Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

Utilization of Thromboelastogram and Inflammatory Markers in the Management of Hypercoagulable State in Patients with COVID-19 Requiring ECMO Support.

The role of extracorporeal membrane oxygenation (ECMO) in the management of critically ill patients with COVID-19 is evolving. Extracorporeal support independently confers an increased predilection for thrombosis, which can be exacerbated by COVID-19-associated coagulopathy. We present the successful management of a hypercoagulable state in two patients who required venovenous ECMO for the treatment of COVID-19. This included monitoring inflammatory markers (D-dimer and fibrinogen), performing a series of therapeutic plasma exchange procedures, and administering high-intensity anticoagulation therapy and thromboelastography- (TEG-) guided antiplatelet therapy. TPE was performed to achieve goal D-dimer less than 3000 ng/mL D-dimer units (N ≤ 232 ng/mL D-dimer units) and goal fibrinogen less than 600 mg/dL (N = 200-400 mg/dL). These therapies resulted in improved TEG parameters and normalized inflammatory markers. Patients were decannulated after 37 days and 21 days, respectively. Post-ECMO duplex ultrasound of the upper and lower extremities and cannulation sites revealed a nonsignificant deep venous thrombosis at the site of femoral cannulation in patient 2 and no deep venous thrombosis in patient 1. The results of this case report show successful management of a hypercoagulable state among COVID-19 patients requiring ECMO support by utilization of inflammatory markers and TEG.

Targeting Circulating Leukocytes and Pyroptosis During Ex Vivo Lung Perfusion Improves Lung Preservation.

BACKGROUND: The role of the circulating leukocytes in lungs and their relationship with circulating proinflammatory cytokines during ischemia-reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to investigate the pathophysiology of isolated lungs, we aimed to identify a therapeutic target to optimize lung preservation leading to successful lung transplantation. METHODS: Rat heart-lung blocks were placed on EVLP for 4 hours with or without a leukocyte-depleting filter (LF). After EVLP, lung grafts were transplanted, and posttransplant outcomes were compared. RESULTS: Lung function was significantly better in lung grafts on EVLP with a LF than in lungs on EVLP without a LF. The interleukin (IL)-6 levels in the lung grafts and EVLP perfusate were also significantly lower after EVLP with a LF. Interestingly, IL-6 levels in the perfusate did not increase after the lungs were removed from the EVLP circuit, indicating that the cells trapped by the LF were not secreting IL-6. The trapped cells were analyzed with flow cytometry to detect apoptosis and pyroptosis; 26% were pyroptotic (Caspase-1-positive). After transplantation, there was better graft function and less inflammatory response if a LF was used or a caspase-1 inhibitor was administered during EVLP. CONCLUSIONS: Our data demonstrated that circulating leukocytes derived from donor lungs, and not circulating proinflammatory cytokines substantially impaired the quality of lung grafts through caspase-1-induced pyroptotic cell death during EVLP. Removing these cells with a LF and/or inhibiting pyroptosis of the cells can be a new therapeutic approach leading to long-term success after lung transplantation.

Optimal ex vivo lung perfusion techniques with oxygenated perfusate.

BACKGROUND: Accumulating evidence supports an increasing role of ex vivo lung perfusion (EVLP) in clinical lung transplantation. However, EVLP has adverse effects on the quality of lung grafts, which have rarely been discussed. Careful optimization of current EVLP protocols might improve outcomes. This study examined effects of different levels of oxygenation of the perfusate circulated through the lungs during EVLP and the impact on post-transplant functional outcomes. METHODS: We compared results of 4 different oxygenation levels in the perfusate during EVLP: 6% oxygen (O2), 40% O2, 60% O2, and 100% O2. We evaluated lung function, compliance, and vascular resistance and levels of glucose and other markers in the perfusate. After EVLP, lung grafts were transplanted, and post-transplant outcomes were compared. RESULTS: Lungs perfused with 40% O2 on EVLP had the lowest glucose consumption compared with the other perfusates. Lungs treated with 40% O2 or 60% O2 exhibited significantly less inflammation, as indicated by reduced pro-inflammatory cytokine messenger RNA levels compared with lungs perfused with 6% O2 or 100% O2. Significantly more oxidative damage was noted after 4 hours of EVLP perfused with 100% O2. After transplantation, lungs perfused with 40% O2 during EVLP had the best post-transplant functional outcomes. CONCLUSIONS: Optimization of O2 levels in the perfusate during EVLP improved outcomes in this rat model. Deoxygenated perfusate, the current standard during EVLP, exhibited significantly more inflammation with compromised cellular metabolic activity and compromised post-transplant outcomes.

Surgical Strategy for Lung Transplantation in Adults With Small Chests: Lobar Transplant Versus a Pediatric Donor.

BACKGROUND: Adult lung transplant recipients with small chests have traditionally received lungs from pediatric donors, placing an additional strain on the already restricted pediatric donor pool. Performing lobar lung transplantation (LLT) can circumvent issues with donor-recipient size mismatch; however, LLT imparts additional risks. Here, we review our experience using LLT and standard lung transplantation using a pediatric donor (PDLT) for adults with small chests. METHODS: We retrospectively reviewed consecutive patients with end-stage lung disease and a height of 65 inches or less who underwent LLT (n = 15) or PDLT (n = 15) between 2006 and 2012 at our institution, a high-volume lung transplant center. RESULTS: Lobar lung transplantation recipients were older (54 ± 10 vs 48 ± 8 years) and had higher pulmonary pressure (57 ± 11 vs 52 ± 27 mmHg) and higher lung allocation scores (70 ± 9 vs 51 ± 8) than PDLT recipients (all P < 0.05). Mean waiting time was 62 days for PDLT and 9 days for LLT. Postoperatively, the incidence of severe primary graft dysfunction and the incidence of acute renal insufficiency were higher, and the mean intensive care unit stay was longer in the LLT group, but the incidence of bronchial anastomotic complications was higher in the PDLT group because of significant size discrepancy in the main bronchus (P < 0.05). Interestingly, long-term functional outcomes and survival rates were similar between the groups. CONCLUSIONS: Both LLT and PDLT are viable surgical options for adult patients with small chests. Because of the potential impact on posttransplant outcomes, the technical complexity of transplantation, decisions regarding the best surgical approach should be made by experienced surgeons.

Contemporary analysis of early outcomes after lung transplantation in the elderly using a national registry.

BACKGROUND: With an increasing number of potential recipients and a comparatively static number of donors, lung transplantation (LT) in the elderly has come under significant scrutiny. Previous studies have been limited by single-center experiences with small population sizes and often mixed results. Using a national registry, we sought to evaluate the following: (1) differences in survival outcomes in septuagenarians compared with sexagenarians; and (2) the effect of temporal trends on the development of other comorbidities in this population. METHODS: We analyzed the Scientific Registry of Transplant Recipients (SRTR) data files from the United Network for Organ Sharing (UNOS) database to identify recipients who underwent LT between the years 2000 and 2013. The study period was divided into two equal eras. Using Kaplan-Meier analysis, we compared the 30-day, 3-month, 1-year, 3-year and 5-year patient survival between septuagenarians and sexagenarians in both eras. Separate multivariate analyses were performed to estimate the risk of renal failure, risk of rejection and length of hospital stay (LOS) post-LT in each of these time periods. RESULTS: A total of 6,596 patients were identified comprising 1,726 (26.2%) during 2000 to 2005 and 4,870 (73.8%) during 2006 to 2012. In the "early era," 32 (1.9%) septuagenarians and 1,694 (98.1%) sexagenarians underwent LT, whereas 543 (11.1%) septuagenarians and 4,327 (88.9%) sexagenarians underwent transplantation in the "latter era." A comparison of patient survival between the two groups in the early era revealed no difference at 30 days (95.7% vs 93.8%, p = 0.65). However, 3-month (91.2% vs 75%, p = 0.04) and 1-year patient survival (79.5% vs 62.5%, p = 0.048) were both lower in the septuagenarian group. In the later era, however, there were no differences in 30-day (96.2% vs 96.8, p = 0.5), 3-month (92.7% vs 91.9%, p = 0.56) or 1-year (81.7% vs 78.6%, p = 0.12) patient survival between the two age groups. Survival rates at 3 years (63.7% vs 49.3%, p < 0.001) and 5 years (47.5% vs 28.2%, p < 0.001) were each significantly lower in the septuagenarian group. CONCLUSION: Overall, LT outcomes for the elderly have improved significantly over time and early outcomes in the modern era rival those found in younger recipients.

Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy in the management of rapidly advancing pulmonary disease.

OBJECTIVE: Improvements in technology have led to a resurgence in the use of extracorporeal membrane oxygenation as a bridge to lung transplantation. By using a national registry, we sought to evaluate how short-term survival has evolved using this strategy. METHODS: With the use of the United Network for Organ Sharing database, we analyzed data from 12,458 adults who underwent lung transplantation between 2000 and 2011. Patients were categorized into 2 cohorts: 119 patients who were bridged to transplantation using extracorporeal membrane oxygenation and 12,339 patients who were not. The study period was divided into four 3-year intervals: 2000 to 2002, 2003 to 2005, 2006 to 2008, and 2009 to 2011. With Kaplan-Meier analysis, 1-year survival was compared for the 2 cohorts of patients in each of the time periods. A propensity score-adjusted Cox regression model was used to estimate the risk of 1-year mortality. RESULTS: Of the total number of recipients, 4 (3.4%) were bridged between 2000 and 2002, 17 (14.3%) were bridged between 2003 and 2005, 31 (26.1%) were bridged between 2006 and 2008, and 67 were bridged (56.3%) between 2009 and 2011. Recipients bridged using extracorporeal membrane oxygenation were more likely to be younger and diabetic and to have higher serum creatinine and bilirubin levels. The 1-year survival for those bridged with extracorporeal membrane oxygenation was significantly lower in subsequent periods: 25.0% versus 81.0% (2000-2002), 47.1% versus 84.2% (2006-2008), and 74.4% versus 85.7% (2009-2011). However, this survival progressively increased with each period, as did the number of patients bridged using extracorporeal membrane oxygenation. CONCLUSIONS: Short-term survival with the use of extracorporeal membrane oxygenation as a bridge to lung transplantation has significantly improved over the past few years.

Rural-Urban Differences in Access to Specialist Providers of Colorectal Cancer Care in the United States: A Physician Workforce Issue.

IMPORTANCE: Although early detection and treatment of colorectal cancer has been shown to improve outcomes, geographic proximity may influence access to these services. OBJECTIVE: To examine the disparities that may exist in colorectal cancer screening and treatment by comparing the distribution of providers of these services in rural and urban counties in the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective population-based study using data obtained from the 2009 Area Resource File for the entire US population within each county. MAIN OUTCOMES AND MEASURES: Counties in the United States were categorized as rural or urban using rural-urban continuum codes as our primary exposure. The proportion of gastroenterologists, general surgeons, and radiation oncologists per 100,000 people in each county was estimated as primary outcomes. Multivariate linear regression analysis adjusted for county-level socioeconomic variables, such as percentages of females, blacks, population without insurance, those with a high school diploma, and median household income, to estimate the relative density of each category of these providers between urban and rural counties. RESULTS: In total, 3220 counties were identified, comprising 1807 rural and 1413 urban counties. An unadjusted analysis showed an increased density of gastroenterologists, general surgeons, and radiation oncologists per 100,000 people in urban vs rural counties. A multivariable analysis revealed a significantly higher density of gastroenterologists (1.63; 95% CI, 1.40-1.85; P < .001), general surgeons (2.01; 95% CI, 1.28-2.73; P < .001), and radiation oncologists (0.68; 95% CI, 0.59-0.77; P < .001) per 100,000 people living in urban vs rural counties. CONCLUSIONS AND RELEVANCE: A rural-urban disparity exists in the density of gastroenterologists, general surgeons, and radiation oncologists who traditionally provide colorectal cancer screening services and treatment. This might affect access to these services and may negatively influence outcomes for colorectal cancer in rural areas.

Repair of rheumatic mitral stenosis with bicommissural release, anterior leaflet augmentation and oversized annuloplasty.

Rheumatic mitral valve disease often manifests with leaflet fibrosis, commissural fusion and early calcific degeneration. The thickening and fibrosis of the valvular and subvalvular apparatus has made prosthetic mitral replacement the traditional surgical solution. However, favourable valve morphology in some patients may permit a durable mitral repair rather than replacement. There is growing interest in reparative techniques that durably improve the mitral orifice while preserving the subvalvular apparatus. Many of these techniques are technically challenging and require complex resections with intricate chordal adjustments, which may have limited their global acceptance. In this report, we outline a three-step technique that does not require significant resection or involve the use of neochords. This offers a potentially simplified approach to the repair of rheumatic mitral stenosis.

Chordal relocation for repair of anterior mitral leaflet flail: a reproducible option.

Repair of anterior mitral leaflet (AML) flail is considered to be among the more technically challenging mitral procedures. While neochord reconstruction is an excellent technique, sizing challenges may limit wide reproducibility. Chordal relocation of secondary or tertiary AML chords can minimize sizing imprecision in open or minimally invasive repair while providing patients with a safe, durable and reproducible option. Native chords can be readily released and re-implanted from positions in the body of the leaflet to provide primary AML support, provided there is preservation of ipsilateral papillary muscle alignment. We illustrate the sole use of this reproducible method to repair AML flail.

Racial disparities and lung cancer care: why the unequal playing field?

The existence of disparities within our healthcare system is receiving considerable national attention, as we seek to understand the magnitude of these disparities with the goal of eliminating them altogether. Herein, we review recent important work that captures the current progress in this important area that has direct implications for the thoracic surgeon's daily practice management.

The effect of provider density on lung cancer survival among blacks and whites in the United States.

INTRODUCTION: Lung cancer mortality rates may vary with access to specialty providers and local resources. We sought to examine the effect of access to care, using density of lung cancer care providers, on lung cancer mortality among blacks and whites in the United States. METHODS: We examined U.S. county-level data for age-adjusted lung cancer mortality rates from 2003 to 2007. Our primary independent variable was per capita number of thoracic oncologic providers, adjusting for county-level smoking rates, socioeconomic status, and other geographic factors. Data were obtained from 2009 Area Resource File, National Center for Health Statistics, and the County Health Rankings Project. RESULTS: Providers of lung cancer care were unevenly distributed among the U.S. counties. For example, 41.4% of the U.S. population reside in counties with less than four thoracic surgeons per 100,000 people, 23.4% in counties with 4 to 15 surgeons per 100,000 people, and 35.3% in counties with more than 15 surgeons per 100,000 people. Geographically, 4.3% of whites compared with 11.2% of blacks lived in high lung cancer mortality zones. Lung cancer mortality did not vary by density of thoracic surgeons or oncology services; however, higher primary care provider density was associated with lung cancer mortality reduction of 4.1 per 100,000 for whites. CONCLUSION: Variation in provider density for thoracic oncology in the United States was not associated with a difference in lung cancer mortality. Lower mortality associated with higher primary care provider density suggests that equitable access to primary care may lead to reduced cancer disparities.

Residential segregation and lung cancer mortality in the United States.

OBJECTIVE: To examine the relationship between race and lung cancer mortality and the effect of residential segregation in the United States. DESIGN: A retrospective, population-based study using data obtained from the 2009 Area Resource File and Surveillance, Epidemiology and End Results program. SETTING: Each county in the United States. PATIENTS: Black and white populations per US county. MAIN OUTCOME MEASURES: A generalized linear model with a Poisson distribution and log link was used to examine the association between residential segregation and lung cancer mortality from 2003 to 2007 for black and white populations. Our primary independent variable was the racial index of dissimilarity. The index is a demographic measure that assesses the evenness with which whites and blacks are distributed across census tracts within each county. The score ranges from 0 to 100 in increasing degrees of residential segregation. RESULTS The overall lung cancer mortality rate was higher for blacks than whites (58.9% vs 52.4% per 100 000 population). Each additional level of segregation was associated with a 0.5% increase in lung cancer mortality for blacks (P < .001) and an associated decrease in mortality for whites (P = .002). Adjusted lung cancer mortality rates among blacks were 52.4% and 62.9% per 100 000 population in counties with the least (<40% segregation) and the highest levels of segregation (≥60% segregation), respectively. In contrast, the adjusted lung cancer mortality rates for whites decreased with increasing levels of segregation. CONCLUSION: Lung cancer mortality is higher in blacks and highest in blacks living in the most segregated counties, regardless of socioeconomic status.

Local anesthesia: a strategy for reducing surgical site infections?

BACKGROUND: Surgical site infections (SSIs) contribute to increased morbidity, mortality, and hospitalization costs. A previously unidentified factor that may reduce SSIs is the use of local anesthesia. The objective of this study was to determine if the use of local anesthesia is independently associated with a lower incidence of SSIs compared to nonlocal anesthesia. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database (2005-2007), we identified all patients undergoing surgical procedures that could be performed using local or general anesthesia, depending on the preference of the surgeon. Logistic regression was used to identify factors independently associated with the use of local anesthesia. Propensity matching was then used to match local and nonlocal anesthesia cases while controlling for patient and operative characteristics. SSI rates were compared using a χ(2) test. RESULTS: Of 111,683 patients, 1928 underwent local anesthesia; and in 109,755 cases the patients were given general anesthesia where a local anesthetic potentially could have used. In the unmatched analysis, patients with local anesthesia had a significantly lower incidence of SSIs than patients with nonlocal anesthesia (0.7 vs. 1.4%, P = 0.013). Similarly, after propensity matching, the incidence of SSIs in patients given local anesthesia was significantly lower than for that of patients given nonlocal anesthesia (0.8 vs. 1.4%, P = 0.043). CONCLUSIONS: Use of local anesthesia is independently associated with a lower incidence of SSIs. It may provide a safe, simple approach to reducing the number of SSIs.

Legislating change in surgical residency.

The Patient Protection and Affordable Care Act, also known as the House of Representatives Bill HR 3590, was created to improve the quality of patient care and access to health care for American citizens. Provisions of this bill are likely to have both intended and unintended consequences on surgical education. The purpose of this article is to explore the ways in which HR 3590 may affect the educational experience of surgical house officers at teaching hospitals.

Medical students' participation in the 2009 Novel H1N1 influenza vaccination administration: policy alternatives for effective student utilization to enhance surge capacity in disasters.

As cases of 2009 novel H1N1 influenza became prevalent in Cincinnati, Ohio, Hamilton County Public Health called upon the University of Cincinnati College of Medicine to enhance its surge capacity in vaccination administration. Although the collaboration was well organized, it became evident that a system should exist for medical students' involvement in disaster response and recovery efforts in advance of a disaster. Therefore, 5 policy alternatives for effective utilization of medical students in disaster-response efforts have been examined: maintaining the status quo, enhancing the Medical Reserve Corps, creating medical school-based disaster-response units, using students within another selected disaster-response organization, or devising an entirely new plan for medical students' utilization. The intent of presenting these policy alternatives is to foster a policy dialogue around creating a more formalized approach for integrating medical students into disaster surge capacity-enhancement strategies. Using medical students to supplement the current and future workforce may help substantially in achieving goals related to workforce requirements. Discussions will be necessary to translate policy into practice.

The impact of high body mass index on postoperative complications and resource utilization in minority patients.

BACKGROUND: Obesity is disproportionately prevalent among minority patients, yet very little has been written about its effect on surgical outcome in this group. OBJECTIVE: We investigated the association of body mass index (BMI) category with perioperative complications and resource utilization. METHODS: Data from the American College of Surgeons National Surgical Quality improvement Program Participant Use Data File was used to calculate the BMI (kg/m2) of all minority patients undergoing inpatient surgery from 2005 to 2008. Patients were stratified into 4 BMI classes, ranging from normal weight to severely obese. Postoperative length of stay (LOS) was used as the main proxy for resource utilization. Stepwise logistic regression was used to calculate odds ratios for prolonged LOS after controlling for clinically relevant cofactors. RESULTS: Among 73978 patients, 28% were in the normal BMI category, 28.9% were overweight, 28.2% were obese, and 14.9% were severely obese. Morbidity and mortality distribution varied significantly by BMI category, with the highest proportion of cases occurring in the normal-BMI group and the lowest in the severely obese patients. Postoperative LOS was longer for patients in the normal-BMI group than for severely obese patients. Other markers of resource utilization also followed the same pattern with progressive decrease from normal-BMI patients to the severely obese group. CONCLUSION: Postoperative morbidity and mortality and markers of hospital resource consumption were highest in the normal-BMI patients and decreased progressively to the severely obese group. This group appears to enjoy a paradoxical protection from perioperative complications and so utilize fewer hospital resources.

Paraneoplastic pemphigus in a burn intensive care unit: case report and review of the literature.

Paraneoplastic pemphigus is a rare cause of acute diffuse blistering in the adult patient. It commonly presents with subepidermal blistering, epidermal necrosis, and symptoms of mucosal irritation, such as conjunctivitis and vaginal ulceration. Because of its rarity, it is frequently misdiagnosed as Stevens-Johnson syndrome or toxic epidermal necrolysis. In this study, the authors will describe clinical and histologic manifestations of paraneoplastic pemphigus. This case report describes a 45-year-old woman with paraneoplastic pemphigus who was admitted and treated in a burn intensive care unit. Although initially diagnosed with Stevens-Johnson syndrome, the patient had progression of desquamation when potentially offending medications were discontinued. Diffuse adenopathy was noted on examination, and biopsy confirmed a low-grade lymphoma. Paraneoplastic pemphigus is a rare but important cause of acute diffuse blistering in adults. This disorder should be considered in the differential diagnosis of patients with diffuse blistering.