Epidemiologic studies show an increased risk of non‐Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen‐stimulation in one disease leads to another. Here we assess shared genetic risk in genome‐wide‐association‐studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B‐cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta‐analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta‐analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS‐based analysis four NHL subtypes and three ADs revealed few weakly‐associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

SUMMARYA decade ago, observations suggested that post-transplant diabetes mellitus (PTDM) was linked to allograft loss and shorter patient survival. Increasing awareness, improvements in care, and changes in the immunosuppressive regimen may have modified this association. Single-center analysis of 1990 (age>18; transplantation date 1996-2012) primary kidney recipients (KTR). Patients with <12 months follow-up were excluded. Diabetes was diagnosed according to ADA criteria and characterized as follows: No diabetes, PTDM in the first post-transplant year not treated with glucose-lowering medications (GLM) at 12 months, PTDM in the first post-transplant year treated with GLM at 12 months, and pretransplant diabetes. Cox proportional hazards models were used to examine the relationship of PTDM with allograft and patient survival. Mean follow-up time was 6.8 years for allograft survival and 7.4 years for patient survival. PTDM treated with medication at year one was not associated with allograft survival (HR 1.28, 95% CI 0.97-1.69), but was significantly associated with overall mortality and death with functioning graft (DWFG) (HR overall: 1.81, 95% CI 1.36-2.39; HR DWFG: 1.59 95% CI 1.05-2.38). In this cohort, KTR with PTDM being treated with glucose-lowering medication at 12 months experienced significantly shorter overall survival and survival with functioning graft.

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ObjectiveWe sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin.MethodsIn a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within 6 months of doxorubicin completion) and 1 – 2 years after doxorubicin completion were quantified. At each follow-up visit, multivariable, propensity-adjusted linear regression models evaluated dexrazoxane’s effects on changes in left ventricular (LV) shortening fraction (SF), structure, strain and wall stress for subgroups divided by sex. Likelihood ratio tests assessed the interaction between sex and dexrazoxane in determining these changes.ResultsEarly after doxorubicin completion, males not treated with dexrazoxane (n = 15) developed increased cavity size and diminished circumferential strain; females (n = 8) developed diminished SF and strain indices, and increased cavity size and wall stress. With dexrazoxane, males (n = 33) demonstrated less deterioration in circumferential strain by 3.4% (95% CI 0.01 to 6.8), and females (n = 29) demonstrated less reduction in SF by 5.7% (95% CI 2.1 to 9.3), and had mitigation of increases in cavity size and wall stress. In interaction analyses, females had greater protection with dexrazoxane with regard to SF (p = 0.019) and cavity size in diastole (p = 0.002) and systole (p ≤ 0.001). These findings largely persisted 1 – 2 years after doxorubicin therapy.ConclusionsEarly, sustained alterations in LV structure and function occur in children with sarcoma after high-dose doxorubicin, with adverse changes and protective effects of dexrazoxane more pronounced in females as compared with males. Dexrazoxane may have sex-specific cardioprotective effects.

Background Transcatheter aortic valve replacement (TAVR) is increasingly offered for aortic stenosis (AS) treatment in patients with a history of cancer. The impact of frailty on outcomes in this specific patient population is not well described. Hypothesis Frailty is associated with mortality and poorer quality of life (QOL) outcomes in patients undergoing TAVR with a history of cancer. Methods This retrospective single center cohort study included AS patients who underwent TAVR from August 1, 2012 to May 15, 2020. Frailty was measured using serum albumin, hemoglobin, gait speed, functional dependence, and cognitive impairment. The primary outcome was a composite of all‐cause mortality and QOL at 1 year. A poor primary outcome was defined as either all‐cause mortality, Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ‐OS) score <45 or a KCCQ‐OS score decline of ≥10 points from baseline. Regression analysis was used to determine the impact of frailty on the primary outcome. Results The study population was stratified into active/recent cancer ( n = 107), remote cancer ( n = 85), and non‐cancer ( n = 448). Univariate analysis of each cohort showed that frailty was associated with the primary outcome only in the non‐cancer cohort ( p = .004). Multivariate analysis showed that cancer history was not associated with a poor primary outcome, whereas frailty was (1.7 odds ratio, 95% confidence interval [CI]: 1.1–2.8; p = .028). Conclusions Frailty is associated with mortality and poor QOL in the overall and non‐cancer cohorts. Further investigation is warranted to understand frailty's effect on the cancer population. Frailty should be heavily considered during TAVR evaluation.