Differences in prevalence, extent, severity, and prognosis of coronary artery disease among patients with and without diabetes undergoing coronary computed tomography angiography: results from 10,110 individuals from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes): an InteRnational Multicenter Registry

OBJECTIVE

We examined the prevalence, extent, severity, and prognosis of coronary artery disease (CAD) in individuals with and without diabetes (DM) who are similar in CAD risk factors.

RESEARCH DESIGN AND METHODS

We identified 23,643 consecutive individuals without known CAD undergoing coronary computed tomography angiography. A total of 3,370 DM individuals were propensity matched in a 1-to-2 fashion to 6,740 unique non-DM individuals. CAD was defined as none, nonobstructive (1–49% stenosis), or obstructive (≥50% stenosis). All-cause mortality was assessed by risk-adjusted Cox proportional hazards models.

RESULTS

At a 2.2-year follow-up, 108 (3.2%) and 115 (1.7%) deaths occurred among DM and non-DM individuals, respectively. Compared with non-DM individuals, DM individuals possessed higher rates of obstructive CAD (37 vs. 27%) and lower rates of having normal arteries (28 vs. 36%) (P < 0.0001). CAD extent was higher for DM versus non-DM individuals for obstructive one-vessel disease (19 vs. 14%), two-vessel disease (9 vs. 7%), and three-vessel disease (9 vs. 5%) (P < 0.0001 for comparison), with higher per-segment stenosis in the proximal and mid-segments of every coronary artery (P < 0.001 for all). Compared with non-DM individuals with no CAD, risk of mortality for DM individuals was higher for those with no CAD (hazard ratio 3.63 [95% CI 1.67–7.91]; P = 0.001), nonobstructive CAD (5.25 [2.56–10.8]; P < 0.001), one-vessel disease (6.39 [2.98–13.7]; P < 0.0001), two-vessel disease (12.33 [5.622–27.1]; P < 0.0001), and three-vessel disease (13.25 [6.15–28.6]; P < 0.0001).

CONCLUSIONS

Compared with matched non-DM individuals, DM individuals possess higher prevalence, extent, and severity of CAD. At comparable levels of CAD, DM individuals experience higher risk of mortality compared with non-DM individuals.Current American Diabetes Association guidelines endorse the widespread use of cardiovascular prevention measures for individuals with diabetes (DM) based upon an abundance of observational and population-based studies demonstrating excess cardiovascular risk and death attributable to diabetes (1). However, previous observational data examining the precise incremental risk of DM for future adverse coronary artery disease (CAD) events have demonstrated variability, and outcomes-based analyses of DM individuals generally have lacked information regarding CAD prevalence, extent, and severity (2–5).Coronary computed tomography angiography (CCTA) is a noninvasive imaging test that demonstrates high diagnostic performance for the detection and exclusion of CAD, with recent multicenter studies demonstrating a robust prognostic utility to CCTA CAD findings for the prediction of mortality and other major adverse cardiac events (6–9). CCTA studies to date have examined CAD findings and prognosis in DM individuals but have been limited to single centers in small patient cohorts (n = 140–313) (10,11). In addition, DM and non-DM individuals within these studies demonstrated important differences in age, sex, and CAD risk factors, thus precluding the precise influence of the DM state to CAD presence and risk.From a large international prospective multicenter observational cohort study of individuals undergoing CCTA, we thus sought to compare the prevalence, extent, severity, and prognosis of CAD for propensity-matched DM and non-DM individuals.     

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

The sentinel lymph node is the initial site of metastasis. Downregulation of antitumor immunity has a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T cells (Foxp3(+)) and dendritic cells (conventional: CD11c(+), mature: CD86(+)) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunological primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared with those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathological variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Antitumor immunity was downregulated in the positive sentinel lymph node with an increase in regulatory T cells compared with the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared with the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions.     

The crimson care collaborative: a student-faculty initiative to increase medical students' early exposure to primary care

The current shortage of primary care physicians (PCPs), particularly as more individuals obtain health insurance and seek primary care services, is a growing national concern. The Crimson Care Collaborative (CCC) is a joint student-faculty initiative in post-health-care-reform Massachusetts that was started with the explicit goal of attracting medical students to primary care careers. It fills a niche for student-run clinics, providing evening access to primary care services for patients without a PCP and urgent care services for patients of a Massachusetts General Hospital-affiliated internal medicine clinic, with the aim of decreasing emergency department use in both groups. Unlike other student-run clinics, CCC is integrated into the mainstream health care structure of an existing primary care clinic and, because of universal health insurance coverage in Massachusetts, can bill for its services. In addition to the clinical services offered, the student-run research team evaluates the quality of care and the patients' experiences at the clinic. This article describes the creation and development of CCC, including a brief overview of clinic operations, social services, research, laboratory services, student and patient education programs, and finance. In the wake of the Patient Protection and Affordable Care Act of 2010, CCC is an example of how students can aid the transition to universal health care in the United States and how medical schools can expose students early in their training to primary care and clinic operations.     

Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact

Autosomal dominant cerebellar ataxias (ADCAs), genetically classified into spinocerebellar ataxias (SCAs), are a highly heterogeneous group of neurodegenerative disorders. Recently, mutations in the fibroblast growth factor 14 gene (FGF14) have been reported to cause SCA27 subtype. To evaluate the frequency of FGF14 mutations in mainland of China, we performed molecular genetic analysis in 67 unrelated familial ataxia cases and 500 normal controls by denaturing high-performance liquid chromatography (DHPLC) and DNA direct sequencing. Interestingly, we found a pair of siblings carried the same heterozygous variation (c.-10delC) characterized by different clinical features, which is probably a novel insertion/deletion (I/D) polymorphism in the 5'UTR region of the exon 1b. It suggests that SCA27 is a rare subtype in China.     

The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP(3), and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system.     

Surveillance and screening practices of New England congenital cardiologists for patients after the Fontan operation

Introduction: Surveillance and management guidelines for Fontan patients are lacking due to the paucity of evidence in the literature of screening efficacy on outcome measures.
Methods: The Fontan Working Group within the New England Congenital Cardiology Association designed an electronic survey to assess surveillance practices for pa‐ tients with Fontan procedures among New England congenital cardiologists and to explore variability in screening low‐risk vs high‐risk Fontan patients across regional programs.
Results: Fifty‐six cardiologists representing 12 regional programs responded to the survey, comprising ~40% of the total New England congenital cardiac physicians. The majority of desired testing and consultation was available within 50 miles of the pa‐ tient's home institution with some limitations of cardiac catheterization and cardiac magnetic resonance imaging availability. Surveillance and screening were less fre‐ quent in low‐risk Fontan patients compared to high‐risk Fontan patients. Counseling practices were similar for both low‐risk and high‐risk Fontan patients. Aspirin mono‐ therapy was recommended by 82% of providers for low‐risk Fontan patients, while anticoagulation regimens were more varied for the high‐risk population. Practitioners with ≤15 years of experience were more likely to provide quality of life testing in both low‐risk and high‐risk Fontan patients. There were no other major differences in test‐ ing frequencies by years of practice, quaternary vs nonquaternary care facility, or the number of Fontan patients in a practice.
Conclusion: This survey provides insight into regional practices of screening and surveillance of Fontan patients. These data may be used to design future research studies and evidence‐based guidelines to streamline the approach to manage these complex patients.