The association between hepatitis C infection and survival after orthotopic liver transplantation

BACKGROUND & AIMS: The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV. METHODS: Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics. RESULTS: Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70). CONCLUSIONS: HCV infection significantly impairs patient and allograft survival after liver transplantation.     

Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.     

Implementing Adolescent Screening,Brief Intervention,and Referral to Treatment (SBIRT) Education in a Pediatric Residency Curriculum

Background: Screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care for adolescents as well as adults. In an effort to promote universal SBIRT, the Substance Abuse and Mental Health Services Administration awarded funding to residency programs to develop and implement SBIRT education and training. Our project focused on creating scientifically based, developmentally appropriate strategies and teaching materials for the adolescent age range. This paper describes curriculum development and implementation and presents evaluation data. Methods: Pediatric and child psychiatry residents were trained. The training consisted of 4 activities: (1) case-based teaching modules, (2) role-play of motivational interviewing and brief interventions, (3) mock interviews with trained adolescents, and (4) supervised “hands-on” screening and brief interventions. Main outcome measures included trainee satisfaction, and SBIRT knowledge, perceived self-efficacy, and self- and observer report of use of the SBIRT algorithm. Results: Among 150 total participants completing the SBIRT training modules, nearly all (92.3%) were satisfied/very satisfied with the training modules. Knowledge accuracy immediately post training was high, but declined significantly by the end of the first residency year, with little change across subsequent years of residency. Confidence ratings also declined over time. Use of the SBIRT algorithm during the Adolescent Medicine rotation was high according to trainee self- and faculty observer report. Conclusions: We found evidence of training satisfaction, increased confidence in talking to adolescents about substance use, and widespread use of recommended practices immediately following training. Use of a highly structured algorithm to guide practice, and simple, highly structured brief interventions was a successful training approach, as residents self-reported accurate use of the SBIRT algorithm immediately after training. Knowledge and self-confidence declined over time. It is possible that “booster” sessions and ongoing opportunities to review materials could help residents retain knowledge and skills.     

The prognostic importance of different definitions of worsening renal function in congestive heart failure

BACKGROUND: Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). METHODS AND RESULTS: The patient population was 49% female, aged 67 +/- 15 years. Twenty-three percent had a prior history of renal failure, 73% had known depressed ejection fraction, and 63% had known CHF. On admission to the hospital, 47% were receiving ACE inhibitors, 22% beta-blockers, 70% diuretics and 6% NAID's. 72% developed increased serum creatinine during the hospitalization, with 20% developing an increase of > or = 0.5 mg/dL. Worsening renal function predicted both in-hospital mortality and length of stay > 10 days. Even an increased creatinine of 0.1 mg/dL was associated with worse outcome. Sensitivity for death decreased from 92% to 65% as the threshold for increased creatinine was raised from 0.1 to 0.5 mg/dL, with specificity increasing from 28% to 81%. At a threshold of a 0.3 mg/dL increase, sensitivity was 81% and specificity was 62% for death and 64% and 65% for length of stay >10 days. Adding a requirement of final creatinine of > or = 1.5 mg/dL improved specificity. CONCLUSIONS: This analysis demonstrates that any detectable decrease in renal function is associated with increased mortality and prolonged hospital stay. This suggests that therapeutic interventions which improve renal function might be beneficial.     

NaCl-induced renal vasoconstriction in salt-sensitive African Americans: antipressor and hemodynamic effects of potassium bicarbonate

In 16 African Americans (blacks, 14 men, 2 women) with average admission mean arterial pressure (MAP, mm Hg) 99.9+/-3.5 (mean+/-SEM), we investigated whether NaCl-induced renal vasoconstriction attends salt sensitivity and, if so, whether supplemental KHCO3 ameliorates both conditions. Throughout a 3-week period under controlled metabolic conditions, all subjects ate diets containing 15 mmol NaCl and 30 mmol potassium (K+) (per 70 kg body wt [BW] per day). Throughout weeks 2 and 3, NaCl was loaded to 250 mmol/d; throughout week 3, dietary K+ was supplemented to 170 mmol/d (KHCO3). On the last day of each study week, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) using renal clearances of PAH and inulin. Ten subjects were salt sensitive (SS) (DeltaMAP >+5%) and 6 salt resistant (SR). In NaCl-loaded SS but not SR subjects, RBF (mL/min/1.73 m2) decreased from 920+/-75 to 828+/-46 (P<0.05); filtration fraction (FF, %) increased from 19. 4+/- to 21.4 (P<0.001); and renal vascular resistance (RVR) (10(3)xmm Hg/[mL/min]) increased from 101+/-8 to 131+/-10 (P<0.001). In all subjects combined, DeltaMAP varied inversely with DeltaRBF (r =-0.57, P=0.02) and directly with DeltaRVR (r = 0.65, P=0.006) and DeltaFF (r = 0.59, P=0.03), but not with MAP before NaCl loading. When supplemental KHCO3 abolished the pressor effect of NaCl in SS subjects, RBF was unaffected but GFR and FF decreased. The results show that in marginally K+-deficient blacks (1) NaCl-induced renal vasoconstrictive dysfunction attends salt sensitivity; (2) the dysfunction varies in extent directly with the NaCl-induced increase in blood pressure (BP); and (3) is complexly affected by supplemented KHCO3, GFR and FF decreasing but RBF not changing. In blacks, NaCl-induced renal vasoconstriction may be a pathogenetic event in salt sensitivity.     

Association between infections with CagA-positive or -negative strains of Helicobacter pylori and risk for gastric cancer in young adults. Research Group on Prevention of Gastric Carcinoma Among Young Adults

OBJECTIVE: We assessed the association between infection with CagA-positive and -negative Helicobacter pylori and the risk of gastric cancer in young adults. METHODS: CagA IgG antibodies were measured in sera of subjects participating in a case-control study in Japan. The study subjects were 103 gastric cancer patients <40 yr of age, 100 inpatients with benign diseases, and 101 screenees younger than age 43 yr. RESULTS: Compared with the H. pylori-negative/CagA-negative (H. pylori-/CagA-) group, both the H. pylori-positive/CagA-negative (H. pylori+/CagA-) group and the H. pylori-positive/CagA-positive (H. pylori+/CagA+) groups showed elevated odds ratios for intestinal-type, diffuse-type, early, advanced, proximal, and distal gastric cancers. All the relationships were significant except for the H. pylori+/CagA- group in relation to proximal cancer. The overall odds ratios (95% confidence intervals) for gastric cancer in the H. pylori+/CagA- and the H. pylori+/CagA+ groups were 15.0 (6.4, 35.2) and 14.6 (6.7, 31.9), respectively. Between these two groups, no significant difference was observed in risks for intestinal-type, diffuse-type, early, advanced, proximal, or distal gastric cancer. CONCLUSIONS: In those <40 yr of age, it is concluded that both CagA-positive and CagA-negative H. pylori infections are related to risks of intestinal-type, diffuse-type, early, advanced, and distal gastric cancers.     

Treating Acute “No-Reflow” with Intracoronary Adenosine in 4 Patients during Percutaneous Coronary Intervention

Angiographic evidence of impaired tissue perfusion, known as the “no-reflow” phenomenon, is a serious complication of percutaneous coronary intervention—one that is associated with increased mortality rates. Adenosine is an endogenous nucleoside that attenuates many of the mechanisms that are responsible for no-reflow. Herein, we report the cases of 4 patients who developed the no-reflow phenomenon after elective percutaneous coronary intervention to their native coronary arteries and saphenous vein grafts. In all 4 patients, and without adverse effects, small bolus doses of adenosine through the guiding catheter improved epicardial perfusion—measured by either Thrombolysis In Myocardial Infarction (TIMI) flow grade or corrected TIMI frame count—and tissue-level perfusion, graded according to myocardial blush. In view of adenosine''s extremely short half-life in blood, the continuous administration of adenosine into the distal vascular bed throughout percutaneous coronary intervention may further improve outcomes by reversing or preventing the no-reflow phenomenon.Key words: Adenosine/administration & dosage/physiology/therapeutic use, angioplasty, transluminal, percutaneous coronary/adverse effects/methods, atherosclerosis/complications/therapy, cardiotonic agents/administration & dosage/therapeutic use, coronary vessels/drug effects, creatine kinase/blood, dose-response relationship, drug, graft occlusion, vascular/therapy, myocardial reperfusion/methods, treatment outcome, vasodilator agents/administration & dosage/therapeutic usePercutaneous coronary intervention (PCI) is frequently used to treat atherosclerosis-induced stenosis in native coronary arteries and in degenerated saphenous vein grafts (SVGs). Although PCI has a high initial success rate, enzymatic evidence of myocardial cell necrosis occurs in 22% to 44% of patients after apparently uneventful PCI procedures.^1,2 Microvascular obstruction (due in part to embolization of platelets and atheromatous débris) and intense vasoconstriction of the distal bed (secondary to the release of potent humoral mediators) are responsible for microinfarction after PCI.^3–6 In some patients, vascular compromise manifests itself during the procedure as an abrupt decrease in epicardial blood flow—Thrombolysis In Myocardial Infarction (TIMI) grade 0 to 1—which is known as the “no-reflow” or “slow-reflow” phenomenon. The compromise occurs in the absence of apparent dissection, coronary spasm, thrombus formation, substantial residual stenosis, or distal-vessel cutoff that is suggestive of macroembolization.Adenosine attenuates mechanisms that are responsible for the no-reflow phenomenon.⁷ We describe here the cases of 4 patients in whom intracoronary adenosine reversed no-reflow during PCI of the native coronary vessels and SVGs, as measured by TIMI flow grade, corrected TIMI frame count (CTFC), and myocardial blush grade (MBG).     

Variables predictive of good functional outcome following thrombolytic therapy in the Thrombolysis in Myocardial Infarction phase II (TIMI II) pilot study

Before commencing the randomized Thrombolysis in Myocardial Infarction phase II (TIMI II) study, 370 patients were administered intravenous recombinant tissue plasminogen activator (rt-PA) within 4 hours of onset of acute myocardial infarction (AMI) and assigned to 2-hour (immediate) percutaneous transluminal angioplasty (n = 33), 18- to 48-hour (delayed) angioplasty (n = 288) or no angioplasty (n = 49) in a nonrandomized, observational pilot study. Left ventricular ejection fraction at rest and during exercise was assessed by gated equilibrium radionuclide ventriculography at hospital discharge and again at 6 weeks. At hospital discharge, ejection fraction averaged 50% at rest and 56% at peak exercise. At 6-week follow-up, ejection fraction averaged 50% at rest and 53% at peak exercise. At 6-week follow-up, resting ejection fraction average 49% in the 2-hour angioplasty group, 49% in the 18- to 48-hour angioplasty group and 55% in the no-angioplasty group. Variables independently predicting "good functional outcome" at 6-week follow-up (survival with resting ejection fraction greater than equal to 50% and no decrease with exercise) in the 18- to 48-hour angioplasty group were fewer leads with ST-segment elevation greater than or equal to 0.1 mV, younger age, rapid normalization during rt-PA infusion of ST segments or dramatic relief of chest pain, absence of arrhythmias within the first 24 hours of treatment initiation, no prior infarction and not a cigarette smoker at entry. Thus, the TIMI II pilot study demonstrates that most patients with AMI of less than or equal to 4-hour duration treated with rt-PA have good ventricular function after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)