue and skeletal muscles, i.e., the amount of intramuscular, intermuscular, and visceral adipose depots, may be of major importance for metabolic health. Traditionally, the generalized and progressive loss of skeletal muscle mass and strength or physical function, named sarcopenia, has been thought to be associated with age. That is why most recently published papers are focused on the investigation of the effect of obesity on skeletal muscle function in older adults. However, accumulated data indicate that sarcopenia may arise in individuals with obesity at any age, so it seems important to clarify the possible mechanisms linking obesity and skeletal muscle dysfunction regardless of age. Since steroids, namely, glucocorticoids (GCs) and sex steroids, have a major impact on the amount and function of both adipose tissue and skeletal muscles, and are involved in the pathogenesis of obesity, in this review, we will also discuss the role of steroids in the interaction of these two metabolically active tissues in the course of obesity.

Genetic landscape in Russian patients with familial left ventricular noncompaction.

Background: Left ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214). Methods: All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines. Results: A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants -8 of 54 (14.8%) -have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 -7.37; p <0.001) per variant after adjustment for sex, age, and family. Conclusion: Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.

Non-Alcoholic Fatty Liver Disease and Bone Tissue Metabolism: Current Findings and Future Perspectives.

Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions worldwide. Moreover, the prevalence of this liver disease is expected to increase rapidly in the near future, aligning with the rise in obesity and the aging of the population. The pathogenesis of NAFLD is considered to be complex and to include the interaction between genetic, metabolic, inflammatory, and environmental factors. It is now well documented that NAFLD is linked to the other conditions common to insulin resistance, such as abnormal lipid levels, metabolic syndrome, and type 2 diabetes mellitus. Additionally, it is considered that the insulin resistance may be one of the main mechanisms determining the disturbances in both bone tissue metabolism and skeletal muscles quality and functions in patients with NAFLD. To date, the association between NAFLD and osteoporosis has been described in several studies, though it worth noting that most of them included postmenopausal women or elderly patients and originated from Asia. However, taking into account the health and economic burdens of NAFLD, and the increasing prevalence of obesity in children and adolescents worldwide, further investigation of the relationship between osteopenia, osteoporosis and sarcopenia in NAFLD, including in young and middle-aged patients, is of great importance. In addition, this will help to justify active screening and surveillance of osteopenia and osteoporosis in patients with NAFLD. In this review, we will discuss various pathophysiological mechanisms and possible biologically active molecules that may interplay between NAFLD and bone tissue metabolism.

Impact of National Tobacco Control Policy on Rates of Hospital Admission for Pneumonia: When Compliance Matters.

A number of studies claim that tobacco control (TC) regulations are associated with reductions in smoking-related hospitalisation rates, but very few have estimated the impact of TC laws (TCL) at both countrywide and regional levels, and none of them have studied the impact of TCL in relation to compliance with TC regulations. This study evaluates the effects of Russian TCL on hospital admission (HA) rates for pneumonia countrywide and in 10 Russian regions and the extent of these effects in connection with the compliance with TCL. Methods: HA rates for pneumonia from 2005-2019 were analysed to compare the periods before and after the adoption of TCL in 2013. An interrupted time series design and a Poisson regression model were used to estimate the immediate and long-term effects of TCL on pneumonia annual hospitalisation rates after the TCL adoption, compared with the pre-law period. The 10 Russian regions were compared using the TCL implementation scale (TCIS) developed on the basis of the results of the Russian TC policy evaluation survey; Spearman's rank correlation and linear regression models were employed. Results showed a 14.3% reduction in HA rates for pneumonia (RR 0.88; p = 0.01) after the adoption of TCL in Russia with significant long-term effect after 2013 (RR 0.86; p = 0.006). Regions with better enforcement of TCL exhibited greater reductions in pneumonia HA rates (rsp = -0.55; p = 0.04); (ß = -4.21; p = 0.02). Conclusions: TCL resulted in a sustained reduction in pneumonia hospitalisation rates, but these effects, varying by region, may depend on the scale of the TCL enforcement.

Missing data and other challenges in assessing inappropriate marketing of baby foods in the Russian Federation: a cross-sectional study.

OBJECTIVES: We used the WHO draft nutrient profile model (NPM) to evaluate baby foods targeted at infants and young children (IYC) aged 6-36 months in the Russian Federation to assess their suitability for marketing. DESIGN: A cross-sectional study in Moscow (Russian Federation). SETTING: Nutrition information of baby food was primarily collected from retailer websites, with some complementary data from physical stores. Both specialist stores for IYC and general supermarkets were included. PARTICIPANTS: Two hundred and thirty baby food products targeted to IYC were selected. Breastmilk substitutes and products targeted at children over 3 years old were excluded. MAIN OUTCOME MEASURES: Per cent of missing nutrition data, per cent of products with added sugar or sweetener and exceeded sodium or salts, per cent of products marketed as suitable for IYC under 6 months. RESULTS: Most products were 'ready-to-eat', including fruit (n=42, 18.5%) and vegetable (n=29, 12.8%) purees, meat, fish or cheese purees (n =26, 11.5%); 'dry or instant cereal/starchy foods' (n=27, 11.9%), including predominantly dry cereals, 'juices and other drinks' (n=26, 11.5%). 95% (n=219/230) of products were missing total sugar information, 78% (n=180/230) were missing either sodium or salt, and 25% (n=57/230) were missing total fat. Among products with sugar and sodium information, 41% (n=94/230) included added sugar or sweeteners, and 48% (n=24/50) exceeded the NPM sodium threshold. 40% of products (n=92/230) were marketed as suitable for IYC aged under 6 months. CONCLUSION: Baby foods marketed for IYC showed a high per cent of missing nutrition information and disparity with WHO's guidelines for complementary feeding, age of introduction, sugar and salt content. Stronger regulation is needed in this area to minimise higher risk of non-communicable diseases (NCDs) in later life.

Examining time-frequency mechanisms of full-fledged deep sleep development in newborns of different gestational age in the first days of their postnatal development.

Early age-related changes in EEG time-frequency characteristics during the restful sleep of newborns of different gestational ages result in the development of conventional EEG signs of deep sleep already during the first postnatal week of their life. Allocating newborns to different groups based on their gestational age and duration of postnatal period allowed demonstrating substantial intergroup differences in brain activity during sleep and wakefulness, along with significant variability in the time-frequency characteristics of brain activity. The process of conventional deep sleep development in infants born prior to the week 35 of gestation is associated with an increase in the power of alpha activity in the sensorimotor cortex of the brain.

Diversities in the Gut Microbial Patterns in Patients with Atherosclerotic Cardiovascular Diseases and Certain Heart Failure Phenotypes.

To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3-V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis. NGS analysis was conducted at the family level. No significant differences between patient's groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota.

Analysis of Adverse Events in the Treatment of Patients with Non-Valvular Atrial Fibrillation with Oral Anticoagulants: Data from the "ANTEY" Observational Study.

Rationale. Therapy with oral anticoagulants (OACs) in patients with atrial fibrillation (AF) is based on finding the optimal balance of efficacy and safety of these drugs. Data from observational studies are an additional source of information for the adverse events (AEs) of pharmacotherapy. Objective: To investigate pharmacotherapy AEs with OACs in the "ANTEY" prospective observational study in patients with non-valvular atrial fibrillation (AF). Material and Methods: A total of 201 people were enrolled (83 (41.3%) were women). The age of subjects was 71.1 ± 8.7 years (data presented as mean with standard deviation). The study protocol included two face-to-face visits (contacts V0 and V1) and one follow-up (FU) phone contact which were made with the patient at an interval of 6 months. At V0, all patients were recommended to take one of the non-vitamin K antagonist oral anticoagulants (NOACs); starting from V1, warfarin could have been prescribed or NOAC could have been changed. Information about AEs and OACsadministration was collected at V0, V1, and FU. Results. During 1 year of observation, 15 out of 201 patients refused to take OACs, and 186 initiated the recommended drug. Rivaroxaban was initiated in 93 patients, dabigatran in 46, apixaban in 40, and warfarin in 7 patients. There were 55 AEs, 25 of which were serious (SAEs), including 4 deaths. Of the 30 AEs, there were 18 bleedings: eight (8.6%) occurred with the administration of rivaroxaban; four (8.5%) with dabigatran, three (7.5%) with apixaban, and three (42.9%) with warfarin. Differences in the incidence of bleeding events between NOACs and warfarin are statistically significant (p = 0.025). Any AEs increased the chance of nonadherence to treatment nine-fold: OR = 9.2 (CI95%: 3.6−23.5), p < 0.0001. Conclusions. The most typical and common AEs in real-world clinical practice settings treatment with OACs were bleedings, the incidence of which was approximately 8% to 9% in the treatment with NOACs and was much higher with warfarin, bleedings in the treatment with OACs are statistically significantly associated with nonadherence to the use of these drugs in the future.

Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial.

BACKGROUND: COVID-19 disease is accompanied by a dysregulated immune response and hypercoagulability. The Anti-Coronavirus Therapies (ACT) inpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with the combination of rivaroxaban and aspirin for prevention of disease progression in patients hospitalised with COVID-19. METHODS: The ACT inpatient, open-label, 2 × 2 factorial, randomised, controlled trial was done at 62 clinical centres in 11 countries. Patients aged at least 18 years with symptomatic, laboratory confirmed COVID-19 who were within 72 h of hospitalisation or worsening clinically if already hospitalised were randomly assigned (1:1) to receive colchicine 1·2 mg followed by 0·6 mg 2 h later and then 0·6 mg twice daily for 28 days versus usual care; and in a second (1:1) randomisation, to the combination of rivaroxaban 2·5 mg twice daily plus aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome, assessed at 45 days in the intention-to-treat population, for the colchicine randomisation was the composite of the need for high-flow oxygen, mechanical ventilation, or death; and for the rivaroxaban plus aspirin randomisation was the composite of major thrombosis (myocardial infarction, stroke, acute limb ischaemia, or pulmonary embolism), the need for high-flow oxygen, mechanical ventilation, or death. The trial is registered at www. CLINICALTRIALS: gov, NCT04324463 and is ongoing. FINDINGS: Between Oct 2, 2020, and Feb 10, 2022, at 62 sites in 11 countries, 2749 patients were randomly assigned to colchicine or control and the combination of rivaroxaban and aspirin or to the control. 2611 patients were included in the analysis of colchicine (n=1304) versus control (n=1307); 2119 patients were included in the analysis of rivaroxaban and aspirin (n=1063) versus control (n=1056). Follow-up was more than 98% complete. Overall, 368 (28·2%) of 1304 patients allocated to colchicine and 356 (27·2%) of 1307 allocated to control had a primary outcome (hazard ratio [HR] 1·04, 95% CI 0·90-1·21, p=0·58); and 281 (26·4%) of 1063 patients allocated to the combination of rivaroxaban and aspirin and 300 (28·4%) of 1056 allocated to control had a primary outcome (HR 0·92, 95% CI 0·78-1·09, p=0·32). Results were consistent in subgroups defined by vaccination status, disease severity at baseline, and timing of randomisation in relation to onset of symptoms. There was no increase in the number of patients who had at least one serious adverse event for colchicine versus control groups (87 [6·7%] of 1304 vs 90 [6·9%] of 1307) or with rivaroxaban and aspirin versus control groups (85 [8·0%] vs 91 [8·6%]). Among patients assigned to colchicine, 8 (0·61%) had adverse events that led to discontinuation of study drug, mostly gastrointestinal in nature. 17 (1·6%) patients assigned to the combination of rivaroxaban and aspirin had bleeding compared with seven (0·66%) of those allocated to control (p=0·042); the number of serious bleeding events was two (0·19%) versus six (0·57%), respectively (p=0·18). No patients assigned to rivaroxaban and aspirin had serious adverse events that led to discontinuation of study drug. INTERPRETATION: Among patients hospitalised with COVID-19, neither colchicine nor the combination of rivaroxaban and aspirin prevent disease progression or death. FUNDING: Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, Thistledown Foundation. TRANSLATIONS: For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

A Splice Variant of the MYH7 Gene Is Causative in a Family with Isolated Left Ventricular Noncompaction Cardiomyopathy.

Variants of the MYH7 gene have been associated with a number of primary cardiac conditions, including left ventricular noncompaction cardiomyopathy (LVNC). Most cases of MYH7-related diseases are associated with such variant types as missense substitutions and in-frame indels. Thus, truncating variants in MYH7 (MYH7tv) and associated mechanism of haploinsufficiency are usually considered not pathogenic in these disorders. However, recent large-scale studies demonstrated evidence of the significance of MYH7tv for LVNC and gave rise to an assumption that haploinsufficiency may be the causal mechanism for LVNC. In this article, we present a family with isolated LVNC and a heterozygous splice variant of the MYH7 gene, analyze possible consequences of this variant and conclude that not all variants that are predicted truncating really act through haploinsufficiency. This study can highlight the importance of a precise assessment of MYH7 splicing variants and their participation in the development of LVNC.

Reduced Quality of Life in Patients with Non-Alcoholic Fatty Liver Disease May Be Associated with Depression and Fatigue.

Non-alcoholic fatty liver disease (NAFLD) is often thought of as clinically asymptomatic. However, many NAFLD patients complain of fatigue and low mood, which may affect their quality of life (QoL). This may create a barrier to weight loss and hinder the achievement of NAFLD therapy goals. Our study aimed to evaluate the QoL in NAFLD patients vs. healthy volunteers, and to analyze likely influencing factors. From March 2021 through December 2021, we enrolled 140 consecutive adult subjects (100 NAFLD patients and 40 controls). Overall, 95 patients with NAFLD and 37 controls were included in the final analysis. Fatty liver was diagnosed based on ultrasonographic findings. We employed 36-Item Short Form Health Survey (SF-36) to evaluate QoL, Hospital Anxiety and Depression Scale (HADS) to identify anxiety and/or depression, and Fatigue Assessment Scale (FAS) to measure fatigue. NAFLD patients had significantly lower physical component summary scores, as well as significantly higher HADS-D scores, compared with the control group (Mann-Whitney U criterion = 1140.0, p = 0.001 and U = 1294.5, p = 0.022, respectively). Likewise, fatigue was more common in NAFLD patients (χ2 = 4.008, p = 0.045). Impaired QoL was significantly associated with fatigue (FAS score ≥ 22, p < 0.001) and depression (HADS-D ≥ 8, p < 0.001). In conclusion, NAFLD patients had significantly poorer QoL vs. controls, in particular with respect to the physical component of health. Impaired QoL may be associated with fatigue and depression, and together they may interfere with increased physical activity and lifestyle modifications in patients with NAFLD.