Diagnostic and prognostic significance of exercise-induced premature ventricular complexes in men and women: A four year follow-up

Two hundred eighty patients (197 men and 83 women) with normal rest electrocardiograms and no history of prior myocardial infarction were referred for evaluation of chest pain. It was found that exercise-induced premature ventricular complexes had a lower sensitivity, specificity, positive predictive value and negative predictive value in predicting significant coronary artery disease than exercise-induced ST segment depression greater than or equal to 1 mm. The incidence of exercise-induced premature ventricular complexes was not significantly different in patients with no significant coronary artery disease, single vessel disease or multivessel disease. The site of origin of exercise-induced premature ventricular complexes was not helpful in predicting the presence or severity of coronary artery disease. At a mean follow-up period of 47.1 months, exercise-induced premature ventricular complexes did not predict coronary events (cardiac death or nonfatal myocardial infarction) in men or women

Microevolution of Group A Streptococci In Vivo: Capturing Regulatory Networks Engaged in Sociomicrobiology, Niche Adaptation, and Hypervirulence

The onset of infection and the switch from primary to secondary niches are dramatic environmental changes that not only alter bacterial transcriptional programs, but also perturb their sociomicrobiology, often driving minor subpopulations with mutant phenotypes to prevail in specific niches. Having previously reported that M1T1 Streptococcus pyogenes become hypervirulent in mice due to selection of mutants in the covRS regulatory genes, we set out to dissect the impact of these mutations in vitro and in vivo from the impact of other adaptive events. Using a murine subcutaneous chamber model to sample the bacteria prior to selection or expansion of mutants, we compared gene expression dynamics of wild type (WT) and previously isolated animal-passaged (AP) covS mutant bacteria both in vitro and in vivo, and we found extensive transcriptional alterations of pathoadaptive and metabolic gene sets associated with invasion, immune evasion, tissue-dissemination, and metabolic reprogramming. In contrast to the virulence-associated differences between WT and AP bacteria, Phenotype Microarray analysis showed minor in vitro phenotypic differences between the two isogenic variants. Additionally, our results reflect that WT bacteria's rapid host-adaptive transcriptional reprogramming was not sufficient for their survival, and they were outnumbered by hypervirulent covS mutants with SpeB−/Sdahigh phenotype, which survived up to 14 days in mice chambers. Our findings demonstrate the engagement of unique regulatory modules in niche adaptation, implicate a critical role for bacterial genetic heterogeneity that surpasses transcriptional in vivo adaptation, and portray the dynamics underlying the selection of hypervirulent covS mutants over their parental WT cells

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

This document was written with the intent to be a complete reference at the time of publication on the topic of managing hypertension in the elderly. This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

This document was written with the intent to be a complete reference at the time of publication on the topic of managing hypertension in the elderly. This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community

Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure: The Ancillary Digitalis Investigation Group Trial

About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study has not been previously published

Hospitalizations Due to Unstable Angina Pectoris in Diastolic and Systolic Heart Failure

Patients with diastolic heart failure (HF) i.e. clinical HF with normal or near normal left ventricular ejection fraction (LVEF) may experience unstable angina pectoris (UAP) due to epicardial atherosclerotic coronary artery disease (CAD) and/or to subendocardial ischemia, even in the absence of CAD. However, the risk of UAP among ambulatory diastolic HF patients has not been well studied. We examined incident hospitalizations due to UAP among 916 diastolic HF (LVEF >45%) patients without significant valvular heart disease and 6800 systolic HF (LVEF ≤45%) patients in the Digitalis Investigation Group trial. During a 38-month median follow-up, 12% (797/6,800) of systolic HF patients (incidence rate, 435/10,000 person-years) and 15% (138/916) of diastolic HF patients (incidence rate, 536/10,000 person-years) were hospitalized for UAP (adjusted hazard ratio for diastolic HF, 1.22; 95% confidence interval, 1.02–1.47; p=0.032). There was a graded increase in incident hospital admissions for UAP with increasing LVEF. Hospitalizations for UAP occurred in 11% (520/4,808; incidence rate, 407/10,000 person-years), 14% (355/2556; incidence rate, 496/10,000 person-years) and 17% (60/352; incidence rate, 613/10,000 person-years) of HF patients, respectively, with LVEF 55%. Compared with HF patients with LVEF 55% were respectively 1.17 (1.02–1.34; p=0.028) and 1.57 (1.20–2.07; p=0.026). In conclusion, in ambulatory chronic HF patients, higher LVEF was associated with increased risk of hospitalizations due to UAP. As in patients with systolic HF, those with diastolic HF should be routinely evaluated for myocardial ischemia and managed accordingly

Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study

Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn’s disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown

The Pediatric Cell Atlas:Defining the Growth Phase of Human Development at Single-Cell Resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families