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.

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.

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.

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.

Teaching hospital status and operative mortality in the United States: tipping point in the volume-outcome relationship following colon resections?

OBJECTIVE: To compare risk- and volume-adjusted outcomes of colon resections performed at teaching hospitals (THs) vs non-THs to assess whether benign disease may influence the volume-outcome effect. DESIGN: Retrospective data analysis examining colon resections determined by International Classification of Diseases, Ninth Revision, Clinical Modification classification performed in the United States from 2001 through 2005 using the Nationwide Inpatient Sample (NIS) and the Area Resource File (2004). Patient covariates used in adjustment included age, sex, race, Charlson Index comorbidity score, and insurance status. Hospital covariates included TH status, presence of a colorectal surgery fellowship approved by the Accreditation Council for Graduate Medical Education, geographical region, institutional volume, and urban vs rural location. County-specific surgeon characteristics used in adjustment included average age of surgeons and proportion of colorectal board-certified surgeons within each county. Environmental or county covariates included median income and percentage of county residents living below the federal poverty level. SETTING: A total of 1045 hospitals located in 38 states in the United States that were included in the NIS. PATIENTS: All patients older than 18 years who had colon resection and were discharged from a hospital included in the NIS. MAIN OUTCOME MEASURES: Operative mortality, length of stay (LOS), and total charges. RESULTS: A total of 115 250 patients were identified, of whom 4371 died (3.8%). The mean LOS was 10 days. Fewer patients underwent surgical resection in THs than in non-THs (46 656 vs 68 589). Teaching hospitals were associated with increased odds of death (odds ratio, 1.14) (P = .03), increased LOS (P = .003), and a nonsignificant trend toward an increase in total charges (P = .36). CONCLUSIONS: With the inclusion of benign disease, colon surgery displays a volume-outcome relationship in favor of non-THs. Inclusion of benign disease may represent a tipping point.

Surgeon- and system-based influences on trauma mortality.

HYPOTHESIS: The mechanism by which trauma systems improve mortality is unknown. Outcomes may be influenced by experienced trauma surgeons treating more patients (surgeon effect) or improving the overall system of care (system effect). We hypothesized that mortality is lower in patients treated by a fellowship-trained senior trauma program director (experienced) vs first-year general surgery attending surgeon (novice) and that patient mortality for novice surgeons would improve after adding a new senior trauma director. DESIGN: Retrospective cohort study. SETTING: Academic level I trauma center. PATIENTS: Individuals who had experienced trauma. MAIN OUTCOME MEASURES: We concurrently compared mortality in trauma patients treated by an experienced trauma surgeon with those admitted by novice surgeons during 5(1/2) years. We also compared mortality in patients treated by novice surgeons before vs after implementation of a more structured trauma program. The chi(2) test and multiple logistic regression analysis were used to compare the groups. Odds ratios (95% confidence intervals) for death were examined. RESULTS: Concurrent comparison of patients treated by novice surgeons vs experienced trauma surgeons demonstrated no difference in mortality (odds ratio, 1.33; 95% confidence interval, 0.82-2.15). At unadjusted univariate analysis, mortality in patients treated by novice surgeons significantly improved over time in the blunt trauma group and all emergency department survivor subgroups. Multivariate analysis demonstrated significantly improved mortality over time in patients treated by novice surgeons (odds ratio, 0.56; 95% confidence interval, 0.37-0.85). CONCLUSIONS: In a structured trauma program, there is no mortality difference between novice surgeons and their experienced trauma director. The organized trauma program and senior surgical mentoring overpower any influence of individual surgeon inexperience.

Racial clustering and access to colorectal surgeons, gastroenterologists, and radiation oncologists by African Americans and Asian Americans in the United States: a county-level data analysis.

BACKGROUND: Minority groups have poor access to quality health care services. This is true of colorectal cancer care and may be related to both geographical proximity and use of surgical, gastroenterology, and radiation oncology services. Without suitable access, many minority patients may present with advanced colorectal cancer and be less likely to receive appropriate adjuvant therapies. We sought to examine the variations in geographical access among minorities at a county level. DESIGN: A retrospective analysis was performed using data from the Area Resource File. Multivariate linear regression analysis was performed to identify the variations in access to colorectal surgeons, gastroenterologists, and radiation oncologists. SETTING: All counties in the United States. PARTICIPANTS: Prevalence rate of African Americans and Asian Americans within a county. MAIN OUTCOME MEASURE: Rate of colorectal surgeons, gastroenterologists, and radiation oncologists. RESULTS: Unadjusted analysis revealed that each percentage point increase in the African American population within a county was associated with a decrease in the number of specialists within that county. Multivariate analysis also revealed a statistically significant decrease in the number of gastroenterologists (P < .001) and radiation oncologists (P < .001) with each percentage point increase in the African American population and a trend toward a decrease in colorectal surgeons within that county (P = .28). Each percentage point increase in the Asian American population was associated with a significant increase in the number of gastroenterologists (P < .001) and radiation oncologists (P < .001) with a similar trend toward an increase in the number of colorectal surgeons within that county (P = .13). CONCLUSION: Increasing numbers of minority patients in counties is accompanied by a differential access to specialists. This may affect the likelihood of a patient to receive appropriate care.

Residual treatment disparities after oncology referral for rectal cancer.

BACKGROUND: Black patients with rectal cancer are considerably less likely than white patients to receive adjuvant therapy. We examined the hypothesis that the lower treatment rate for blacks is due to underreferral to medical and radiation oncologists. METHODS: We used 1992-1999 Surveillance, Epidemiology, and End Results-Medicare data to identify elderly (> or = 66 years of age) patients who had been hospitalized for resection of stage II or III rectal cancer (n = 2716). We used chi(2) tests to examine associations between race and 1) consultation with an oncologist and 2) receipt of adjuvant therapy. We then used logistic regression to analyze the influence of sociodemographic and clinical characteristics (age at diagnosis, sex, marital status, median income and education in area of residence, comorbidity, and cancer stage) on black-white differences in the receipt of adjuvant therapy. All statistical tests were two-sided. RESULTS: There was no statistically significant difference between the 134 black patients and the 2582 white patients in the frequency of consultation with a medical oncologist (73.1% for blacks vs 74.9% for whites, difference = 1.8%, 95% confidence interval [CI] = > 5.9% to 9.5%, P = .64) or radiation oncologist (56.7% vs 64.8%, difference = 8.1%, 95% CI = > 0.5% to 16.7%, P = .06), but blacks were less likely than whites to consult with both a medical oncologist and a radiation oncologist (49.2% vs 58.8%, difference = 9.6%, 95% CI = 0.9% to 18.2%, P = .03). Among patients who saw an oncologist, black patients were less likely than white patients to receive chemotherapy (54.1% vs 70.2%, difference = 16.1%, 95% CI = 6.0% to 26.2%, P = .006), radiation therapy (73.7% vs 83.4%, difference = 9.7%, 95% CI = 0.4% to 19.8%, P = .06), or both (60.6% vs 76.9%, difference = 16.3%, 95% CI = 4.3% to 28.3%, P = .008). Patient and provider characteristics had minimal influence on the racial disparity in the use of adjuvant therapy. CONCLUSION: Racial differences in oncologist consultation rates do not explain disparities in the use of adjuvant treatment for rectal cancer. A better understanding of patient preferences, patient-provider interactions, and potential influences on provider decision making is necessary to develop strategies to increase the use of adjuvant treatment for rectal cancer among black patients.