Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis.

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.

Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis.

Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC.

Targeting cells causing split tolerance allows fully allogeneic islet survival with minimal conditioning in NOD mixed chimeras.

Donor-specific tolerance induced by mixed chimerism is one approach that may eliminate the need for long-term immunosuppressive therapy, while preventing chronic rejection of an islet transplant. However, even in the presence of chimerism it is possible for certain donor tissues or cells to be rejected whereas others from the same donor are accepted (split tolerance). We previously developed a nonmyeloablative protocol that generated mixed chimerism across full major histocompatability complex plus minor mismatches in NOD (nonobese diabetic) mice, however, these chimeras demonstrated split tolerance. In this study, we used radiation chimeras and found that the radiosensitive component of NOD has a greater role in the split tolerance NOD mice develop. We then show that split tolerance is mediated primarily by preexisting NOD lymphocytes and have identified T cells, but not NK cells or B cells, as cells that both resist chimerism induction and mediate split tolerance. Finally, after recognizing the barrier that preexisting T cells impose on the generation of fully tolerant chimeras, the chimerism induction protocol was refined to include nonmyeloablative recipient NOD T cell depletion which generated long-term mixed chimerism across fully allogeneic barriers. Furthermore, these chimeric NOD mice are immunocompetent, diabetes free and accept donor islet allografts.

The benefits of bariatric surgery in obese patients with hip and knee osteoarthritis: a systematic review.

Osteoarthritis is a common progressive disease leading to joint pain and severe disability. It is a complex multifactorial disease leading to damage of cartilage, deposition of subchondral bone matrix and release of pro-inflammatory cytokines. Obesity is an emerging epidemic and also an important risk factor for osteoarthritis. Weight loss has been shown to improve pain and function in hip and knee joints with osteoarthritis. Bariatric surgery currently is the only evidence-based approach to marked weight loss in obese individuals. However, there is currently limited literature to evaluate the role of bariatric surgery in hip and knee osteoarthritis. The objective of the present study was to systematically review the literature regarding the effectiveness of bariatric surgery in obese adult patients in improving large weight-bearing joint (hip and knee) osteoarthritis. Published English-language manuscripts were considered for review inclusion. A comprehensive search of electronic databases using broad search terms was completed. From a total of 400 articles, eight articles were identified. A total of six studies were included for qualitative analysis. A general trend was identified indicating improved hip and knee osteoarthritis following marked weight loss secondary to bariatric surgery. This systematic review demonstrates that bariatric surgery may benefit obese patients with hip or knee osteoarthritis. However, this review identifies the need for randomized controlled trials to clarify the role and indications for bariatric surgery.