The Future of Islet Transplantation Is Now

Milestones in the history of diabetes therapy include the discovery of insulin and successful methods of beta cell replacement including whole pancreas and islet cell transplantation options. While pancreas transplantation remains the gold standard for patients who have difficulty controlling their symptoms with exogenous insulin, islet allotransplantation is now able to provide similar results with some advantages that make it an attractive potential alternative. The Edmonton Protocol, which incorporated a large dose of islets from multiple donors with steroid-free immunosuppression helped to establish the modern era of islet transplantation almost 20 years ago. While islet allotransplantation is recognized around the world as a powerful clinical therapy for type 1 diabetes it is not yet recognized by the Federal Drug Administration of the United States. Large-scale clinical trials administered by the Clinical Islet Transplantation Consortium have recently demonstrated that the well-regulated manufacture of a human islet product transplanted into patients with difficult to control type 1 diabetes and with a history of severe hyperglycemic episodes can safely and efficaciously maintain glycemic balance and eliminate the most severe complications associated with diabetes. The results of these clinical trials have established a strong basis for licensure of clinical islet allotransplantation in the US. Recognition by the Federal Drug Administration would likely lead to third party reimbursement for islet allotransplantation as a therapeutic option in the United States and would make the treatment available to many more patients. The high costs of rampant diabetes justify the expense of the treatment, which is in-line with the costs of clinical pancreas transplantation. While much enthusiasm and hope is raised toward the development and optimization of stem cell therapy, the islet transplantation community should push toward licensure, if that means broader access of this procedure to patients who may benefit from it. Even as we prepare to take the first steps in that direction, we must acknowledge the new challenges that a shift from the experimental to clinical will bring. Clinical islet allotransplantation in the United States would be a game-changing event in the treatment of type 1 diabetes and also generate enthusiasm for continued research

'High dose' aprotinin and heparin-coated circuits: clinical efficacy and inflammatory response

Heparin-coated cardiopulmonary bypass circuits reduce the inflammatory response to cardiopulmonary bypass circuit, improve biocompatibility and may protect the postoperative hemostasic mechanisms in routine coronary bypass operations. 'High-dose' aprotinin reduces bloodloss, transfusion needs, and re-explorations as a result of bleeding, and may have an additional role in reducing the inflammatory response of the body to cardiopulmonary bypass circuit. It has not been established, however, if the addition of a heparin-coated circuit to the intraoperative administration of 'high dose' aprotinin further reduces the whole-body inflammatory response to cardiopulmonary bypass circuit and improves the postoperative clinical course of the patients who are undergoing coronary surgery. Thirty patients undergoing primary elective coronary artery bypass grafting were studied. All the patients received, intraoperatively, the serine-protease inhibitor aprotinin according to the 'Hammersmith' protocol and full heparin dose. Patients were randomly allocated to be treated either with a circuit completely coated with surface-bound heparin (n = 15) or with an uncoated, but otherwise identical, circuit (n = 15). Differences in the clinical course of the two groups of patients, as well as differences in the behavior of hematological and inflammatory (interleukin-6 (IL-6) and C-reactive protein) factors before, during and after bypass, were analyzed. There were no significant differences between the two groups in terms of bleeding and transfusional requirements, the time spent on a ventilator, or in duration of stay in the intensive care unit (ICU). In all patients, a significant increase in the total white blood cell count, neutrophils, serum IL-6 and C-reactive protein occurred in relation to cardiopulmonary bypass. This was not influenced by heparin precoating of the circuit. In addition, there was an increase in the monocyte count during follow-up, and there was a trend towards higher monocyte counts in the patients who were treated with heparin-coated circuits. These results suggest that the addition of a heparin-coated circuit to the intraoperative 'high-dose' aprotinin therapy probably had little influence on the clinical course and on the time-course of the inflammatory parameters of the adult patients undergoing primary coronary surgery with a full heparinization protocol

Il consumo di ossigeno nella chirurgia cardiovascolare condotta con l'utilizzo della circolazione extracorporea

Whole-body oxygen consumption (VO2) is universally considered both a measure of the metabolic activity of the body and an indicator of the adequacy of tissue perfusion during cardiopulmonary bypass as well. There is little agreement in the literature about the main determinants of oxygen consumption during CPB, except for the role of temperature in reducing the metabolic activity of the body. Many studies, which have been performed both on animals and in humans, have reached some contradictory conclusions about the role of delivery and perfusion flow rates, of haemodynamic variables, of the acid-base status, and of drugs influencing the variations of oxygen consumption during CPB. Aim of this paper is to review the evidences in literature about the determinants of whole-body oxygen consumption during cardiopulmonary bypass in man

In vivo comparison of the optiflow and EZ glide aortic dispersion cannulas

OBJECTIVES: Morbidity associated with coronary artery bypass grafts and embolization during aortic cannulation is strongly related to patient characteristics/comorbidities, arterial cannulation site used and the shape of arterial cannulae tips. The desired features of an arterial cannula should be to mitigate the morbid effects of these cannulas and to focus on achieving higher blood flows with lower cannula pressures (CPs). MATERIALS AND METHODS: To evaluate the in vivo performance of two aortic dispersion flow cannulas: the Optiflow (Sorin Group, Italy) and EZ Glide (Edwards Lifesciences). They were evaluated for CPs, pump-flow rates (FRs), and plasma-free hemoglobin (Hb) over a 12-month period. Data were collected in a prospective, randomized (1:1), nonblinded, monocentric study with a cohort of 30 patients (optiflow group N\u2009=\u200915; EZ Glide group N\u2009=\u200915). RESULTS: The optiflow cannula was found to have decreasing CPs as the pump FRs were increased (112.3\u2009\ub1\u200910.9 vs 131.1\u2009\ub1\u200911.4\u2009mm\u2009Hg; P\u2009<\u2009.001). Results indicated no significant differences between groups for increases in plasma free Hb (P\u2009=\u2009.41) and total microembolic signals counts during the period of cardiac surgery (P\u2009=\u2009.63). CONCLUSIONS: Both optiflow and EZ Glide dispersion flow arterial cannulas performed well, but the optiflow cannula demonstrated an ability to increase pump FRs with lower arterial line and CPs than the EZ Glide cannula. This implies an ability to improve peripheral perfusion while reducing cannula shear stress and the risk of endothelial damage, thereby having the potential to reduce the risk of atherosclerotic plaque dislodgement

Centrifugal pump and reduction of neurological risk in adult cardiac surgery

This study was performed to assess if the kind of pump used for CPB (roller vs. centrifugal) can influence neurological outcomes of adult cardiac surgery patients. Between 1994 and 1998, 3438 patients underwent coronary and/or valve surgery at our hospital; of these, 1805 (52.5%) underwent surgery with the use of a centrifugal pump, and 1633 (47.5%) were operated with a roller pump. The effect of the type of the pump and of common preoperative and intraoperative risk factors for five different neurological outcomes (permanent neurological deficit, coma, delirium, transient neurological deficit, overall neurological complications) were assessed with univariate and multivariate analyses in the whole patients population, in patients > or = 75 years old and in patients with histories of previous neurological events. Centrifugal pump use was the only protective factor for perioperative permanent neurological deficit in multivariable models developed for the whole patient population and for patients > or = 75 years old. In addition, it resulted as the only protective factor for perioperative coma occurrence in multivariable models developed for patients > or = 75 years old, and for patients with histories of previous neurological events. The use of the centrifugal pump provided a risk reduction for the considered events ranging from 23 to 84%. Centrifugal pump use can be helpful in reducing the occurrence of some of the most feared neurological complications of adult cardiac surgery patients