BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.     

Assessment of ventricular dyssynchrony: global or regional function?

A common cliché states that if you stand still every10 years, you will find yourself in the forefront of fashion.Thus it seems with the analysis of ventricular function. Ithas been recognized for many years that incoordinate or non-uniformcontraction reduces global left ventricular (LV) function. Wiggersdemonstrated in 1922 that stimulation from a ventricular focusrather than supraventricular produced a reduced pulse pressure,prolonged isometric contraction, and systolic ejection timein normal hearts. Although regional wall motion abnormalitieswere recognized early in ischaemic heart disease, it was alsodemonstrated later that it occurs in dilated or hypertrophiccardiomyopathy.¹ However, the realization that asynchronouswall motion due to delayed activation such as in the presenceof a left bundle branch block profoundly affected global functiondid not take place until more recently.² Developments in cardiacimaging     

Symptoms and health status before and six weeks after open cholecystectomy: a European cohort study.ECHSS Group. European Collaborative Health Services Study Group.

The impact of open cholecystectomy on patients' symptoms and health status and their level of satisfaction has been examined to provide a basis for comparison with newer rival treatments. A prospective cohort study using patient and surgeon completed questionnaires before and six weeks after surgery was carried out in 14 general hospitals in eight European countries. Five hundred and eighty three patients were recruited consecutively in 1990 to 1991. Information on their symptoms, general health status, activities of daily living, and satisfaction with their care were collected. After surgery 42.8% of patients reported that they were free of symptoms. Symptoms varied in their responsiveness to surgery--six weeks after surgery 89% of those who had complained of vomiting had improved, 81% of nausea, 69% of loss of appetite, 65% of abdominal pain, and 51% of flatulence. In contrast 28.1% of patients still suffered from flatulence and 23.5% continued to complain of abdominal pain. Most patients' (62.7%) general health improved, 28% were unchanged, and 9.3% were worse. After surgery most patients reported no restrictions in their normal social activities (75-90% depending on the activity) and most (89.5%) felt the results of their operation had been as expected or better than expected. Most patients undergoing open cholecystectomy reported an improvement in their symptoms, health status, and social functioning. This was reflected in their high level of satisfaction. Some patients, however, gained no benefit and a small proportion were worse than before surgery.     

Role of 4-1BB in Allograft Rejection Mediated by CD8+ T Cells

Blockade of traditional costimulatory molecules fails to inhibit rejection in many models where CD8+ T cells are sufficient to mediate rejection. This observation demonstrates that in many settings CD8+ T cells are not dependent upon CD28 or CD154 signals to mediate rejection. 4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models. Here we show that blocking the 4-1BB pathway significantly inhibited rejection of intestinal allografts by CD8+ but not CD4+ T cells. This effect was associated with significantly decreased expression of the genes encoding TNFalpha and secondary lymphoid chemokine (SLC) within the spleens of recipient mice. Disruption of the 4-1BB pathway also impaired the priming of alloantigen-specific CD8+ T cells and the accumulation of recipient dendritic cells within the spleen. These data directly demonstrate an important role for 4-1BB in allograft rejection; particularly rejection mediated by CD8+ T cells. Our data suggest that in addition to providing a direct costimulatory signal to T cells, the 4-1BB pathway may regulate other important steps in the immune response such as the migration of T cells and dendritic cells.