Publications by authors named "Matthew E Kutcher"

43 Publications

Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.

N Engl J Med 2021 Aug 4;385(9):777-789. Epub 2021 Aug 4.

From the University of Toronto (E.C.G., P.R.L., L.C.G., M.E.F., V.D., R.A.F., J.P.G., M.H., A.S.S.), University Health Network (E.C.G., M.H.), Peter Munk Cardiac Centre at University Health Network (P.R.L., L.C.G., M.E.F., V.D.), Ozmosis Research (L.B., V.W.), Sunnybrook Health Sciences Centre (J.P.G.), Toronto, Ottawa Hospital Research Institute (M. Carrier, L.A.C., D.A.F., G.L.G., D.M.S.), Institut du Savoir Montfort (M. Carrier, G.L.G.), and the University of Ottawa (L.A.C., D.A.F., D.M.S.), Ottawa, the University of Manitoba (A. Kumar, B.L.H., R.Z., S.A.L., D.S., G.V.-G.) and CancerCare Manitoba (B.L.H., R.Z.), Winnipeg, Université Laval and Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Quebec, QC (A.F.T.), McGill University, Montreal (S.R.K., E.G.M.), St. Michael's Hospital Unity Health, Toronto (J.C.M., Z.B., M.S., A.S.S.), McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (P.L.G.) Université de Sherbrooke, Sherbrooke, QC (F.L.), St. Boniface Hospital, Winnipeg, MB (N.M.), the University of British Columbia, Vancouver (S. Murthy), and the University of Alberta, Edmonton (S.D.) - all in Canada; University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust, Bristol (C.A.B.), the London School of Hygiene and Tropical Medicine (B.-A.K.), Imperial College London (A.C.G., F.A.-B., M.A.L.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), University College London Hospital (R.H.), Kings Healthcare Partners (B.J.H.), and Intensive Care National Audit and Research Centre (ICNARC) (P.R.M., K.R.), London, Queen's University Belfast and Royal Victoria Hospital, Belfast (D.F.M.), and Oxford University (A. Beane, L.J.E., S.J.S.) and NHS Blood and Transplant (L.J.E., S. Mavromichalis, S.J.S.), Oxford - all in the United Kingdom; the University of Pittsburgh (B.J.M., D.C.A., M.M.B., M.D.N., H.F.E., J.D.F., Z.F., D.T.H., A.J.K., C.M.L., K.L., M.M., S.K.M., C.W.S., Y.Z.), University of Pittsburgh Medical Center (B.J.M., D.C.A., M.D.N., K.L.), the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh (T.D.G.), and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (C.M. Horvat) - all in Pittsburgh; New York University (NYU) Grossman School of Medicine (J.S.B., H.R.R., J.S.H., T.C., A.C., N.M.K., S. Mavromichalis, S.P.), NYU Langone Health, NYU Langone Hospital (T.A., T.C., A.C., J.M.H., E.Y.), and Bellevue Hospital (N.M.K.), Icahn School of Medicine at Mount Sinai (R.S.R.), and Mount Sinai Heart (R.S.R.), New York, Montefiore Medical Center (M.N.G., H.H.B., S.C., J.-T.C., A.A. Hope, R.N.) and Albert Einstein College of Medicine (M.N.G., H.H.B., B.T.G., A.A. Hope), Bronx, and NYU Langone Long Island, Mineola (A.A. Hindenburg) - all in New York; Zuckerberg San Francisco General Hospital-University of California, San Francisco (L.Z.K., C.M. Hendrickson, M.M.K., A.E.K., B.N.-G., J.J.P.), Harbor-UCLA Medical Center, Torrance (R.J.L.), Global Coalition for Adaptive Research (M. Buxton) and the University of California, Los Angeles (G.L.), Los Angeles, the University of California San Diego School of Medicine, San Diego (T.W.C.), and Stanford University School of Medicine, Palo Alto (J.G.W.) - all in California; the University of Illinois (K.S.K., J.R.J., J.G.Q.), the University of Chicago (J.D.P.), and the Chartis Group (J.S.) - all in Chicago; University Medical Center Utrecht, Utrecht University (L.P.G.D., M. Bonten, R.E.G.S., W.B.-P.), and Utrecht University (R.E.G.S.), Utrecht, and Radboud University Medical Center, Nijmegen (S. Middeldorp, F.L.V.) - all in the Netherlands; Larner College of Medicine at the University of Vermont, Burlington (M. Cushman); Inselspital, Bern University Hospital, University of Bern, Bern (T.T.), and SOCAR Research, Nyon (B.-A.K., S. Brouwer) - both in Switzerland; Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (L.C.G., F.G.L., J.C.N.), Avanti Pesquisa Clínica (A.S.M.), and Hospital 9 de Julho (F.O.S.), Sao Paulo, Hospital do Coração de Mato Grosso do Sul (M.P.), the Federal University of Mato Grosso do Sul (M.P.), Hospital Universitário Maria Aparecida Pedrossia (D.G.S.), and Hospital Unimed Campo Grande (D.G.S.), Campo Grande, and Instituto Goiano de Oncologia e Hematologia, Clinical Research Center, Goiânia (M.O.S.) - all in Brazil; the Australian and New Zealand Intensive Care Research Centre, Monash University (Z.M., C.J.M., S.A.W., A. Buzgau, C.G., A.M.H., S.P.M., A.D.N., J.C.P.), Monash University (A.C.C.), and Alfred Health (A.C.C., A.D.N.), Melbourne, VIC, St. John of God Subiaco Hospital, Subiaco, WA (S.A.W., E. Litton), Flinders University, Bedford Park, SA (S. Bihari), and Fiona Stanley Hospital, Perth, WA (E. Litton) - all in Australia; Berry Consultants, Austin (R.J.L., L.R.B., E. Lorenzi, S.M.B., M.A.D., M.F., A.M., C.T.S.), and Baylor Scott and White Health, Temple (R.J.W.) - both in Texas; Auckland City Hospital (C.J.M., S.P.M., R.L.P.) and the University of Auckland (R.L.P.), Auckland, and the Medical Research Institute of New Zealand, Wellington (C.J.M., A.M.T.) - all in New Zealand; Fédération Hospitalo-Universitaire Saclay and Paris Seine Nord Endeavour to Personalize Interventions for Sepsis (FHU-SEPSIS), Raymond Poincaré Hospital, Université de Versailles Saint-Quentin-en-Yvelines, Garches (D. Annane), and Aix-Marseille University, Marseille (B.C.) - both in France; King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia (Y.M.A.); Nepal Mediciti Hospital, Lalitpur (D. Aryal), and the Nepal Intensive Care Research Foundation, Kathmandu (D. Aryal); Versiti Blood Research Institute, Milwaukee (L.B.K.); National Intensive Care Surveillance (NICS)-Mahidol Oxford Tropical Medicine Research Unit (MORU), Colombo, Sri Lanka (A. Beane); Jena University Hospital, Jena, Germany (F.B.); Cleveland Clinic, Cleveland (A.D.), and the University of Cincinnati, Cincinnati (K.H.) - both in Ohio; Ochsner Medical Center, University of Queensland-Ochsner Clinical School, New Orleans (M.B.E.); Instituto Mexicano del Seguro Social, Mexico City (J.E., E.M.G.); Brigham and Women's Hospital (B.M.E., Y.K., S.M.H.), Massachusetts General Hospital (N.S.R., A.B.S.), and Harvard Medical School (B.M.E., Y.K., N.S.R., A.B.S.) - all in Boston; University of Alabama, Birmingham (S.G.); TriStar Centennial Medical Center, Nashville (A.L.G.); University of Antwerp, Wilrijk, Belgium (H.G.); Rutgers New Jersey Medical School, Newark, New Jersey (Y.Y.G.); University of Oxford, Bangkok, Thailand (R.H.); the University of Michigan, Ann Arbor (R.C.H., P.K.P.), Beaumont Health, Royal Oak (G.B.N.), and Oakland University William Beaumont School of Medicine, Auburn Hills (G.B.N.) - all in Michigan; Apollo Speciality Hospital OMR, Chennai, India (D.J.); Oregon Health and Science University, Portland (A. Khan); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (A. Kindzelski, E.S.L.); University of Mississippi Medical Center, Jackson (M.E.K.); IdiPaz Research Institute, Universidad Autonoma, Madrid (J.L.-S.); University College Dublin, Dublin (A.D.N.); the University of Kansas School of Medicine, Kansas City (L.S.); and Duke University Hospital, Durham, North Carolina (L.W.).

Background: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.

Methods: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.

Results: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.

Conclusions: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
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http://dx.doi.org/10.1056/NEJMoa2103417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362592PMC
August 2021

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

N Engl J Med 2021 Aug 4;385(9):790-802. Epub 2021 Aug 4.

From the Peter Munk Cardiac Centre at University Health Network (P.R.L., M.E.F., V.D., J.P.G., L.C.G., G.H.), the University of Toronto (P.R.L., E.C.G., A.S.S., M.E.F., V.D., R.A.F., L.C.G., G.H., M.H.), University Health Network (E.C.G., M.H.), St. Michael's Hospital Unity Health (A.S.S., Z.B., J.C.M., M.S.), Ozmosis Research (L.B., L.P.G.D., V.W.), and Sunnybrook Health Sciences Centre (J.P.G.), Toronto, Ottawa Hospital Research Institute (M. Carrier, L.A.C., D.A.F., G.L.G., D.M.S.), Institut du Savoir Montfort (Marc Carrier, G.L.G.), and the University of Ottawa (L.A.C., D.A.F., D.M.S.), Ottawa, Université Laval (A.F.T.) and CHU de Québec-Université Laval Research Center (A.F.T.), Quebec, QC, the University of Manitoba (B.L.H., A. Kumar, R.Z., S.A.L., D.S., G.V.-G.), CancerCare Manitoba (B.L.H., R.Z.), and St. Boniface Hospital (N.M.), Winnipeg, MB, McGill University, Montreal (S.R.K., E.G.M.), McMaster University (P.L.G.) and the Thrombosis and Atherosclerosis Research Institute (P.L.G.), Hamilton, ON, Université de Sherbrooke, Sherbrooke, QC (F.L.), the University of British Columbia, Vancouver (S. Murthy, K.R.), and the University of Alberta, Edmonton (S.D.) - all in Canada; NYU Grossman School of Medicine (J.S.B., H.R.R., J.S.H., T.C., N.M.K., S.P.), the Icahn School of Medicine at Mount Sinai and Mount Sinai Heart (R.S.R.), NYU Langone Health, NYU Langone Hospital (T.C., J.M.H., E.Y.), and Bellevue Hospital (N.M.K.), New York, Montefiore Medical Center (M.N.G., H.H.B., S.C., J.T.C., R.N.) and Albert Einstein College of Medicine (M.N.G., H.H.B., B.T.G., A. Hope), Bronx, and NYU Langone Long Island, Mineola (R.D.H., A. Hindenburg) - all in New York; the University of Pittsburgh (M.D.N., B.J.M., D.T.H., M.M.B., D.C.A., A.J.K., C.M.L., K.L., S.K.M., C.W.S.), UPMC (M.D.N., B.J.M., D.C.A., K.L., S.K.M.), the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh (T.D.G.), and UPMC Children's Hospital of Pittsburgh (C. Horvat), Pittsburgh, and Emergency Medicine, Penn State Hershey Medical Center, Hershey (S.C.M.) - all in Pennsylvania; Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (J.C.N., L.C.G., F.G.L.), Avanti Pesquisa Clínica (A.S.M.), Hospital de Julho (F.O.S.), and Hospital do Coracao (F.G.Z.), Sao Paulo, Hospital do Coração de Mato Grosso do Sul and the Federal University of Mato Grosso do Sul (M.P.), Hospital Universitário Maria Aparecida Pedrossia (D.G.S.J.), and Hospital Unimed Campo Grande (D.G.S.J.), Campo Grande, and INGOH, Clinical Research Center, Goiânia (M.O.S.) - all in Brazil; Instituto Mexicano del Seguro Social, Mexico City (J.E., Y.S.P.G.); the University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust (C.A.B.), Bristol, Imperial College London (A.C.G., F.A.-B., M.A.L.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), the London School of Hygiene and Tropical Medicine (B.-A.K.), University College London Hospital (R.H.), Kings Healthcare Partners (B.J.H.), the Intensive Care National Audit and Research Centre (P.R.M.), Guy's and St. Thomas' NHS Foundation Trust (M.S.-H.), and King's College London (M.S.-H.), London, Oxford University (A. Beane, S.J.S.) and NHS Blood and Transplant (L.J.E., S.J.S.), Oxford, and Queen's University Belfast and Royal Victoria Hospital, Belfast (D.F.M.) - all in the United Kingdom; Zuckerberg San Francisco General Hospital, University of California, San Francisco (L.Z.K., C. Hendrickson, M.M.K., A.E.K., M.A.M., B.N.-G.), Harbor-UCLA Medical Center, Torrance (R.J.L., S. Brouwer), Global Coalition for Adaptive Research (M. Buxton) and the University of California Los Angeles (G.L.), Los Angeles, the University of California San Diego School of Medicine, San Diego (T.W.C.), and Stanford University School of Medicine, Palo Alto (J.G.W.) - all in California; Larner College of Medicine at the University of Vermont, Burlington (M. Cushman); Australian and New Zealand Intensive Care Research Centre, Monash University (Z.M., A.M.H., C.J.M., S.A.W., A. Buzgau, C.G., S.P.M., A.D.N., J.C.P., A.C.C.), and Alfred Health (A.C.C., A.D.N.), Melbourne, VIC, St. John of God Subiaco Hospital (S.A.W., E. Litton) and Fiona Stanley Hospital (E. Litton), Perth, WA, and Flinders University, Bedford Park, SA (S. Bihari) - all in Australia; the University of Illinois (K.S.K., J.R.J., J.G.Q.), Cook County Health and Rush Medical College (S. Malhotra), and the University of Chicago (J.D.P.) - all in Chicago; SOCAR Research SA, Nyon (B.-A.K.), and Inselspital, Bern University Hospital, University of Bern (T.T.), Bern - all in Switzerland; Berry Consultants, Austin (R.J.L., E. Lorenzi, S.M.B., L.R.B., M.A.D., M.F., A.M., C.T.S.), University of Texas Southwestern Medical Center, Dallas (A.P.), and Baylor Scott and White Health, Temple (R.J.W.) - all in Texas; Auckland City Hospital (C.J.M., S.P.M., R.L.P.) and the University of Auckland (R.L.P.), Auckland, and the Medical Research Institute of New Zealand, Wellington (C.J.M., A.M.T.) - all in New Zealand; Vanderbilt University Medical Center (A.W.A.) and TriStar Centennial Medical Center (A.L.G.) - both in Nashville; Fédération Hospitalo Universitaire, Raymond Poincaré Hospital, Université de Versailles Saint-Quentin-en-Yvelines, Garches (D. Annane), and Aix-Marseille University, Marseille (B.C.) - both in France; King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.M.A.); Nepal Mediciti Hospital, Lalitpur, and Nepal Intensive Care Research Foundation, Kathmandu (D. Aryal) - both in Nepal; Versiti Blood Research Institute, Milwaukee (L.B.K., L.J.E.), and the University of Wisconsin School of Medicine and Public Health, Madison (J.P.S.); National Intensive Care Surveillance-Mahidol Oxford Tropical Medicine Research Unit, Colombo, Sri Lanka (A. Beane); the University Medical Center Utrecht, Utrecht University, Utrecht (M. Bonten, R.E.G.S., W.B.-P.), and Radboud University Medical Center, Nijmegen (S. Middeldorp, F.L.V.) - both in the Netherlands; Jena University Hospital, Jena, Germany (F.B.); Cleveland Clinic (A.D.) and Case Western Reserve University, the Metro Health Medical Centre (V.K.) - both in Cleveland; Ochsner Medical Center, University of Queensland-Ochsner Clinical School, New Orleans (M.B.E.); Harvard Medical School (B.M.E., Y.K., N.S.R., A.B.S), Brigham and Women's Hospital (B.M.E., Y.K., S.M.H.), Boston University School of Medicine and Boston Medical Center (N.M.H.), and Massachusetts General Hospital (A.B.S., N.S.R.) - all in Boston; University of Alabama, Birmingham (S.G.); Hospital Ramón y Cajal (S.G.-M., J.L.L.-S.M., R.M.G.) and IdiPaz Research Institute, Universidad Autonoma (J.L.-S.), Madrid, and University Hospital of Salamanca-University of Salamanca-IBSAL, Salamanca (M.M.) - all in Spain; University of Antwerp, Wilrijk, Belgium (H.G.); Rutgers New Jersey Medical School, Newark (Y.Y.G.); University of Oxford, Bangkok, Thailand (R.H.); Ascension St. John Heart and Vascular Center, Tulsa (N.H.), and the University of Oklahoma College of Medicine, Oklahoma City (N.H.); the University of Cincinnati, Cincinnati (K.H.); University of Michigan, Ann Arbor (R.C.H., P.K.P.), Beaumont Health, Royal Oak, and the OUWB School of Medicine, Auburn Hills (G.B.N.) - all in Michigan; Mayo Clinic, Rochester (V.N.I.), and the Hennepin County Medical Center, Minneapolis (M.E.P.) - both in Minnesota; Apollo Speciality Hospital-OMR, Chennai, India (D.J.); Oregon Health and Science University, Portland (A. Khan, E.S.L.); the National Heart, Lung, and Blood Institute, Bethesda, MD (A.L.K.); University of Mississippi Medical Center, Jackson (M.E.K.); University College Dublin, Dublin (A.D.N.); University of Kansas School of Medicine, Kansas City (L.S.); Duke University Hospital, Durham, NC (L.W.); and Emory University, Atlanta (B.J.W.).

Background: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.

Methods: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.

Results: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.

Conclusions: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).
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http://dx.doi.org/10.1056/NEJMoa2105911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362594PMC
August 2021

Predicting pain among female survivors of recent interpersonal violence: A proof-of-concept machine-learning approach.

PLoS One 2021 29;16(7):e0255277. Epub 2021 Jul 29.

Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.

Interpersonal violence (IPV) is highly prevalent in the United States and is a major public health problem. The emergence and/or worsening of chronic pain are known sequelae of IPV; however, not all those who experience IPV develop chronic pain. To mitigate its development, it is critical to identify the factors that are associated with increased risk of pain after IPV. This proof-of-concept study used machine-learning strategies to predict pain severity and interference in 47 young women, ages 18 to 30, who experienced an incident of IPV (i.e., physical and/or sexual assault) within three months of their baseline assessment. Young women are more likely than men to experience IPV and to subsequently develop posttraumatic stress disorder (PTSD) and chronic pain. Women completed a comprehensive assessment of theory-driven cognitive and neurobiological predictors of pain severity and pain-related interference (e.g., pain, coping, disability, psychiatric diagnosis/symptoms, PTSD/trauma, executive function, neuroendocrine, and physiological stress response). Gradient boosting machine models were used to predict symptoms of pain severity and pain-related interference across time (Baseline, 1-,3-,6- follow-up assessments). Models showed excellent predictive performance for pain severity and adequate predictive performance for pain-related interference. This proof-of-concept study suggests that machine-learning approaches are a useful tool for identifying predictors of pain development in survivors of recent IPV. Baseline measures of pain, family life impairment, neuropsychological function, and trauma history were of greatest importance in predicting pain and pain-related interference across a 6-month follow-up period. Present findings support the use of machine-learning techniques in larger studies of post-IPV pain development and highlight theory-driven predictors that could inform the development of targeted early intervention programs. However, these results should be replicated in a larger dataset with lower levels of missing data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255277PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320990PMC
July 2021

The effects of increased donor support time from organ donation referral to donor procurement on heart transplant recipient survival.

J Card Surg 2021 Jun 22;36(6):1892-1899. Epub 2021 Feb 22.

Lutheran Medical Group, Indiana University School of Medicine, Fort Wayne, Indiana, USA.

Introduction: Given the known deleterious cardiac effects of brain death (BD) physiology, we hypothesized that time from cardiac donation referral to procurement (donor support time [DST]), would negatively impact cardiac transplant recipient survival.

Methods: The United Network for Organ Sharing database was queried from 2007 to 2018, identifying 22,593 donor hearts for analysis. Multivariate logistic models for 30-day and 1-year survival, as well as Cox models for overall survival and posttransplant rejection, were used to assess adjusted outcomes.

Results: median DST was 3 days (interquartile range: 2-5 days). Ischemic time; distance between donor and recipient hospitals; and recipient age, creatinine, waitlist time, and length of stay were adjusted predictors of survival and rejection. DST was not associated with either outcome in aggregate; however, differential association by donor race was identified, with DST in any race recipient associated with 4% higher odds of 1-year mortality (p = .001; p value for interaction .005) but only a trend towards worse overall mortality (p = .064; p value for interaction .046).

Conclusion: Thus, duration of exposure to BD physiology may have a differential impact on recipient outcomes based on donor race, suggesting that additional research is needed on donor immunologic, socioeconomic, and healthcare access factors that may impact cardiac transplant recipient outcomes.
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http://dx.doi.org/10.1111/jocs.15442DOI Listing
June 2021

Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes.

Int J Mol Sci 2021 Jan 8;22(2). Epub 2021 Jan 8.

Department of Surgery, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216-4500, USA.

Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT™ PicoGreen dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70-85%, both < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP.
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http://dx.doi.org/10.3390/ijms22020564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826953PMC
January 2021

Dynamics and determinants of cortisol and alpha-amylase responses to repeated stressors in recent interpersonal trauma survivors.

Psychoneuroendocrinology 2020 12 6;122:104899. Epub 2020 Oct 6.

Department of Psychiatry & Human Behavior, Department of Pediatrics and Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Children's Hospital of Orange County, Orange, CA, USA.

Background: Alterations in major stress response systems are present during the immediate aftermath of trauma and may play a role in determining risk for developing posttraumatic stress disorder (PTSD). However, the dynamics and determinants of stress responses during this acute recovery phase, and their relevance for longitudinal clinical course and prognosis, have yet to be fully examined. The objectives of the present study were to characterize stress response and habituation patterns to repeated social stressors in women who recently experienced interpersonal trauma and to determine the extent to which these stress responses were associated with PTSD during prospective follow-up.

Method: This longitudinal study examined salivary cortisol and alpha-amylase and heart rate (HR) responses to repeated stressors in 98 young women (ages 18-30). Participants included women who had experienced an incident of interpersonal trauma (i.e., physical and/or sexual assault) in the three months prior to their baseline assessment (n = 58) and a comparison group of healthy, non-traumatized women (n = 40). Women completed the Trier Social Stress Test (TSST), clinical interviews to evaluate posttraumatic stress symptom severity at the baseline assessment and again at 1-, 3-, and 6-month follow-ups.

Results: Multilevel models revealed a pattern of robust initial cortisol TSST responses and habituation across successive TSSTs; alpha-amylase and HR responses showed no evidence of habituation across TSSTs. Among interpersonal trauma survivors, current PTSD status was associated with more pronounced cortisol responses to the first TSST. Survivors exhibited similarly blunted cortisol responses across follow-up TSSTs regardless of PTSD status, suggesting habituation of cortisol responses among survivors who developed PTSD. PTSD re-experiencing symptoms were uniquely associated with blunting of cortisol TSST responses.

Conclusion: Findings suggest that PTSD as a diagnostic entity is meaningfully associated with cortisol responses to repeated social stressors. Social-evaluative threat is a salient form of danger for interpersonal trauma survivors. Identifying the determinants of cortisol (non)habituation to repeated social-evaluative threat among interpersonal trauma survivors could inform the development of early interventions for PTSD.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686015PMC
December 2020

Does pediatric heart transplant survival differ with various cardiac preservation solutions?

Clin Transplant 2020 12 22;34(12):e14122. Epub 2020 Nov 22.

Lutheran Medical Hospital, Fort Wayne, IN, USA.

Background: Few studies directly compare outcomes between the most commonly used preservation solutions in pediatric heart transplantation in a large cohort of recipients. The purpose of this study is to investigate the effect of cardiac preservation solution on survival in pediatric heart transplant recipients.

Methods: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from 01/2004-03/2018 for pediatric donor hearts. Saline, University of Wisconsin (UW), "cardioplegia," Celsior, and Custodiol preservation solutions were evaluated. The primary endpoints were recipient survival at 30 days, 1 year, and long term.

Results: After exclusion criteria, 3012 recipients had preservation solution data available. The most common preservation solution used was UW in 1203 patients (40%), followed by Celsior in 542 (18%), cardioplegia in 461 (15%), saline in 408 (14%), and Custodiol in 398 (13%). Survival of recipients whose donor hearts were procured with UW was as follows: 97%-30 day, 92%-1 year; Celsior: 97%-30 day, 92%-1 year; cardioplegia: 97%-30 day, 91%-1 year; saline: 97%-30 day, 91%-1 year; and Custodiol: 96%-30 day and 92%-1 year. Analysis of Cox models for 30-day and long-term survival revealed no statistical differences when comparing UW to Celsior (p = .333), cardioplegia (p = .914), saline (p = .980), or Custodiol (p = .642) in adjusted models.

Conclusions: There were no significant differences in 30-day or 1-year survival detected between commonly used preservation solutions in the pediatric heart transplant population.
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http://dx.doi.org/10.1111/ctr.14122DOI Listing
December 2020

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis.

N Engl J Med 2020 11 5;383(20):1907-1919. Epub 2020 Oct 5.

The affiliations of the members of the writing committee are as follows: the University of Washington (D.R.F., G.H.D., S.M., A.K.S., E.F., D.C.L., B.A.C., P.J.H., L.G.K.), the Washington State Hospital Association (B.B.), Harborview Medical Center (H.E., J.C.), the Swedish Medical Center (K.A.M.), and the Virginia Mason Medical Center (J.T.Y., A.W.), Seattle, Madigan Army Medical Center, Tacoma (V.S., K.M.), and Providence Regional Medical Center Everett, Everett (C.S.F., S.M.S.) - all in Washington; Beth Israel Deaconess Medical Center (N.I.S., S.R.O.) and Boston University Medical Center (S.E.S., F.T.D.) - both in Boston; Columbia University Medical Center (K.F.), Tisch Hospital, NYU Langone Medical Center (P.A.-C., W.C.), Bellevue Hospital Center, NYU School of Medicine (P.A.-C., W.C.), and Weill Cornell Medical Center (R.J.W., S.C.) - all in New York; Henry Ford Health, Detroit (J.J., J.H.P.), and the University of Michigan, Ann Arbor (H.B.A., P.K.P.); University of Iowa Hospitals and Clinics, Iowa City (B.A.F., D.A.S.); the University of Texas Lyndon B. Johnson Medical Center (M.K.L.) and the University of Texas Health Science Center at Houston (L.S.K.) - both in Houston; the University of Mississippi Medical Center, Jackson (M.E.K.); Maine Medical Center, Portland (B.C., D.W.C.); Ohio State University Medical Center, Columbus (A.R., S.S.); Rush University Medical Center, Chicago (T.P.P.); UCHealth University of Colorado Hospital, Denver (L.F., M.S.); Harbor UCLA Medical Center (D.A.D., A.H.K.), Olive View UCLA Medical Center (G.J.M., D.S., A.K.), and Ronald Reagan UCLA Medical Center (D.A.T.) - all in Los Angeles; and Vanderbilt University Medical Center, Nashville (C.M.T., W.H.S.).

Background: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis.

Methods: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith.

Results: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50).

Conclusions: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).
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http://dx.doi.org/10.1056/NEJMoa2014320DOI Listing
November 2020

A rat model of orthopedic injury-induced hypercoagulability and fibrinolytic shutdown.

J Trauma Acute Care Surg 2020 11;89(5):926-931

From the Division of Trauma, Critical Care, and Acute Care Surgery, Department of Surgery (K.T.C., A.C.P., F.T.S., B.M.W., L.M., M.E.K.), and Department of Physiology and Biophysics (R.L.H.), University of Mississippi Medical Center, Jackson, Mississippi.

Background: Postinjury hypercoagulability occurs in >25% of injured patients, increasing risk of thromboembolic complications despite chemoprophylaxis. However, few clinically relevant animal models of posttraumatic hypercoagulability exist. We aimed to evaluate a rodent model of bilateral hindlimb injury as a preclinical model of postinjury hypercoagulability.

Methods: Forty Wistar rats were anesthetized with isoflurane: 20 underwent bilateral hindlimb fibula fracture, soft tissue and muscular crush injury, and bone homogenate injection intended to mimic the physiological severity of bilateral femur fracture. Twenty sham rats underwent anesthesia only. Terminal citrated blood samples were drawn at 0, 6, 12, and 24 hours (n = 5 per timed group) for analysis by native thromboelastography in the presence and absence of taurocholic acid to augment fibrinolysis. Plasminogen activator inhibitor 1 and α-2 antiplasmin levels in plasma were assessed via enzyme-linked immunosorbent assay.

Results: Injured rats became hypercoagulable relative to baseline by 6 hours based on thromboelastography maximal amplitude (MA) and G (p < 0.005); sham rats became hypercoagulable to a lesser degree by 24 hours (p < 0.005). Compared with sham animals, injured rats were hypercoagulable by MA and G within 6 hours of injury, remained hypercoagulable by MA and G through at least 24 hours (all p < 0.01), and showed impaired fibrinolysis by taurocholic acid LY30 at 12 hours (p = 0.019) and native LY30 at 24 hours (p = 0.045). In terms of antifibrinolytic mediators, α-2 antiplasmin was elevated in trauma animals at 24 hours (p = 0.009), and plasminogen activator inhibitor 1 was elevated in trauma animals at 6 hours (p = 0.004) and 12 hours (p < 0.001) when compared with sham.

Conclusions: Orthopedic injury in rodents induced platelet and overall hypercoagulability within 6 hours and fibrinolytic impairment by 12 to 24 hours, mimicking postinjury hypercoagulability in injured patients. This rodent model of orthopedic injury may serve as a preclinical testing ground for potential therapies to mitigate hypercoagulability, maintain normal fibrinolysis, and prevent thromboembolic complications.
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http://dx.doi.org/10.1097/TA.0000000000002924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897415PMC
November 2020

Contemporary management of traumatic cervical and thoracic esophageal perforation: The results of an Eastern Association for the Surgery of Trauma multi-institutional study.

J Trauma Acute Care Surg 2020 10;89(4):691-697

From the Division of Acute Care Surgery, Department of Surgery (L.A.R.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Ascension St. John Medical Center Trauma Services (E.A.S.), Tulsa, Oklahoma; Department of Surgery (R.G.M., B.R.H.R.), Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington; Division of Acute Care Surgery, Department of Surgery (J.J.), University of Alabama at Birmingham, Birmingham, Alabama; Department of Surgery (M.R.N., Z.S.), Allegheny General Hospital, Pittsburgh, Pennsylvania; Department of General Surgery (E.C., J.C.), Denver Health Medical Center, Denver, Colorado; University of Nevada at Las Vegas School of Medicine (S.S., J.T.C.), Las Vegas, Nevada; Department of Trauma (L.E.J., J.W.), St. Vincent Indianapolis Hospital, Indianapolis, Indiana; Department of Surgery (A.J.Y., J.P.), University of Pennsylvania, Philadelphia, Pennsylvania; Department of Surgery (S.B., D.G.), Loma Linda Medical Center, Loma Linda, California; Division of Trauma, Burns, and Surgical Critical Care, Department of Surgery (J.N.), University of California at Irvine, Orange, California; Department of Surgery (M.E.K.), University of Mississippi Medical Center, Jackson, Mississippi; Division of Trauma and Acute Care Surgery, Department of Surgery (N.B., K.J.), Tufts Medical Center, Boston, Massachusetts; and Division of Acute Care Surgery, Department of Surgery (P.B.), Banner University Medical Center, University of Arizona College of Medicine, Phoenix, Arizona.

Background: Traumatic esophageal perforation is rare and associated with significant morbidity and mortality. There is substantial variability in diagnosis and treatment. Esophageal stents have been increasingly used for nontraumatic perforation; however, stenting for traumatic perforation is not yet standard of care. The purpose of this study was to evaluate current management of traumatic esophageal perforation to assess the frequency of and complications associated with esophageal stenting.

Methods: This was an Eastern Association for the Surgery of Trauma multi-institutional retrospective study from 2011 to 2016 of patients with traumatic cervical or thoracic esophageal injury admitted to one of 11 participating trauma centers. Data were collected and sent to a single institution where it was analyzed. Patient demographics, injury characteristics, initial management, complications, and patient mortality were collected. Primary outcome was mortality; secondary outcomes were initial treatment, esophageal leak, and associated complications.

Results: Fifty-one patients were analyzed. Esophageal injuries were cervical in 69% and thoracic in 31%. Most patients were initially managed with operative primary repair (61%), followed by no intervention (19%), esophageal stenting (10%), and wide local drainage (10%). Compared with patients who underwent operative primary repair, patients managed with esophageal stenting had an increased rate of esophageal leak (22.6% vs. 80.0%, p = 0.02). Complication rates were higher in blunt compared with penetrating mechanisms (100% vs. 31.8%, p = 0.03) despite similar Injury Severity Score and neck/chest/abdomen Abbreviated Injury Scale. Overall mortality was 9.8% and did not vary based on location of injury, mechanism of injury, or initial management.

Conclusion: Most patients with traumatic esophageal injuries still undergo operative primary repair; this is associated with lower rates of postoperative leaks as compared with esophageal stenting. Patients who have traumatic esophageal injury may be best managed by direct repair and not esophageal stenting, although further study is needed.

Level Of Evidence: Therapeutic, level IV.
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http://dx.doi.org/10.1097/TA.0000000000002841DOI Listing
October 2020

Analysis of Plasma Products for Cellular Contaminants: Comparing Standard Preparation Methods.

J Am Coll Surg 2020 04;230(4):596-602

Department of Surgery, The University of South Alabama, Mobile, AL; Department of Cellular and Molecular Pharmacology, The University of South Alabama, Mobile, AL. Electronic address:

Background: Recent reports suggest that component plasma products contain significant quantities of cellular contamination. We hypothesized that leukoreduction of whole blood before preparation of derived plasma is an effective method to prevent cellular contamination of stored plasma.

Study Design: Samples of never-frozen liquid plasma prepared by standard methods (n = 25) were obtained from 3 regional blood centers that supply 3 major trauma centers. Samples were analyzed for leukocyte and platelet contamination by flow cytometry. To determine if leukoreduction of whole blood before centrifugation and expression of plasma prevents cellular contamination of liquid plasma, 1 site generated 6 additional units of liquid plasma from leukoreduced whole blood, which were then compared with units of liquid plasma derived by standard processing.

Results: Across all centers, each unit of never-frozen liquid plasma contained a mean of 12.8 ± 3.0 million leukocytes and a mean of 4.6 ± 2 billion platelets. Introduction of whole blood leukoreduction (LR) before centrifugation and plasma extraction essentially eliminated all contaminating leukocytes (Non-LR: 12.3 ± 2.9 million vs LR: 0.05 ± 0.05 million leukocytes) and platelets (Non-LR: 4.2 ± 0.3 billion platelets vs LR: 0.00 ± 0.00 billion platelets).

Conclusions: Despite widespread belief that stored plasma is functionally acellular, testing of liquid plasma from 3 regional blood banks revealed a significant amount of previously unrecognized cellular contamination. Introduction of a leukoreduction step before whole blood centrifugation essentially eliminated detectable leukocyte and platelet contaminants from plasma. Therefore, our study highlights a straightforward and cost-effective method to eliminate cellular contamination of stored plasma.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.12.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682813PMC
April 2020

Alterations in platelet behavior after major trauma: adaptive or maladaptive?

Platelets 2021 Apr 27;32(3):295-304. Epub 2020 Jan 27.

Pittsburgh Trauma Research Center and Division of Trauma and Acute Care Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Platelets are damage sentinels of the intravascular compartment, initiating and coordinating the primary response to tissue injury. Severe trauma and hemorrhage induce profound alterations in platelet behavior. During the acute post-injury phase, platelets develop a state of impaired agonist responsiveness independent of platelet count, associated with systemic coagulopathy and mortality risk. In patients surviving the initial insult, platelets become hyper-responsive, associated with increased risk of thrombotic events. Beyond coagulation, platelets constitute part of a sterile inflammatory response to injury: both directly through release of immunomodulatory molecules, and indirectly through modifying behavior of innate leukocytes. Both procoagulant and proinflammatory aspects have implications for secondary organ injury and multiple-organ dysfunction syndromes. This review details our current understanding of adaptive and maladaptive alterations in platelet biology induced by severe trauma, mechanisms underlying these alterations, potential platelet-focused therapies, and existing knowledge gaps and their research implications.
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http://dx.doi.org/10.1080/09537104.2020.1718633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382983PMC
April 2021

Outcomes in patients with gunshot wounds to the brain.

Trauma Surg Acute Care Open 2019 17;4(1):e000351. Epub 2019 Nov 17.

Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Introduction: Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR.

Methods: We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation.

Results: 825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation.

Conclusion: We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition.

Level Of Evidence: Level II.
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http://dx.doi.org/10.1136/tsaco-2019-000351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861103PMC
November 2019

Heparin-Sparing Anticoagulation Strategies Are Viable Options for Patients on Veno-Venous ECMO.

J Surg Res 2019 11 2;243:399-409. Epub 2019 Jul 2.

Division of Cardiothoracic Surgery, University of Mississippi Medical Center, Jackson, Mississippi. Electronic address:

Background: Extracorporeal membrane oxygenation (ECMO), a rescue therapy for pulmonary failure, has traditionally been limited by anticoagulation requirements. Recent practice has challenged the absolute need for anticoagulation, expanding the role of ECMO to patients with higher bleeding risk. We hypothesize that mortality, bleeding, thrombotic events, and transfusions do not differ between heparin-sparing and full therapeutic anticoagulation strategies in veno-venous (VV) ECMO management.

Materials And Methods: Adult VV ECMO patients between October 2011 and May 2018 at a single center were reviewed. A heparin-sparing strategy was implemented in October 2014; we compared outcomes in an as-treated fashion. The primary end point was survival. Secondary end points included bleeding, thrombotic complications, and transfusion requirements.

Results: Forty VV ECMO patients were included: 17 (147 circuit-days) before and 23 (214 circuit-days) after implementation of a heparin-sparing protocol. Patients treated with heparin-sparing anticoagulation had a lower body mass index (28.5 ± 7.1 versus 38.1 ± 12.4, P = 0.01), more often required inotropic support before ECMO (82 versus 50%, P = 0.05), and had a lower mean activated clotting time (167 ± 15 versus 189 ± 15 s, P < 0.01). There were no significant differences in survival to decannulation (59 versus 83%, P = 0.16) or discharge (50 versus 72%, P = 0.20), bleeding (32 versus 33%, P = 1.0), thromboembolic events (18 versus 39%, P = 0.17), or transfusion requirements (median 1.1 versus 0.9 unit per circuit-day, P = 0.48).

Conclusions: Survival, bleeding, thrombotic complications, and transfusion requirements did not differ between heparin-sparing and full therapeutic heparin strategies for management of VV ECMO. VV ECMO can be a safe option in patients with traditional contraindications to anticoagulation.
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http://dx.doi.org/10.1016/j.jss.2019.05.050DOI Listing
November 2019

Predisposed to failure? The challenge of rescue in the medical intensive care unit.

J Trauma Acute Care Surg 2019 10;87(4):774-781

From the Division of Trauma and General Surgery, University of Pittsburgh Medical Center (A.B., R.H., A.B.P., R.M.F.), Pittsburgh, Pennsylvania; Division of Trauma and Acute Care Surgery, Dartmouth Hitchcock Medical Center (A.B.), Lebanon, New Hampshire; and Department of Surgery, University of Mississippi Medical Center (M.E.K.), Jackson, Mississippi.

Background: Medical intensive care unit (MICU) patients develop acute surgical processes that require operative intervention. There are limited data addressing outcomes of emergency general surgery (EGS) in this population. The aim of our study was to characterize the breadth of surgical consults from the MICU and assess mortality after abdominal EGS cases.

Methods: All MICU patients with an EGS consult in an academic medical center between January 2010 and 2016 were identified from an electronic medical record-based registry. Charts were reviewed to determine reason for consult, procedures performed, and to obtain additional clinical data. A multivariate logistic regression was used to determine patient factors associated with patient mortality.

Results: Of 911 MICU patients seen by our service, 411(45%) required operative intervention, with 186 patients undergoing an abdominal operation. The postoperative mortality rate after abdominal operations was 37% (69/186), significantly higher than the mortality of 16% (1833/11192) for all patients admitted to the MICU over the same period (p < 0.05). Damage-control procedures were performed in 64 (34%) patients, with 46% mortality in this group. The most common procedures were bowel resections, with mortality of 42% (28/66) and procedures for severe clostridium difficile, mortality of 38% (9/24). Twenty-seven patients met our definition of surgical rescue, requiring intervention for complications of prior procedures, with mortality of 48%. Need for surgical rescue was associated with increased admission mortality (odds ratio, 13.07; 95% confidence interval, 2.86-59.77). Twenty-six patients had pathology amenable to surgical intervention but did not undergo operation, with 100% mortality. In patients with abdominal pathology at the time of operation, in-hospital delay was associated with increased mortality (odds ratio, 5.13; 95% confidence interval, 1.11-23.77).

Conclusion: Twenty percent of EGS consults from the MICU had an abdominal process requiring an operative intervention. While the MICU population as a whole has a high baseline mortality, patients requiring abdominal surgical intervention are an even higher risk.

Level Of Evidence: Prognostic and epidemiological, level III.
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http://dx.doi.org/10.1097/TA.0000000000002411DOI Listing
October 2019

Early versus late venous thromboembolism: A secondary analysis of data from the PROPPR trial.

Surgery 2019 09 21;166(3):416-422. Epub 2019 Jun 21.

Department of General Surgery, The University of Pittsburgh Medical Center, Pittsburgh, PA.

Background: Factors predicting timing of post-traumatic venous thromboembolism (VTE) remain incompletely understood. Because the balance between hemorrhage and thrombosis is dynamic during a patient's hospital course, early and late VTE may be physiologically discrete processes. This secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial aims to explore whether certain risk factors are associated with early versus late VTE.

Methods: The PROPPR trial investigated post-traumatic resuscitation with platelets, plasma, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Multinomial regression based on a threshold determined by cubic spline analysis tested the association of clinical variables with early or late VTE, a composite of deep vein thrombosis and pulmonary embolus, adjusting for predetermined confounders.

Results: Of the 87 patients (13%) with VTE, pulmonary embolus was predominant in the first 72 hours. A statistically determined threshold at 12 days corresponded to change in odds of early versus late events. Variables associated with early VTE included plasma transfusion (risk ratio [RR] 1.14; 95% confidence interval, 1.00, 1.30; P = .05), sepsis (RR 0.05; 95% confidence interval, 1.40, 6.64; P = .01), pelvic or femur fracture (RR 2.62; 95% confidence interval, 1.00, 6.90; P = .05). Late VTE was associated with dialysis (RR 7.37; 95% confidence interval, 1.59, 34.14; P = .01), older age (RR 1.02; 95% confidence interval 1.00, 1.04; P = .05), and delayed resuscitation approaching ratios of 1:1:1 among patients randomized to 1:1:2 therapy (RR 2.06; 95% confidence interval, 0.28, 3.83; P = .02). Cyroprecipitate increased risk of early (RR 1.04, 95% confidence interval, 1.00,1.08; P < .03) and late VTE (1.05; 95% confidence interval, 1.01, 1.09; P = .01). Prolonged lagtime (coeffcient 0.06, 95% confidence interval, 0.02, 0.10; P < .01) and time-to-peak thrombin generation (coeffcient 0.04, 95% confidence interval, 0.02, 0.07; P < .01) were associated with increased risk of early VTE.

Conclusion: Early and late VTE may differ in their risk factors. Defining temporal trends in VTE may allow for a more individualized approach to thromboprophylaxis.
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http://dx.doi.org/10.1016/j.surg.2019.04.014DOI Listing
September 2019

Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism.

J Trauma Acute Care Surg 2019 01;86(1):20-27

From the Department of General Surgery (S.P.M., M.R.R., J.L.S., A.B.P., J.B.B., M.D.N.), The University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and Division of Trauma and Critical Care (M.E.K.), The University of Mississippi Medical Center, Jackson, Mississippi.

Background: Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE.

Methods: This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality.

Results: Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12-27) and 14 (interquartile range, 8-22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3-9.1; p = 0.02). Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23-3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11-5.29; p = 0.03).

Conclusion: Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms.

Level Of Evidence: Therapeutic, level III.
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http://dx.doi.org/10.1097/TA.0000000000002061DOI Listing
January 2019

Surgical rescue: The next pillar of acute care surgery.

J Trauma Acute Care Surg 2017 02;82(2):280-286

From the Division of Trauma and General Surgery (M.E.K., J.L.S., M.R.R., D.M., M.K.H., M.D.N., L.H.A., G.A.W., J.C.P., G.M.B., V.D.S., A.F., T.Z., S.J.Z., T.R.B., R.M.F., B.S.Z., A.B.P.), Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA; and Section of General Surgery (R.D.B.), Trauma, and Surgical Critical Care, Yale School of Medicine, New Haven, CT.

Background: The evolving field of acute care surgery (ACS) traditionally includes trauma, emergency general surgery, and critical care. However, the critical role of ACS in the rescue of patients with a surgical complication has not been explored. We here describe the role of "surgical rescue" in the practice of ACS.

Methods: A prospective, electronic medical record-based ACS registry spanning January 2013 to May 2014 at a large urban academic medical center was screened by ICD-9 codes for acute surgical complications of an operative or interventional procedure. Long-term outcomes were derived from the Social Security Death Index.

Results: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute obstruction (15%). The majority of complications (85%) were related to an operation; 15% were related to interventional procedures. The most common rescue interventions required were bowel resection (23%), wound debridement (18%), and source control of infection (17%); 63% of patients required operative intervention, and 22% required surgical critical care. Thirty-six percent of complications occurred in ACS primary patients ("local"), whereas 38% were referred from another surgical service ("institutional") and 26% referred from another institution ("regional"). Hospital length of stay was longer, and in-hospital and 1-year mortalities were higher in rescue patients compared with those without a complication. Outcomes were equivalent between "local" and "institutional" patients, but hospital length of stay and discharge to home were significantly worse in "institutional" referrals.

Conclusion: We here describe the distinct role of the acute care surgeon in the surgical management of complications; this is an additional pillar of ACS. In this vital role, the acute care surgeon provides crucial support to other providers as well as direct patient care in the "surgical rescue" of surgical and procedural complications.

Level Of Evidence: Epidemiological study, level III; therapeutic/care management study, level IV.
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http://dx.doi.org/10.1097/TA.0000000000001312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703180PMC
February 2017

Inducing Acute Traumatic Coagulopathy In Vitro: The Effects of Activated Protein C on Healthy Human Whole Blood.

PLoS One 2016 23;11(3):e0150930. Epub 2016 Mar 23.

Department of Surgery, University of California San Francisco and San Francisco General Hospital, San Francisco, California, United States of America.

Introduction: Acute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM) and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC).

Methods: Whole blood was collected from 20 healthy human subjects, and was "spiked" with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL). PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters.

Results: In all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT) and clot formation time (CFT), decreased alpha angle (α), impaired early clot formation (a10 and a20), and reduced maximum clot firmness (MCF). PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity.

Conclusion: A phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805205PMC
July 2016

Emergency preservation and resuscitation for cardiac arrest from trauma.

Int J Surg 2016 Sep 20;33(Pt B):209-212. Epub 2015 Oct 20.

Department of Surgery, RA Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, USA.

The advent of cardiopulmonary resuscitation (CPR) revolutionized the care of patients with cardiac arrest, now allowing survival of up to 30% after out-of-hospital arrest due to arrhythmia; however, outcomes for cardiac arrest after trauma remain dismal, with less than 10% survival despite the most aggressive modern resuscitation techniques. The short time interval between cardiac arrest and brain ischemia, the reduced efficacy of CPR in the patient with profound hypovolemia due to hemorrhage, and the speed of exsanguination from major vascular injury all conspire to limit the effectiveness of standard CPR in the critically injured patient. Beginning in the 1980s, researchers began to harness the effects of profound hypothermia in order to extend the window of survivability after traumatic arrest, allowing the critical time needed to obtain surgical hemostasis in otherwise lethal exsanguinating injuries. These studies have culminated in the emergency preservation and resuscitation (EPR) of the trauma patient. Rapid central arterial access is obtained and profound (<10 °C) hypothermia induced with aortic infusion of cold saline. During this window of up to 1 h, damage control surgical techniques are applied to control hemorrhage and repair injuries, followed by controlled rewarming and reperfusion using cardiopulmonary bypass. In this review, we trace these techniques from their early theoretical development, through refinement in clinically relevant animal models, and into their present application in a currently-enrolling human clinical trial of EPR for cardiac arrest from trauma (EPR-CAT), as well as examine current topics, ongoing challenges, and future directions for emergency preservation and resuscitation research.
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September 2016

The role of computed tomographic scan in ongoing triage of operative hepatic trauma: A Western Trauma Association multicenter retrospective study.

J Trauma Acute Care Surg 2015 Dec;79(6):951-6; discussion 956

From the Division of Trauma and General Surgery (M.E.K., J.J.W., J.I.S., J.L.S.), Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Surgery (S.S.S., K.L.K.), Community Regional Medical Center, University of California, San Francisco-Fresno Campus, Fresno, California; Division of Acute Care Surgery (R.A.K., R.A.W.), Department of Surgery, University of Texas Health Science Center at Houston, Houston, Texas; Division of General Surgery (E.A.E., S.M.L.), Department of Surgery, Medical University of South Carolina, Charleston, South Carolina; and Department of Surgery (M.M.C., G.M.), The Medical Center of Plano, Plano, Texas.

Background: A subset of patients explored for abdominal injury have persistent hepatic bleeding on postoperative computed tomography (CT) and/or angiography, either not identified or not manageable at initial laparotomy. To identify patients at risk for ongoing hemorrhage and guide triage to angiography, we investigated the relationship of early postoperative CT scan with outcomes in operative hepatic trauma.

Methods: This is a retrospective review of 528 patients with hepatic injury taken to laparotomy without imaging within 6 hours of arrival to six trauma centers from 2007 to 2013, coordinated through the Western Trauma Association multicenter trials group.

Results: A total of 528 patients were identified, with a mean age of 31 years, 82% male, and 37% blunt injury; mean (SD) Injury Severity Score (ISS) was 27 (16) and base deficit was -9 (6); in-hospital mortality was 26%. Seventy-three patients died during initial exploration. Of 455 early survivors, 123 (27%) had a postoperative contrast CT scan within 24 hours of laparotomy. CT patients had more common blunt injury, higher ISS, and lower base deficit than those who did not undergo CT. CT identified hepatic contrast extravasation or pseudoaneurysm in 10 patients (8%). Hepatic bleeding on CT was 83% sensitive and 75% specific (likelihood ratio, 3.3) for later positive angiography; negative CT finding was 96% sensitive and 83% specific (likelihood ratio, 5.7) for later negative or not performed angiography. Despite occurring in a more severely injured cohort, performance of early postoperative CT was associated with reduced mortality (odds ratio, 0.16) in multivariate analysis. Blunt mechanism was also a multivariate predictor of mortality (odds ratio, 3.0).

Conclusion: Early postoperative CT scan after laparotomy for hepatic trauma identifies clinically relevant ongoing bleeding and is sufficiently sensitive and specific to guide triage to angiography. Contrast CT should be considered in the management algorithm for hepatic trauma, particularly in the setting of blunt injury. Further study should identify optimal patient selection criteria and CT scan timing in this population.

Level Of Evidence: Care management/therapeutic study, level IV; epidemiologic/prognostic study, level III.
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December 2015

Surgical Rescue: An Essential Component of Acute Care Surgery.

Scand J Surg 2015 Sep;104(3):135-6

Department of Surgery, University of Pittsburgh, U.S.A Abdominal Center, Meilahti Hospital, University of Helsinki, Finland.

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September 2015

Evolving beyond the vicious triad: Differential mediation of traumatic coagulopathy by injury, shock, and resuscitation.

J Trauma Acute Care Surg 2015 Mar;78(3):516-23

From the *Department of Surgery (M.E.K., B.M.H., M.J.C.), University of California, San Francisco, and San Francisco General Hospital, San Francisco; and Division of Biostatistics and School of Public Health (A.E.H., A.L.D.), University of California at Berkeley, Berkeley, California; Department of Surgery (J.L.S.), University of Pittsburgh Medical Center and Presbyterian University Hospital, Pittsburgh, Pennsylvania; Department of Surgery (J.C., R.V.M.), University of Washington School of Medicine and Harborview Medical Center, Seattle, Washington; Department of Surgery (J.P.M.), University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Texas; Department of Surgery (E.E.M.), University of Colorado Health Sciences Center and Denver Health Medical Center, Denver, Colorado; and Department of Surgery (B.H.B.), Washington University School of Medicine; St. Louis, Missouri.

Background: A subset of trauma patients with critical injury present with coagulopathy, portending markedly worse outcomes. Clinical practice is evolving to treat the classical risk factors of hypothermia, hemodilution, and acidosis; however, coagulopathy persists even in the absence of these factors. We sought to determine the relative importance of injury- and shock-specific factors compared with resuscitation-associated factors in coagulopathy after trauma.

Methods: Comprehensive demographic data, laboratory data, and outcomes data were prospectively collected from seven trauma centers over 8 years (November 2003 to August 2011) as part of the Inflammation and the Host Response to Injury Large-Scale Collaborative Program. A total of 1,537 critically injured patients with blunt trauma and hemorrhagic shock were analyzed to evaluate predictors of admission coagulopathy (international normalized ratio [INR] ≥ 1.3), multiorgan failure, and mortality.

Results: Of 1,537 patients, 578 (37.6%) had admission INR of 1.3 or greater. Coagulopathic patients had more severe injury, more severe base deficit and lactate levels, as well as lower admission temperature, lower pH, and higher prehospital crystalloid volume (all p < 0.001). Coagulopathic patients required more blood products and mechanical ventilation and had higher rates of nosocomial infection, multiorgan failure, and mortality (all p < 0.02). Injury severity, temperature, and acidosis (all p < 0.02) independently predicted coagulopathy in multivariate analysis, with a significant interaction between lactate and prehospital crystalloid. In Cox regression models, however, coagulopathy itself remained an independent predictor of both multiorgan failure and mortality (p < 0.02) even when adjusted for injury severity, shock, and elements of the vicious triad.

Conclusion: Most patients with coagulopathy after trauma have mixed risk factors; however, coagulopathy has deleterious effects independent of injury severity, shock, and the vicious triad. Better understanding of the biochemical mechanisms of acute traumatic coagulopathy may facilitate biochemically targeted resuscitation strategies and improve outcomes.

Level Of Evidence: Prognostic and epidemiologic study, level II.
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March 2015

The natural history and effect of resuscitation ratio on coagulation after trauma: a prospective cohort study.

Ann Surg 2014 Dec;260(6):1103-11

From the Department of Surgery, San Francisco General Hospital, San Francisco, CA; and the University of California at San Francisco, San Francisco, CA.

Objective: To investigate the natural history of coagulation factor perturbation after injury and identify longitudinal differences in clotting factor repletion by red blood cell:fresh frozen plasma (RBC:FFP) transfusion ratio.

Background: Hemostatic transfusion ratios of RBC to FFP approaching 1:1 are associated with a survival advantage in traumatic hemorrhage, even in patients with normal coagulation studies.

Methods: Plasma was prospectively collected from 336 trauma patients during their intensive care unit stay for up to 72 hours from February, 2005, to October, 2011. Standard coagulation studies as well as pro- and anticoagulant clotting factors were measured. RBC:FFP transfusion ratios were calculated at 6 hours after arrival and dichotomized into "low ratio" (RBC:FFP ≤ 1.5:1) and "high ratio" (RBC:FFP > 1.5:1) groups.

Results: Factor-level measurements from 193 nontransfused patients provide an early natural history of clotting factor-level changes after injury. In comparison, 143 transfused patients had more severe injury, prolonged prothrombin time and partial thromboplastin time (PTT), and lower levels of both pro- and anticoagulants up to 24 hours. PTT was prolonged up to 12 hours and only returned to admission baseline at 48 hours in "high ratio" patients versus correction by 6 hours in "low ratio" patients. Better repletion of factors V, VIII, and IX was seen longitudinally, and both unadjusted and injury-adjusted survival was significantly improved in "low ratio" versus "high ratio" groups.

Conclusions: Resuscitation with a "low ratio" of RBC:FFP leads to earlier correction of coagulopathy, and earlier and prolonged repletion of some but not all procoagulant factors. This prospective evidence suggests hemostatic resuscitation as an interim standard of care for transfusion in critically injured patients pending the results of ongoing randomized study.
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http://dx.doi.org/10.1097/SLA.0000000000000366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971769PMC
December 2014

Fibrinogen and platelet contributions to clot formation: implications for trauma resuscitation and thromboprophylaxis.

J Trauma Acute Care Surg 2014 Feb;76(2):255-6; discussion 262-3

From the Department of Surgery, San Francisco General Hospital, University of California, San Francisco, San Francisco, California.

Background: Thromboelastography (TEG) is used to diagnose perturbations in clot formation and lysis that are characteristic of acute traumatic coagulopathy. With novel functional fibrinogen (FF) TEG, fibrin- and platelet-based contributions to clot formation can be elucidated to tailor resuscitation and thromboprophylaxis. We sought to describe the longitudinal contributions of fibrinogen and platelets to clot strength after injury, hypothesizing that low levels of FF and a low contribution of fibrinogen to clot strength on admission would be associated with coagulopathy, increased transfusion requirements, and worse outcomes.

Methods: A total of 603 longitudinal plasma samples were prospectively collected from 251 critically injured patients at a single Level 1 trauma center from 0 hour to 120 hours. TEG maximal amplitude (MA), FF MA, FF levels, von Clauss fibrinogen, and standard coagulation measures were performed in parallel. Percentage contributions of FF (%MA(FF)) and platelets (%MA(platelets)) were calculated as each MA divided by overall kaolin TEG MA.

Results: Coagulopathic patients (international normalized ratio ≥ 1.3) had significantly lower admission %MA(FF) than noncoagulopathic patients (24.7% vs. 31.2%, p < 0.05). Patients requiring plasma transfusion had a significantly lower admission %MA(FF) (26.6% vs. 30.6%, p < 0.05). Higher admission %MA(FF) was predictive of reduced mortality (hazard ratio, 0.815, p < 0.001). %MA(platelets) was higher than %MA(FF) at all time points, decreased over time, and stabilized at 72 hours (69.4% at 0 hour, 56.2% at 72 hours). In contrast, %MA(FF) increased over time and stabilized at 72 hours (30.6% at 0 hour, 43.8% at 72 hours).

Conclusion: FF TEG affords differentiation of fibrin- versus platelet-based clot dynamics. Coagulopathy and plasma transfusion were associated with a lower %MA(FF). Despite this importance of fibrinogen, platelets had a greater contribution to clot strength at all time points after injury. This suggests that attention to these relative contributions should guide resuscitation and thromboprophylaxis and that antiplatelet therapy may be of underrecognized importance to thromboprophylaxis after trauma.

Level Of Evidence: Prognostic study, level III.
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http://dx.doi.org/10.1097/TA.0000000000000108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238905PMC
February 2014

Mechanical ventilation weaning and extubation after spinal cord injury: a Western Trauma Association multicenter study.

J Trauma Acute Care Surg 2013 Dec;75(6):1060-9; discussion 1069-70

From the Department of Surgery (L.Z.K., M.E.K., R.A.C., B.J.R., M.J.C.), University of California San Francisco, San Francisco General Hospital, San Francisco; and Department of Surgery (K.L.K.), Community Regional Medical Center/University of California San Francisco, Fresno, California; Trauma Services (C.K.H.), Scottsdale Healthcare Osborn Medical Center, Scottsdale, Arizona; Department of Surgery (T.H.C.), Gundersen Lutheran Medical Foundation, La Crosse, Wisconsin; Department of Surgery (C.C.Ba.), Virginia Tech Carilion School of Medicine, Carilion Roanoke Memorial Hospital, Roanoke, Virginia; Division of Trauma, Surgical Critical Care, and Acute Care Surgery (M.L.S.), Duke University Medical Center, Durham, North Carolina; Department of Surgery (C.C.Bu.), Denver Health Medical Center, University of Colorado, Denver, Colorado; Division of Trauma, Emergency Surgery and Surgical Critical Care (M.D.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Surgery (J.M.H.), Via Christi Regional Medical Center, Wichita, Kansas; Department of Surgery (C.H.K.), New York University Langone Medical Center, New York, New York; Department of General Surgery and Trauma (S.J.Z.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Surgery (S.D.G.), Oregon Health Sciences University, Portland, Oregon; Department of Surgery (D.V.S.), University of California, Davis Medical Center, Davis, California; Department of Surgery (D.B.P.), Grant Medical Center, Columbus, Ohio.

Background: Respiratory failure after acute spinal cord injury (SCI) is well recognized, but data defining which patients need long-term ventilator support and criteria for weaning and extubation are lacking. We hypothesized that many patients with SCI, even those with cervical SCI, can be successfully managed without long-term mechanical ventilation and its associated morbidity.

Methods: Under the auspices of the Western Trauma Association Multi-Center Trials Group, a retrospective study of patients with SCI at 14 major trauma centers was conducted. Comprehensive injury, demographic, and outcome data on patients with acute SCI were compiled. The primary outcome variable was the need for mechanical ventilation at discharge. Secondary outcomes included the use of tracheostomy and development of acute lung injury and ventilator-associated pneumonia.

Results: A total of 360 patients had SCI requiring mechanical ventilation. Sixteen patients were excluded for death within the first 2 days of hospitalization. Of the 344 patients included, 222 (64.5%) had cervical SCI. Notably, 62.6% of the patients with cervical SCI were ventilator free by discharge. One hundred forty-nine patients (43.3%) underwent tracheostomy, and 53.7% of them were successfully weaned from the ventilator, compared with an 85.6% success rate among those with no tracheostomy (p < 0.05). Patients who underwent tracheostomy had significantly higher rates of ventilator-associated pneumonia (61.1% vs. 20.5%, p < 0.05) and acute lung injury (12.8% vs. 3.6%, p < 0.05) and fewer ventilator-free days (1 vs. 24 p < 0.05). When controlled for injury severity, thoracic injury, and respiratory comorbidities, tracheostomy after cervical SCI was an independent predictor of ventilator dependence with an associated 14-fold higher likelihood of prolonged mechanical ventilation (odds ratio, 14.1; 95% confidence interval, 2.78-71.67; p < 0.05).

Conclusion: While many patients with SCI require short-term mechanical ventilation, the majority can be successfully weaned before discharge. In patients with SCI, tracheostomy is associated with major morbidity, and its use, especially among patients with cervical SCI, deserves further study.

Level Of Evidence: Prognostic study, level III.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837348PMC
December 2013

Cause and timing of death in massively transfused trauma patients.

J Trauma Acute Care Surg 2013 Aug;75(2 Suppl 2):S255-62

Division of Burn/Trauma/Critical Care, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9158, USA.

Background: The purpose of this study was to characterize the cause of death in severely injured trauma patients to define potential responses to resuscitation.

Methods: Prospective analysis of 190 critically injured patients who underwent massive transfusion protocol (MTP) activation or received massive transfusion (>10 U of packed red blood cells [RBC] per 24 hours). Cause of death was adjudicated into one of four categories as follows: (1) exsanguination, (2) early physiologic collapse, (3) late physiologic collapse, and (4) nonsurvivable injury.

Results: A total 190 patients underwent massive transfusion or MTP with 76 deaths (40% mortality), of whom 72 deaths were adjudicated to one of four categories: 33.3% died of exsanguination, 16.6% died of early physiologic collapse, 11.1% died of late physiologic collapse, while 38.8% died of nonsurvivable injuries. Patients who died of exsanguination were younger and had the highest RBC/fresh frozen plasma ratio (2.97 [2.24]), although the early physiologic collapse group survived long enough to use the most blood products (p < 0.001). The late physiologic collapse group had significantly fewer penetrating injuries, was older, and had significantly more crystalloid use but received a lower RBC/fresh frozen plasma ratio (1.50 [0.42]). Those who were determined to have a nonsurvivable injury had a lower presenting Glasgow Coma Scale (GCS) score, fewer penetrating injuries, and higher initial blood pressure reflecting a preponderance of nonsurvivable traumatic brain injury. The average survival time for patients with potentially survivable injuries was 2.4 hours versus 18.4 hours for nonsurvivable injuries (p < 0.001).

Conclusion: Severely injured patients requiring MTP have a high mortality rate. However, no studies to date have addressed the cause of death after MTP. Characterization of cause of death will allow targeting of surgical and resuscitative conduct to allow extension of the physiologic reserve time, therefore rendering previously nonsurvivable injury potentially survivable.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773975PMC
August 2013

A paradigm shift in trauma resuscitation: evaluation of evolving massive transfusion practices.

JAMA Surg 2013 Sep;148(9):834-40

Department of Surgery, San Francisco General Hospital, University of California.

Importance: The evolution of damage control strategies has led to significant changes in the use of resuscitation after traumatic injury.

Objective: To evaluate changes in the administration of fluids and blood products, hypothesizing that a reduction in crystalloid volume and a reduced red blood cell (RBC) to fresh frozen plasma (FFP) ratio over the last 7 years would correlate with better resuscitation outcomes.

Design: Observational prospective cohort study.

Setting: Urban level I trauma center.

Participants: A total of 174 trauma patients receiving a massive transfusion (>10 units of RBCs in 24 hours) or requiring the activation of the institutional massive transfusion protocol from February 2005 to June 2011.

Exposure: Patients had to either receive a massive transfusion or require the activation of the institutional massive transfusion protocol.

Main Outcomes And Measures: In-hospital mortality.

Results: The mean (SD) Injury Severity Score was 28.4 (16.2), the mean (SD) base deficit was -9.8 (6.3), and median international normalized ratio was 1.3 (interquartile range, 1.2-1.6); the mortality rate was 40.8%. Patients received a median of 6.1 L of crystalloid, 13 units of RBCs, 10 units of FFP, and 1 unit of platelets over 24 hours, with a mean RBC:FFP ratio of 1.58:1. The mean 24-hour crystalloid infusion volume and number of the total blood product units given in the first 24 hours decreased significantly over the study period (P < .05). The RBC:FFP ratio decreased from a peak of 1.84:1 in 2007 to 1.55:1 in 2011 (P = .20). Injury severity and mortality remained stable over the study period. When adjusted for age and injury characteristics using Cox regression, each decrease of 0.1 achieved in the massive transfusion protocol's RBC:FFP ratio was associated with a 5.6% reduction in mortality (P = .005).

Conclusions And Relevance: There has been a shift toward a reduced crystalloid volume and the recreation of whole blood from component products in resuscitation. These changes are associated with markedly improved outcomes and a new paradigm in the resuscitation of severely injured patients.
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September 2013

The "found down" patient: a diagnostic dilemma.

J Trauma Acute Care Surg 2013 Jun;74(6):1548-52

Department of Surgery, San Francisco General Hospital, and University of California, San Francisco, CA 94110, USA.

Background: "Found down" patients present to the emergency department (ED) after being discovered unconscious and are selected for trauma or medical evaluation based on ED triage. Occult injury is an important part of the differential diagnosis in these patients. Rational use of trauma resources and optimal care of these patients requires clear triage criteria and timely evaluation.

Methods: After an institutional review board approval was obtained, we retrospectively identified 201 "found down" patients from ED triage logs at an urban Level I trauma center between 2007 and 2011. Physician researchers reviewed these records for demographics, injuries, medical diagnoses, and mortality.

Results: Of the 201 "found down" patients, 86 (42.7%) had injuries on evaluation in the ED and 9 (4.5%) required urgent surgical intervention. Previous ED visits, homelessness, psychiatric diagnoses, and alcohol and substance use were strikingly common. The 41 patients (20.4%) triaged to admission by the trauma service were younger, predominantly male, and more likely to be intoxicated. Overall, 28 patients (13.4%) required consultation by the service to which they were not initially triaged. Nineteen (11.9%) of the medically triaged patients required trauma service consultation. Eight (19.5%) of the patients triaged to the trauma service required medical consultation, and 4 patients (9.8%) were ultimately admitted to a medicine service after a complete trauma evaluation. Six (14.6%) of the trauma patients and 3 (1.9%) of the medical patients had a delay in diagnosis of occult injuries.

Conclusion: Nearly half of "found down" patients had clinically significant injuries, and late identified injuries were present in both trauma and medical patients. Twenty-eight (13.4%) of patients required consultation by the medical or trauma surgery service to which they were not initially triaged, highlighting pervasive triage discordance in this population. Early trauma surgery consultation and triage flexibility are critical to avoid missed injuries in "found down" patients.

Level Of Evidence: Epidemiological study, level IV.
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June 2013
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