The Prognostic Significance of Iliac Vessel Calcification in Renal Transplantation

BackgroundPeripheral vascular disease and major extremity amputation are common in patients with established renal failure and are associated with considerable morbidity. Several studies have shown high rates of amputation following simultaneous pancreas-kidney transplantation, but there is minimal literature on the incidence of amputation following renal transplantation. Furthermore, there is little evidence regarding the best method of predicting which patients might be at risk of developing peripheral vascular complications after transplantation.MethodsWe undertook a 5 year follow-up on the cohort of patients who were on our renal transplant waiting list 5 years ago (January 2007). At this time, it was standard practice within our unit for all patients to have routine pelvic x-rays to assess for vascular calcification of the iliac vessels at the time of activation onto the transplant waiting list. Any patients with moderate/severe calcification on x-ray, which may complicate transplantation, were referred for computed tomography angiogram (CTA) of their aorto-iliac vessels. Mortality, transplantation outcomes, and amputation rates at 5 years were correlated with the severity of calcification on preoperative imaging.ResultsOne hundred eighty-seven patients were on the waiting list for renal transplantation in January 2007 (92 men; mean age, 58.3 +/? 6.2 years). Ninety-three patients received a transplant during the subsequent 5 years. By January 2012, 82 patients had a functioning transplant, 45 remained on the waiting list (5 suspended), 40 patients had died, and 20 were alive but no longer on the waiting list. Seventy-three (39.5%) had moderate or severe calcification on plain x-ray and went on to have CTA. Of these patients, 16 (21.9%) had extensive calcification affecting all the iliac vessels and were removed from the waiting list as a result. Preoperative imaging was useful in determining the side for surgery in a further 18 patients (24.3%). Twenty-two patients developed vascular complications. Nineteen (86.4%) had moderate-severe vascular calcification on imaging. Four of the patients with vascular complications (18.2%) underwent transplantation (2 had below knee amputation (BKA) prior to transplantation; 1 developed distal ischemia on the same side as the transplantation 2 years postoperatively; 1 had bilateral above knee amputation (AKA) approximately 2 years after transplantation). Eleven (50%) of the patients with vascular complications were dead at 5 years of follow-up. Mortality and amputation rates were higher in patients with moderate-severe calcification than minimal calcification (30.1% vs 16.6%; P = .02 and 10.9% vs 1.8%; P = .003, respectively). There was no difference in rates of delayed graft function (DGF), biopsy-proven acute rejection (BPAR), or creatinine at 1 year between patients who underwent transplantation with moderate-severe calcification and those without, however, intraoperative vascular complications (26.7% vs 3%; P < .001), graft loss (28.1% vs 3.4%; P = .01), and death with a functioning transplant (9.7% vs 1.6%; P = .04) rates were higher in patients with extensive calcification compared with those without.ConclusionsPlain x-ray of the pelvis is a useful screening tool to identify those patients who may require further detailed vascular imaging prior to transplantation. Amputation rates following renal transplantation are low and peripheral vascular disease (PVD) in isolation should not preclude transplantation. Nevertheless, significant vascular calcification is predictive of mortality both with and without transplantation and graft loss in patients with a renal transplant.     

Annexin A2 is regulated by ovarian cancer-peritoneal cell interactions and promotes metastasis

Our recent research identified the protein annexin A2 to be regulated by ovarian cancer-peritoneal cell interactions. This study investigated the role of annexin A2 in ovarian cancer metastasis and its potential utility as a novel therapeutic target, using in vitro and in vivo ovarian cancer models. Annexin A2 expression was examined by qRT-PCR and western blotting in ovarian cancer cell lines and immunohistochemistry in serous ovarian carcinoma tissues. Annexin A2 siRNAs were used to evaluate the effects of annexin A2 suppression on ovarian cancer cell adhesion, motility, and invasion. Furthermore, annexin A2 neutralizing antibodies were used to examine the role of annexin A2 in tumor invasion and metastasis in vivo using a chick chorioallantoic membrane assay and an intraperitoneal xenograft mouse model. Strong annexin A2 immunostaining was observed in 90% (38/42) of the serous ovarian cancer cells and was significantly increased in the cancer-associated stroma compared to non-malignant ovarian tissues. Annexin A2 siRNA significantly inhibited the motility and invasion of serous ovarian cancer cells and adhesion to the peritoneal cells. Annexin A2 neutralizing antibodies significantly inhibited OV-90 cell motility and invasion in vitro and in vivo using the chick chorioallantoic membrane assay. The growth of SKOV-3 cells and their peritoneal dissemination in nude mice was significantly inhibited by annexin A2 neutralizing antibodies. Annexin A2 plays a critical role in ovarian cancer metastasis and is therefore a potential novel therapeutic target against ovarian cancer.     

乙型肝炎病毒耐药性临床需知

慢性乙型肝炎(CHB)的治疗已取得实质性进展.现有干扰和核苷类似物这两类药物治疗CHB,尤其是后者为口服给药,使用方便,不良反应少,但长期应用可导致耐药.     

Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation

A series of monoclonal antibodies that define B cell restricted and associated antigens was utilized in an attempt to characterize tumors of B lineage and to relate these tumors to B cell differentiative stages. Antigens that were previously shown to be B cell restricted on normal B lymphocytes were similarly expressed only on B cell malignancies. In contrast, antigens that were B cell associated were also found on tumors of other lineages. Moreover, on the basis of cell surface phenotypes, tumors of B cell origin were divided into three major subgroups, which corresponded to the level of differentiation of the malignant tumor cell: pre-B cell stage (non-T acute lymphoblastic leukemia and chronic myelocytic leukemia in lymphoid blast crisis); the mid-B cell stage (chronic lymphocytic leukemia, poorly differentiated lymphomas); and secretory B cell stage (large cell lymphomas and plasma cell tumors). A hypothetical model is derived that relates the malignant B cell to its normal cellular counterpart on the basis of cell surface expression of this panel of B cell-restricted and B cell- associated antigens.     

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates: I. Effects of anti-T11 antibodies on the circulating T cell pool

The effects of in vivo administration of three monoclonal antibodies specific for T11, the E rosette receptor on T lymphocytes, were examined in the rhesus monkey (Macaca mulatta). These three monoclonal antibodies were of different isotypes and were shown in in vitro studies to have differing affinities for the monkey T11 structure. Furthermore, each antibody induced antigenic modulation of T11 from the cell membrane of the lymphocytes to varying degrees in vitro. In vivo infusion of each of these antibodies into normal rhesus monkeys caused remarkably different effects on the circulating T lymphocyte pool. Infusion of these antibodies at doses of 2 mg/kg caused the coating of circulating T lymphocytes with antibody, the modulation of T11 off the T cell surface and the transient clearance of T cells from the circulation. Yet, the variation in the extent to which these effects were seen with these different antibodies indicates that extrapolating from studies of the in vivo use of one antibody to the use of another may be quite difficult. These studies clearly indicate the strengths of this nonhuman primate system for exploring the uses of monoclonal antilymphocyte antibodies as therapeutic agents. They, however, also demonstrate that differences may exist in the affinity of a particular antibody for homologous lymphocyte surface structures in humans and in a nonhuman primate species. These differences may make it difficult to predict the precise effects that the infusion of an antibody will cause in humans on the basis of alterations it induces in nonhuman primates.     

Double-balloon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: a meta-analysis

BACKGROUND & AIMS: The aim of this study was to compare the diagnostic yield of capsule endoscopy (CE) with double-balloon enteroscopy (DBE) in small-bowel (SB) disease using meta-analysis. METHODS: We performed a search of studies comparing CE with DBE in SB disease. Data on diagnostic yield of CE and DBE were extracted, pooled, and analyzed. The weighted incremental yield (IY(W)) (yield of CE--yield of DBE) of CE over DBE and 95% confidence intervals (95% CIs) for pooled data were calculated using a fixed-effect model (FEM) for analyses without, and a random-effect model (REM) for analyses with, significant heterogeneity. RESULTS: Eleven studies compared CE and DBE; the pooled overall yield for CE and DBE was 60% (n = 397) and 57% (n = 360), respectively (IY(W), 3%; 95% CI, -4% to 10%; P = .42; FEM). Ten studies reported vascular findings; the pooled yield for CE and DBE was 24% (n = 371) and 24% (n = 364), respectively (IY(W), 0%; 95% CI, -5% to 6%; P = .88; REM). Nine studies reported inflammatory findings; the pooled yield for CE and DBE was 18% (n = 343) and 16% (n = 336), respectively (IY(W), 0%; 95% CI, -5% to 6%; P = .89; FEM). Nine studies reported polyps/tumors; the pooled yield for CE and DBE was 11% (n = 343) and 11% (n = 336), respectively (IY(W), -1%; 95% CI, -5% to 4%; P = .76; FEM). CONCLUSIONS: CE and DBE have comparable diagnostic yield in SB disease, including obscure gastrointestinal bleeding. CE should be the initial diagnostic test because of its noninvasive quality, tolerance, ability to view the entire SB, and for determining the initial route of DBE. Because of its therapeutic capabilities, DBE may be indicated in patients with a positive finding on CE requiring a biopsy or therapeutic intervention, if suspicion for a SB lesion is high despite a negative CE, and in patients with active bleeding.