Whole-Organ Pancreas and Islets Transplantations in UK: An Overview and Future Directions.

Whole-organ pancreas and islets transplantations are two therapeutic options to treat type 1 diabetic patients resistant to optimised medical treatment in whom severe complications develop. Selection of the best option for ß-cell replacement depends on several factors such as kidney function, patient comorbidities, and treatment goals. For a patient with end-stage kidney disease, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK). However, it remains a major surgical procedure in patients with multiple comorbidities and therefore it is important to select those who will benefit from it. Additionally, in view of the organ shortage, new strategies to improve outcomes and reduce immune reactions have been developed, including dynamic organ perfusion technologies, pancreas bioengineering, and stem cell therapies. The purpose of this article is to review the indications, surgical techniques, outcomes, and future directions of whole-organ pancreas and islets transplantations.

Blocking TGF-ß and ß-Catenin Epithelial Crosstalk Exacerbates CKD.

The TGF-ß and Wnt/ß-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-ß has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-ß signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-ß type 2 receptor specifically in this epithelial segment. Compared with littermate controls, mice lacking the proximal tubular TGF-ß receptor had significantly increased tubular injury and tubulointerstitial fibrosis in two different models of CKD. RNA sequencing indicated that deleting the TGF-ß receptor in proximal tubule cells modulated many growth factor pathways, but Wnt/ß-catenin signaling was the pathway most affected. We validated that deleting the proximal tubular TGF-ß receptor impaired ß-catenin activity in vitro and in vivo Genetically restoring ß-catenin activity in proximal tubules lacking the TGF-ß receptor dramatically improved the tubular response to CKD in mice. Deleting the TGF-ß receptor alters many growth factors, and therefore, this ameliorated response may be a direct effect of ß-catenin activity or an indirect effect of ß-catenin interacting with other growth factors. In conclusion, blocking TGF-ß and ß-catenin crosstalk in proximal tubules exacerbates tubular injury in two models of CKD.

Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis.

BACKGROUND: Cancer patients and oncologists believe that psychological variables influence the course of cancer, but the evidence remains inconclusive. This meta-analysis assessed the extent to which depressive symptoms and major depressive disorder predict disease progression and mortality in cancer patients. METHODS: Using the MEDLINE, PsycINFO, CINAHL, and EMBASE online databases, the authors identified prospective studies that examined the association between depressive symptoms or major/minor depression and risk of disease progression or mortality in cancer patients. Two raters independently extracted effect sizes using a random effects model. RESULTS: Based on 3 available studies, depressive symptoms were not shown to significantly predict cancer progression (risk ratio [RR] unadjusted = 1.23; 95% confidence interval [CI], 0.85-1.77; P = .28). Based on data from 25 independent studies, mortality rates were up to 25% higher in patients experiencing depressive symptoms (RR unadjusted = 1.25; 95% CI, 1.12-1.40; P < .001), and up to 39% higher in patients diagnosed with major or minor depression (RR unadjusted = 1.39; 95% CI, 1.10-1.89; P = .03). In support of a causal interpretation of results, there was no evidence that adjusting for known clinical prognostic factors diminished the effect of depression on mortality in cancer patients. CONCLUSIONS: This meta-analysis presented reasonable evidence that depression predicts mortality, but not progression, in cancer patients. The associated risk was statistically significant but relatively small. The effect of depression remains after adjustment for clinical prognosticators, suggesting that depression may play a causal role. Recommendations were made for future research to more clearly examine the effect of depression on cancer outcomes.

Prostate cancer stories in the Canadian print media: representations of illness, disease and masculinities.

Despite the popularity of print media as an information source for men with prostate cancer, the representation of prostate cancer within this medium remains relatively understudied. This article details the findings from an analysis of prostate cancer articles published in two Canadian national newspapers, The Globe and Mail and the National Post, from January 2001 through to December 2006. The 817 prostate cancer articles published during this period were retrieved and reviewed using manifest and latent analyses. Three article categories, illness perspectives, medical perspectives and supplementary were identified in the manifest analysis. The latent analysis was guided by the connections between masculinities and prostate cancer in the newspapers' stories. Findings indicated a low frequency of articles that substantively discussed prostate cancer and that the descriptive content reproduced hegemonic masculine ideals, such as competition and stoicism. The presentation of a truncated illness trajectory and privileging of the curative aspects of biomedicine also depicted medicalised male bodies. Any discussion on the negative effects of treatment or explicit references to marginalized forms of masculinity was conspicuously absent. These findings support how representations of prostate cancer in Canadian newspapers predominately replicate detrimental ideologies and perspectives of men's health.

Can psychological factors account for a lack of nocturnal blood pressure dipping?

BACKGROUND: In healthy individuals, blood pressure (BP) decreases, or "dips", during sleep. Ethnicity and high daytime blood pressure level are known markers of nondipping status. The literature on psychological markers of nondipping is scant but suggests that anger/hostility and chronic stress may be contributors to nondipping. PURPOSE: We have investigated this phenomenon in drug-free hypertensives who participated in a clinical trial and supplied extensive demographic, psychological, and biological risk factor data after medication washout prior to any treatment. METHOD: Sixty-two patients were available for analysis (n = 30 nondippers). While most studies focus only on systolic BP nondipping, we explicitly studied both systolic and diastolic BP dipping as outcomes given that both have prognostic value. RESULTS: Hierarchical multiple regression revealed that predictor variables in total accounted for 38% of variance in systolic blood pressure dipping and 44% of variance in diastolic blood pressure dipping. A significant positive predictor was alcohol consumption (beta = 0.37, t = 2.8, p = 0.007) for systolic BP and beta = 0.43, t = 3.7, p = 0.001 for diastolic BP), and an anger diffusion preference was also a positive predictor (beta = 0.42, t = 2.7, p = 0.01) for systolic BP dipping. No measure of trait negative affect reached significance as a predictor for systolic or diastolic BP dipping. CONCLUSION: These findings suggest that for a better understanding of the nondipping phenomenon, behavioral risk factors are important, and anger response styles may also be worthy of further study. Furthermore, anger coping preferences may be as important, or even more so, than levels of negative affect.

Women and prostate cancer support groups: the gender connect?

There are more than 100 prostate cancer support groups (PCSGs) in Canada, most of which meet on a monthly basis-yet little attention has been paid to the role of women at these groups. As part of an ongoing ethnographic study of PCSGs, we examined women's motivations for attending the groups, their ways of functioning in PCSGs and the benefits they accrued. Participant observations conducted at 13 British Columbian-based PCSGs and individual interview data from 20 women who regularly attended PCSG meetings were analyzed. Although the groups did not overtly limit women's attendance, the women's decisions to attend and their participation at group meetings were subject to much self-reflection, uncertainty and tension. Motivations to access a PCSG included a desire to support their partners, develop understandings about the illness and disease, and to manage their own experience of prostate cancer. Our analyses revealed that women assume three roles in PCSGs: social facilitator, background supporter and cancer co-survivor. The women reported many interrelated benefits as a result of attending, including information, hope and reassurance, and connecting with other women in similar circumstances. The results from this study reveal how traditional feminine ideals, such as nurturing and caring for the men in their lives, facilitating social connections and the desire to share emotional experiences guided the behaviors. Based on the study findings, we suggest that efforts to support women's involvement in PCSGs are critical to enhancing the effectiveness of the groups for both men and women.

Immunosuppressive therapy for ocular mucous membrane pemphigoid strategies and outcomes.

PURPOSE: To evaluate the effectiveness and toxicity of a stepladder immunosuppression strategy, including the use of mycophenolate mofetil and combination therapy, in the treatment of ocular mucous membrane pemphigoid. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Two hundred twenty-three eyes of 115 patients. METHODS: Patients with a diagnosis of ocular mucous membrane pemphigoid commencing immunosuppression between January 1994 and July 2005 were identified. A treatment episode was defined by the use of a particular therapy or combination of therapies. MAIN OUTCOME MEASURES: For each treatment episode, success of immunosuppressive therapy in controlling ocular inflammation was graded as a success (S), qualified success (QS), or failure (F). Initial and final visual acuities (VAs), stage of cicatrization (Foster, Mondino), grade of conjunctival inflammation, and side effects were recorded. RESULTS: In 70% (80/115) of patients, inflammation was controlled by the end of the study. At least 6 months remission off treatment occurred in 16 patients (14%). Of the 388 treatment episodes, 50% were classified as S; 27%, QS; and 23%, F. The most successful therapies were based on cyclophosphamide (S, 69%; QS, 21%; F, 10%), followed by mycophenolate (S, 59%; QS, 22%; F, 19%), azathioprine (S, 47%; QS, 24%; F, 29%), dapsone (S, 47%; QS, 30%; F, 23%), and sulfapyridine (S, 38%; QS, 27%; F, 35%). Combination sulfa-steroid-myelosuppressive agent therapy increased the response from 73% with single-agent therapy to 87%. Side effects were the reason for 29% of changes in therapy. These were most prominent with azathioprine (40%) and least with mycophenolate (15%). Initial best-corrected VA (BCVA) was 6/60 or less in 17% (37/223) of eyes, pemphigoid being the cause in 13% (29/223). Final BCVA was 6/60 or less in 34% (76/223) of eyes, pemphigoid being the cause in 26% (57/223). By the end of the study, Mondino stage cicatrization had progressed in 41% (92/223) of eyes and 53% (61/115) of patients. CONCLUSIONS: Mycophenolate mofetil seems to be an effective and well-tolerated immunosuppressant for moderately active ocular mucous membrane pemphigoid. Combination sulfa-steroid-myelosuppressive agent therapy in a stepladder regimen is a useful strategy to improve disease control. Cicatrization and VA may still progress and worsen despite adequate control of inflammation.

Psychological treatment of cardiac patients: a meta-analysis.

Previous reports of the effectiveness of psychological treatments (PTs) for cardiac patients reveal inconsistent results. We determined overall effects and gender differences. Eligible studies were randomized controlled trials, containing a PT arm. The authors identified 43 relevant randomized trials; 23 reported mortality data for 9856 patients. The odds-ratio (OR) for all-cause mortality at follow-up of 2 years or less, comparing PT plus usual care vs. usual care only, was OR 0.72 [95% confidence interval (CI) 0.56-0.94], but weakened with longer follow-up (OR 0.89; 95% CI 0.80-1.10). Mortality benefits only applied to men (OR 0.73, 95% CI 0.57-1.00; OR 1.01; 95% CI 0.87-1.72 for women). Trials initiating treatment at least 2 months after a cardiac event showed greater mortality benefits than those initiating treatment right after the event (OR 0.28; 95% CI 0.11-0.70 vs. OR 0.87; 95% CI 0.86-1.15, respectively). Mortality benefits due to PT were achieved despite small concomitant changes in negative affect. PT of cardiac patients reduces mortality and event recurrence. The mortality benefits appeared only in men even after controlling for age differences. The timing for the initiation of PT may be a critical mediating variable for mortality outcomes.