Survival of liver transplant recipients with hemochromatosis in the United States

BACKGROUND AND AIMS: Earlier studies have suggested that patients with hemochromatosis have poor post-transplantation survival. We aimed to compare patients with hemochromatosis to those with other causes of liver disease with regard to post-transplantation survival. METHODS: We compared the post-transplant survival of patients with and without hemochromatosis using data provided by the United Network for Organ Sharing on 50,306 adult, cadaveric liver transplantations performed in the United States between January 1, 1990, and July 18, 2006. RESULTS: During 1990-1996, the post-transplantation survival of patients with hemochromatosis (n = 177) at 1 year (79.1%), 3 years (71.8%), and 5 years (64.6%) was lower than the average 1-year (86.4%), 3-year (79.5%), and 5-year (73.8%) survival of all other transplant recipients (hazard ratio for death, 1.38; 95% confidence interval [CI], 1.12-1.71). In contrast, during 1997-2006, patients with hemochromatosis (n = 217) had excellent 1-year (86.1%), 3-year (80.8%), and 5-year (77.3%) post-transplantation survival, which was not different from the 1-year (88.4%), 3-year (80.3%), and 5-year (74.0%) post-transplantation survival of all other transplant recipients (hazard ratio for death, 0.89; 95% CI, 0.65-1.22). Adjustment for donor and recipient characteristics did not substantially change these results. Compared with recipients without hemochromatosis, those with hemochromatosis were more likely to die of cardiovascular diseases and less likely to die as a result of graft failure. CONCLUSIONS: The post-transplantation survival of patients with hemochromatosis, which was previously reported to be poor, has been excellent in the United States during the past 10 years.     

Abdominal obesity and body mass index as risk factors for Barrett's esophagus

BACKGROUND: Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but little is known about its associations with body mass index (BMI) or abdominal obesity. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. Persons with a new diagnosis of Barrett's esophagus (cases) were matched to subjects with gastroesophageal reflux disease (GERD) without Barrett's esophagus and to population controls. Subjects completed questionnaires and an anthropometric examination. RESULTS: We interviewed 320 cases, 316 patients with GERD, and 317 controls. There was a general association between Barrett's esophagus and a larger abdominal circumference (independent of BMI) compared with population controls (odds ratio, 2.24; 95% confidence interval, 1.21-4.15; circumference, >80 cm vs <80 cm). There was a possible risk plateau, with increased risk evident only at circumferences >80 cm and no significant trend for further increases in circumference. There was a trend for association compared with patients with GERD (test for trend, P = .03). There was no association between Barrett's esophagus and BMI. Abdominal circumference was associated with GERD symptom severity (odds ratio, 1.86; 95% confidence interval, 1.03-3.38; risk of severe weekly GERD, per 10-cm circumference); adjustment for GERD partially attenuated the association between Barrett's esophagus and circumference. CONCLUSIONS: Waist circumference, but not BMI, had some modest independent associations with the risk of Barrett's esophagus. The findings provide partial support for the hypothesis that abdominal obesity contributes to GERD, which may in turn increase the risk of Barrett's esophagus.     

A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5

BACKGROUND & AIMS: A genome-wide association scan of nonsynonymous DNA polymorphisms identified association of a threonine-to-alanine substitution (T300A) in the autophagy-related 16-like gene ATG16L1 with Crohn's disease. We investigated this association in independent U.K. cohorts of Crohn's disease and ulcerative colitis. METHODS: The T300A variant (rs2241880) was genotyped in an independent sample of 727 Crohn's disease and 877 ulcerative colitis cases, and in 579 controls. We then performed an extension analysis combining these data with the U.K. data from the initial study to give a total of 1236 U.K. Crohn's disease cases and 1235 controls to estimate disease risk and test for interaction with the CARD15 and IBD5 risk loci and for association with disease subtypes. RESULTS: The association of T300A was replicated in the independent sample of 727 Crohn's disease cases (P = .001), and was strongly associated in the extended analysis of 1236 Crohn's cases (P = 2.4 x 10(-6)). The 300A/A genotype conferred a 1.65-fold risk of Crohn's disease, with a 2.2-fold risk of ileal disease. Analysis of the interaction of ATG16L1 with CARD15 and IBD5 indicated that all 3 loci contribute independently to disease risk. Homozygosity for the risk allele at all 3 loci conferred a combined risk of 20.4 (95% confidence interval: 8.71, 47.7) for Crohn's disease. The ATG16L1 risk genotype showed a modest but significant association with ulcerative colitis (P = .026). CONCLUSIONS: The association of ATG16L1 with Crohn's disease and possibly with ulcerative colitis supports a role for autophagy in the pathogenesis of inflammatory bowel disease.     

Tissue Doppler imaging a new prognosticator for cardiovascular diseases

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is > or =15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score.     

Perioperative management of patients with coronary stents

Perioperative coronary stent thrombosis is a catastrophic complication that can occur in patients receiving both bare-metal and drug-eluting stents. Noncardiac surgery appears to increase the risk that recently-placed stents thrombose, especially when surgery is performed early after stenting, and particularly if dual antiplatelet therapy is discontinued. We reviewed the existing data about the frequency of stent thrombosis after noncardiac surgery and explored the impact of delay from surgery and discontinuation of antiplatelet therapy. We also reviewed the data about the impact of preoperative revascularization in patients known to require noncardiac surgery. Based on these published data, we offer recommendations that can be used to guide the treatment of patients who require noncardiac surgery after having received a stent.