Diet Quality as a Mediator of the Relation between Income-to-Poverty Ratio and Overweight/Obesity among Adults: Moderating Effect of Sex

Poverty status influences obesity and dietary quality, and dietary quality influences obesity. How these relationships differ by sex is unclear. The current study aims were to 1) determine whether dietary quality mediates the relation between income-to-poverty ratio (IPR) and overweight/obesity (OV/OB) among men and women, separately, and 2) determine whether either of the mediated paths differs by sex. Four cycles of NHANES (2007-2014) were merged to obtain an unweighted study sample of 12,768 adults with complete data. Exposure variables included self-reported measures of IPR, Healthy Eating index (HEI) total score to measure diet quality, and sex. Direct assessment of height and weight was used to create OV/OB vs. normal weight categories of interest. A multiple-group moderated mediation model was conducted to evaluate the moderating effect of sex on the association between IPR and OV/OB through HEI. Covariates included age, race, marital status, education, employment, meeting physical activity recommendations, and daily sedentary time. A greater proportion of females experienced OV/OB, lower IPR, and higher HEI. The association between IPR and HEI did not differ by sex. Greater IPR was associated with lower odds of experiencing OV/OB for women and higher odds of experiencing OV/OB among men. For both males and females, HEI partially mediated the relationship between IPR and OV/OB (p \u3c .05). While efforts to improve dietary quality of all adults regardless of income and sex is needed, improving the dietary quality of higher income men may assist with reducing their experiences with OV/OB

Diet Quality as a Mediator of the Relation between Income-to- Poverty Ratio and Overweight/Obesity among Adults: Moderating Effect of Sex

Poverty status influences obesity and dietary quality, and dietary quality influences obesity. How these relationships differ by sex is unclear. The current study aims were to 1) determine whether dietary quality mediates the relation between income-to-poverty ratio (IPR) and overweight/obesity (OV/OB) among men and women, separately, and 2) determine whether either of the mediated paths differs by sex. Four cycles of NHANES (2007-2014) were merged to obtain an unweighted study sample of 12,768 adults with complete data. Exposure variables included self-reported measures of IPR, Healthy Eating index (HEI) total score to measure diet quality, and sex. Direct assessment of height and weight was used to create OV/OB vs. normal weight categories of interest. A multiple-group moderated mediation model was conducted to evaluate the moderating effect of sex on the association between IPR and OV/OB through HEI. Covariates included age, race, marital status, education, employment, meeting physical activity recommendations, and daily sedentary time. A greater proportion of females experienced OV/OB, lower IPR, and higher HEI. The association between IPR and HEI did not differ by sex. Greater IPR was associated with lower odds of experiencing OV/OB for women and higher odds of experiencing OV/OB among men. For both males and females, HEI partially mediated the relationship between IPR and OV/OB (p \u3c .05). While efforts to improve dietary quality of all adults regardless of income and sex is needed, improving the dietary quality of higher income men may assist with reducing their experiences with OV/OB

American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and European Society for Blood and Marrow Transplantation Clinical Practice Recommendations for Transplantation and Cellular Therapies in Mantle Cell Lymphoma

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated, with a few key statements as follows: in the first line setting, auto-HCT consolidation represents standard of care in eligible patients, whereas there is no clear role of allo-HCT or CAR T cell therapy outside of clinical trials. In the R/R setting, the preferential option is CAR T cell therapy, especially in patients with MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T cell therapy fails or is infeasible. Several recommendations were based on expert opinion, where the panel developed consensus statements for important real-world clinical scenarios to guide clinical practice. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL

Vascular mechanisms of post-COVID-19 conditions: rho-kinase is a novel target for therapy

BackgroundIn post-COVID-19 conditions (Long COVID), systemic vascular dysfunction is implicated but the mechanisms are uncertain, and treatment is imprecise.MethodsPatients convalescing after hospitalisation for COVID-19 and risk-factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated.ResultsThirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) three months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (p = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (p < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries (Masson's Trichrome (MT) 69.7% [95%CI: 67.8, 71.7]; picrosirius red 68.6% [95% CI: 64.4, 72.8]) versus controls (MT 64.9% [95%CI:59.4, 70.3] [p = 0.028]; picrosirius red 60.1% [95% CI: 55.4, 64.8], [p = 0.029]). Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9, 49.3) vs. controls (10.0%; 95% CI: 4.4, 15.6) (p < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated.ConclusionPatients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials

High-Grade B-cell Lymphoma, Not Otherwise Specified: A Multi-Institutional Retrospective Study

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ( double hit ). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase \u3e3 × upper limit of normal, and a dual-expressor immunophenotype. Age \u3e60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS

Post-COVID-19 illness trajectory: a multisystem investigation [Pre-print]

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis. Results: 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17; 10%), unlikely (n=56; 35%), probable (n=67; 42%) or very likely (n=21; 13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84); p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87); p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (p&lt;0.001), illness perception (p&lt;0.001), anxiety and depression (p&lt;0.001), physical activity (p&lt;0.001) and predicted maximal oxygen utilization (ml/kg/min) (p&lt;0.001). These measures were associated with adjudicated myocarditis. Conclusions: The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration: ClinicalTrials.gov identifier is NCT04403607

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization

Background The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain. Methods A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28–60 days post-discharge. The study encompassed research blood tests, patient-reported outcome measures, and multisystem imaging (including chest computed tomography (CT) with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging). Primary and secondary outcomes were analysed in relation to socioeconomic status, using the Scottish Index of Multiple Deprivation (SIMD). The EQ-5D-5L, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire-4 (PHQ-4) for Anxiety and Depression, and the Duke Activity Status Index (DASI) were used to assess health status. Results Of the 252 enrolled patients (mean age 55.0 ± 12.0 years; 40% female; 23% with diabetes), deprivation status was linked with increased BMI and diabetes prevalence. 186 (74%) returned for the follow-up. Within this group, findings indicated associations between deprivation and lung abnormalities (p = 0.0085), coronary artery disease (p = 0.0128), and renal inflammation (p = 0.0421). Furthermore, patients with higher deprivation exhibited worse scores in health-related quality of life (EQ-5D-5L, p = 0.0084), illness perception (BIPQ, p = 0.0004), anxiety and depression levels (PHQ-4, p = 0.0038), and diminished physical activity (DASI, p = 0.002). At the 3-month mark, those with greater deprivation showed a higher frequency of referrals to secondary care due to ongoing COVID-19 symptoms (p = 0.0438). However, clinical outcomes were not influenced by deprivation. Conclusions In a post-hospital COVID-19 population, socioeconomic deprivation was associated with impaired health status and secondary care episodes. Deprivation influences illness trajectory after COVID-19

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Cardiovascular outcomes of glucose lowering therapy in chronic kidney disease patients: a systematic review with meta-analysis

Chronic kidney disease (CKD) and cardiovascular disease share common risk factors such as hypertension, diabetes mellitus and dyslipidemia. Patients with CKD carry a high burden of cardiovascular disease and may be excluded from clinical trials on the basis of safety. There are an increasing number of clinical trials which predefine sub-group analysis for CKD. This systematic review with fixed-effect meta-analysis investigates glucose lowering therapy and cardiovascular outcomes in relation to CKD. We included randomized controlled trials (RCT) of glucose lowering treatments performed in adults (aged ≥ 18 years), humans, with no restriction on date, and English-language restriction in patients with pre-existing CKD regardless of diabetes status. Embase &amp; Ovid Medline databases were searched up to April 2021. Risk of bias was assessed according to Revised Cochrane risk-of-bias tool. We included 7 trials involving a total of 48,801 participants. There were 4 sodium-glucose cotransporter-2 inhibitors (SGLT2i), 2 glucagon-like peptide-1 receptor (GLP-1R) agonists and 1 Dipeptidyl-peptidase 4 (DPP4) inhibitor identified. SGLT2i (relative risk (RR) = 0.90, 95% confidence interval (CI) [0.79–1.02]) and GLP-1R agonists (RR = 0.83, 95% CI [0.72–0.96]) were associated with a reduction in cardiovascular death. SGLT2i (RR = 0.69, 95% CI [0.63–0.75]) are also associated with a reduction in hospitalization for heart failure. In summary, this meta-analysis of large, RCTs of glucose lowering therapies has demonstrated that treatment with SGLT2i or GLP-1R agonists may improve 3 point-MACE and cardiovascular outcomes in patients with chronic renal failure compared with placebo. This systematic review was registered with the PROSPERO network (registration number: CRD42021268563) and follows the PRISMA guidelines on systematic reviews and metanalysis