NADPH oxidase overexpression and mitochondrial OxPhos impairment are more profound in human hearts donated after circulatory death than brain death.

This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups (n = 6) based on different WITs (20, 40, and 60 min). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 h. Left ventricular biopsies were performed at hours 0, 2, 4, and 6. Cardiac stress [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: 47-kDa protein of phagocyte oxidase (p47phox), 91-kDa glycoprotein of phagocyte oxidase (gp91phox)] and mitochondrial oxidative phosphorylation [OxPhos, complex I (NADH dehydrogenase) subunit of ETC (CI)-complex V (ATP synthase) subunit of ETC (CV)] proteins were measured in cardiac tissue and mitochondria respectively. Modulation of cardiac stress and mitochondrial dysfunction were observed in both DCD and DBD hearts. However, DCD hearts suffered more cardiac stress (overexpressed NADPH oxidase subunits) and diminished mitochondrial OxPhos than DBD hearts. The severity of cardiac stress and impaired oxidative phosphorylation in DCD hearts correlated with the longer WIT and subsequent cold storage time. More drastic changes were evident in DCD hearts with a WIT of 60 min or more. Activation of NADPH oxidase via overproduction of p47phox and gp91phox proteins in cardiac tissue may be responsible for cardiac stress leading to diminished mitochondrial oxidative phosphorylation. These protein changes can be used as biomarkers for myocardium damage and might help assess DCD and DBD heart transplant suitability.NEW & NOTEWORTHY First human DCD heart research studied cardiac stress and mitochondrial dysfunction concerning WIT and the efficacy of del Nido cardioplegia as an organ procurement solution and subsequent cold storage. Mild to moderate cardiac stress and mitochondrial dysfunction were noticed in DCD hearts with WIT 20 and 40 min and cold storage for 4 and 2 h, respectively. These changes can serve as biomarkers, allowing interventions to preserve mitochondria and extend WIT in DCD hearts.

Direct cardiac reprogramming: A new technology for cardiac repair.

Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide, with myocardial infarctions being amongst the deadliest manifestations. Reduced blood flow to the heart can result in the death of cardiac tissue, leaving affected patients susceptible to further complications and recurrent disease. Further, contemporary management typically involves a pharmacopeia to manage the metabolic conditions contributing to atherosclerotic and hypertensive heart disease, rather than regeneration of the damaged myocardium. With modern healthcare extending lifespan, a larger demographic will be at risk for heart disease, driving the need for novel therapeutics that surpass those currently available in efficacy. Transdifferentiation and cellular reprogramming have been looked to as potential methods for the treatment of diseases throughout the body. Specifically targeting the fibrotic cells in cardiac scar tissue as a source to be reprogrammed into induced cardiomyocytes remains an appealing option. This review aims to highlight the history of and advances in cardiac reprogramming and describe its translational potential as a treatment for cardiovascular disease.

Dispersion of National Institute of Health Funding to Departments of Surgery Is Contracting.

INTRODUCTION: NIH funding to departments of surgery reported as benchmark Blue Ridge Institute for Medical Research (BRIMR) rankings are unclear. METHODS: We analyzed inflation-adjusted BRIMR-reported NIH funding to departments of surgery and medicine between 2011 and 2021. RESULTS: NIH funding to departments of surgery and medicine both increased 40% from 2011 to 2021 ($325 million to $454 million; $3.8 billion to $5.3 billion, P < 0.001 for both). The number of BRIMR-ranked departments of surgery decreased 14% during this period while departments of medicine increased 5% (88 to 76 versus 111 to 116; P < 0.001). There was a greater increase in the total number of medicine PIs versus surgery PIs during this period (4377 to 5224 versus 557 to 649; P < 0.001). These trends translated to further concentration of NIH-funded PIs in medicine versus surgery departments (45 PIs/program versus 8.5 PIs/program; P < 0.001). NIH funding and PIs/program in 2021 were respectively 32 and 20 times greater for the top versus lowest 15 BRIMR-ranked surgery departments ($244 million versus $7.5 million [P < 0.01]; 20.5 versus 1.3 [P < 0.001]). Twelve (80%) of the top 15 surgery departments maintained this ranking over the 10-year study period. CONCLUSIONS: Although NIH funding to departments of surgery and medicine is growing at a similar rate, departments of medicine and top-funded surgery departments have greater funding and concentration of PIs/program versus surgery departments overall and lowest-funded surgery departments. Strategies used by top-performing departments to obtain and maintain funding may assist less well-funded departments in obtaining extramural research funding, thus broadening the access of surgeon-scientists to perform NIH-supported research.

Readmissions After Surgical Aortic Valve Replacement: Influence of Prosthesis Type.

INTRODUCTION: Prosthesis choice during aortic valve replacement (AVR) weighs lifelong anticoagulation with mechanical valves (M-AVR) against structural valve degeneration in bioprosthetic valves (B-AVR). METHODS: The Nationwide Readmissions Database was queried to identify patients who underwent isolated surgical AVR between January 1, 2016 and December 31, 2018, stratifying by prothesis type. Propensity score matching was used to compare risk-adjusted outcomes. Readmission at 1 y was estimated with Kaplan-Meier (KM) analysis. RESULTS: Patients (n = 109,744) who underwent AVR (90,574 B-AVR and 19,170 M-AVR) were included. B-AVR patients were older (median 68 versus 57 y; P < 0.001) and had more comorbidities (mean Elixhauser score: 11.8 versus 10.7; P < 0.001) compared to M-AVR patients. After matching (n = 36,951), there was no difference in age (58 versus 57 y; P = 0.6) and Elixhauser score (11.0 versus 10.8; P = 0.3). B-AVR patients had similar in-hospital mortality (2.3% versus 2.3%; P = 0.9) and cost (mean: $50,958 versus $51,200; P = 0.4) compared with M-AVR patients. However, B-AVR patients had shorter length of stay (8.3 versus 8.7 d; P < 0.001) and fewer readmissions at 30 d (10.3% versus 12.6%; P < 0.001) and 90 d (14.8% versus 17.8%; P < 0.001), and 1 y (P < 0.001, KM analysis). Patients undergoing B-AVR were less likely to be readmitted for bleeding or coagulopathy (5.7% versus 9.9%; P < 0.001) and effusions (9.1% versus 11.9%; P < 0.001). CONCLUSIONS: B-AVR patients had similar early outcomes compared to M-AVR patients, but lower rates of readmission. Bleeding, coagulopathy, and effusions are drivers of excess readmissions in M-AVR patients. Readmission reduction strategies targeting bleeding and improved anticoagulation management are warranted in the first year following AVR.

A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction.

Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion of Tsc22d3-expressing macrophages-all of which may limit inflammatory damage. SRC stimulation with MCB-613 (and derivatives) is a potential therapeutic approach for inhibiting cardiac dysfunction after MI.

Aberrant Fibrin Clot Structure Visualized Ex Vivo in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

OBJECTIVES: Disseminated fibrin-rich microthrombi have been reported in patients who died from COVID-19. Our objective is to determine whether the fibrin clot structure and function differ between critically ill patients with or without COVID-19 and to correlate the structure with clinical coagulation biomarkers. DESIGN: A cross-sectional observational study. Platelet poor plasma was used to analyze fibrin clot structure; the functional implications were determined by quantifying clot turbidity and porosity. SETTING: ICU at an academic medical center and an academic laboratory. PATIENTS: Patients admitted from July 1 to August 1, 2020, to the ICU with severe acute respiratory syndrome coronavirus 2 infection confirmed by reverse transcription-polymerase chain reaction or patients admitted to the ICU with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood was collected from 36 patients including 26 ICU patients with COVID-19 and 10 ICU patients with sepsis but without COVID-19 at a median of 11 days after ICU admission (interquartile range, 3-16). The cohorts were similar in age, gender, body mass index, comorbidities, Sequential Organ Failure Assessment (SOFA) score, and mortality. More patients with COVID-19 (100% vs 70%; p = 0.003) required anticoagulation. Ex vivo fibrin clots formed from patients with COVID-19 appeared to be denser and to have smaller pores than those from patients with sepsis but without COVID-19 (percent area of fluorescent fibrin 48.1% [SD, 16%] vs 24.9% [SD, 18.8%]; p = 0.049). The turbidity and flow-through assays corroborated these data; fibrin clots had a higher maximum turbidity in patients with COVID-19 compared with patients without COVID-19 (0.168 vs 0.089 OD units; p = 0.003), and it took longer for buffer to flow through these clots (216 vs 103 min; p = 0.003). In patients with COVID-19, d-dimer levels were positively correlated with percent area of fluorescent fibrin (ρ = 0.714, p = 0.047). Denser clots (assessed by turbidity and thromboelastography) and higher SOFA scores were independently associated with delayed clot lysis. CONCLUSIONS: We found aberrant fibrin clot structure and function in critically ill patients with COVID-19. These findings may contribute to the poor outcomes observed in COVID-19 patients with widespread fibrin deposition.

Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.

BACKGROUND: Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect. METHODS: The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1 × 109, 1 × 1010, 4 × 1010, and 1 × 1011 viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency. CONCLUSIONS: The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation. CLINICAL TRIAL REGISTRATION: NCT04125732.

Consistent improvements in short- and long-term survival following heart transplantation over the past three decades.

BACKGROUND: Despite noted improvements in short-term survival outcomes following orthotopic heart transplantation (OHT), review of the relevant literature suggests little improvement in long-term outcomes for patients surviving beyond 1 year. METHODS: All OHT cases performed between 1989 and 2019 within the United Network for Organ Sharing (UNOS) database were reviewed. Adults who underwent isolated OHT were included in a 1-year survival analysis. Those who survived at least 1 year post-transplant were included in a long-term survival analysis. Demographic factors were assessed using Students' t test and chi-square analysis. Survival trends and risk factors were assessed using the Kaplan-Meier and the Cox regression analysis, respectively. RESULTS: A total of 53 265 and 46 372 recipients were included in the short-term and long-term cohorts, respectively. In an adjusted analysis, the reference implant era 2014-2019 had significantly better short-term survival outcomes when compared with earlier implant eras: 1989-1993 (HR: 2.92), 1994-1998 (HR: 1.53), 1999-2003 (HR: 1.27), 2004-2008 (HR: 1.11), and 2009-2013 (HR: 1.02). The same trend was recognized for long-term outcomes: 1989-1993 (HR: 1.87), 1994-1998 (HR: 1.27), 1999-2003 (HR: 1.09), and 2004-2008 (HR: 1.03). CONCLUSIONS: Despite increases in multiple traditional risk factors, both short-term and long-term survival outcomes have consistently improved over the past 30 years, suggesting other factors are contributing to improved outcomes in recent eras.

Allograft discard risk index for heart transplantation.

BACKGROUND: The numberof patients awaiting heart transplantation (HTx) substantially exceeds the number of donor hearts transplanted each year, yet nearly 65% of eligible donor hearts are discarded rather than transplanted. METHODS: Deceased organ donors listed within the UNOS Deceased Donor Database between 2010 and 2020 were reviewed. Those greater than 10 years old and consented for heart donation were included and randomly separated into training (n = 48 435) and validation (n = 24 217) cohorts. A discard risk index (DSRI) was created using the results of univariable and multivariable analyses. Discard data were assessed at DSRI value deciles, and stratum-specific likelihood ratio (SSLR) analysis and Kaplan-Meier survival function were used for mortality data. RESULTS: Factors associated with higher DSRI values included donor age > 45, LVEF, HBV-core antibodies, hypertension, and diabetes. The DSRI C-statistic was .906 in the training cohort and .904 in the validation cohort. The DSRI did not reliably predict 30-day or 1-year mortality after transplantation (C-statistic .539 and .532, respectively). CONCLUSIONS: The factors leading to heart allograft discard are not correlated to the same degree with post-transplant outcomes. This suggests that optimizing utilization of certain allografts with slightly higher risk of discard could increase the heart donor pool with limited impact on posttransplant mortality.

A Wrist-Worn Sensor-Derived Frailty Index Based on an Upper-Extremity Functional Test in Predicting Functional Mobility in Older Adults.

INTRODUCTION: Preoperative frailty is an independent risk factor for postoperative complications across surgical specialties. Functional mobility such as gait, timed up and go (TUG), and 5 times sit-to-stand (5-STS) are popular preoperative frailty measurements but are not suitable for patients with severe mobility impairment. A wrist-worn sensor-derived frailty index based on an upper-extremity functional test (20-s repetitive elbow flexion-extension task; UEFI) was developed previously; however, its association with functional mobility remained unexplored. We aimed to investigate the predictive power of the UEFI in predicting functional mobility. METHODS: We examined correlation between the UEFI and gait speed, TUG duration, and 5-STS duration in 100 older adults (≥ 65 years) using multivariate regression analysis. The UEFI was calculated using slowness, weakness, exhaustion, and flexibility of the sensor-based 20-s repetitive elbow flexion-extension task. RESULTS: The UEFI was a significant predictor for gait speed and TUG duration and 5-STS duration (all R ≥ 0.60; all p < 0.001) with the variance (adjusted R2) of 35-37% for the dependent variables. The multivariate regression analysis revealed significant associations between the UEFI and gait speed (ß = -0.84; 95% confidence interval [95% CI] = [-1.19, -0.50]; p < 0.001) and TUG duration (ß = 16.2; 95% CI = [9.59, 22.8]; p < 0.001) and 5-STS duration (ß = 33.3; 95% CI = [23.6, 43.2]; p < 0.001), found after accounting for confounding variables (e.g., age and fear of falling scale). CONCLUSIONS: Our findings suggest that the UEFI can be performed with a wrist-worn sensor and has been validated with other established measures of preoperative frailty. The UEFI can be applied in a wide variety of patients, regardless of mobility limitations, in an outpatient setting.

Cardiac surgery during the COVID-19 sine wave: Preparation once, preparation twice. A view from Houston.

The novel coronavirus disease (COVID-19) pandemic has created major challenges and disruptions to hospitals throughout the world, with profound implications for cardiac surgery and cardiac surgeons. In this review, we highlight the hospital and cardiac surgical experience at Baylor St. Luke's Medical Center in the Texas Medical Center in Houston, Texas as of mid-July 2020. Our local experience has consisted of a spring surge (early March to early May), followed by a relative flattening and then a summer surge (early June to present day), similar to a sine wave. Throughout the entire pandemic, our simultaneous medical priorities have been treating the growing number of patients with COVID-19 while continuing to provide needed care for those without COVID-19. The current situation will be the "new normal" until a vaccine becomes available. It will be vital to stay attuned to epidemiologists, public health officials, and infection control experts, because what they see today, the intensive care units will see tomorrow. The lessons we have learned are outlined in this review but can be summarized most succinctly: preparation. We must prepare in advance, stockpile supplies and personal protective equipment, have rapid and vigorous testing protocols in place, utilize technology (eg, online meetings, videoconference "office visits"), and encourage hospital-wide and community protective efforts (social distancing, mask wearing, hand hygiene). Hopefully, the lessons learned through this challenging experience will prepare us for the next time.

Twelve Tips on enhancing global health education in graduate medical training programs.

Investment in healthcare infrastructure in resource-limited settings is a vital and cost-effective approach for diminishing world-wide disease burden, increasing quality of life, and lengthening life expectancy. Graduate medical trainees enthusiastically express interest in supporting global health efforts that expand healthcare access and capacity in resource-limited settings. Academic institutions are responding by developing training programs to equip graduate medical trainees with the technical, interpersonal, scholastic, and ethical skillsets necessary for the pursuit of global health efforts. Drawn from real-world experience and current literature, the following twelve tips will strengthen a global health curriculum in graduate medical training programs with dedicated global health education.

Mid-Term Efficacy of Subxiphoid Versus Transpleural Pericardial Window for Pericardial Effusion.

BACKGROUND: The optimal surgical technique for drainage of pericardial effusions is frequently debated. Transpleural drainage via thoracotomy or thoracoscopy is hypothesized to provide more durable freedom from recurrent pericardial effusion than a subxiphoid pericardial window. We sought to compare operative outcomes and mid-term freedom from recurrent effusion between both approaches in patients with nontraumatic pericardial effusions. METHODS: All patients at our institution who underwent a pericardial window from 2001 to 2018 were identified. After excluding those who underwent recent cardiothoracic surgery or trauma, patients (n = 46) were stratified by surgical approach and presence of malignancy. Primary outcome was freedom from recurrent moderate or greater pericardial effusion. Secondary outcomes included operative mortality and morbidity and mid-term survival. Follow-up was determined by medical record review, with a follow-up of 67 patient-years. Fisher's exact test and Wilcoxon rank-sum test were used to compare groups. Mid-term survival and freedom from effusion recurrence were determined using Kaplan-Meier method. RESULTS: Subxiphoid windows (n = 31; 67%) were more frequently performed than transpleural windows (n = 15; 33%) and baseline characteristics were similar. Effusion etiologies included malignancy (n = 22; 48%), idiopathic (n = 12; 26%), uremia (n = 8; 17%), and collagen vascular disease (n = 4; 9%). Perioperative outcomes were comparable between the two surgical approaches, except for longer drain duration (7 versus 4 d, P = 0.029) in the subxiphoid group. Operative mortality was 19.6% overall and 36.4% in patients with malignancy. Mid-term survival and freedom from moderate or greater pericardial effusion recurrence was 37% (95% confidence interval [CI]: 19%-54%) and 69% (95% CI: 52%-86%) at 5 y, respectively. There was no difference in mid-term survival (P = 0.90) or freedom from pericardial effusion recurrence (P = 0.70) between surgical approaches. Although malignant etiology had worse late survival (P < 0.01), freedom from effusion recurrence was similar to nonmalignant etiology (P = 0.70). CONCLUSIONS: Pericardial window provides effective mid-term relief of pericardial effusion. Subxiphoid and transpleural windows are equivalent in mid-term efficacy and both surgical approaches can be considered. Patients with malignancy have acceptable operative mortality with low incidence of recurrent effusion, supporting palliative indications.

An Academic Relative Value Unit System for Incentivizing the Academic Productivity of Surgery Faculty Members.

OBJECTIVE: The objective of this study was to evaluate a new academic relative-value unit (aRVU) scoring system linked to faculty compensation and analyze its association with overall departmental academic productivity. SUMMARY BACKGROUND DATA: Faculty are often not incentivized or financially compensated for educational and research activities crucial to the academic mission. METHODS: We launched an online, self-reporting aRVU system in 2015 to document and incentivize the academic productivity of our faculty. The system captured 65 specific weighted scores in 5 major categories of research, education, innovation, academic service, and peer review activities. The aRVU scores were rank-aggregated annually, and bonuses were distributed to faculty members in 3 tiers: top 10%, top third, and top half. We compared pre-aRVU (academic year 2015) to post-aRVU (academic year 2017) departmental achievement metrics. RESULTS: Since 2015, annual aRVU bonuses totaling $493,900 were awarded to 59 faculty members (58% of eligible department faculty). Implementing aRVUs was associated with significant increases in several key departmental academic achievement metrics: presentations (579 to 862; P = 0.02; 49% increase), publications (390 to 446; P = 0.02; 14%), total research funding ($4.6 M to $8.4 M; P < 0.001; 83%), NIH funding ($0.6 M to $3.4 M; P < 0.001; 467%), industry-sponsored clinical trials (8 to 23; P = 0.002; 188%), academic society committee positions (226 to 298; P < 0.001; 32%), and editorial leadership positions (50 to 74; P = 0.01; 48%). CONCLUSIONS: Implementing an aRVU system was associated with increases in departmental academic productivity. Although other factors undoubtedly contributed to these increases, an aRVU program may represent an important mechanism for tracking and rewarding academic productivity in surgery departments.

Aortic Stenosis.

This issue provides a clinical overview of aortic stenosis, focusing on screening, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

Knockdown of SALL4 Protein Enhances All-trans Retinoic Acid-induced Cellular Differentiation in Acute Myeloid Leukemia Cells.

All-trans retinoic acid (ATRA) is a differentiation agent that revolutionized the treatment of acute promyelocytic leukemia. However, it has not been useful for other types of acute myeloid leukemia (AML). Here we explored the effect of SALL4, a stem cell factor, on ATRA-induced AML differentiation in both ATRA-sensitive and ATRA-resistant AML cells. Aberrant SALL4 expression has been found in nearly all human AML cases, whereas, in normal bone marrow and peripheral blood cells, its expression is only restricted to hematopoietic stem/progenitor cells. We reason that, in AMLs, SALL4 activation may prevent cell differentiation and/or protect self-renewal that is seen in normal hematopoietic stem/progenitor cells. Indeed, our studies show that ATRA-mediated myeloid differentiation can be largely blocked by exogenous expression of SALL4, whereas ATRA plus SALL4 knockdown causes significantly increased AML differentiation and cell death. Mechanistic studies indicate that SALL4 directly associates with retinoic acid receptor α and modulates ATRA target gene expression. SALL4 is shown to recruit lysine-specific histone demethylase 1 (LSD1) to target genes and alter the histone methylation status. Furthermore, coinhibition of LSD1 and SALL4 plus ATRA treatment exhibited the strongest anti-AML effect. These findings suggest that SALL4 plays an unfavorable role in ATRA-based regimes, highlighting an important aspect of leukemia therapy.

Comparison of Laser Doppler and Laser-Assisted Indocyanine Green Angiography Prediction of Flap Survival in a Novel Modification of the McFarlane Flap.

BACKGROUND: The McFarlane rat ischemic dorsal skin flap model has been commonly used for clinical vector studies, as well as the testing of noninvasive diagnostics. However, variability of this model secondary to flap contact with the wound bed has led many to question its validity. Here we present a novel modification to the McFarlane skin flap using sterile silicone. We also use this model to test the prognostic efficacy of laser-assisted indocyanine green (ICG) angiography and laser Doppler imaging (LDI). METHODOLOGY: A 3 × 9-cm dorsal skin flap with a cranially based pedicle was created, centered 1 cm distal to the scapulae. The flap was undermined, and in one of the 2 groups, a sterile silicone sheet was placed onto the wound bed. All flaps were then reapproximated with sutures 1-cm intervals. Clinical assessment and perfusion imaging was performed immediately postoperative, and at 24, 48, and 72 hours postsurgery. Postoperative day 7 clinical assessment was obtained before euthanasia. RESULTS: A comparative study using silicone blocked versus unblocked models (n = 6 per group) showed that, clinically, both models had equivalent flap survival [8.5 (0.913) vs 9.5 (1.01) cm]. However, a statistically significant increase in perfusion in the mid-third of unblocked models was observed on POD3 [20.28% (2.7%) vs blocked 13.45% (2.5%), P < 0.05], with a similar increase in the distal third on POD7 [18.73% (2.064%) vs 10.91% (4.19%), P < 0.05]. A prognostic study comparing LDI and ICG angiography prediction of POD7 survival at early time points (n = 10) found that LDI underpredicted flap survival at early time points [84.2% (12.03%) on POD0, 87.35% (16.11%) on POD1]. In contrast, ICG was more proficient [100.1% (10.1%) on POD0]. CONCLUSIONS: We present a modification of the McFarlane skin flap model that results in similar clinical results, but with a noted reduction in perfusion inconsistencies noted in unblocked models. The ICG angiography is superior to LDI in predicting POD7 flap necrosis within the first 48 hours postinjury. Future work will focus on histologic validation of our model, and vector efficacy testing.

Myocardial edema, inflammation, and injury in human heart donated after circulatory death are sensitive to warm ischemia and subsequent cold storage.

BACKGROUND: Single-dose del Nido solution was recently used in human donation after circulatory death (DCD) heart procurement. We compared the effect of del Nido cardioplegia on myocardial edema, inflammatory response, and injury in human DCD hearts and human donation after brain death (DBD) hearts with different warm ischemic times (WIT) and subsequent cold saline storage times (CST). METHODS: A total of 24 human hearts, including 6 in the DBD group and 18 in the DCD group-were procured for the research study. The DCD group was divided into 3 subgroups based on WIT: 20, 40, and ≥60 minutes. All hearts received 1 L of del Nido cardioplegia before being placed in cold saline for 6 hours. Left ventricular biopsies were performed at 0, 2, 4, and 6 hours. Temporal changes in myocardial edema, inflammatory cytokines (TNF-α, IL-6, and IL-1ß), and histopathology injury scores were compared between the DBD and DCD groups. RESULTS: DCD hearts showed more profound changes in myocardial edema, inflammation, and injury than DBD hearts at baseline and subsequent CST. The DCD heart with WIT of 20 and 40 minutes with CST of 4 and 2 hours, respectively, appeared to have limited myocardial edema, inflammation, and injury. DCD hearts with WIT ≥60 minutes showed severe myocardial edema, inflammation, and injury at baseline and subsequent CST. CONCLUSIONS: Single-dose cold del Nido cardioplegia and subsequent cold normal saline storage can preserve both DCD and DBD hearts. DCD hearts have been shown to be able to tolerate a WIT of 20 minutes and subsequent CST of 4 hours without experiencing significant myocardial edema, inflammation, and injury.

Outcomes after bioprosthetic versus mechanical mitral valve replacement for infective endocarditis in the United States.

Objective: In patients who underwent mitral valve replacement for infectious endocarditis, we evaluated the association of prosthesis choice with readmission rates and causes (the primary outcomes), as well as with in-hospital mortality, cost, and length of stay (the secondary outcomes). Methods: Patients with infectious endocarditis who underwent isolated mitral valve replacement from January 2016 to December 2018 were identified in the United States Nationwide Readmissions Database and stratified by valve type. Propensity score matching was used to compare adjusted outcomes. Results: A weighted total of 4206 patients with infectious endocarditis underwent bioprosthetic mitral valve replacement (n = 3132) and mechanical mitral valve replacement (n = 1074) during the study period. Patients in the bioprosthetic mitral valve replacement group were older than those in the mechanical mitral valve replacement group (median 57 vs 46 y, P < .001). After propensity matching, the bioprosthetic mitral valve replacement group (n = 1068) had similar in-hospital mortality, length of stay, and costs compared with the mechanical mitral valve replacement group (n = 1056). Overall, 90-day readmission rates were high (28.9%) and comparable for bioprosthetic mitral valve replacement (30.5%) and mechanical mitral valve replacement (27.5%, P = .4). Likewise, there was no difference in readmissions over a calendar year by prosthesis type. Readmissions for infection and bleeding were common for both bioprosthetic mitral valve replacement and mechanical mitral valve replacement groups. Conclusions: Outcomes and readmission rates were similar for mechanical mitral valve replacement and bioprosthetic mitral valve replacement in infectious endocarditis, suggesting that valve choice should not be determined by endocarditis status. Additionally, strategies to mitigate readmission for infection and bleeding are needed for both groups.

Fidelity in Academic Global Surgery and Research: Incorporating Trustworthiness in the Development of Research Partnerships, Infrastructure, and Policy.

Academic global surgery consists of collaborative partnerships that address surgical inequities through research, training, education, advocacy, and diplomacy. It has been characterized by increased scholastic production through global surgery publications, dedicated global surgery sessions within scientific conferences, global surgery-specific research grants, database development to support global surgery research, global surgery research fellowships, and global surgery-based academic promotion paradigms. The increased emphasis on global surgery research has been accompanied by multiple ethical challenges. This article reviews critical ethical dilemmas presented by global surgery research efforts and proposes interventions on the partnership, infrastructural, and policy levels to enhance fidelity within research partnerships.