Citations

Background There is wide variability in cardiac rehabilitation (CR) dose (ie, number of sessions) delivered, and no evidence‐based recommendations regarding what dose to prescribe. We aimed to test what CR dose impacts major adverse cardiovascular events (MACEs). Methods and Results This is an historical cohort study of all patients who had coronary artery disease and who initiated supervised CR between 2002 and 2012 from a single major CR center. CR dose was defined as number of visits including exercise and patient education. Follow‐up was performed using record linkage from the Rochester Epidemiology Project. MACEs included acute myocardial infarction, unstable angina, ventricular arrhythmias, stroke, revascularization, or all‐cause mortality. Dose was analyzed in several ways, including tertiles, categories, and as a continuous variable. Cox models were adjusted for factors associated with dose and MACE. The cohort consisted of 2345 patients, who attended a mean of 12.5±11.1 of 36 prescribed sessions. After a mean follow‐up of 6 years, 695 (29.65%) patients had a MACE, including 231 who died. CR dose was inversely associated with MACE (hazard ratio, 0.66 [95% CI]; 0.55–0.91) in those completing ≥20 sessions, when compared with those not exposed to formal exercise sessions (≤1 session; log‐rank P =0.007). We did not find evidence of nonlinearity ( P ≥0.050), suggesting no minimal threshold nor ceiling. Each additional session was associated with a lower rate of MACE (fully adjusted hazard ratio, 0.98 [95% CI, 0.97–0.99]). Greater session frequency was also associated with lower MACE risk (fully adjusted hazard ratio, 0.74 [95% CI, 0.58–0.94]). Conclusions CR reduces MACEs, but the benefit appears to be linear, with greater risk reduction with higher doses, and no upper threshold.

Abstract The TDP-43 type C pathological form of frontotemporal lobar degeneration is characterized by the presence of immunoreactive TDP-43 short and long dystrophic neurites, neuronal cytoplasmic inclusions, neuronal loss and gliosis and the absence of neuronal intranuclear inclusions. Frontotemporal lobar degeneration-TDP-type C cases are commonly associated with the semantic variant of primary progressive aphasia or behavioural variant frontotemporal dementia. Here, we provide detailed characterization of regional distributions of pathological TDP-43 and neuronal loss and gliosis in cortical and subcortical regions in 10 TDP-type C cases and investigate the relationship between inclusions and neuronal loss and gliosis. Specimens were obtained from the first 10 TDP-type C cases accessioned from the Northwestern Alzheimer’s Disease Research Center (semantic variant of primary progressive aphasia, n = 7; behavioural variant frontotemporal dementia, n = 3). A total of 42 cortical (majority bilateral) and subcortical regions were immunostained with a phosphorylated TDP-43 antibody and/or stained with haematoxylin–eosin. Regions were evaluated for atrophy, and for long dystrophic neurites, short dystrophic neurites, neuronal cytoplasmic inclusions, and neuronal loss and gliosis using a semiquantitative 5-point scale. We calculated a ‘neuron-to-inclusion’ score (TDP-type C mean score – neuronal loss and gliosis mean score) for each region per case to assess the relationship between TDP-type C inclusions and neuronal loss and gliosis. Primary progressive aphasia cases demonstrated leftward asymmetry of cortical atrophy consistent with the aphasic phenotype. We also observed abundant inclusions and neurodegeneration in both cortical and subcortical regions, with certain subcortical regions emerging as particularly vulnerable to dystrophic neurites (e.g. amygdala, caudate and putamen). Interestingly, linear mixed models showed that regions with lowest TDP-type C pathology had high neuronal dropout, and conversely, regions with abundant pathology displayed relatively preserved neuronal densities (P < 0.05). This inverse relationship between the extent of TDP-positive inclusions and neuronal loss may reflect a process whereby inclusions disappear as their associated neurons are lost. Together, these findings offer insight into the putative substrates of neurodegeneration in unique dementia syndromes.

The aim of this study was to identify the optimal echocardiographic measurement of aortic regurgitation (AR) in continuous flow left ventricular assist devices (LVAD) and determine risk factors and clinical implications of de novo AR. Echocardiographic images from consecutive patients who underwent LVAD implantation from February 2007 to March 2017 were reviewed. Severity of de novo AR was determined by vena contracta (VC). Preimplant clinical characteristics, LVAD settings at discharge, and outcomes including heart failure hospitalizations, all-cause mortality, and ventricular arrhythmias of patients with greater than or equal to moderate de novo AR were compared with those with mild or no AR. Among 219 patients, greater than or equal to moderate de novo AR occurred in 65 (29.7%). Left ventricular assist devices support duration was longer with greater than or equal to moderate AR than no or mild AR. In multivariable analysis, preimplant trivial AR and persistent aortic valve (AV) closure were independently associated with de novo AR. By time-varying covariate analysis, survival and freedom from cardiovascular events in greater than or equal to moderate AR were significantly worse (hazard ratio [HR] = 3.947, p < 0.001 and HR = 4.666, p < 0.001). In conclusion, de novo greater than or equal to moderate AR measured by VC increases risk of adverse events. Longer LVAD support duration, preimplant trivial AR, and a closed AV are associated with occurrence of greater than or equal to moderate de novo AR.

Objective Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF), but large-scale studies are lacking. We aimed to investigate the incidence, risk factors and outcomes of incident GD-related HF. Methods Patients with GD (2009–2019) were retrospectively included. HF with reduced ejection fraction (HFrEF) was defined by left ventricular ejection fraction <50% and Framingham criteria, while HF with preserved ejection fraction (HFpEF) was defined according to the HFA-PEFF criteria. HF due to ischaemia, valve disorder or other structural heart disease was excluded. Proportional hazards regression was used to analyse risk factors and outcomes. Results Of 1371 patients with GD, HF occurred in 74 (5.4%) patients (31 (2.3%) HFrEF; 43 (3.1%) HFpEF). In HFrEF, atrial fibrillation (AF) (HR 10.5 (3.0–37.3), p<0.001) and thyrotropin receptor antibody (TRAb) level (HR 1.05 (1.01–1.09) per unit, p=0.007) were independent risk factors. In HFpEF, the independent risk factors were chronic obstructive pulmonary disease (HR 7.2 (3.5–14.6), p<0.001), older age (HR 1.5 (1.2–2.0) per 10 years, p=0.001), overt hyperthyroidism (HR 6.4 (1.5–27.1), p=0.01), higher body mass index (BMI) (HR 1.07 (1.03–1.10) per unit, p=0.001) and hypertension (HR 3.1 (1.3–7.2), p=0.008). The risk of cardiovascular hospitalisations was higher in both HFrEF (HR 10.3 (5.5–19.4), p<0.001) and HFpEF (HR 6.7 (3.7–12.2), p<0.001). However, only HFrEF was associated with an increased risk of all-cause mortality (HR 5.17 (1.3–19.9), p=0.02) and ventricular tachycardia/fibrillation (HR 64.3 (15.9–259.7), p<0.001). Conclusion De novo HF occurs in 5.4% of patients with GD and is associated with increased risk of cardiovascular hospitalisations and mortality. Risk factors include AF, higher TRAb, higher BMI and overt hyperthyroidism.

Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. Design: Retrospective study. Setting: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. Patients: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. Interventions: None. Measurements and Main Results: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25–14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16–25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2–7.7 d) and 4 days (1.9–7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. Conclusions: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Abstract Background : Non‐motor symptoms are well established phenotypic components of adult‐onset idiopathic, isolated, focal cervical dystonia (AOIFCD). However, improved understanding of their clinical heterogeneity is needed to better target therapeutic intervention. Here, we examine non‐motor phenotypic features to identify possible AOIFCD subgroups. Methods : Participants diagnosed with AOIFCD were recruited via specialist neurology clinics (dystonia wales: n = 114, dystonia coalition: n = 183). Non‐motor assessment included psychiatric symptoms, pain, sleep disturbance, and quality of life, assessed using self‐completed questionnaires or face‐to‐face assessment. Both cohorts were analyzed independently using Cluster, and Bayesian multiple mixed model phenotype analyses to investigate the relationship between non‐motor symptoms and determine evidence of phenotypic subgroups. Results : Independent cluster analysis of the two cohorts suggests two predominant phenotypic subgroups, one consisting of approximately a third of participants in both cohorts, experiencing increased levels of depression, anxiety, sleep impairment, and pain catastrophizing, as well as, decreased quality of life. The Bayesian approach reinforced this with the primary axis, which explained the majority of the variance, in each cohort being associated with psychiatric symptomology, and also sleep impairment and pain catastrophizing in the Dystonia Wales cohort. Conclusions : Non‐motor symptoms accompanying AOIFCD parse into two predominant phenotypic sub‐groups, with differences in psychiatric symptoms, pain catastrophizing, sleep quality, and quality of life. Improved understanding of these symptom groups will enable better targeted pathophysiological investigation and future therapeutic intervention.