Citations

Abstract OBJECTIVES This study describes coronary revascularization strategies used by sex and age in the USA. METHODS A sex-stratified cohort study from the National Inpatient Sample from the Agency for Healthcare Research and Quality (USA) including patients admitted for coronary revascularization with primary or secondary diagnoses of chronic coronary syndrome or non-ST elevation myocardial infarction who underwent ≥3-vessel coronary artery bypass grafting or percutaneous coronary intervention from January 2019 to December 2020. The primary outcome was the use rate of coronary artery bypass grafting or multivessel percutaneous coronary intervention. Prespecified subgroups included age and non-ST elevation myocardial infarction. RESULTS Among 121 150 patients (21.7% women), there were no sex differences in age (women: 66.6 [66.5–66.7], men: 67.6 [67.5–67.7], standardized mean difference: 0.1) or non-ST elevation myocardial infarction incidence (women: 37.4%, men: 45.7%, standardized mean difference: 0.17). The majority of women (74.2%) and men (84.9%) underwent bypass grafting, which was unaffected by age, race or non-ST elevation myocardial infarction. Women were less likely to undergo bypass grafting than percutaneous intervention (adjusted odds ratio 0.49, 95% confidence interval 0.44–0.54; P < 0.001) and a disparity most pronounced in patients >80 years old (adjusted odds ratio 0.31, 95% confidence interval 0.22–0.45; P < 0.001). CONCLUSIONS Most patients with multivessel coronary artery disease needing revascularization undergo bypass grafting, irrespective of sex, age or clinical presentation. The sex disparity in the use of bypass grafting is mostly seen among patients >80 years old.

Abstract The geroscience hypothesis suggests that addressing the fundamental mechanisms driving aging biology will prevent or mitigate the onset of multiple chronic diseases, for which the largest risk factor is advanced age. Research that investigates the root causes of aging is therefore of critical importance given the rising healthcare burden attributable to age-related diseases. The third annual Midwest Aging Consortium symposium was convened as a showcase of such research performed by investigators from institutions across the Midwestern United States. This report summarizes the work presented during a virtual conference across topics in aging biology, including immune function in the lung—particularly timely given the Corona Virus Immune Disease-2019 pandemic—along with the role of metabolism and nutrient-regulated pathways in cellular function with age, the influence of senescence on stem cell function and inflammation, and our evolving understanding of the mechanisms underlying observation of sex dimorphism in aging-related outcomes. The symposium focused on early-stage and emerging investigators, while including keynote presentations from leaders in the biology of aging field, highlighting the diversity and strength of aging research in the Midwest.

AbstractBackgroundInaccurate manual organ delineation is one of the high‐risk failure modes in radiation treatment. Numerous automated contour quality assurance (QA) systems have been developed to assess contour acceptability; however, manual inspection of flagged cases is a time‐consuming and challenging process, and can lead to users overlooking the exact error location.PurposeOur aim is to develop and validate a contour QA system that can effectively detect and visualize subregional contour errors, both qualitatively and quantitatively.Methods/MaterialsA novel contour subregion error detection (CSED) system was developed using subregional surface distance discrepancies between manual and deep learning auto‐segmentation (DLAS) contours. A validation study was conducted using a head and neck public dataset containing 339 cases and evaluated according to knowledge‐based pass criteria derived from a clinical training dataset of 60 cases. A blind qualitative evaluation was conducted, comparing the results from the CSED system with manual labels. Subsequently, the CSED‐flagged cases were re‐examined by a radiation oncologist.ResultsThe CSED system could visualize the diverse types of subregional contour errors qualitatively and quantitatively. In the validation dataset, the CSED system resulted in true positive rates (TPR) of 0.814, 0.800, and 0.771; false positive rates (FPR) of 0.310, 0.267, and 0.298; and accuracies of 0.735, 0.759, and 0.730, for brainstem and left and right parotid contours, respectively. The CSED‐assisted manual review caught 13 brainstem, 19 left parotid, and 21 right parotid contour errors missed by conventional human review. The TPR/FPR/accuracy of the CSED‐assisted manual review improved to 0.836/0.253/0.784, 0.831/0.171/0.830, and 0.808/0.193/0.807 for each structure, respectively. Further, the time savings achieved through CSED‐assisted review improved by 75%, with the time for review taking 24.81 ± 12.84, 26.75 ± 10.41, and 28.71 ± 13.72 s for each structure, respectively.ConclusionsThe CSED system enables qualitative and quantitative detection, localization, and visualization of manual segmentation subregional errors utilizing DLAS contours as references. The use of this system has been shown to help reduce the risk of high‐risk failure modes resulting from inaccurate organ segmentation.

Purpose of review Early recurrence of atrial tachyarrhythmia (ERAT) during blanking period (BP) is not uncommon after catheter ablation of AF. Current guidelines and consensus statements recommend conservative treatment of ERAT. This review summarized recent studies, underlying mechanism and clinical managements of ERAT, and proposed a reconsideration of the definition and clinical significance of BP. Recent findings Recent studies have shown that the entity of ERAT in the very early phase of BP (i.e., first 4 weeks of the 3-month period) is different from those ERATs occurring late which is strongly associated with the late recurrence of atrial tachyarrhythmia. The optimal BP duration suggested by clinical observation ranges from 21 to 58 days. Using antiarrhythmic drugs and early electrical cardioversion are the effective management for ERAT, whereas re-ablation is a reasonable strategy although remains controversial. Summary The definition of BP with a shorter duration, that is, 1 month instead of 3 months post AF ablation, is supported by the observations of latest clinical studies. Recurrent atrial tachyarrhythmia beyond the 1-month time frame is associated with higher risk of late recurrence and may warrant repeat ablation. A revisit to the guideline recommendation on management of ERAT is needed to change clinical practice.

SummaryVenetoclax (VEN) is an FDA‐approved selective inhibitor of B‐cell leukaemia/lymphoma‐2 (BCL‐2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high‐risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating DDX41‐mutated (mDDX41) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of mDDX41 MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.