Faculty Bibliography

Purpose of Review: Diagnosis of pediatric heart transplant rejection has historically relied on endomyocardial biopsy and clinical assessment. This review will describe novel techniques that may aid and refine diagnosis of rejection. Recent Findings: Donor-derived cell-free DNA and gene expression profiling assays provide diagnostics of rejection that are less invasive than surveillance endomyocardial biopsy. Imaging with echocardiography, cardiac magnetic resonance, and cardiac computed tomography are common for pediatric cardiology patients, and their role in detecting and monitoring rejection of heart transplants continues to be modified and expanded. Summary: Novel diagnostic tools have the potential to lead to less invasive and more precise diagnosis of transplant rejection, ideally improving the long-term care of pediatric heart transplant recipients.

Lung transplantation has become an established therapy for end-stage lung diseases. Early postoperative complications can impact immediate, mid-term, and long-term outcomes. Appropriate management, prevention, and early detection of these early postoperative complications can improve the overall transplant course. In this review, we highlight the incidence, detection, and management of these early postoperative complications in lung transplant recipients.

BACKGROUND:Interest in nephrology careers is declining, possibly due to perceptions of the field and/or training aspects. Understanding practices of medical schools successfully instilling nephrology interest could inform efforts to attract leading candidates to the specialty. METHODS:The American Society of Nephrology Workforce Committee's Best Practices Project was one of several initiatives to increase nephrology career interest. Board-certified nephrologists graduating medical school between 2002 and 2009 were identified in the American Medical Association Masterfile and their medical schools ranked by production. Renal educators from the top 10 producing institutions participated in directed focus groups inquiring about key factors in creating nephrology career interest, including aspects of their renal courses, clinical rotations, research activities, and faculty interactions. Thematic content analysis of the transcripts (with inductive reasoning implementing grounded theory) was performed to identify factors contributing to their programs' success. RESULTS:The 10 schools identified were geographically representative, with similar proportions of graduates choosing internal medicine (mean 26%) as the national graduating class (26% in the 2017 residency Match). Eighteen educators from 9 of these 10 institutions participated. Four major themes were identified contributing to these schools' success: (1) nephrology faculty interaction with medical students; (2) clinical exposure to nephrology and clinical relevance of renal pathophysiology materials; (3) use of novel educational modalities; and (4) exposure, in particular early exposure, to the breadth of nephrology practice. CONCLUSION:Early and consistent exposure to a range of clinical nephrology experiences and nephrology faculty contact with medical students are important to help generate interest in the specialty.

BACKGROUND: Individuals with chronic kidney disease (CKD) have high rates of myocardial infarction (MI), but whether the nature of coronary lesions susceptible to plaque rupture is altered and whether the high rate of MI is related to a greater burden of atherosclerotic lesions in individuals with CKD is uncertain. METHODS: We used quantitative coronary angiography to assess atherosclerotic plaque location and characteristics at baseline and at the time of MI in 62 patients with and without CKD. Univariate and multivariable conditional logistic regression models were used to assess whether the association between pre-MI angiographic findings and MI differs in individuals with and without CKD. RESULTS: The risk of MI rose as the distance from the coronary ostium decreased both in patients with CKD (odds ratio per 10 mm 0.92 [95 % CI 0.87-0.99]) and in those without CKD (odds ratio 0.83 [95 % CI 0.75-0.93]). Although tighter degrees of coronary stenosis were associated with increased risks of MI in patients with and without CKD, the majority of MIs (70.9 % in patients with CKD and 89.5 % in those without CKD) occurred in segments with <50 % diameter stenosis at baseline. CONCLUSIONS: The characteristics of lesions progressing to MI are similar in individuals with and without CKD and the majority of events occur in areas with <50 % stenosis at baseline. Given the high burden of non-stenotic lesions in patients with CKD, an interventional strategy aimed solely at sites with high-grade stenosis is unlikely to markedly reduce the risk of MI in patients with CKD.

BACKGROUND:Patients with chronic kidney disease have been under-represented in randomized trials of drug-eluting stents relative to bare-metal stents and are at high risk of mortality. STUDY DESIGN/METHODS:Cohort study with propensity score matching. SETTINGS & PARTICIPANTS/METHODS:All adults with chronic kidney disease and severely decreased glomerular filtration rate (GFR; serum creatinine >2.0 mg/dL or dialysis dependence) undergoing percutaneous coronary intervention with stent placement between April 1, 2003, and September 30, 2005, at all acute-care nonfederal hospitals in Massachusetts. PREDICTOR/METHODS:Patients were classified as drug-eluting stent-treated if all stents were drug eluting and bare-metal stent-treated if all stents were bare metal. Patients treated with both types of stents were excluded from the primary analysis. OUTCOMES & MEASUREMENTS/METHODS:2-year crude mortality risk differences (drug-eluting - bare-metal stents) were determined from vital statistics records, and risk-adjusted mortality, myocardial infraction (MI), and revascularization differences were estimated using propensity score matching of patients with severely reduced GFR based on clinical and procedural information collected at the index admission. RESULTS:1,749 patients with severely reduced GFR (24% dialysis dependent) were treated with drug-eluting (n = 1,256) or bare-metal stents (n = 493) during the study. Overall 2-year mortality was 32.8% (unadjusted drug-eluting stent vs bare-metal stent; 30.1% vs 39.8%; P < 0.001). After propensity score matching 431 patients with a drug-eluting stent to 431 patients with a bare-metal stent, 2-year risk-adjusted mortality, MI, and target-vessel revascularization rates were 39.4% versus 37.4% (risk difference, 2.1%; 95% CI, -4.3 to 8.5; P = 0.5), 16.0% versus 19.0% (risk difference, -3.0%; 95% CI, -8.2 to 2.1; P = 0.3), and 13.0% versus 17.6% (risk difference, -4.6%; 95% CI, -9.5 to 0.3; P = 0.06). LIMITATIONS/CONCLUSIONS:Observational design, ascertainment of serum creatinine level >2.0 mg/dL and dialysis dependence from case report forms. CONCLUSIONS:In patients with severely decreased GFR, treatment with drug-eluting stents was associated with a modest decrease in target-vessel revascularization not reaching statistical significance and was not associated with a difference in risk-adjusted rates of mortality or MI at 2 years compared with bare-metal stents.

BACKGROUND:Patients with diabetes mellitus (DM) are at high risk for restenosis, myocardial infarction, and cardiac mortality after coronary stenting, and the long-term safety of drug-eluting stents (DES) relative to bare-metal stents (BMS) in DM is uncertain. We report on a large consecutive series of patients with DM followed up for 3 years after DES and BMS from a regional contemporary US practice with mandatory reporting. METHODS AND RESULTS/RESULTS:All adults with DM undergoing percutaneous coronary intervention with stenting between April 1, 2003, and September 30, 2004, at all acute care nonfederal hospitals in Massachusetts were identified from a mandatory state database. According to index admission stent type, patients were classified as DES treated if all stents were drug eluting and as BMS treated if all stents were bare metal; patients treated with both types of stents were excluded from the primary analysis. Mortality rates were obtained from vital statistics records, and myocardial infarction and revascularization rates were obtained from the state database with complete 3 years of follow-up on the entire cohort. Risk-adjusted mortality, myocardial infarction, and revascularization differences (DES-BMS) were estimated with propensity-score matching based on clinical, procedural, hospital, and insurance information collected at the index admission. DM was present in 5051 patients (29% of the population) treated with DES or BMS during the study. Patients with DM were more likely to receive DES than BMS (66.1% versus 33.9%; P<0.001). The unadjusted cumulative incidence of mortality at 3 years was 14.4% in DES versus 22.2% in BMS (P<0.001). Based on propensity-score analysis of 1:1 matched DES versus BMS patients (1476 DES:1476 BMS), the risk-adjusted mortality, MI, and target vessel revascularization rates at 3 years were 17.5% versus 20.7% (risk difference, -3.2%; 95% confidence interval, -6.0 to -0.4; P=0.02), 13.8% versus 16.9% (-3.0%; 95% confidence interval, -5.6 to 0.5; P=0.02), and 18.4% versus 23.7% (-5.4%; confidence interval, -8.3 to -2.4; P<0.001), respectively. CONCLUSIONS:In a real-world diabetic patient population with mandatory reporting and follow-up, DES were associated with reduced mortality, myocardial infarction, and revascularization rates at long-term follow-up compared with BMS.

BACKGROUND:Studies comparing percutaneous coronary intervention (PCI) with drug-eluting and bare-metal coronary stents in acute myocardial infarction have been limited in size and duration. METHODS:We identified all adults undergoing PCI with stenting for acute myocardial infarction between April 1, 2003, and September 30, 2004, at any acute care, nonfederal hospital in Massachusetts with the use of a state-mandated database of PCI procedures. We performed propensity-score matching on three groups of patients: all patients with acute myocardial infarction, all those with acute myocardial infarction with ST-segment elevation, and all those with acute myocardial infarction without ST-segment elevation. Propensity-score analyses were based on clinical, procedural, hospital, and insurance information collected at the time of the index procedure. Differences in the risk of death between patients receiving drug-eluting stents and those receiving bare-metal stents were determined from vital-statistics records. RESULTS:A total of 7217 patients were treated for acute myocardial infarction (4016 with drug-eluting stents and 3201 with bare-metal stents). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for drug-eluting stents than for bare-metal stents among all patients with myocardial infarction (10.7% vs. 12.8%, P=0.02), among patients with myocardial infarction with ST-segment elevation (8.5% vs. 11.6%, P=0.008), and among patients with myocardial infarction without ST-segment elevation (12.8% vs. 15.6%, P=0.04). The 2-year, risk-adjusted rates of recurrent myocardial infarction were reduced in patients with myocardial infarction without ST-segment elevation who were treated with drug-eluting stents, and repeat revascularization rates were significantly reduced with the use of drug-eluting stents as compared with bare-metal stents in all groups. CONCLUSIONS:In patients presenting with acute myocardial infarction, treatment with drug-eluting stents is associated with decreased 2-year mortality rates and a reduction in the need for repeat revascularization procedures as compared with treatment with bare-metal stents.

AIMS/OBJECTIVE:Determine A1C, blood pressure (BP), and total cholesterol (TC) (Diabetes ABCs) control in a community-based endocrinology practice (CBEP) and compare levels to national averages. Additionally, determine patient factors associated with ABC control. METHODS:A retrospective chart audit of 395 consecutive patients seen for diabetes management was conducted for years 2000-2004 to examine levels of control of the ABCs. Multivariate models were used to determine patient factors associated with control. RESULTS:Significantly more patients met the goal of A1C <7% in the CBEP compared to national estimates (CBEP: 47.1% vs. NHANES 1999-2000: 37%, p=0.003). Similar patterns were observed for BP (CBEP: 53.2% vs. NHANES 1999-2000: 35.8%, p<0.0001), TC (CBEP: 82% vs. NHANES 1999-2000: 48.2%, p<0.0001), and all three ABCs (CBEP: 22%, vs. NHANES 1999-2000: 7.3%, p<0.0001). The proportion of patients meeting all three ABC goals in the CBEP increased significantly over time (p<0.0001). Multivariate models demonstrated that patients not needing insulin (p<0.0001), and taking fewer BP (p<0.0001), and cholesterol-lowering medications (p<0.02) were significantly more likely to have ABCs in control. CONCLUSIONS:Attainment of ABC goals is feasible in a CBEP and can be achieved at rates higher than national averages. Attention to factors that affect these goals is warranted.

Vessel wall matrix changes occur after injury, although this has not been well studied in the venous system. This study tested the hypothesis that the thrombus dictates the vein wall response and vein wall damage is directly related to the duration of thrombus contact. To determine the injury response over time, rats underwent inferior vena cava (IVC) ligation to produce a stasis thrombus, with harvest at various time points to 28 days (d). Significant vein wall matrix changes occurred with biomechanical injury (stiffness) peaking at 7-14 d, with concurrent early reduction in total collagen, an increase in early matrix metalloproteinase (MMP)-9 and late MMP-2, and concomitant increase in tumor necrosis factor (TNF)alpha, monocyte chemoattractant(MCP)-1 and tumor growth factor (TGF)beta (all P<0.05). To isolate the effect of the thrombus and its mechanism of genesis, rats underwent 7 d or limited stasis (24 hours), non-stasis thrombosis, or non-thrombotic IVC occlusion (Silicone plug). Vein wall stiffness was increased seven-fold, with a five-fold reduction in collagen, and 5.5- to seven-fold increase in TNFalpha, MCP-1, and TGFbeta with 7 d stasis as compared with controls (all P<0.05). By Picosirus red staining analysis, collagenolysis was significantly greater with 7 d stasis injury (P=0.01) but neither MMP-9 nor MMP-2 activity correlated with injury mechanism. In addition, vein wall cellular proliferation and uPA gene expression paralled the stasis thrombotic injury. Limited stasis, non-stasis thrombosis and non-thrombotic IVC occlusion showed a lesser inflammatory response. These data suggest both a static component and the thrombus directs vein wall injury via multiple mechanisms.

OBJECTIVE:Although the treatment for acute deep vein thrombosis (DVT) is uniform, the circumstances under which it develops vary widely and may impact outcomes. This study compared clinical features and outcomes in patients who developed a primary DVT associated with a defined risk to those without any proximate risk factor. METHODS:Consecutive patients with a primary DVT and no past venous thromboembolism history from 2000 to 2002 were abstracted for demographics, risk factors, DVT anatomical characteristics, treatment, and outcomes of death and new pulmonary embolism. Comparison between patients with a proximate risk event within 30 days of DVT (Inpt) and those presenting with DVT with no defined proximate event (Outpt) was done by univariable and multivariable statistics. A validated survey was mailed to all living patients to assess long-term sequela. RESULTS:A total of 293 patients with a mean age of 55 years and 49% men had confirmed DVT by objective means (92% duplex) with a mean follow-up of 25 +/- 21 months. Inpts were more likely to have recent surgery or blunt trauma, bilateral DVT, less use of low molecular weight heparin (LMWH), and new pulmonary emboli (all P <.05). Outpts with DVT were more likely to have a history of malignancy, tibial-popliteal DVT compared with iliofemoral DVT, higher use of LMWH, and coumadin. However, there was no difference in mortality. From the patient survey (21% response), Outpts were more likely than Inpts to develop later varicosities and have daily frustration related to their legs (P < .05), but no difference in edema or ulceration. Considering the entire group, independent factors associated with freedom from PE included ambulation (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.1-5.0; P = .04) while bilateral DVT (OR = .26; 95% CI = .09-.76; P = .013) or subcutaneous heparin (OR = 22; 95% CI = .05-.98; P = .047) were associated with greater risk. Independent factors associated with survival included ambulation (OR = 3.0; 95% CI = 1.3-7.2; P = .02), Coumadin use (OR = 2.7; 95% CI = 1.2-6.1; P = .015), and tibiopopliteal DVT (OR = 2.4; 95% = 1.1-5.5; P = .03), while malignancy (OR = 0.1; 95% CI = .05-.24; P < .01) and myocardial infarction (OR = 0.12; 95% CI = .01-.92; P = .04) were associated with lower survival. CONCLUSION/CONCLUSIONS:Patients who develop DVT related to a defined proximate risk event (Inpt) generally have more extensive DVT, an increased risk of PE, but less long-term functional morbidity and no difference in long-term mortality compared to those with no proximate risk.