National outcomes of bridge to multiorgan cardiac transplantation using mechanical circulatory support.

BACKGROUND: Little is known regarding the profile of patients with multiorgan failure listed for simultaneous cardiac transplantation and secondary organ. In addition, few studies have reported how these patients are bridged with mechanical circulatory support (MCS). In this study, we examined national data of patients listed for multiorgan transplantation and their outcomes after bridging with or without MCS. METHODS: United Network for Organ Sharing data were reviewed for adult multiorgan transplantations from 1986 to 2019. Post-transplant patients and total waitlist listings were examined and stratified according to MCS status. Survival was assessed via Cox regression in the post-transplant cohort and Fine-Gray competing risk regression with transplantation as a competing risk in the waitlist cohort. RESULTS: There were 4534 waitlist patients for multiorgan transplant during the study period, of whom 2117 received multiorgan transplants. There was no significant difference in post-transplant survival between the MCS types and those without MCS in the whole cohort and heart-kidney subgroup. Fine-Gray competing risk regression showed that patients bridged with extracorporeal membrane oxygenation had significantly greater waitlist mortality compared with those without MCS when controlling for preoperative characteristics (subdistribution hazard ratio, 2.27; 95% confidence interval, 1.48-3.47; P < .001), whereas those bridged with a ventricular assist device had a decreased incidence of death compared with those without MCS (subdistribution hazard ratio, 0.78; 95% confidence interval, 0.63-0.96; P = .017). CONCLUSIONS: MCS, as currently applied, does not appear to compromise the survival of multiorgan heart transplant patients. Waitlist data show that extracorporeal membrane oxygenation patients have profoundly worse survival irrespective of preoperative factors including organ type listed. Survival on the waitlist for multiorgan transplant has improved across device eras.

Higher Institutional Volume Reduces Mortality in Reoperative Proximal Thoracic Aortic Surgery.

OBJECTIVE: This study aims to determine the impact of institutional volume on mortality in reoperative proximal thoracic aortic surgery patients using national outcomes data. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 for patients with diagnoses of thoracic aneurysm and/or dissection who underwent open mediastinal repair. A total of 103,860 patients were identified. A total of 1,430 patients had prior cardiac surgery. Patients were further stratified into groups by institutional aortic volume: low (<12 cases/year), medium (12-39 cases/year), and high (40+ cases/year) volume. Multivariable risk-adjusted analysis accounting for emergent status and aortic dissection among other factors was performed to determine the impact of institutional volume on mortality. RESULTS: Overall mortality was 12% in the reoperative population. When the redo cohort was divided into tertiles, high-volume group had a 5% operative mortality compared with 9 and 15% for the medium- and low-volume groups, respectively. Multivariable analysis revealed that patients operated on at low- (odds ratio [OR] = 5.0, 95% confidence interval [CI]: 2.6-9.6, p < 0.001) and medium-volume centers (OR = 2.1, 95% CI: 1.1-4.2, p = 0.03) had higher odds of mortality when compared with patients operated on at high-volume centers. CONCLUSIONS: High-volume aortic centers can significantly reduce mortality for reoperative aortic surgery, compared with lower volume institutions.

Outcomes of bridge to cardiac retransplantation in the contemporary mechanical circulatory support era.

BACKGROUND: Outcomes have improved in patients bridged to heart transplant on contemporary continuous-flow ventricular assist devices over the past decade. We evaluated mechanical circulatory support as a means to bridge patients to cardiac retransplantation. METHODS: We retrospectively reviewed 464 patients who underwent cardiac retransplant from the United Network for Organ Sharing database between January 2006 and November 2016. Pre- and post-transplant data were compared between patients bridged to retransplant with mechanical circulatory support (n = 81) and those without mechanical circulatory support (n = 383). RESULTS: The mean ages for the patients in the mechanical circulatory support and nonmechanical circulatory support cohorts were 41.2 ± 16 years and 42.1 ± 15.7 years, respectively (P = .64). Patients bridged with mechanical circulatory support were placed on extracorporeal membrane oxygenation (n = 29, 35.8%), a total artificial heart (n = 13, 16.0%), or a temporary or durable ventricular assist device (n = 39, 48.1%). Twelve patients (14.8%) were placed on a second device before retransplant. Thirty-nine percent of the mechanical circulatory support group were indicated for listing because of primary graft dysfunction or acute rejection versus 6% of the nonmechanical circulatory support group (P < .01). Likewise, 30% of patients in the mechanical circulatory support group were listed for cardiac allograft vasculopathy compared with 59% of the nonmechanical circulatory support group (P < .01). Thirty-day mortality was significantly higher in the mechanical circulatory support group (17.8% vs 4.8%, P < .01). However, patients who were bridged with a ventricular assist device or total artificial heart had comparable midterm outcomes to the nonmechanical circulatory support group. CONCLUSIONS: Patients who require mechanical circulatory support bridge to retransplantation belong to a high-risk cohort. Comparable midterm outcomes to the nonmechanical circulatory support cohort were demonstrated when patients' conditions allow for bridge with a ventricular assist device or total artificial heart. Bridging to retransplantation with extracorporeal membrane oxygenation remains a relative contraindication.

Development and Evaluation of a Multiplexed Immunoassay for Simultaneous Detection of Serum IgG Antibodies to Six Human Coronaviruses.

Known human coronaviruses (hCoV) usually cause mild to moderate upper-respiratory tract illnesses, except SARS-CoV and MERS-CoV, which, in addition to mild illness can also be associated with severe respiratory diseases and high mortality rates. Well-characterized multiplexed serologic assays are needed to aid in rapid detection and surveillance of hCoVs. The present study describes development and evaluation of a multiplexed magnetic microsphere immunoassay (MMIA) to simultaneously detect immunoglobulin G (IgG) antibodies specific for recombinant nucleocapsid proteins (recN) from hCoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV. We used paired human sera to screen for IgG with reactivity against six hCoVs to determine assay sensitivity, specificity and reproducibility. We found no signal interference between monoplex and multiplex assay formats (R2 range = 0.87-0.97). Screening of paired human sera using MMIA, resulted in 92 of 106 (sensitivity: 86%) as positive and 68 of 80 (specificity: 84%) as negative. This study serves as a proof of concept that it is feasible to develop and use a multiplexed microsphere immunoassay as a next generation screening tool for use in large scale seroprevalence studies of hCoVs.

Use Side Branch of the Aortic Graft to Facilitate Coronary Reconstruction During Complex Aortic Surgery.

The interposition graft could be used for difficult coronary reconstruction during aortic root replacement. We introduced a new technique that utilizes side branch of an aortic graft to facilitate coronary reconstruction. The present study describes this technique and its outcomes. We retrospectively reviewed 234 patient charts of those who underwent aortic root replacement between January 2013 and November 2017. Within this group, 6 patients required coronary reconstruction with branches of aortic graft and were included in this study. All patients were reoperative cases, 3 of which were for acute type A aortic dissection. The mean cardiopulmonary and aortic cross clamp times were 317.2 ± 35.1 minutes and 153.3 ± 75.4 minutes, respectively. All patients survived to discharge with a median hospital stay of 20.5 days (interquartile range: 13.75-27.75). During a median follow-up of 221 days (interquartile range: 197.78-1208), no patients experienced major adverse cardiovascular events. Four patients underwent radiographic follow-up, which confirmed patent interposition grafts (5/5). The use of branches from the aortic graft for coronary reconstruction is feasible with satisfactory outcomes.

Evidence of Kinetic Cooperativity in Dimeric Ketopantoate Reductase from Staphylococcus aureus.

Ketopantoate reductase (KPR) catalyzes the NADPH-dependent production of pantoate, an essential precursor in the biosynthesis of coenzyme A. Previous structural studies have been limited to Escherichia coli KPR, a monomeric enzyme that follows a sequential ordered mechanism. Here we report the crystal structure of the Staphylococcus aureus enzyme at 1.8 Å resolution, the first description of a dimeric KPR. Using sedimentation velocity analysis, we show that the S. aureus KPR dimer is stable in solution. In fact, our structural analysis shows that the dimeric assembly we identify is present in the majority of KPR crystal structures. Steady state analysis of S. aureus KPR reveals strong positive cooperativity with respect to NADPH (Hill coefficient of 2.5). In contrast, high concentrations of the substrate ketopantoate (KP) inhibit the activity of the enzyme. These observations are consistent with a random addition mechanism in which the initial binding of NADPH is the kinetically preferred path. In fact, Förster resonance energy transfer studies of the equilibrium binding of NADPH show only a small degree of cooperativity between subunits (Hill coefficient of 1.3). Thus, the apparently strong cooperativity observed in substrate saturation curves is due to a kinetic process that favors NADPH binding first. This interpretation is consistent with our analysis of the A181L substitution, which increases the Km of ketopantoate 844-fold, without affecting kcat. The crystal structure of KPRA181L shows that the substitution displaces Ser239, which is known to be important for the binding affinity of KP. The decrease in KP affinity would enhance the already kinetically preferred NADPH binding path, making the random mechanism appear to be sequentially ordered and reducing the kinetic cooperativity. Consistent with this interpretation, the NADPH saturation curve for KPRA181L is hyperbolic.