Kyle D. Hart

Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial.

Importance Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results Of the 185 trial participants, 89 were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa levels in intervention patients were not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, which was similar between the control and intervention groups (10.4% vs 13.5%; P = .68). The time to enoxaparin initiation was similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P = .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated as weight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05). Conclusions and Relevance The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported. Trial Registration clinicaltrials.gov Identifier: NCT00990236.

The Natural History of Indeterminate Blunt Cerebrovascular Injury

IMPORTANCE The Denver criteria grade blunt cerebrovascular injuries (BCVIs) but fail to capture many patients with indeterminate findings on initial imaging. OBJECTIVE To evaluate outcomes and clinical significance of indeterminate BCVIs (iBCVIs). DESIGN, SETTING, AND PARTICIPANTS A retrospective review of all patients treated for BCVIs at our institution from January 1, 2007, through July 31, 2014, was completed. Patients were divided into 2 groups: those with true BCVIs as defined by the Denver criteria and those with iBCVIs, which was any initial imaging suggestive of a cerebrovascular arterial injury not classifiable by the Denver criteria. MAIN OUTCOMES AND MEASURES Primary outcomes were rate of resolution of iBCVIs, freedom from cerebrovascular accident (CVA) or transient ischemic attack (TIA), and 30-day mortality. RESULTS We identified 100 patients with 138 BCVIs: 79 with true BCVIs and 59 with iBCVIs. With serial imaging, 23 iBCVIs (39.0%) resolved and 21 (35.6%) remained indeterminate, whereas 15 (25.4%) progressed to true BCVI. The rate of CVA or TIA in the iBCVI group was 5.1% compared with 15.2% in the true BCVI group (P = .06). Of the 15 total CVAs or TIAs, 11 (73.3%) resulted from carotid injury and 4 (26.7%) from vertebral artery occlusion (P = .03). By Kaplan-Meier analysis, there was no difference in freedom from CVA or TIA for the 2 groups (P = .07). Median clinical follow-up was 91 days. Overall and 30-day mortality for the entire series were 17.4% and 15.2%, respectively. There was no difference in long-term or 30-day mortality between true BCVI and iBCVI groups. CONCLUSIONS AND RELEVANCE Detection of iBCVI has become a common clinical conundrum with improved and routine imaging. Indeterminate BCVI is not completely benign, with 25.4% demonstrating anatomical progression to true BCVI and 5.1% developing cerebrovascular symptoms. We therefore recommend serial imaging and antiplatelet therapy for iBCVI.

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios can Predict Treatment Response to Neoadjuvant Therapy in Esophageal Cancer.

IntroductionWe hypothesized that serum neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict pathologic complete response to neoadjuvant chemoradiotherapy in esophageal cancer patients. The ability to predict favorable treatment response to therapy may aid in determining optimal treatment regimens.Materials and MethodsA retrospective review of a prospective esophageal disease registry was conducted. Neutrophil-to-lymphocyte ratio was defined as the pre-chemoradiotherapy serum neutrophil count divided by lymphocyte count. Platelet-to-lymphocyte ratio was similarly defined. Logistic regression was applied to analyze these ratios and their effect on pathologic complete response. A Cox proportional-hazards model was used to analyze survival.ResultsSixty patients were included. Elevated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were both negative predictors of pathologic complete response (odds ratio: 0.62; 95% confidence interval: 0.37–0.89, P = 0.037 and odds ratio: 0.91; 95% confidence interval: 0.82–0.98, P = 0.028, respectively). Only platelet-to-lymphocyte ratio was predictive of decreased overall survival (hazard ratio: 1.05, 95% confidence interval: 0.94–1.16, P = 0.40).ConclusionElevated neutrophil and platelet-to-lymphocyte ratios were significant predictors of a poor treatment response to neoadjuvant therapy. Only elevated platelet-to-lymphocyte ratio was predictive of worse overall survival. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may offer a simple serum test to assess the likelihood of a pathologic complete response after neoadjuvant therapy in esophageal cancer.

HIV positivity and anal cancer outcomes: A single-center experience

BACKGROUND Anal cancer remains common among human immunodeficiency virus (HIV) patients. Chemoradiation has had mixed results. We evaluated outcome differences by HIV status. METHODS We retrospectively analyzed 14 HIV+ and 72 HIV- anal cancer patients (2000 to 2013). Outcomes included chemoradiation tolerance, recurrence, and survival. RESULTS HIV+ patients were more often male (100% vs 38%, P < .001) but diagnosed at similar stages (P = .49). They were less likely to receive traditional chemotherapy (36% vs 86%, P < .001). Recurrence (P = .55) and survival time (P = .48) were similar across groups. HIV+ patients had similar colostomy-free survival (P = .053). Receipt of 5-fluorouracil/mitomycin C (MMC) chemotherapy predicted recurrence-free and overall survival (Hazard ratios .278, .32). HIV status did not worsen recurrence (P = .71) or survival (P = .57). CONCLUSIONS HIV+ patients received more non-MMC-based chemoradiation but had equivalent colostomy-free, recurrence, and overall survival. Use of 5-fluorouracil/MMC chemotherapy increased after 2008.

Paraesophageal hernia repair outcomes using minimally invasive approaches

This study of inpatient admissions for paraesophageal hernia repair analyzes use of minimally invasive approaches and rates of intraoperative injury and in-hospital mortality.

Patterns of Care in Hospitalized Vascular Surgery Patients at End of Life

Importance There is limited literature reporting circumstances surrounding end-of-life care in vascular surgery patients. Objective To identify factors driving end-of-life decisions in vascular surgery patients. Design, Setting, and Participants In this cohort study, medical records were reviewed for all vascular surgery patients at a tertiary care university hospital who died during their hospitalization from 2005 to 2014. Main Outcomes and Measures Patient, family, and hospitalization variables potentially important to influencing end-of-life decisions. Results Of 111 patients included (67 [60%] male; median age, 75 [range, 24-94] years), 81 (73%) were emergent vs 30 (27%) elective admissions. Only 15 (14%) had an advance directive. Of the 81 (73%) patients placed on comfort care, 31 (38%) had care withheld or withdrawn despite available medical options, 15 (19%) had an advance directive, and 28 (25%) had a palliative care consultation. The median time from palliative care consultation to death was 10 hours (interquartile range, 3.36-66 hours). Comparing the 31 patients placed on comfort care despite available medical options with an admission diagnosis–matched cohort, we found that more than 5 days admitted to the intensive care unit (odds ratio [OR], 4.11; 95% CI, 1.59-10.68; P < .001), more than 5 days requiring ventilator support (OR, 9.45; 95% CI, 3.41-26.18; P < .001), new renal failure necessitating dialysis (OR, 14.48; 95% CI, 3.69-56.86; P < .001), and new respiratory failure necessitating tracheostomy (OR, 23.92; 95% CI, 2.80-204; P < .001) correlated with transition to comfort care. Conclusions and Relevance Palliative care consultations may be underused at the end of life. A large percentage of patients were transitioned to comfort measures despite available treatment, yet few presented with advance directives. In high-risk patients, discussions regarding extended stays in the intensive care unit, prolonged ventilator management, and possible dialysis and tracheostomy should be communicated with patients and families at time of hospitalization and advance directives solicited.

Neoadjuvant chemoradiotherapy with concurrent cisplatin/5-fluorouracil is associated with increased pathologic complete response and improved survival compared to carboplatin/paclitaxel in patients with locally advanced esophageal cancer.

Trimodal therapy consisting of neoadjuvant chemoradiation followed by esophagectomy has become the standard of care in North America for locally advanced esophageal cancer. While cisplatin/5-fluorouracil has been a common concurrent chemotherapy regimen since the 1980s, its utilization has declined in recent years as the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial regimen of carboplatin/paclitaxel has become widely adopted. The efficacy of the CROSS regimen compared to alternate chemotherapy choices, however, has rarely been evaluated when each is used as a component of a trimodal treatment approach. The aim of this study is to report our institutional experience with these two concurrent chemotherapy regimens at a specialized esophageal cancer center.We performed an Institutional Review Board-approved retrospective review of a prospectively maintained institutional foregut registry from a single National Cancer Institute-designated cancer center. Esophageal cancer patients who completed trimodal therapy with a chemotherapy regimen of either carboplatin/paclitaxel or cisplatin/5-fluorouracil were identified and divided into groups based on their chemotherapy regimens. Multivariable logistic regression was used to analyze pathologic complete response rates, while the Kaplan-Meier and Cox proportional hazards models were utilized to evaluate recurrence-free and overall survival. Analytical models were adjusted for age, clinical stage, radiation dose, histologic subtype (adenocarcinoma vs. squamous cell carcinoma), and time interval from completion of neoadjuvant therapy to surgery.One hundred and forty-two patients treated between January of 2000 and July of 2015 were identified as meeting inclusion criteria. Of this group, 87 had received the CROSS regimen of carboplatin/paclitaxel, while 55 had completed cisplatin/5-fluorouracil. Multivariable analysis demonstrated that the cisplatin/5-fluorouracil.group had an increased odds of pathologic complete response (odds ratio = 2.68, 95% confidence interval, P = 0.032), as well as significantly improved recurrence-free survival (hazard ratio = 0.39, 95% confidence interval 0.21-0.73, P = 0.003) and overall survival (hazard ratio = 0.46, 95% confidence interval 0.24-0.87, P = 0.016), compared to the carboplatin/paclitaxel group.Concurrent chemotherapy with cisplatin/5-fluorouracil in locally advanced esophageal cancer is associated with higher rates of pathologic complete response and improved recurrence-free and overall survival compared to the CROSS regimen of carboplatin/paclitaxel. This suggests that, for select patients, alternate neoadjuvant chemotherapy approaches, such as cisplatin/5-fluorouracil, merit reconsideration as potential primary treatment choices in the management of this highly morbid disease.

Damage control laparotomy utilization rates are highly variable among Level I trauma centers: Pragmatic, Randomized Optimal Platelet and Plasma Ratios findings

BACKGROUND Damage control laparotomy (DCL) is intended to limit deleterious effects from trauma-induced coagulopathy. DCL has been associated with mortality reduction, but may increase complications including sepsis, abscess, respiratory failure, hernia, and gastrointestinal fistula. We hypothesized that (1) DCL incidence would vary between institutions; (2) mortality rates would vary with DCL rates; (3) standard DCL criteria of pH, international normalized ratio, temperature and major intra-abdominal vascular injury would not adequately capture all patients. METHODS Trauma patients at 12 Level 1 North American trauma centers were randomized based on transfusion ratios as described in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. We analyzed outcomes after emergent laparotomy using a mixed-effects logistic model comparing DCL versus definitive surgical management with random effect for study site. Primary outcomes were 24-hour and 30-day mortality. RESULTS Three hundred twenty-nine patients underwent emergent laparotomy: 213 (65%) DCL and 116 (35%) definitive surgical management. DCL rates varied between institutions (33–83%), (p = 0.002). Median Injury Severity Score (ISS) was higher in the DCL group, 29 (interquartile range, 13–34) versus 21 (interquartile range, 22–41) (p < 0.001). Twenty-four-hour mortality was 19% with DCL versus 4% (p < 0.001); 30-day mortality was 28% with DCL versus 19% (p < 0.001). In a mixed-effects model, ISS and major intra-abdominal vascular injury were correlates of DCL (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02–1.07 and OR, 2.7; 95% CI, 1.4–5.2). DCL was not associated with 30-day mortality (OR, 2.33; 95% CI, 0.97–5.60). Correlates included ISS (OR, 1.06; 95% CI, 1.02–1.09), PRBCs in 24 hours (OR, 1.10; 95% CI, 1.03–1.18), and age (OR, 1.04; 95% CI, 1.01–1.06). No significant mortality difference was detected between institutions (p = 0.63). Sepsis and VAP occurred more frequently with DCL (p < 0.05). Eighty percent (135/213) of DCL patients met standard criteria. CONCLUSION Although DCL utilization varied significantly between institutions, there was no significant mortality difference between centers. This finding suggests tempering DCL use may not decrease mortality, but could decrease related complications. Level of Evidence Therapeutic study, level III.

Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas

OBJECTIVE There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. METHODS Retrospective review of a prospectively collected multi-institutional melanoma database. RESULTS Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. CONCLUSIONS PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.