Severe re‐expansion pulmonary edema after conventional cardiac surgery: Identification and management

Re‐expansion Pulmonary Edema (REPE) is a recognized but rare complication of lung re‐inflation after pathologic collapse or intentional deflation. The presentation of REPE may be highly variable, ranging from a clinically asymptomatic, incidental radiologic finding to acute respiratory failure accompanied by severe, life‐threatening hypoxemia. With the current report, we present a patient with severe aortic insufficiency, severe mitral regurgitation, coronary artery disease, pulmonary hypertension, who underwent aortic valve replacement, mitral valvuloplasty, coronary artery bypass grafting, and developed at the immediate post‐ operative period severe respiratory failure due to REPE, requiring venous‐venous Extracorporeal Membrane Oxygenation (VV‐ECMO).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149568/1/jocs14057.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149568/2/jocs14057_am.pd

Europa Clipper Preliminary Design Review Propellant Slosh Analysis

This presentation outlines the preliminary design review (PDR) propellant slosh analysis done for the Europa Clipper Mission. It provides sample results for both high acceleration pendulum-damper models and low acceleration pendulum-spring-damper models. The high acceleration pendulum-damper models were derived from STAR-CCM+ computational fluid dynamic (CFD) simulations and the low acceleration pendulum-spring-damper models were derived from Surface Evolver models

Simulation of Many-Body Fermi Systems on a Universal Quantum Computer

We provide fast algorithms for simulating many body Fermi systems on a universal quantum computer. Both first and second quantized descriptions are considered, and the relative computational complexities are determined in each case. In order to accommodate fermions using a first quantized Hamiltonian, an efficient quantum algorithm for anti-symmetrization is given. Finally, a simulation of the Hubbard model is discussed in detail.Comment: Submitted 11/7/96 to Phys. Rev. Lett. 10 pages, 0 figure

Outcomes of surgical coronary revascularization performed pre-solid abdominal organ transplant

Background Cardiac risk stratification and coronary angiography are routinely performed as part of kidney and liver transplant candidacy evaluation. There are limited data on the outcomes of surgical coronary revascularization in this patient population. We investigated outcomes in patients with end stage renal or hepatic disease undergoing coronary artery bypass grafting (CABG) to attain kidney or liver transplant candidacy. Methods Retrospective analysis of all patients who underwent isolated CABG at our institution between 2010 and 2016. Patients were divided into two cohorts: Pre-transplant (those undergoing surgery to attain renal or hepatic transplant candidacy) and Non-transplant (all others). Baseline characteristics and postoperative outcomes were compared between groups. Results A total of 1801 patients were included: 28 in Pre-transplant (n=22 kidney, n=7 liver) and 1773 in Non-transplant. Major adverse postoperative outcomes were significantly greater in Pre-transplant compared to Non-transplant: 30-day mortality (14.3% vs. 2.8%, p=0.009), neurologic events (17.9% vs. 4.8%, p=0.011), re-intubation (21.4% vs. 5.8%, p=0.005) and total postoperative ventilation (5.2 vs. 5.0 hours, p=0.0124). One- and five-year mortality in Pre-transplant was 17.9% and 53.6%, respectively. Of the Pre-transplant cohort, three patients (10.7%) underwent organ transplantation (all kidneys) at a mean 436 days after CABG. No patients received liver transplantation. Conclusions Outcomes following CABG in the pre-kidney and pre-liver transplant population are poor. Despite surgical revascularization, the vast majority of patients do not ultimately undergo transplantation. Revascularization strategies and optimal management in this high-risk population warrants further study

Mobilization of xanthine oxidase from the gastrointestinal tract in acute pancreatitis

BACKGROUND: Xanthine oxidoreductase has been proposed to play a role in the development of local and systemic effects of acute pancreatitis. Under physiologic conditions, the enzyme exists mainly as xanthine dehydrogenase (XDH) but can be converted by proteolytic cleavage to its superoxide-generating form xanthine oxidase (XOD). In addition to its intracellular location XDH/XOD is also associated to the polysaccharide chains of proteoglycans on the external endothelial cell membrane. In the early stages of acute pancreatitis, this enzyme seems to be arising from its mobilization from the gastrointestinal endothelial cell surface. Taking into account the ability of α-amylase to hydrolyze the internal α-1,4 linkages of polysaccharides, we wanted to elucidate the involvement of α-amylase in XDH/XOD mobilization from the gastrointestinal endothelial cell surface and the relevance of the ascitic fluid (AF) as the source of α-amylase in experimental acute pancreatitis. METHODS: Acute pancreatitis was induced in male Wistar rats by intraductal administration of 5% sodium taurocholate. In another experimental group 3000 U/Kg α-amylase was i.v. administered. The concentrations of XDH, XOD and α-amylase in plasma and AF and myeloperoxidase (MPO) in lung have been evaluated. In additional experiments, the effect of peritoneal lavage and the absorption of α-amylase present in the AF by an isolated intestine have been determined. RESULTS: Similar increase in XDH+XOD activity in plasma was observed after induction of acute pancreatitis and after i.v. administration of α-amylase. Nevertheless, the conversion from XDH to XOD was only observed in the pancreatitis group. Lung inflammation measured as MPO activity was observed only in the pancreatitis group. In addition peritoneal lavage prevented the increase in α-amylase and XDH+XOD in plasma after induction of pancreatitis. Finally, it was observed that α-amylase is absorbed from the AF by the intestine. CONCLUSIONS: During the early stages of acute pancreatitis, α-amylase absorbed from AF through the gastrointestinal tract could interfere with the binding of XDH/XOD attached to glycoproteins of the endothelial cells. Proteolytic enzymes convert XDH into its oxidase form promoting an increase in circulating XOD that has been reported to be one of the mechanisms involved in the triggering of the systemic inflammatory process

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III)

Background: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20–40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier 1), followed by phone screening and medical records review (tier 2) prior to a final in-person visit to confirm eligibility and consent. Methods: Two tiers of screening were established: an initial screen of general eligibility using a patient-facing web portal (tier 1), followed by a more detailed screen that included phone survey and medical record review (tier 2). If potential participants passed the tier 2 screen, they were referred directly to visit 1 at a study site, where final in-person screening and consent were performed. Rates of screening were tracked during the period of trial recruitment and sources of referrals were noted. Results: The approach to screening and recruitment resulted in 6125 tier 1 screens, leading to 1121 referrals to tier 2. The tier 2 screening resulted in 224 medical record requests and identification of 86 qualifying participants for referral to sites. The study attained a viable recruitment rate of 6 enrolled per month prior to being disrupted by COVID 19. Conclusions: A tiered approach to eligibility screening using a hybrid of web-based portals to self-identify and screen for general eligibility followed by a more detailed phone and medical record review allowed the study to use fewer sites and reduce cost. Despite the difficult and narrow population of patients suffering moderate chronic disability from stroke, this strategy produced a viable recruitment rate for this invasive study of intracranially injected neural stem cells

Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6–12 months after an index ischemic stroke. Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6–12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate or moderately severe disability (mRS 3 or 4), with the preservation of some residual upper limb movement. All patients received a standardized regimen of home physical therapy following the intervention. Study outcomes: The primary outcome measure is improvement in the modified Rankin Scale (mRS) of disability at 6 months post treatment. Secondary outcomes include assessment of activities of daily living (Barthel Index), functional mobility (Timed Up and Go; Fugl Meyer Assessment), neurological impairment (NIHSS), upper limb function (Chedoke Arm and Hand Inventory), as well as patient related quality of life and global rating scales. Discussion: PISCES III was designed as a randomized trial directly comparing the effects of intraparenchymal injection of a conditional stem cell line vs. sham procedure in patients with subacute stroke. This is one of the first studies of this type to include a standardized minimum rehabilitation protocol. As there are a limited number of studies evaluating invasive stem cell administration in the chronic setting of CNS injury, study design considerations are discussed