Adequacy of Cancer Screening in Adult Women with Congenital Heart Disease

Adults with congenital heart disease (ACHD) face noncardiac healthcare challenges as the population ages. We assessed whether women with ACHD have comparable cancer screening rates to non-ACHD women in a cardiac practice and to the general population. We performed a retrospective review of 175 adult women seen in a cardiac care center in 2009–2011. Data on Pap tests, mammography, and colonoscopies, were collected through electronic medical records and primary care provider records. Adequate documentation was available for 100 individuals with ACHD and 40 comparator cardiac patients. The adequacy of screening was determined using guidelines set forth by the American Cancer Society in 2010. Compared with the national average, ACHD patients had significantly lower rates of Pap tests (60% versus 83%, P < 0.001) and mammography (48% versus 72%, P < 0.001). Compared with non-ACHD women in the same practice, ACHD patients had consistently lower rates of mammography (48% versus 81%, P = 0.02) and colonoscopies (54% versus 82%, P = 0.23). As the population of ACHD individuals ages, attention to cancer screening becomes increasingly important but may be overlooked in this population. Primary care physicians and cardiologists should collaborate to ensure appropriate cancer screening for this growing population

Elimination of Transcoarctation Pressure Gradients Has No Impact on Left Ventricular Function or Aortic Shear Stress After Intervention in Patients With Mild Coarctation

Objectives: This study sought to investigate the impact of transcatheter intervention on left ventricular function and aortic hemodynamics in patients with mild coarctation of the aorta (COA). Background: The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak transcoarctation pressure gradient  < 20 mm Hg). Debate rages regarding the risk/benefit ratio of intervention versus long-term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function, and peripheral perfusion. Methods: We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (before and after intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the left ventricle in 34 patients with mild COA to make these correlations. Results: Despite dramatic reduction in the transcoarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced by 75% and 47.3%, respectively), there was only modest effect on aortic flow and no significant impact on aortic shear stress (the maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve left ventricular function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%, respectively). Conclusions: Transcatheter intervention that successfully relieves mild COA pressure gradients does not translate to decreased myocardial strain. The effects of the intervention were determined to the greatest degree by ventricular–vascular coupling hemodynamics and provide a novel valuable mechanism to evaluate patients with COA that may influence clinical practice. Key Words: aortic hemodynamics, left ventricle function, mild coarctation, peak-to-peak pressure gradient, transcatheter interventionNational Institute of Mental Health (U.S.) (R01 GM 49039)American Heart Association (Postdoctoral Fellowship 16POST26420039

Diversity of resistance mechanisms in carbapenem-resistant Enterobacteriaceae at a health care system in Northern California, from 2013 to 2016

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) blaKPC, 20.8% (5/24) blaNDM, 20.8% (5/24) blaSME, 8.3% (2/24) blaIMP, and 4.2% (1/24) blaVIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing blaKPC were 100% susceptible to ceftazidime–avibactam, meropenem–vaborbactam, and imipenem–relebactam; blaOXA-48 like–positive isolates were 100% susceptible to ceftazidime–avibactam; and metallo β-lactamase–positive isolates were nearly all nonsusceptible to above antibiotics. Carbapenemase gene-negative CRE were 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) susceptible to ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, and ceftolozane–tazobactam, respectively. None of the CRE strains were identical by whole genome sequencing. At this health system, CRE were mediated by diverse mechanisms with predictable susceptibility to newer β-lactamase inhibitors

Hypoplastic Left Heart Syndrome Current Considerations and Expectations

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

This article analyzes the "Global Burden of Disease Study 2010" and examines the study's implications for neglected tropical diseases

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Collaborative Intelligence to catalyze the digital transformation of healthcare

Abstract Collaborative intelligence reflects the promise and limits of leveraging artificial intelligence (AI) technologies in clinical care. It involves the use of advanced analytics and computing power with an understanding that humans bear responsibility for the accuracy, completeness and any inherent bias found in the training data. Clinicians benefit from using this technology to address increased complexity and information overload, support continuous care and optimized resource allocation, and to enact efforts to eradicate disparities in health care access and quality. This requires active clinician engagement with the technology, a general understanding of how the machine produced its insight, the limitations of the algorithms, and the need to screen datasets for bias. Importantly, by interacting, the clinician and the analytics will create trust based on the clinician’s critical thinking skills leveraged to discern value of machine outputs within clinical context. Utilization of collaborative intelligence should be staged with the level of understanding and evidence. It is particularly well suited to low-complexity non-urgent care and to identifying individuals at rising risk within a population. Clinician involvement in algorithm development and the amassing of evidence to support safety and efficacy will propel adoption. Utilization of collaborative intelligence represents the natural progression of health care innovation, and if thoughtfully constructed and equitably deployed, holds the promise to decrease clinician burden and improve access to care

Adequacy of Cancer Screening in Adult Women with Congenital Heart Disease

Adults with congenital heart disease (ACHD) face noncardiac healthcare challenges as the population ages. We assessed whether women with ACHD have comparable cancer screening rates to non-ACHD women in a cardiac practice and to the general population. We performed a retrospective review of 175 adult women seen in a cardiac care center in 2009–2011. Data on Pap tests, mammography, and colonoscopies, were collected through electronic medical records and primary care provider records. Adequate documentation was available for 100 individuals with ACHD and 40 comparator cardiac patients. The adequacy of screening was determined using guidelines set forth by the American Cancer Society in 2010. Compared with the national average, ACHD patients had significantly lower rates of Pap tests (60% versus 83%, P < 0.001) and mammography (48% versus 72%, P < 0.001). Compared with non-ACHD women in the same practice, ACHD patients had consistently lower rates of mammography (48% versus 81%, P = 0.02) and colonoscopies (54% versus 82%, P = 0.23). As the population of ACHD individuals ages, attention to cancer screening becomes increasingly important but may be overlooked in this population. Primary care physicians and cardiologists should collaborate to ensure appropriate cancer screening for this growing population