Does the Presence of a Measurable Blood Alcohol Level in a Potential Organ Donor Affect the Outcome of Liver Transplantation?

The widespread application of hepatic transplantation has created a tremendous demand for donor organs. An assessment of donor parameters is thought to be important in selecting good donors; however, the criteria utilized have not been standardized. This study was performed to determine the effect of a measurable donor blood alcohol level on graft survival. Fifty‐two patients who underwent orthotopic liver transplantation at the University of Pittsburgh were included in the study. Twenty‐five patients received liver grafts from donors having a blood alcohol level between 0.04 and 0.4 g/I with a mean of 0.17 g/I. Twenty‐seven patients received a liver graft from a donor who had no measurable blood alcohol. There were no differences between these two groups of donors regarding the time of initial hospitalization until the time of donation. Graft failure within the first 30 days was 24% for those receiving an organ from an alcohol‐positive donor as compared with 22.2% in those receiving an organ from an alcohol negative donor. The recipient mortality rate was 16% and 11%, respectively. No relationships between the donor blood alcohol level and organ performance, frequency of primary graft nonfunction, or number of episodes of acute cellular rejection were evident. Based upon these data, the presence of a measurable blood alcohol level in a donor should not mitigate against organ donation. Copyright © 1991, Wiley Blackwell. All rights reserve

Effectiveness of smoking cessation therapies: a systematic review and meta-analysis

BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (~3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55–1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60–1.99), NRT gum (OR 1.60, 95% CI, 1.37–1.86) or patch (OR 1.63, 95% CI, 1.41–1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77–2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10–2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72–2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20–6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12–4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65–5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22–2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16–2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17–2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22–2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness

Perceptions of surgeons: What characteristics do women surgeons prefer in a colleague?

© 2014 Elsevier Inc. Background Perceptions underlie bias and drive behavior. This study assessed female surgeons' implicit perceptions of surgeons, with a focus on the roles of sex and demeanor (communal = supportive, associated with women; agentic = assertive, associated with men)Methods: Electronic surveys were administered via the Association of Women Surgeons e-mail listserve to 550 post-training female surgeons. Each survey had one of the 4 possible scenarios that varied by surgeon sex (male/female) and surgeon demeanor (agentic/communal). Respondents rated their perception of the surgeon through 5 questions regarding preference and 5 questions regarding professional opinion (1 to 5 scale)Results: We received 212 surveys. In both preference and professional scores, female surgeons were rated significantly higher compared with their male counterparts (4.7 vs 4.4 and 4.3 vs 4.0, respectively). Communal surgeons were rated significantly higher versus agentic surgeons in both scores (4.7 vs 4.4 and 4.6 vs 3.7)Conclusions: Female surgeons demonstrated a significant preference for female surgeons and for communal surgeons

Perceptions of surgeons: What characteristics do women surgeons prefer in a colleague?

© 2014 Elsevier Inc. Background Perceptions underlie bias and drive behavior. This study assessed female surgeons' implicit perceptions of surgeons, with a focus on the roles of sex and demeanor (communal = supportive, associated with women; agentic = assertive, associated with men)Methods: Electronic surveys were administered via the Association of Women Surgeons e-mail listserve to 550 post-training female surgeons. Each survey had one of the 4 possible scenarios that varied by surgeon sex (male/female) and surgeon demeanor (agentic/communal). Respondents rated their perception of the surgeon through 5 questions regarding preference and 5 questions regarding professional opinion (1 to 5 scale)Results: We received 212 surveys. In both preference and professional scores, female surgeons were rated significantly higher compared with their male counterparts (4.7 vs 4.4 and 4.3 vs 4.0, respectively). Communal surgeons were rated significantly higher versus agentic surgeons in both scores (4.7 vs 4.4 and 4.6 vs 3.7)Conclusions: Female surgeons demonstrated a significant preference for female surgeons and for communal surgeons

A dendritic cell line genetically modified to express CTLA4-IG as a means to prolong islet allograft survival

Background. Dendritic cells are potent antigen-presenting cells that bind allogeneic T cells. They are thus candidates for targeting immunoregulatory molecules to the alloreactive T cell compartment and suppressing the alloimmune response. Method. A dendritic cell line derived from the BALB/c mouse (H2d) was genetically modified to express the immunoregulatory molecule CTLA4-Ig. The ability of these dendritic cell transfectants to down-regulate the alloimmune response was tested in an islet transplant model. Allogeneic C57Bl/6 (H2b) mice were rendered diabetic with streptozocin, and they received BALB/c islet (H2d) transplants. Mice were administered 25 million untransfected or CTLA4-Ig-transfected D2SC/1 cells i.v. on the day of islet transplantation and 6 days later[fnc]. Result. Mice treated with CTLA4-Ig-transfected D2SC/1 cells demonstrated prolonged allograft survival (mean=20 days, median=17 days, SD=9.39) compared with mice treated with untransfected D2SC/1 cells (mean=12 days, median=11 days, SD=2.74) or untreated control mice (mean=11 days, median=11 days SD=1.41). Third party allograft survival was not prolonged in mice receiving similar treatment. Conclusions. These results demonstrate that a genetically modified dendritic cell line can suppress the alloimmune response and prolong islet allograft survival in an allospecific manner. The findings also suggest that genetically modified dendritic cells may be useful in targeting alloreactive T cells and prolonging allograft survival

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants

Background. Fas ligand (FasL) mediates apoptosis of susceptible Fas-expressing lymphocytes, and may contribute to the maintenance of peripheral tolerance. In transplantation models, however, artificial expres- sion of FasL on cellular as well as islet transplants results in accelerated rejection by neutrophils. The mechanism of the neutrophilic response to FasL ex- pression is unknown. FasL, like other members of the tumor necrosis factor family, is cleaved to a soluble form by metalloproteases. We tested the hypothesis that soluble FasL (sFasL) was responsible for neutro- phil migration by creating a non-cleavable mutant of FasL. Methods. Three mutants of FasL with serial dele- tions in the putative proteolytic cleavage site of hu- man FasL were made using inverse polymerase chain reaction. The relative fractions of sFasL and mem- brane-bound FasL were assessed by Western blot and immunoprecipitation, as well as by cytotoxicity assay using Fas-expressing target cells. The fully non-cleav- able mutant was transduced into murine islets as well as myoblasts and tumor cell lines, and tested in a mu- rine transplantation model. Results. Serial deletions in the putative metallopro- tease site of FasL resulted in a fully non-cleavable mutant of FasL (ncFasL). Expression of ncFasL in tu- mor lines induced higher levels of apoptosis in Fas bearing targets than wild-type FasL. Transplantation of ncFasL-expressing islets under the kidney capsule of allogenic mice resulted in accelerated rejection identical to that seen with wild-type Fas ligand-expressing islets. Myoblasts and tumor cell lines express- ing ncFasL also induced neutrophil infiltration. Conclusions. Membrane-bound Fas ligand is fully ca- pable of inducing a neutrophilic response to trans- plants, suggesting an activation by Fas ligand of neu- trophil chemotactic factors