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The mechanisms underlying discrimination between "self" and "non-self", a central immunological principle, require careful consideration in immune oncology therapeutics where eliciting anti-cancer immunity must be weighed against the risk of autoimmunity due to the self origin of tumors. Whole cell vaccines are one promising immunotherapeutic avenue whereby a myriad of tumor antigens are introduced in an immunogenic context with the aim of eliciting tumor rejection. Despite the possibility collateral damage to healthy tissues, cancer immunotherapy can be designed such that off target autoimmunity remains limited in scope and severity or completely non-existent. Here we provide an immunological basis for reconciling the safety of cancer vaccines, focusing on tumor endothelial cell vaccines, by discussing the following topics: (a) Antigenic differences between neoplastic and healthy tissues that can be leveraged in cancer vaccine design; (b) The layers of tolerance that control T cell responses directed against antigens expressed in healthy tissues and tumors; and, (c) The hierarchy of antigenic epitope selection and display in response to whole cell vaccines, and how antigen processing and presentation can afford a degree of selectivity against tumors. We conclude with an example of early clinical data utilizing ValloVax™, an immunogenic placental endothelial cell vaccine that is being advanced to target the tumor endothelium of diverse cancers, and we report on the safety and efficacy of ValloVax™ for inducing immunity against tumor endothelial antigens.

Summary: A clinical score to identify kidneys from donors after cardiac death (DCD) with a high risk of dysfunction following transplantation could be a useful tool to guide the introduction of new algorithms for the preservation of these organs and improve their outcome after transplantation. We investigated whether the deceased donor score (DDS) system could identify DCD kidneys with higher risk of early post-transplant dysfunction. The DDS was validated in a cohort of 168 kidney transplants from donors after brain death (DBD) and then applied to a cohort of 56 kidney transplants from DCD. In the DBD cohort, the DDS grade predicted the incidence of delayed graft function (DGF) and levels of serum creatinine at 3 and 12 months post-transplant. Similarly, in the DCD cohort, the DDS grade correlated with DGF and also predicted the levels of serum creatinine at 3 and 12 months. Interestingly, the DDS identified a subgroup of marginal DCD kidneys in which minimization of cold ischemia time produced better early clinical outcome. These results highlight the impact of early interventions on clinical outcome of marginal DCD kidneys and open the possibility of using the DDS to identify those kidneys that may benefit most from therapeutic interventions before transplantation.

Pulsatile perfusion (PP) might be a cost-effective cold preservation technique to reduce the incidence of delayed graft function (DGF) in kidneys from deceased donors. With the aim to address whether PP can reduce the incidence of DGF in kidneys from controlled donors after cardiac death (cDCD), we compared the clinical outcome of 30 recipients of kidneys from cDCD preserved by static cold storage (cDCD-SCS) with 30 recipients of cDCD kidneys preserved by PP (cDCD-PP). The end-points were the incidence of primary nonfunction (PNF), DGF and acute rejection (AR), the length of hospitalization, 1, 3, 6 and 12-months graft function, graft survival and patient survival. Donor, recipient and preimplantation data were well matched. DGF was significantly lower (53.3% vs. 86.6% P<0.001) and the length of hospitalization shorter (10 vs. 14 days P<0.033) in the cDCD-PP group. Similarly, postoperative and short-term graft function (7 and 30 days and 6 and 12 months, respectively) was statistically better in the cDCD-PP than in the cDCD-SCS. In summary, in this cohort, clinical introduction of PP was associated with a significant reduction of DGF, shorter hospitalization and better graft function than SCS.

Background: Advanced age, major orthopedic surgery, neoplastic disease, prolonged operations, varicose veins, immobilization, estrogen-containing medications, and obesity are known risk factors for the development of postoperative thromboembolic complications. Perioperative heparin is useful for reducing the incidence of deep venous thrombosis (DVT), but it is associated with a discrete bleeding rate. The purpose of this study was to determine the incidence of clinically evident DVT in morbidly obese patients after laparoscopic Roux-en-Y gastric bypass when a pneumatic compression hose is used as the only prophylaxis against DVT instead of anticoagulants., Methods: From April 2000 to April 2003, 380 patients underwent laparoscopic Roux-en-Y gastric bypass for morbid obesity by one surgeon (R.H.C.). Prospectively, each patient was clinically evaluated for the presence of DVT during the postoperative period. Calf-length pneumatic compression stockings were placed before the procedure began, and remained in place until the patient was ambulatory. Ambulation was encouraged on the evening of the operation. No pharmacologic anticoagulant was used as a prophylaxis against DVT., Results: Of the 380 patients, 346 were women and 34 were men with a mean age of 39.3 +/- 9.4 years (range, 14-65 years). The mean weight of these patients was 299.5 +/- 53.6 lb (range, 188-483 lb), and their mean body mass index was 48.5 +/- 6.6 (range, 36-70). The mean operative time was 103. 3 +/- 24.3 min (range, 62-227 min), and mean American Society of Anesthesiology (ASA) score was 2.6. Nine patients had clinical evidence of severe, chronic venous disease preoperatively. One patient (0.26%) experienced a clinically evident DVT limited to the popliteal vein on duplex ultrasonography. The clot resolved completely, as evidenced by follow-up duplex ultrasonography after 2 weeks of subcutaneously injected fractionated heparin. No clinically evident pulmonary thromboembolism occurred in this study group., Conclusions: The incidence of clinically evident DVT after laparoscopic Roux-en-Y gastric bypass is low when the procedure is accomplished with a relatively short operative time, with the initiation of calf-length pneumatic compression hose before the induction of anesthesia, and with routine early ambulation. No form of heparin anticoagulation is mandatory when these conditions can be met.