Along party Lines: Examining the gubernatorial party difference in COVID-19 mortality rates in U.S. Counties.

Drawing upon the literatures on risk factors for COVID-19 and the roles of political party and political partisanship in COVID-19 policies and outcomes, this study quantifies the extent to which differences in Republican- and Democrat-governed counties' observable characteristics explain the Republican - Democrat gap in COVID-19 mortality rate in the United States. We analyze the county COVID-19 mortality rate between February 1 and December 31, 2020 and employ the Blinder-Oaxaca decomposition method. We estimate the extent to which differences in county characteristics - demographic, socioeconomic, employment, health status, healthcare access, area geography, and Republican vote share, explain the difference in COVID-19 mortality rates in counties governed by Republican vs Democrat governors. Among 3,114 counties, Republican-governed counties had significantly higher COVID-19 mortality than did Democrat-governed counties (127 ± 86 vs 97 ± 80 per 100,000 population, p < 0.001). Results are sensitive to which weights are used: of the total gap of 30.3 deaths per 100,000 population, 12.8 to 20.5 deaths, or 42.2-67.7 %, are explained by differences in observable characteristics of Republican- and Democratic-governed counties. Difference in support for President Trump between Republican- and Democrat-governed counties explains 25 % of the additional deaths in Republican counties. Policies aimed at improving population health and lowering racial disparity in COVID-19 outcomes may also be correlated with reducing the partisan gap in COVID-19 mortality.

Prolonged (≥24 Hours) Normothermic (≥32 °C) Ex Vivo Organ Perfusion: Lessons From the Literature.

For 2 centuries, researchers have studied ex vivo perfusion intending to preserve the physiologic function of isolated organs. If it were indeed possible to maintain ex vivo organ viability for days, transplantation could become an elective operation with clinicians methodically surveilling and reconditioning allografts before surgery. To this day, experimental reports of successfully prolonged (≥24 hours) organ perfusion are rare and have not translated into clinical practice. To identify the crucial factors necessary for successful perfusion, this review summarizes the history of prolonged normothermic ex vivo organ perfusion. By examining successful techniques and protocols used, this review outlines the essential elements of successful perfusion, limitations of current perfusion systems, and areas where further research in preservation science is required.

Narrowing performance gap between rural and urban hospitals for acute myocardial infarction care.

BACKGROUND: Rural communities experience significant barriers to quality healthcare, including disparities in medical care following acute myocardial infarctions (AMI). This study sought to determine if the population density of the county where Medicare patients were hospitalized following AMI predicted short-term outcomes and to quantify longitudinal changes in hospital performance on quality of care metrics. METHODS: Hospital-level data was queried from the 2012 and 2018 Centers for Medicare & Medicaid Services archives. Each hospital was classified based on residing county using the National Center for Health Statistics Rural-Urban Continuum Codes (RUCC). Variations and longitudinal changes in risk-adjusted outcomes and quality of care metrics were stratified by RUCC classification and analyzed. RESULTS: Among the 4798 hospitals identified, rural hospitals had significantly higher risk-adjusted 30-day mortality (rs = 0.095, p < 0.001) and decreased statin prescribed at discharge (rs = -0.066, p = 0.004). Only aspirin (R2 = 0.003, p = 0.024) and statin (R2 = 0.006, p = 0.001) prescribed at discharge were correlated with improved 30-day mortality. Despite these differences, from 2012 to 2018 the performance gap between rural and urban hospitals narrowed for all but one quality of care metric, with concurrent 1.83% [95% CI 1.76-1.90] and 3.37% [95% CI 3.30-3.44] reductions in mortality and hospital readmissions, respectively. CONCLUSIONS: In the United States, only modest variations currently exist between rural and urban hospitals in the medical care of AMI. Although the performance gap has narrowed, new strategies to improve timely and effective care are necessary to alleviate residual cardiovascular healthcare disparities in rural communities.

Impact of Left Atrial Decompression on Patient Outcomes During Pediatric Venoarterial Extracorporeal Membrane Oxygenation: A Case-Control Study.

Left heart distension during venoarterial extracorporeal membrane oxygenation (VA ECMO) often necessitates decompression to facilitate myocardial recovery and prevent life-threatening complications. The objectives of this study were to compare clinical outcomes between patients who did and did not undergo left atrial (LA) decompression, quantify decompression efficacy, and identify risk factors for development of left heart distension. This was a single-center retrospective case-control study. Pediatric VA ECMO patients who underwent LA decompression from June 2004 to March 2016 were identified, and a control cohort of VA ECMO patients who did not undergo LA decompression were matched based on diagnosis, extracorporeal cardiopulmonary resuscitation, and age. Among 194 VA ECMO cases, 21 (11%) underwent LA decompression. Compared to the control cohort, patients with decompression had longer hospital length of stay (60 ± 55 vs. 27 ± 23 days, p = 0.012), but similar in-hospital mortality (29% vs. 38%, p = 0.513). Decompression successfully decreased mean LA pressure (24 ± 11 to 14 ± 4 mmHg, p = 0.022) and LA:RA pressure gradient (10 ± 7 to 0 ± 1 mmHg, p = 0.011). No significant differences in early quantitative measures of cardiac function were observed between cases and controls to identify risk factors for left heart distension. Despite higher qualitative risk for impaired cardiac recovery, patients who underwent LA decompression had comparable outcomes to those who did not. Given that traditional quantitative measures of cardiac function are insufficient to predict development of eventual left heart distension, a combination of clinical history, radiographic findings, hemodynamic monitoring, and laboratory markers should be used during the evaluation and management of these patients.

Single Muscle Fibre Contractility Testing in Rats to Quantify Ischaemic Muscle Damage During Reperfusion Injury.

OBJECTIVES: In this study, the aim was to investigate the potential for single muscle fibre contractility (SMFC) testing to detect the extent of reperfusion injury following various reperfusion periods. The hypothesis was that force generated by muscle fibres will correlate inversely with the extent of reperfusion injury. METHODS: Twenty-four Lewis rats were distributed among five groups. Group 1 served as normal muscle control. In all other groups, femoral artery flow was occluded for four hours. Muscle biopsies were obtained at 0 hour, six hours, day two, and day seven after reperfusion in Groups 2, 3, 4, and 5, respectively. Samples then underwent ultrastructural analysis (H&E stain) and SMFC testing. RESULTS: The maximum isometric force (mN) generated on Days two and seven after reperfusion decreased from baseline by 21% (p < 0.05), and 53% (p < .001), respectively. The specific force (kPa) followed a similar pattern with a 13% decrease at Day two (p > 0.05) and 31% decrease at Day 7 (p < .001). These results correlated inversely with the extent of quantitative injury on histology. CONCLUSIONS: The study demonstrated an inverse relationship between single muscle fibre contractility testing and neutrophil infiltration during the reperfusion phase. Further clinical studies are needed to evaluate its potential in providing prognostic information for patient outcomes.

Relationship Between Time to Left Atrial Decompression and Outcomes in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation Support: A Multicenter Pediatric Interventional Cardiology Early-Career Society Study.

OBJECTIVES: To assess the variation in timing of left atrial decompression and its association with clinical outcomes in pediatric patients supported with venoarterial extracorporeal membrane oxygenation across a multicenter cohort. DESIGN: Multicenter retrospective study. SETTING: Eleven pediatric hospitals within the United States. PATIENTS: Patients less than 18 years on venoarterial extracorporeal membrane oxygenation who underwent left atrial decompression from 2004 to 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 137 patients (median age, 4.7 yr) were included. Cardiomyopathy was the most common diagnosis (47%). Cardiac arrest (39%) and low cardiac output (50%) were the most common extracorporeal membrane oxygenation indications. Median time to left atrial decompression was 6.2 hours (interquartile range, 3.8-17.2 hr) with the optimal cut-point of greater than or equal to 18 hours for late decompression determined by receiver operating characteristic curve. In univariate analysis, late decompression was associated with longer extracorporeal membrane oxygenation duration (median 8.5 vs 5 d; p = 0.02). In multivariable analysis taking into account clinical confounder and center effects, late decompression remained significantly associated with prolonged extracorporeal membrane oxygenation duration (adjusted odds ratio, 4.4; p = 0.002). Late decompression was also associated with longer duration of mechanical ventilation (adjusted odds ratio, 4.8; p = 0.002). Timing of decompression was not associated with in-hospital survival (p = 0.36) or overall survival (p = 0.42) with median follow-up of 3.2 years. CONCLUSIONS: In this multicenter study of pediatric patients receiving venoarterial extracorporeal membrane oxygenation, late left atrial decompression (≥ 18 hr) was associated with longer duration of extracorporeal membrane oxygenation support and mechanical ventilation. Although no survival benefit was demonstrated, the known morbidities associated with prolonged extracorporeal membrane oxygenation use may justify a recommendation for early left atrial decompression.

Development of an Ex-Situ Limb Perfusion System for a Rodent Model.

Ex-situ perfusion (ESP) is a promising method in preserving vascularized composite tissue allografts (VCAs) with potential to widen donor procurement to larger geographic areas. To optimize the method of preservation, we developed a small animal model to conduct biomolecular investigations. Twenty rat hind limbs (18.2 ± 1.3 g) were procured and connected to our custom-made ESP system. Perfusion pressure and flow parameters were measured with hourly blood gas analysis under near-normothermic (30-35˚C) conditions. Perfusate was prepared with swine hemoglobin (6-9 g/dL) and STEEN Solution. After 6 hours of perfusion, gastrocnemius muscles were evaluated for their histology and metabolomic profiling. Following 3 sets of experiments, perfusion was maintained at an average flow of 0.9 ± 0.24 mL/min and resulted in lactate levels of 3.78 ± 1.02 mmol/L. Metabolomic analysis revealed maintained cellular energy stores (total adenylates perfusion 0.698 ± 0.052 versus baseline 0.685 ± 0.091 umols/ug, p = 0.831), and histologic analysis revealed no evidence of barotrauma or myodegeneration. Rat hind limbs were viable after 6 hours of ESP on our miniaturized ESP system. This study is the first to document the ex-situ hind limb perfusion platform on a rodent model. These experimental findings have potential to guide future research to extend the viable duration of VCA preservation.

Incidence of Fever and Positive Bacterial Cultures in Neonates Receiving Prostaglandin.

Prostaglandin E (PGE1) is necessary to maintain ductus arteriosus patency in many newborns with congenital heart disease. Because PGE1 therapy commonly leads to fever, and given this population's fragile state, a complete sepsis workup is often performed in febrile, but otherwise asymptomatic, patients. This practice of liberal evaluation with bacterial cultures, empiric antibiotic treatment, and delays in essential surgical intervention may result in poor resource utilization and lead to increased iatrogenic morbidity. This study sought to determine the incidence of fever and culture-positive infection in patients receiving PGE1, and identify diagnostic variables that predict culture-positive infection. The study included a single-center retrospective review of all neonates receiving PGE1 between 2011 and 2014. Logistic regression and receiver operator characteristic analysis were used to identify significant predictors of positive bacterial cultures. Among 435 neonates, 175 (40%) had fevers (≥ 38.3 °C) while concurrently receiving PGE1, but only 9 (2%) had culture-positive infection and 1 (< 1%) had culture-positive bacteremia. Among 558 cultures collected, only 16 (3%) had bacterial growth. Multivariable analysis revealed age (p = 0.049, AUC 0.604), hospital length of stay (p = 0.002, AUC 0.764) and hypoxemia (p = 0.044, AUC 0.727) as the only significant predictors of positive cultures. Fever (p = 0.998, AUC 0.424) was not a significant predictor. In conclusion, given that fever occurs frequently in neonates receiving PGE1 and it is a very non-specific marker and not a predictor of positive cultures, the common practice of complete sepsis workup should be re-examined in febrile patients at low risk of bacterial illness.

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation.

Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3-12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

Ex Situ Perfusion of Human Limb Allografts for 24 Hours.

BACKGROUND: Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. METHODS: Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. RESULTS: Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. CONCLUSIONS: Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

Development of a Model of Pediatric Lung Failure Pathophysiology.

A pediatric artificial lung (PAL) is under development as a bridge to transplantation or lung remodeling for children with end-stage lung failure (ESLF). To evaluate the efficiency of a PAL, a disease model mimicking the physiologic derangements of pediatric ESLF is needed. Our previous right pulmonary artery (rPA) ligation model (rPA-LM) achieved that goal, but caused immediate mortality in nearly half of the animals. In this study, we evaluated a new technique of gradual postoperative right pulmonary artery occlusion using a Rummel tourniquet (rPA-RT) in seven (25-40 kg) sheep. This technique created a stable model of ESLF pathophysiology, characterized by high alveolar dead space (58.0% ± 3.8%), pulmonary hypertension (38.4 ± 2.2 mm Hg), tachypnea (79 ± 20 breaths per minute), and intermittent supplemental oxygen requirement. This improvement to our technique provides the necessary physiologic derangements for testing a PAL, whereas avoiding the problem of high immediate perioperative mortality.

Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload.

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts.

Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12 hour experiments demonstrated lower potassium (4.3 ± 0.8 vs. 5.0 ± 1.2 mmol/L; p = 0.018) and lactate (3.5 ± 2.8 vs. 4.5 ± 2.9 mmol/L; p = 0.139) levels, and histopathology revealed less tissue damage (p = 0.003) and less weight gain (p = 0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

Large Animal Model of Pumpless Arteriovenous Extracorporeal CO2 Removal Using Room Air via Subclavian Vessels.

End-stage lung disease (ESLD) causes progressive hypercapnia and dyspnea and impacts quality of life. Many extracorporeal support (ECS) configurations for CO2 removal resolve symptoms but limit ambulation. An ovine model of pumpless ECS using subclavian vessels was developed to allow for ambulatory support. Vascular grafts were anastomosed to the left subclavian vessels in four healthy sheep. A low-resistance membrane oxygenator was attached in an arteriovenous (AV) configuration. Device function was evaluated in each animal while awake and spontaneously breathing and while mechanically ventilated with hypercapnia induced. Sweep gas (FiO2 = 0.21) to the device was increased from 0 to 15 L/min, and arterial and postdevice blood gases, as well as postdevice air, were sampled. Hemodynamics remained stable with average AV shunt flows of 1.34 ± 0.14 L/min. In awake animals, CO2 removal was 3.4 ± 1.0 ml/kg/min at maximum sweep gas flow. Respiratory rate decreased from 60 ± 25 at baseline to 30 ± 11 breaths per minute. In animals with induced hypercapnia, PaCO2 increased to 73.9 ± 15.1. At maximum sweep gas flow, CO2 removal was 3.4 ± 0.4 ml/kg/min and PaCO2 decreased to 49.1 ± 6.7 mm Hg. Subclavian AV access is effective in lowering PaCO2 and respiratory rate and is potentially an effective ambulatory destination therapy for ESLD patients.

The Implantable Pediatric Artificial Lung: Interim Report on the Development of an End-Stage Lung Failure Model.

An implantable pediatric artificial lung (PAL) may serve as a bridge to lung transplantation for children with end-stage lung failure (ESLF); however, an animal model of pediatric lung failure is needed to evaluate the efficacy of PAL before it can enter clinical trials. The objective of this study was to assess ligation of the right pulmonary artery (rPA) as a model for pediatric ESLF. Seven lambs weighing 20-30 kg underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic dead space fraction (Vd/Vt; baseline = 48.6 ± 5.7%, rPA ligation = 60.1 ± 5.2%, p = 0.012), mean pulmonary arterial pressure (mPPA; baseline = 17.4 ± 2.2 mm Hg, rPA ligation = 28.5 ± 5.2 mm Hg, p < 0.001), and arterial partial pressure of carbon dioxide (baseline = 40.4 ± 9.3 mm Hg, rPA ligation = 57.3 ± 12.7 mm Hg, p = 0.026). Of the seven lambs, three were unable to be weaned from mechanical ventilation postoperatively, three were successfully weaned but suffered cardiorespiratory failure within 4 days, and one survived all 4 days. All four animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA = 28.6 ± 2.2 mm Hg) and remained tachypneic (respiratory rate = 63 ± 21 min). Three of the four recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric ESLF and may be suitable for testing and implanting a PAL.

A novel rotary pulsatile flow pump for cardiopulmonary bypass.

It has been suggested that pulsatile blood flow is superior to continuous flow (CF) in cardiopulmonary bypass (CPB). However, adoption of pulsatile flow (PF) technology has been limited because of practicality and complexity of creating a consistent physiologic pulse. A pediatric pulsatile rotary ventricular pump (PRVP) was designed to address this problem. We evaluated the PRVP in an animal model and determined its ability to generate PF during CPB. The PRVP (modified peristaltic pump, with tapering of the outlet of the pump chamber) was tested in four piglets (10-12 kg). Cannulation was performed with right atrial and aortic cannulae, and pressure sensors were inserted into the femoral arteries. Pressure curves were obtained at different levels of flow and compared with both the animal's baseline physiologic function and a CF roller pump. Pressure and flow waveforms demonstrated significant pulsatility in the PRVP setup compared with CF at all tested conditions. Measurement of hemodynamic energy data, including the percentage pulsatile energy and the surplus hydraulic energy, also revealed a significant increase in pulsatility with the PRVP (p < 0.001). The PRVP creates physiologically significant PF, similar to the pulsatility of a native heart, and has the potential to be easily implemented in pediatric CPB.