Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease.

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post-transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post-LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow-up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation.     

Early Low-Grade Proteinuria: Causes, Short-Term Evolution and Long-Term Consequences in Renal Transplantation

Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after transplantation and its short-term change affect long-term graft survival. The effects of proteinuria and its change on long-term graft survival were retrospectively assessed in 484 renal transplant recipients. One- and 3-month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One- and 3-month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p<0.0001)-especially low-grade proteinuria (HR: 1.20 and 1.26, p<0.0001)-were powerful, independent predictors of graft loss. Its short-term reduction correlated with arterial pressure (AP) (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of increasing proteinuria during 1-3 months and 3-12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p=0.01 and 0.85, respectively, p=0.02), and was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p<0.0001), independently of initial proteinuria. Early low-grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and immunologic injuries is a potent predictor of graft loss. Short-term reduction in proteinuria is associated with improved long-term graft survival.     

Tobacco use following liver transplantation for alcoholic liver disease: an underestimated problem.

Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post-LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post-LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post-LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post-LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre- and post-LTX periods.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Comparison of Methodologies for Calculating Quality Measures Based on Administrative Data versus Clinical Data from an Electronic Health Record System: Implications for Performance Measures

New reimbursement policies and pay-for-performance programs to reward providers for producing better outcomes are proliferating. Although electronic health record (EHR) systems could provide essential clinical data upon which to base quality measures, most metrics in use were derived from administrative claims data. We compared commonly used quality measures calculated from administrative data to those derived from clinical data in an EHR based on a random sample of 125 charts of Medicare patients with diabetes. Using standard definitions based on administrative data (which require two visits with an encounter diagnosis of diabetes during the measurement period), only 75% of diabetics determined by manually reviewing the EHR (the gold standard) were identified. In contrast, 97% of diabetics were identified using coded information in the EHR.The discrepancies in identified patients resulted in statistically significant differences in the quality measures for frequency of HbA1c testing, control of blood pressure, frequency of testing for urine protein, and frequency of eye exams for diabetic patients. New development of standardized quality measures should shift from claims-based measures to clinically based measures that can be derived from coded information in an EHR. Using data from EHRs will also leverage their clinical content without adding burden to the care process.     

Comparison of chitin and Amberlite IRA-938 for alpha-galactosidase immobilization

Watermelon alpha-galactosidase (EC 3.2.1.22) was immobilized on a natural (chitin) and a synthetic anion-exchange (Amberlite IRA-938) support by covalent coupling methods. The procedure entails the activation of supports with 1,1'-carbonyldiimidazole (CDI), followed by immobilization of the enzyme on to these supports without and with a spacer arm; gamma-aminobutyric acid (GABA). Optimization of activation was performed by changing the CDI concentrations and coupling efficiencies. The comparison of two immobilization techniques for both chitin and Amberlite IRA-938 was made by comparing different enzyme concentrations against enzyme activity yield. Furthermore, the storage stability of the immobilized enzymes was also investigated and chitin immobilized alpha-galactosidase was found to be better. Although the activity yield of immobilized enzymes were the same for both supports, the short storage stability of immobilized enzyme on Amberlite IRA-938 is currently a drawback to its applications.     

Arginine selective biosensor based on arginase-urease immobilized in gelatin

Arginase and urease enzymes were immobilized on the surface of pH electrode by using gelatin membrane which is then cross-linked with glutaraldehyde. Sensor response was maximum when 2.5 mM, Tris-HCl buffer (pH 8.5) was used at 25 degrees C. The biosensor response depends linearly on arginine concentration between 0.025-0.310 mM with response time 10 min. Furthermore, application of the system for the arginine detection in serum samples was also tested.     

Impact of Varying Stages of Endometriosis on the Outcome of In Vitro Fertilization–Embryo Transfer

Purpose: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. Methods: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed. Results: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0,004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. Conclusions: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.     

Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.