Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The 2014 Zaire Ebola virus disease epidemic accelerated vaccine development for the virus. We aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in adults. METHODS: This phase 2, randomised, observer-blind, controlled trial was done in study centres in Cameroon, Mali, Nigeria, and Senegal. Healthy adults (≥18 years) were randomly assigned with a web-based system (1:1; minimisation procedure accounting for age, gender, centre) to receive ChAd3-EBO-Z (day 0), or saline placebo (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind until planned interim day 30 analysis, single-blind until month 6, and open-label after month 6 vaccination. Primary outcomes assessed in the total vaccinated cohort, which comprised all participants with at least one study dose administration documented, were serious adverse events (up to study end, month 12); and for a subcohort were solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). Secondary endpoints (subcohort; per-protocol cohort) evaluated anti-glycoprotein Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02485301. FINDINGS: Between July 22, 2015, and Dec 10, 2015, 3030 adults were randomly assigned; 3013 were included in the total vaccinated cohort (1509 [50·1%] in the ChAd3-EBO-Z group and 1504 [49·9%] in the placebo/ChAd3-EBO-Z group), 17 were excluded because no vaccine was administered. The most common solicited injection site symptom was pain (356 [48%] of 748 in the ChAd3-EBO-Z group vs 57 [8%] of 751 in the placebo/ChAd3-EBO-Z group); the most common solicited general adverse event was headache (345 [46%] in the ChAd3-EBO-Z group vs 136 [18%] in the placebo/ChAd3-EBO-Z group). Unsolicited adverse events were reported by 123 (16%) of 749 in the ChAd3-EBO-Z group and 119 (16%) of 751 in the placebo/ChAd3-EBO-Z group. Serious adverse events were reported for 11 (1%) of 1509 adults in the ChAd3-EBO-Z group, and 18 (1%) of 1504 in the placebo/ChAd3-EBO-Z group; none were considered vaccination-related. No clinically meaningful thrombocytopenia was reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentration was 900 (95% CI 824-983) in the ChAd3-EBO-Z group. There were no treatment-related deaths. INTERPRETATION: ChAd3-EBO-Z was immunogenic and well tolerated in adults. Our findings provide a strong basis for future development steps, which should concentrate on multivalent approaches (including Sudan and Marburg strains). Additionally, prime-boost approaches should be a focus with a ChAd3-based vaccine for priming and boosted by a modified vaccinia Ankara-based vaccine. FUNDING: EU's Horizon 2020 research and innovation programme and GlaxoSmithKline Biologicals SA

Regional Variation in Arterial Saturation and Oxygen Delivery during Venoarterial Extracorporeal Membrane Oxygenation

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be lifesaving in patients with cardiopulmonary collapse. However, observation studies have implied that oxygenated blood does not pass in a retrograde fashion from the VA-ECMO circuit to the aortic root and arch when the femoral artery (FA) is used. This study aims at accurately measuring the oxygen saturation in various arteries during VA-ECMO through different cannula sites. A total of 20 patients with VA-ECMO were in the study. Fourteen patients had FA cannulation, two patients received axillary arterial (AA) cannulation, and four patients received cannulation of the ascending aorta. Oxygen saturation was measured simultaneously in the radial artery and oxygenator outlet. In the patient group with FA cannulation, the oxygen saturation was lower in the radial artery (97%) when compared with the oxygenator outlet (>99%). In the subset group of patients with severe lung dysfunction, oxygen saturation was even lower in the radial artery (73% saturation). In the patient group with AA cannulation, the oxygen saturation and partial oxygen pressure (PO2) in the oxygenator outlet and radial artery were similar (99% or greater). In the patient group with direct ascending aorta cannulation, the oxygen saturation and PO2 in the oxygenator outlet and radial artery were similar as well. Regional variations occur in the blood oxygen saturation depending on the site of the arterial cannulation in patients with VA-ECMO. With FA cannulation, the oxygen saturation in the radial artery is significantly lower than the one in the oxygenator outlet. This may imply that the coronaries and the brain receive hypoxic blood from the left ventricle. These results suggest that antegrade cannulation for VA-ECMO improves oxygen delivery to the proximal aorta distribution

Is Blood Conservation Optimally Utilized?

Blood conservation and the subsequent prevention of transfusion have assumed an increasingly important role in cardiac surgery. The concern is one of preventing transmission of transfusion related diseases and of conserving an extremely valuable resource (1,2). Cardiac surgery with cardiopulmonary bypass has become the most common operation performed, thus attracting much analysis of transfusion practices. It is estimated that of the approximately 250,000 cardiopulmonary bypass procedures done in the United States each year, the majority require transfusion of blood products (3). It has been calculated that the cardiac surgery services throughout the United States use somewhat over 10% of all the blood product resources that are transfused in this country (4,5). Many methods of blood conservation have been described (Table 1), but there still exists a wide variance in blood product utilization for adult patients undergoing cardiopulmonary bypass procedures. A review of the literature reveals average packed red blood cell transfusion rates from 0.3 up to 8 units per patient (4,6-8). If we further add the transfusion of platelets, fresh frozen plasma, and cryoprecipitate, the total donor exposure to the patient goes up substantially more. A varied patient population has been cited as the reason for these discrepancies but it has been demonstrated in similarly matched groups of patients receiving transfusions, that the patterns were based to some extent upon "prevailing practice" rather than on need (9,10). The purpose of this study was to identify which methods of blood conservation were being practiced in a major metropolitan area within the United States where the risk of transfusion related disease is relatively high. Secondly, to stratify the frequency of use of particular blood conservation methods in order to estimate how often a particular method was utilized and by what percentage of respondents. Finally, to increase the awareness of the options and difficulties associated with current modalities of transfusion practice and blood conservation

Variability in End-Organ Perfusion with Femoral-Femoral Venoarterial Extracorporeal Membrane Oxygenation: Aortographic Evidence

In femoral-femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO), the outflow of oxygenated blood from the circuit enters the aorta in retrograde fashion. As a result, variability in end-organ oxygenation (e.g., cerebral vs. splanchnic) may arise—particularly, when the heart is unable to contribute forward flow. We present the case of a 74-year-old man supported by femoral-femoral VA-ECMO in whom aortography was used to visualize the retrograde distribution of arterial ECMO flow that can produce such differences in end-organ perfusion. We do this by describing a series of still images captured during the aortography; we then discuss the importance of monitoring end-organ oxygenation in this setting and outline several interventions that can ameliorate this flow phenomenon

A Novel Method for Percutaneous Insertion of a Right Ventricular Assist Device

Right heart failure is a rare but often fatal complication both in the pre- and postoperative setting. Right heart support with a ventricular assist device inserted in the operating room through median sternotomy can be a time-consuming procedure that requires a reoperation for removal. In cases of urgent need of right heart support, a percutaneous technique option may be of benefit. We present our initial experience with a percutaneously inserted right ventricular assist device (RVAD) in an elderly patient with severe right heart failure. An 81-year-old female patient underwent combined aortic and mitral valve replacement at our institution. During the first postoperative evening, the patient sustained sudden cardiovascular collapse and a bedside transesophageal echocardiogram revealed severe right heart failure. A coronary angiogram showed thrombosis of the right coronary artery, which was cleared with a suction device. As a result of the patient’s critical condition, it was decided that an RVAD was needed as a bridge to recovery. The patient’s condition improved significantly almost immediately. Her right heart function recovered over the next few days and the RVAD was removed at the bedside. She made a complete recovery and was discharged home. This patient is a prime example that a totally RVAD can be inserted in urgent situations easily and safely under fluoroscopic and echocardiographic guidance. More clinical experience with percutaneous RVADs is required to establish this technique as an alternative equivalent to the traditional open method. Right heart failure complicates many heart diseases both in the pre- and the postoperative setting. In cases of urgent need of right heart support, a percutaneous technique of a RVAD is needed for a successful outcome. We present our initial experience with a percutaneously inserted RVAD in an elderly patient with severe postoperative right heart failure

Improved Environmental Impact with Diversion of Perfusion Bypass Circuit to Municipal Solid Waste

The project goal was to reduce waste disposal volume, costs and minimize the negative impact that regulated waste treatment and disposal has on the environment. This was accomplished by diverting bypass circuits from the traditional regulated medical waste (RMW) to clear bag waste, or municipal solid waste (MSW). To qualify circuits to be disposed of through MSW stream, the circuits needed to be void of any free-flowing blood and be “responsibly clear.” Traditionally the perfusion bypass circuit was emptied through the cardioplegia pump starting shortly after decannulation and heparin reversal. Up to 2000 mL of additional prime solution was added until the bypass circuit was rinsed clear. Three hundred sixty of 400 procedures (90%) had a complete circuit rinse and successful diversion to MSW. An additional 240 mL of processed cell salvage blood was available for transfusion. No additional time was spent in the operating room as a result of this procedure. Based on our procedure case volume and circuit weight of 15 pounds, almost 15,000 pounds (7.5 tons) of trash will be diverted from RMW. This technique represents another way for perfusionists to participate in sustainability efforts. Diverting the bypass circuit to clear bag waste results in a reduced environmental impact and annual cost savings. The treatment of RMW is associated with various environmental implications. MSW, or clear bag waste, on the other hand can now be disposed of in waste-to-energy facilities. This process not only releases a significantly less amount of carbon dioxide into the environment, but also helps generate renewable energy. Therefore, the bypass circuit diversion pilot project effectively demonstrates decreases in the carbon footprint of our organization and overall operating costs

Extracorporeal Membrane Oxygenation as a Bridge through Chemotherapy in B-Cell Lymphoma

A 41-year-old female presented with a large anterior mediastinal mass adjacent to the heart. Biopsy demonstrated lymphoma. Upon administration of chemotherapy, she developed cardiogenic shock requiring a 5-day course of extracorporeal membrane oxygenation (ECMO) as a bridge through her treatment. After one cycle of chemotherapy, ECMO was discontinued and the patient completed her course of chemotherapy and recovered to hospital discharge

Centrifugal Pumping: The Patient Outcome Benefits Following Coronary Artery Bypass Surgery

The increased use of the centrifugal pump during coronary artery bypass surgery has been based primarily on theoretical data related to patient safety. There is minimal evidence suggesting improved outcome when compared to the traditional roller pump technology. We prospectively randomized 200 patients undergoing elective coronary artery bypass grafting into centrifugal pump (100 patients) and roller pump (100 patients) groups to compare differences in blood product usage, complication rate, length of stay and net hospital financial balance. Moderate hypothermic bypass was employed on all patients. Cardiopulmonary bypass circuits were similar in both groups with the exception of the arterial pump. Both groups were statistically identical in regard to age, sex, surgeon, complications, total pump time, aortic cross clamp time, prebypass hematocrit and platelet count. The twenty-four hour postoperative hematocrits, platelet counts, red blood cell requirements, blood loss and mortality (2%) were identical in both groups. The centrifugal pump patients had less 24 hour weight gain than their peers in the roller pump group (p=0.05) The length of stay and net hospital financial balance were also statistically favored in the centrifugal pump group (p<0.05). These latter findings were significant when studied in all payors and coronary artery bypass diagnostic related group classifications. Although the mechanism for improvement in length of stay and net hospital financial balance cannot fully be explained, the ramifications in an increasingly cost conscious environment are obvious

Cardiopulmonary Bypass in Patients With Pre-existing Coagulopathy

Patients with pre-existing coagulopathies who undergo surgical interventions are at increased risk for bleeding complications. This risk is especially true in cardiac surgical procedures with cardiopulmonary bypass (CPB) because of the necessity for heparinization and the use of the extracorporeal circuits, which have destructive effects on most of the blood components. In this review, cases of cardiac surgeries in patients with certain pre-existing coagulopathies are summarized, which could shed a light on future managements of such patients undergoing cardiac procedures with CPB. Pre-existing coagulopathies include antithrombin III deficiency, heparin-induced thrombocytopenia, cancer, factor XII deficiency, hemophilia, idiopathic thrombocytopenic purpura, protein S deficiency, and drug-induced platelet inhibition. In summary, pre-existing coagulopathy in patients undergoing open-heart surgeries, if not recognized and appropriately managed, can cause serious complications. Management of patients undergoing cardiac procedures should include a routine coagulation work-up and a thorough past medical history examination. If any of the foregoing is abnormal, further evaluation is warranted. Proper diagnosis and management of the pre-existing coagulopathy disorders is of crucial importance to the surgical outcome and long-term morbidity