Excorporeal normothermic machine perfusion resuscitates pig DCD livers with extended warm ischemia.

Background: The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system.

Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

Background: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs).

Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts.

Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP.

Autoimmune bullous skin diseases. Part 2: diagnosis and therapy.

Autoimmune bullous skin diseases represent a heterogenous group of disorders of skin and mucosa which are commonly associated with IgG or IgA autoantibodies against distinct adhesion molecules of the skin. The antibodyinduced loss of adhesion between epidermis and dermis results in blister formation and extensive erosions. There is a great need for rapidly establishing the diagnosis of these disorders since they may run a severe and potentially life-threatening course.

Autoimmune bullous skin diseases. Part 1: Clinical manifestations.

Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation.

Bullous cryothermic dermatitis artefacta induced by deodorant spray abuse.

Background: Dermatitis artefacta belongs to a broad spectrum of factitious diseases of lesions usually self-induced by patients. Here we report a surprisingly effective induction of blisters and thermic dermatitis by excessive abuse of common deodorant sprays.

Objectives: We evaluated the clinical course and outcome in three patients with dermatitis artefacta induced by deodorant spray.

Demonstration of epitope-spreading phenomena in bullous pemphigoid: results of a prospective multicenter study.

Bullous pemphigoid (BP), the most common autoimmune subepidermal bullous disease, is associated with an autoantibody response to BP180 and BP230, two components of junctional adhesion complexes in human skin promoting dermo-epidermal cohesion. Retrospective analyses demonstrated that these autoantigens harbor several epitopes targeted by autoaggressive B and T cells. The aim of this prospective multicenter study was to assess the evolution of IgG autoantibodies in 35 BP patients over a 12-month observation period.

Hepatocyte viability and adenosine triphosphate content decrease linearly over time during conventional cold storage of rat liver grafts.

Introduction: The gold standard in organ preservation is static cold storage (SCS) using University of Wisconsin solution (UW). Although it is well-known that there is a finite limit to SCS preservation, and that there is a correlation between the adenosine triphosphate (ATP) levels and organ function post-preservation, a quantitative relationship has not been established, which is important in understanding the fundamental limitations to preservation, minimizing cold ischemic injury, and hence maximizing use of the donor organ pool.

Aim: This study determines the time limits of cellular viability and metabolic function during SCS, and characterizes the relationship between cellular viability and energetic state using clinically relevant techniques in organ preservation.

Immunofluorescence serration pattern analysis as a diagnostic criterion in antilaminin-332 mucous membrane pemphigoid: immunopathological findings and clinical experience in 10 Dutch patients.

Background: Antilaminin-332 mucous membrane pemphigoid (anti-LN-332 MMP) is a chronic subepidermal blistering disease characterized by IgG anti-epidermal basement membrane zone (BMZ) autoantibodies against laminin-332 (LN-332).

Patients: with anti-LN-332 MMP have an increased relative risk of malignancy. Laboratory techniques that are difficult to obtain are needed for diagnosis of anti-LN-332 MMP.

Development of an ELISA for sensitive and specific detection of IgA autoantibodies against BP180 in pemphigoid diseases.

Background: Pemphigoids are rare diseases associated with IgG, IgE and IgA autoantibodies against collagen XVII/BP180. An entity of the pemphigoid group is the lamina lucida-type of linear IgA disease (IgA pemphigoid) characterized by IgA autoantibodies against BP180. While for the detection of IgG and IgE autoantibodies specific to collagen XVII several ELISA systems have been established, no quantitative immunoassay has been yet developed for IgA autoantibodies.

A prospective, randomized comparison of bovine carotid artery and expanded polytetrafluoroethylene for permanent hemodialysis vascular access.

Background: Many patients on hemodialysis do not have adequate anatomy for native arteriovenous fistulas. In these patients, synthetic conduits remain an alternative option for permanent hemodialysis access. We sought to compare the standard cuffed expanded polytetrafluoroethylene (ePTFE) graft with the bovine carotid artery (BCA) graft.

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID).

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.

Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases.

IgG autoantibodies against desmocollin 3 in pemphigus sera induce loss of keratinocyte adhesion.

Pemphigus is considered an autoimmune bullous skin disorder associated with IgG against the desmosomal components, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). This concept is supported by the in vitro and in vivo pathogenicity of anti-Dsg3/Dsg1 IgG and the mucosal blistering phenotype of mice with a genetic deficiency of Dsg3. Mice deficient for another desmosomal adhesion molecule, desmocollin 3 (Dsc3), show a similar pemphigus phenotype, and we investigated the pathogenicity of Dsc3-reactive IgG autoantibodies that were identified previously in a subset of patients with atypical pemphigus.

Partial abdominal evisceration and intestinal autotransplantation to resect a mesenteric carcinoid tumor.

Background: Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia.

Case Presentation: We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds.

Induction with Rabbit Antithymocyte Globulin following Orthotopic Liver Transplantation for Hepatitis C.

Background: Hepatitis C (HCV) is the most common indication for liver transplantation in the US.

Objective: Since steroids are the major stimulus of viral replication, we postulated that steroid-free immunosuppression might be a safer approach.

Methods: From January 1995 to October 2002, we used steroid plus calcineurin inhibitor (CNI) immunosuppression after liver transplantation for HCV (steroid group, n=81).

Changing pattern of organ donation at a single center: are potential brain dead donors being lost to donation after cardiac death?

Donation after cardiac death (DCD) has proven effective at increasing the availability of organs for transplantation.We performed a retrospective examination of Massachusetts General Hospital (MGH) records of all 201 donors from 1/1/98 to the 11/2008, including 54 DCD, 115 DBD and 32 DCD candidates that did not progress to donation (DCD-dnp). Comparing three time periods, era 1 (01/98-12/02), era 2 (01/03-12/05) and era 3 (01/06-11/08), DCD’s comprised 14.

Diluted blood reperfusion as a model for transplantation of ischemic rat livers: alanine aminotransferase is a direct indicator of viability.

Donors after cardiac death present a significant pool of untapped organs for transplantation, and use of machine perfusion strategies has been an active focus area in experimental transplantation. However, despite 2 decades of research, a gold standard has yet to emerge for machine perfusion systems and protocols. Whole blood reperfusion has been used as a surrogate for organ transplantation, especially as a model for the short-term response posttransplantation, and for optimization of perfusion systems.

[Autoimmune bullous skin disorders].

Autoimmune bullous skin disorders are rare, potentially fatal disorders of skin and mucous membranes which are associated with IgG or IgA autoantibodies against distinct adhesion molecules of the epidermis and dermal epidermal basement membrane zone, respectively. These autoantibodies lead to a loss of skin adhesion which shows up clinically as the formation of blisters or erosions. In pemphigus, loss of adhesion occurs within the epidermis while in the pemphigoids, linear IgA dermatosis, epidermolysis bullosa acquisita and dermatitis herpetiformis, loss of adhesion takes place within or underneath the basement membrane zone.

Long-term experience with liver transplantation for hepatocellular carcinoma.

Background: The effect of the model for end-stage liver disease (MELD) system on the post-transplant survival of patients with hepatocellular carcinoma (HCC) has not been fully elucidated. Our objective is to review the results of liver transplantation (LT) for HCC at the Massachusetts General Hospital over a period of 12 years, with special emphasis on the effect of the MELD system.

Methods: A retrospective review of 73 patients who underwent liver transplantation for HCC between 1995 and 2007.

Targeted immunotherapy with rituximab leads to a transient alteration of the IgG autoantibody profile in pemphigus vulgaris.

In pemphigus vulgaris (PV), IgG autoantibodies against the ectodomain of desmoglein 3 (Dsg3) have been shown to be directly responsible for the loss of keratinocyteadhesion. The aim of the present study was to study the effect of the B cell depleting anti-CD20 monoclonal antibody, rituximab, on the profile of pathogenic IgG against distinct regions of the Dsg3 ectodomain in 22 PV patients who were followed up clinically and serologically by Dsg3 ELISA over 12-24 months. Prior to rituximab, all the 22 PV patients showed IgG against Dsg3 (Dsc3EC1-5).