Examining Race and Patient-Reported Outcomes After Contralateral Prophylactic Mastectomy with Reconstruction.

BACKGROUND: Little is known regarding racial differences in satisfaction and quality of life (QOL) after contralateral prophylactic mastectomy (CPM). In this study, we aim to characterize associations between race, and postoperative satisfaction and well-being, utilizing the validated BREAST-Q patient-reported outcome measure. PATIENTS AND METHODS: Patients were eligible if they were diagnosed with stage 0-III unilateral breast cancer and underwent mastectomy with immediate reconstruction at our institution between 2016 and 2022. BREAST-Q surveys were administered in routine clinical care preoperatively and postoperatively to assess QOL. We assessed whether the relationship between race, and domains of satisfaction with breasts and psychosocial well-being differed by receipt of CPM compared with unilateral mastectomy at 6 months, 1 year, 2 years, and 3 years following reconstruction. RESULTS: Of 3334 women, 2040 (61%) underwent unilateral mastectomy and 1294 (39%) underwent CPM. Compared with White and Asian women who received CPM, Black women who underwent CPM were more likely to have higher BMI (p < 0.001), undergo autologous reconstruction (p = 0.006), and receive postmastectomy radiation (PMRT) (p < 0.001). There was no association between race and domains of satisfaction of breasts or psychosocial well-being for women who underwent unilateral mastectomy (p = 0.6 and p > 0.9, respectively) or CPM (p = 0.8 and p = 0.9, respectively). PMRT was negatively associated with both satisfaction with breasts (p < 0.001) and psychosocial well-being (p = 0.007). CONCLUSIONS: Differences in satisfaction with breasts and psychosocial well-being at 3-year follow-up were not associated with race but rather treatment variables, particularly the receipt of PMRT. Further investigations with a larger and more diverse population are needed to validate these findings.

Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects. METHODS: From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status. RESULTS: Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5). CONCLUSIONS: This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.

Satisfaction and Well-Being After Contralateral Prophylactic Mastectomy Among BRCA Mutation Carriers and Noncarriers: A Longitudinal Analysis of BREAST-Q Domains.

INTRODUCTION: Contralateral prophylactic mastectomy (CPM) is recommended for BRCA mutation carriers; its use in noncarriers relies on patient choice. We characterized differences in satisfaction and well-being after CPM between BRCA carriers and noncarriers. METHODS: BREAST-Q data were obtained before and after CPM with immediate reconstruction performed at a single institution from 2016 to 2022. Associations between BRCA status and satisfaction with breasts, psychosocial well-being, and sexual well-being were assessed, with adjustment for preoperative scores and relevant confounders. RESULTS: In total, 149 BRCA carriers and 842 noncarriers were included. Response rates varied over time (preoperative, 56%; 6 months, 78%; 1 year, 51%; 2 years, 52%; 3 years, 59%). BRCA carriers were younger (p < 0.001), with a higher rate of neoadjuvant chemotherapy (p < 0.001). More noncarriers had HR+/HER2- tumors (p < 0.001) and underwent endocrine therapy (p < 0.001). Baseline satisfaction with breasts was higher among BRCA carriers (median [interquartile range] score, 70 [53-82] vs. 58 [48-70]; p = 0.006); psychosocial (p = 0.20) and sexual (p = 0.14) well-being were not significantly different between groups. BRCA carriers had a greater decrease in satisfaction with breasts (p = 0.04) and psychological well-being (p = 0.05) from baseline to 6 months; decrease in sexual well-being (p = 0.38) was not significantly different between groups. On univariate and multivariable analyses, BRCA status was not associated with satisfaction with breasts, sexual well-being, or psychosocial well-being. CONCLUSIONS: Satisfaction and well-being were similar between BRCA carriers and noncarriers treated with CPM. Relative to noncarriers, BRCA carriers experienced a greater decline in satisfaction with breasts and psychological well-being at 6 months after CPM.

Impact of holistic review on diversity of interviewed and matriculating residents in graduate medical education: a systematic review protocol.

INTRODUCTION: Diversity in the physician workforce improves patient-centred outcomes. Patients are more likely to trust in and comply with care when seeing gender/racially concordant providers. A current emphasis on standardised metrics in academic achievement often serves as a barrier to the recruitment and retention of gender and racial minorities in medicine. Holistic review of residency applicants has been supported as a means of encouraging diversification but is not yet standardised. The current body of evidence examining the effects of holistic review on the recruitment of racial and gender minorities in surgical residencies is small. We therefore propose a systematic review to summarise the state of holistic review in graduate medical education in the USA and its impact on diversification. METHODS AND ANALYSIS: Our systematic review protocol has been designed with plans to report our review findings in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. PubMed and Embase will be searched with the assistance of a health sciences librarian with expertise in systematic review. We will include studies of graduate medical education programmes that describe the implementation of holistic review, outline the components of their holistic review process and compare proportions of under-represented minorities (URM) and women interviewed and matriculating before and after holistic review implementation. We will first report a summary of the findings regarding the operationalisation of holistic review as described by studies included. We will then pool the percentages of URM and women for interviewee and matriculant populations from each study and report the collective odds ratios of each for holistic review compared with traditional review as our primary outcome. ETHICS AND DISSEMINATION: This study is a protocol for systematic review, and therefore does not involve any human subjects. Findings will be published in the form of a manuscript submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023401389.

Exploring Characteristics of Academic General Surgery Residency Applicants: A Group Concept-Mapping Approach.

OBJECTIVE: Holistic review, which emphasizes qualitative attributes over objective measures, has been proposed as a method for selecting candidates for surgical residency in order to improve diversity in graduate medical education, and, ultimately, the field of surgery. This study seeks to articulate desirable traits of applicants as a first-step in standardizing the holistic review process. DESIGN: Using Group Concept Mapping, a web-based mixed-methods participatory research methodology, residency selection committee members were asked to 1) list desirable characteristics of applicants, 2) group these into categories, 3) rate their importance to academic/clinical success on a 5-point Likert scale (1 = not at all important, 5 = extremely important), and 4) rate the degree to which each characteristic is feasible to assess on a 3-point Likert scale (1 = not at all feasible, 3 = very feasible). Grouped characteristics submitted to hierarchical cluster analysis depicted committee's consensus about desirable qualities/criteria for applicants. Bivariate scatter-plots and pattern-matching graphics demonstrated which of these criteria were most important and reliably assessed. SETTING: A single academic general surgery residency training program in Western Pennsylvania. PARTICIPANTS: Members of the selection committee for the UPMC General Surgery Residency program who had participated in at least 1 prior cycle of applicant selection. RESULTS: Desirable characteristics of highly qualified applicants into an academic general surgery residency were clustered into domains of 1) scholarly work and research, 2) grades/formal assessments, 3) program fit, 4) behavioral assets, and 5) aspiration. Behavioral assets, which was felt to be the most important to clinical and academic success were considered to be the least feasible to reliably assess. Within this domain, initiative, being self-motivated, intellectual curiosity, work ethic, communication skills, maturity and self-awareness, and thoughtfulness were viewed as most frequently reliably assessed from the application and interview process. CONCLUSIONS: High quality applicants possess several behavioral assets that faculty deem are important to academic and clinical success. Adapting validated metrics for assessing these assets, may provide a solution for addressing subjectivity and other challenges scrutinized by critics of holistic review.

Cost-effectiveness of Choosing Wisely guidelines for axillary observation in women older than age 70 years with hormone receptor-positive, clinically node-negative, operable breast tumors.

BACKGROUND: The Society for Surgical Oncology's Choosing Wisely guidelines recommend against sentinel lymph node biopsy (SLNB) in favor of observation in this population. Recent analyses reveal that this has not been widely adopted. The purpose of this cost-effectiveness analysis is to compare the costs and benefits associated with observation or SLNB in women >70 years old with hormone receptor-positive, clinically node-negative, operable breast cancer. METHODS: A decision tree with Markov modeling was created to compare treatment strategies using long-term follow-up data from clinical trials in this population. Costs were estimated from published literature and publicly available databases. Breast cancer-specific health-state utilities were derived from the literature and expert opinion. One-way, 2-way, and probabilistic sensitivity analyses were conducted. A structural sensitivity analysis was performed to assess the effect of functional status and anxiety from nonevaluation of the axilla on cost-effectiveness. Costs and benefits, measured in life-years (LYs) and quality-adjusted life-years (QALYs), were tabulated across 10, 15, and 20 years and compared using incremental cost-effectiveness ratios (ICERs). RESULTS: SLNB is not cost-effective from the payer or societal perspectives with ICERs of $138,374/LY and $131,900/LY, respectively. When QALYs were considered, SLNB provided fewer QALYs (SLNB, 10.33 QALYs; observation, 10.53 QALYs) at a higher cost (SLNB, $15,845; observation, $4020). Structural sensitivity analysis revealed that SLNB was cost-effective in certain patients with significant anxiety related to axillary observation (ICER, $39,417/QALY). CONCLUSIONS: Routine SLNB in this population is not cost-effective. The cost-effectiveness of SLNB, however, is dependent on individual patient factors, including functional status as well as patient preference.

Investigation into the Cost-Effectiveness of Extended Posttraumatic Thromboprophylaxis.

BACKGROUND: Severely injured patients are at particularly high risk for venous thromboembolism (VTE). Although thromboprophylaxis (PPX) is employed during the inpatient period, patients may continue to be at high risk after discharge. Comparative evidence from surgical subspecialities (eg oncology) reveals benefits of postdischarge (ie extended) PPX. We hypothesized that an extended, postinjury oral thromboprophylaxis regimen would be cost-effective. STUDY DESIGN: A cost-utility model compared no PPX with a 30-day course of apixaban, dabigatran, enoxaparin, fondaparinux, or rivaroxaban in trauma patients. Immediate events including deep venous thrombosis, pulmonary embolus, or bleeding within 30 days of injury were modeled in a decision tree with patients entering a Markov process to account for sequelae of VTE, including postthrombotic syndrome and chronic thromboembolic pulmonary hypertension. Effectiveness was measured in quality-adjusted life years. One-way and probabilistic sensitivity analyses were performed to identify conditions under which the preferred PPX strategy changed. RESULTS: Rivaroxaban was the dominant strategy (ie less costly and more effective) compared with no PPX or alternative regimens, delivering 30.21 quality-adjusted life years for $404,546.38. One-way sensitivity analyses demonstrated robust preference for rivaroxaban. When examining only patients with moderate-high or high VTE Risk Assessment Profile scores, rivaroxaban remained the preferred strategy. Probabilistic sensitivity analysis demonstrated a preference for rivaroxaban in 100% of cases at a standard willingness-to-pay threshold of $100,000/quality-adjusted life year. CONCLUSIONS: A 30-day course of rivaroxaban is a cost-effective extended thromboprophylaxis strategy in trauma patients in this theoretical study. Prospective studies of postdischarge thromboprophylaxis to prevent postinjury VTE are warranted.

Healthcare providers' perceived support from their organization is associated with lower burnout and anxiety amid the COVID-19 pandemic.

BACKGROUND: Professional burnout represents a significant threat to the American healthcare system. Organizational and individual factors may increase healthcare providers' susceptibility or resistance to burnout. We hypothesized that during the COVID-19 pandemic, 1) higher levels of perceived organizational support (POS) are associated with lower risk for burnout and anxiety, and 2) anxiety mediates the association between POS and burnout. METHODS: In this longitudinal prospective study, we surveyed healthcare providers employed full-time at a large, multihospital healthcare system monthly over 6 months (April to November 2020). Participants were randomized using a 1:1 allocation stratified by provider type, gender, and academic hospital status to receive one of two versions of the survey instrument formulated with different ordering of the measures to minimize response bias due to context effects. The exposure of interest was POS measured using the validated 8-item Survey of POS (SPOS) scale. Primary outcomes of interest were anxiety and risk for burnout as measured by the validated 10-item Burnout scale from the Professional Quality (Pro-QOL) instrument and 4-item Emotional Distress-Anxiety short form of the Patient Reported Outcome Measurement Information System (PROMIS) scale, respectively. Linear mixed models evaluated the associations between POS and both burnout and anxiety. A mediation analysis evaluated whether anxiety mediated the POS-burnout association. RESULTS: Of the 538 participants recruited, 402 (75%) were included in the primary analysis. 55% of participants were physicians, 73% 25-44 years of age, 73% female, 83% White, and 44% had ≥1 dependent. Higher POS was significantly associated with a lower risk for burnout (-0.23; 95% CI -0.26, -0.21; p<0.001) and lower degree of anxiety (-0.07; 95% CI -0.09, -0.06; p = 0.010). Anxiety mediated the associated between POS and burnout (direct effect -0.17; 95% CI -0.21, -0.13; p<0.001; total effect -0.23; 95% CI -0.28, -0.19; p<0.001). CONCLUSION: During a health crisis, increasing the organizational support perceived by healthcare employees may reduce the risk for burnout through a reduction in anxiety. Improving the relationship between healthcare organizations and the individuals they employ may reduce detrimental effects of psychological distress among healthcare providers and ultimately improve patient care.

Association of Tumor Molecular Subtype and Stage with Breast and Axillary Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Axillary pathologic complete response (pCR) confers higher overall and recurrence-free survival than residual axillary disease. Although breast pCR (ypT0) is associated with a pathologically negative axilla (ypN0) in human epidermal growth factor receptor 2-positive (HER2+) and triple-negative breast cancer (TNBC), how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes is incompletely understood. METHODS: A single-institution cancer registry was retrospectively reviewed for patients receiving neoadjuvant chemotherapy (NAC) followed by surgery from 2010 to 2018. Fisher's exact tests compared proportion of breast and axillary pCR by tumor subtype (hormone receptor [HR]-positive /HER2-,HR+/HER2+,HR-/HER2+,HR-/HER2-). Logistic regression determined factors associated with ypN0. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. RESULTS: The study enrolled 1348 patients. The median age was 54 years (interquartile range [IQR], 44-63 years), and 55% of the patients (n = 736) were postmenopausal. The tumor subtypes were HR+/HER2- (12%, n = 155), HR+/HER2+ (48%, n = 653), HR-/HER2+ (25%, n = 343), and TNBC (15%, n = 197). In the study, cT included T0 (1%, n = 18), T1 (20%, n = 272), T2 (53%, n = 713), T3 (17%, n = 230), and T4 (9%, n = 111), and cN included cN0 (51%, n = 687), cN1 (41%, n = 549), cN2 (5%, n = 61), and cN3 (3%, n = 43). Breast pCR and ypN0 occurred most in the HER2+ and TNBC subtypes. A negative association was found between ypN0 and age at diagnosis (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99; p < 0.001), cT4 stage (OR, 0.29; 95% CI, 0.09-0.91; p = 0.034), and HR+ subtypes (HR+/HER2-: OR, 0.54; 95% CI, 0.31-0.94; p = 0.028; HR+/HER2+: OR, 0.60; 95% CI, 0.39-0.93; p = 0.024). The HR-/HER2+ subtype was associated with ypN0 (OR, 1.70; 95% CI, 1.05-2.73; p = 0.030), and cN2/cN3 was negatively associated with ypN0 in HR+/HER2+ disease (OR, 0.26; 95% CI, 0.11-0.61; p = 0.002), HR-/HER2+ disease (OR, 0.42; 95% CI, 0.22-0.77; p = 0.005), and TNBC (OR, 0.11; 95% CI, 0.03-0.40; p = 0.001). CONCLUSION: Tumor subtype, clinical stage, and age at diagnosis may be important in consideration of de-escalation of axillary staging.

Effects of Gender Bias and Stereotypes in Surgical Training: A Randomized Clinical Trial.

Importance: Factors contributing to underrepresentation of women in surgery are incompletely understood. Pro-male bias and stereotype threat appear to contribute to gender imbalance in surgery. Objectives: To evaluate the association between pro-male gender bias and career engagement and the effect of stereotype threat on skill performance among trainees in academic surgery. Design, Setting, and Participants: A 2-phase study with a double-blind, randomized clinical trial component was conducted in 3 academic general surgery training programs. Residents were recruited between August 1 and August 15, 2018, and the study was completed at the end of that academic year. In phase 1, surveys administered 5 to 6 months apart investigated the association of gender bias with career engagement. In phase 2, residents were randomized 1:1 using permuted-block design stratified by site, training level, and gender to receive either a trigger of or protection against stereotype threat. Immediately after the interventions, residents completed the Fundamentals of Laparoscopic Surgery (FLS) assessment followed by a final survey. A total of 131 general surgery residents were recruited; of these 96 individuals with academic career interests met eligibility criteria; 86 residents completed phase 1. Eighty-five residents were randomized in phase 2, and 4 residents in each arm were lost to follow-up. Intervention: Residents read abstracts that either reported that women had worse laparoscopic skill performance than men (trigger of stereotype threat [A]) or had no difference in performance (protection against stereotype threat [B]). Main Outcomes and Measures: Association between perception of pro-male gender bias and career engagement survey scores (phase 1) and stereotype threat intervention and FLS scores (phase 2) were the outcomes. Intention-to-treat analysis was conducted. Results: Seventy-seven residents (38 women [49.4%]) completed both phases of the study. The association between pro-male gender bias and career engagement differed by gender (interaction coefficient, -1.19; 95% CI, -1.90 to -0.49; P = .02); higher perception of bias was associated with higher engagement among men (coefficient, 1.02; 95% CI, 0.19-2.24; P = .04), but no significant association was observed among women (coefficient, -0.25; 95% CI, -1.59 to 1.08; P = .50). There was no evidence of a difference in FLS score between interventions (mean [SD], A: 395 [150] vs B: 367 [157]; P = .51). The response to stereotype threat activation was similar in men and women (interaction coefficient, 15.1; 95% CI, -124.5 to 154.7; P = .39). The association between stereotype threat activation and FLS score differed by gender across levels of susceptibility to stereotype threat (interaction coefficient, -35.3; 95% CI, -47.0 to -23.6; P = .006). Higher susceptibility to stereotype threat was associated with lower FLS scores among women who received a stereotype threat trigger (coefficient, -43.4; 95% CI, -48.0 to -38.9; P = .001). Conclusions and Relevance: Perception of pro-male bias and gender stereotypes may influence career engagement and skill performance, respectively, among surgical trainees. Trial Registration: ClinicalTrials.gov Identifier: NCT03623009.

Sex Comparisons in Opioid Use and Pain After Colorectal Surgery Using Enhanced Recovery Protocols.

BACKGROUND: Differences in nociception and use of opioids between sexes are of particular interest, considering higher rates of persistent opioid use among women after surgery. Although enhanced recovery protocols (ERPs) have improved postoperative pain control in colorectal surgery, sex-based comparisons of inpatient opioid use after surgery in an ERP remain understudied. METHODS: This retrospective study analyzed data from adults after colorectal surgery using an ERP at a single hospital between 2015 and 2017. The main outcome was the rate of opioid consumption measured as oral morphine equivalents per inpatient day. Poisson regression determined association between sex and opioid consumption, accounting for early discharge, using inverse probability weighting and adjusting for covariates that retained significance on univariate analysis. Linear regression assessed the association between sex and pain scores on postoperative days 0-5 adjusting for covariates. RESULTS: Of 588 patients included, 43% were men and 57% were women. In the unadjusted model, malignancy, prehospital psychiatric medication and analgesic use, tobacco, ileostomy creation, operative time, and postoperative complications were associated with increased opioid consumption. In multivariate analyses, prehospital opioid and nonopioid analgesic use, operative time, anastomotic leak, and postoperative ileus remained significantly associated with increased inpatient opioid consumption. However, there was no significant association between sex and opioid use in crude or adjusted analysis (incidence rate ratio: 1.09; 95% confidence interval: 0.90, 1.32). Women reported higher average daily pain scores (coefficient: 0.29; 95% confidence interval: 0.04, 0.55) in adjusted analyses. CONCLUSIONS: Among patients undergoing colorectal surgery using an ERP, sex-based differences exist in pain scores but not early postoperative opioid consumption. Identification of intragroup differences in postoperative pain and opioid use among patients managed with an ERP serves as targets for customization and enhancement of current protocols. Furthermore, incongruence between reported pain and analgesic administration may have important implications for sex-related differences in persistent opioid use.

A systematic review and meta-analysis of traumatic intracranial hemorrhage in patients taking prehospital antiplatelet therapy: Is there a role for platelet transfusions?

BACKGROUND: Platelet transfusion has been utilized to reverse platelet dysfunction in patients on preinjury antiplatelets who have sustained a traumatic intracranial hemorrhage (tICH); however, there is little evidence to substantiate this practice. The objective of this study was to perform a systematic review on the impact of platelet transfusion on survival, hemorrhage progression and need for neurosurgical intervention in patients with tICH on prehospital antiplatelet medication. METHODS: Controlled, observational and randomized, prospective and retrospective studies describing tICH, preinjury antiplatelet use, and platelet transfusion reported in PubMed, Embase, Cochrane Reviews, Cochrane Trials and Cochrane DARE databases between January 1987 and March 2019 were included. Investigations of concomitant anticoagulant use were excluded. Risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled estimates of relative effect of platelet transfusion on the risk of death, hemorrhage progression and need for neurosurgical intervention using the methods of Dersimonian-Laird random-effects meta-analysis. Sensitivity analysis established whether study size contributed to heterogeneity. Subgroup analyses determined whether antiplatelet type, additional blood products/reversal agents, or platelet function assays impacted effect size using meta-regression. RESULTS: Twelve of 18,609 screened references were applicable to our questions and were qualitatively and quantitatively analyzed. We found no association between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.76-2.18; p = 0.346; I = 32.5%). There was no significant reduction in hemorrhage progression (OR, 0.88; 95% CI, 0.34-2.28; p = 0.788; I = 78.1%). There was no significant reduction in the need for neurosurgical intervention (OR, 1.00; 95% CI, 0.53-1.90, p = 0.996; I = 59.1%; p = 0.032). CONCLUSION: Current evidence does not support the use of platelet transfusion in patients with tICH on prehospital antiplatelets, highlighting the need for a prospective evaluation of this practice. LEVEL OF EVIDENCE: Systematic Reviews and Meta-Analyses, Level III.

Correlation of Thromboelastography with Apparent Rivaroxaban Concentration: Has Point-of-Care Testing Improved?

BACKGROUND: Concern remains over reliable point-of-care testing to guide reversal of rivaroxaban, a commonly used factor Xa inhibitor, in high-acuity settings. Thromboelastography (TEG), a point-of-care viscoelastic assay, may have the ability to detect the anticoagulant effect of rivaroxaban. The authors ascertained the association of apparent rivaroxaban concentration with thromboelastography reaction time, i.e., time elapsed from blood sample placement in analyzer until beginning of clot formation, as measured using TEG and TEG6S instruments (Haemonetics Corporation, USA), hypothesizing that reaction time would correlate to degree of functional factor Xa impairment. METHODS: The authors prospectively performed a diagnostic accuracy study comparing coagulation assays to apparent (i.e., indirectly assessed) rivaroxaban concentration in trauma patients with and without preinjury rivaroxaban presenting to a single center between April 2016 and July 2018. Blood samples at admission and after reversal or 24 h postadmission underwent TEG, TEG6S, thrombin generation assay, anti-factor Xa chromogenic assay, prothrombin time (PT), and ecarin chromogenic assay testing. The authors determined correlation of kaolin TEG, TEG6S, and prothrombin time to apparent rivaroxaban concentration. Receiver operating characteristic curve compared capacity to distinguish therapeutic rivaroxaban concentration (i.e., greater than or equal to 50 ng/ml) from nontherapeutic concentrations. RESULTS: Eighty rivaroxaban patients were compared to 20 controls. Significant strong correlations existed between rivaroxaban concentration and TEG reaction time (ρ = 0.67; P < 0.001), TEG6S reaction time (ρ = 0.68; P < 0.001), and prothrombin time (ρ = 0.73; P < 0.001), however reaction time remained within the defined normal range for the assay. Rivaroxaban concentration demonstrated strong but not significant association with coagulation assays postreversal (n = 9; TEG reaction time ρ = 0.62; P = 0.101; TEG6S reaction time ρ = 0.57; P = 0.112) and small nonsignificant association for controls (TEG reaction time: ρ = -0.04; P = 0.845; TEG6S reaction time: ρ = -0.09; P = 0.667; PT-neoplastine: ρ = 0.19; P = 0.301). Rivaroxaban concentration (area under the curve, 0.91) and TEG6S reaction time (area under the curve, 0.84) best predicted therapeutic rivaroxaban concentration and exhibited similar receiver operating characteristic curves (P = 0.180). CONCLUSIONS: Although TEG6S demonstrates significant strong correlation with rivaroxaban concentration, values within normal range limit clinical utility rendering rivaroxaban concentration the gold standard in measuring anticoagulant effect.

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

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.