Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. SUMMARY BACKGROUND DATA: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopedic trauma patients: A secondary analysis of the PREVENT CLOT trial.

BACKGROUND: The PREVENT CLOT trial concluded that thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin (LMWH) in preventing death after orthopedic trauma. However, it was unclear if these results applied to patients at highest risk of thrombosis. Therefore, we assessed if the effect of aspirin versus LMWH differed based on patients' baseline risk of venous thromboembolism (VTE). METHODS: The PREVENT CLOT trial enrolled 12,211 adult patients with fractures. This secondary analysis stratified the study population into VTE risk quartiles: low (<1%) to high (>10%) using the Caprini score. We assessed stratum-specific treatment effects using the win ratio method, in which each patient assigned to aspirin was paired with each assigned to LMWH. In each pair, we compared outcomes hierarchically, starting with death, then pulmonary embolism, deep vein thrombosis, and bleeding. The secondary outcome added patients' medication satisfaction as a fifth composite component. RESULTS: In the high-risk quartile (n = 3052), 80% had femur fracture, pelvic, or acetabular fractures. Thoracic (47%) and head (37%) injuries were also common. In the low risk quartile (n = 3053), most patients had a tibia fracture (67%), 5% had a thoracic injury, and less than 1% had head or spinal injuries. Among high risk patients, thromboembolic events did not differ statistically between aspirin and LMWH (win ratio, 0.94; 95% confidence interval [CI], 0.82-1.08, p = 0.42). This result was consistent in the low (win ratio, 1.15; 95% CI, 0.90-1.47, p = 0.27), low-medium (win ratio, 1.05; 95% CI, 0.85-1.29, p = 0.68), and medium-high risk quartiles (win ratio, 0.94; 95% CI, 0.80-1.11, p = 0.48). When medication satisfaction was considered, favorable outcomes were 68% more likely with aspirin (win ratio, 1.68; 95% CI, 1.60-1.77; p < 0.001). CONCLUSION: Thromboembolic outcomes were similar with aspirin or LMWH, even among patients at highest risk of VTE. Aspirin was favored if medication satisfaction was also considered. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Increased platelet mitochondrial function correlates with clot strength in a rodent fracture model.

BACKGROUND: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function but has not yet been correlated with functional coagulation studies. METHODS: Wistar rats underwent anesthesia and either immediate sacrifice for baseline values (n = 6) or (1) bilateral hindlimb orthopedic injury (n = 12), versus (2) sham anesthesia (n = 12) with terminal phlebotomy/hepatectomy after 24 hours. High-resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex I- and Complex II-driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate. RESULTS: Citrated native TEG maximal amplitude was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared with sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol O 2 /[s × 10 8 cells], p = 0.045), with similar trends in mitochondrial leak rate ( p = 0.19) when compared with sham animals. Overall, platelet basal respiration significantly correlated with TEG maximal amplitude ( r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex I-driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e - /min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen. CONCLUSION: Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.

Deleterious effects of plasma-derived cellular debris in a porcine model of hemorrhagic shock.

BACKGROUND: Recent studies identify large quantities of inflammatory cellular debris within Fresh Frozen Plasma (FFP). As FFP is a mainstay of hemorrhagic shock resuscitation, we used a porcine model of hemorrhagic shock and ischemia/reperfusion to investigate the inflammatory potential of plasma-derived cellular debris administered during resuscitation. METHODS: The porcine model of hemorrhagic shock included laparotomy with 35 % hemorrhage (Hem), 45 min of ischemia from supraceliac aortic occlusion with subsequent clamp release (IR), followed by protocolized resuscitation for 6 h. Cellular debris (Debris) was added to the resuscitation phase in three groups. The four groups consisted of Hem + IR (n = 4), Hem + IR + Debris (n = 3), Hem + Debris (n = 3), and IR + Debris (n = 3). A battery of laboratory, physiologic, cytokine, and outcome data were compared between groups. RESULTS: As expected, the Hem + IR group showed severe time dependent decrements in organ function and physiologic parameters. All animals that included both IR and Debris (Hem + IR + Debris or IR + Debris) died prior to the six-hour end point, while all animals in the Hem + IR and Hem + Debris survived. Cytokines measured at 30-60 min after initiation of resuscitation revealed significant differences in IL-18 and IL-1ß between all groups. CONCLUSIONS: Ischemia and reperfusion appear to prime the immune system to the deleterious effects of plasma-derived cellular debris. In the presence of ischemia and reperfusion, this model showed the equivalency of 100 % lethality when resuscitation included quantities of cellular debris at levels routinely administered to trauma patients during transfusion of FFP. A deeper understanding of the immunobiology of FFP-derived cellular debris is critical to optimize resuscitation for hemorrhagic shock.

Adiposity and Coagulation: Predicting Postinjury Coagulation With Advanced Imaging Analysis.

INTRODUCTION: Anatomic distribution of adipose tissue has demonstrated variable associations with hypercoagulability. Utilizing a retrospective analysis of a previously enrolled prospective cohort, we assessed computed tomography (CT) scan-based anthropometric and volumetric measures of adiposity as predictors of postinjury hypercoagulability. METHODS: Segmentation analysis of arrival CT scans in significantly injured patients at a single level-I trauma center enrolled from December 2017 to August 2021 were analyzed for anthropometric indices of waist circumference (WC) and sagittal abdominal diameter (SAD), and volumetric parameters of visceral adipose tissue, superficial/deep subcutaneous adipose tissue, psoas/paravertebral muscle volume, and abdominal wall muscle volume. Associations with thromboelastography (TEG) were explored. RESULTS: Data from 91 patients showed strong correlations between body mass index and standard anthropometric measures of WC and SAD (P < 0.001); calculated volumes of subcutaneous adipose tissue and visceral adipose tissue (P < 0.001); and ratios of subcutaneous adipose:psoas muscle (SP ratio) and visceral adipose:psoas muscle ratio (both with P < 0.001, respectively). Correlation between TEG maximal amplitude (MA) and body mass index and SAD were not significant, with only weak correlation between TEG-MA and WC (r = 0.238, P = 0.041). Moderate but significant correlations existed between SP ratio and TEG-MA (r = 0.340, P = 0.005), but not visceral adipose:psoas muscle ratio (r = 0.159, P = 0.198). The relationship between TEG-MA and SP ratio remained significant when adjusted for injury severity score and lactate level (b = 0.302, P = 0.001). CONCLUSIONS: SP ratio is more strongly correlated with TEG-MA than standard obesity measures, and independently predicts increasing clot strength/stability after injury. Coagulation-relevant measures of sarcopenic obesity can be measured on CT scan, and may be used to optimize thromboprophylaxis strategies for obese injured patients.

Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.

Importance: Platelet activation is a potential therapeutic target in patients with COVID-19. Objective: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients. Intervention: Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis. Results: At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77). Conclusions and Relevance: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Survey of venous thromboembolism prophylaxis in trauma patients: current prescribing practices and concordance with clinical practice guidelines.

Objectives: Pharmacological venous thromboembolism (VTE) prophylaxis is recommended in the vast majority of trauma patients. The purpose of this study was to characterize current dosing practices and timing of initiation of pharmacological VTE chemoprophylaxis at trauma centers. Methods: This was an international, cross-sectional survey of trauma providers. The survey was sponsored by the American Association for the Surgery of Trauma (AAST) and distributed to AAST members. The survey included 38 questions about practitioner demographics, experience, level and location of trauma center, and individual/site-specific practices regarding the dosing, selection, and timing of initiation of pharmacological VTE chemoprophylaxis in trauma patients. Results: One hundred eighteen trauma providers responded (estimated response rate 6.9%). Most respondents were at level 1 trauma centers (100/118; 84.7%) and had >10 years of experience (73/118; 61.9%). While multiple dosing regimens were used, the most common dose reported was enoxaparin 30 mg every 12 hours (80/118; 67.8%). The majority of respondents (88/118; 74.6%) indicated adjusting the dose in patients with obesity. Seventy-eight (66.1%) routinely use antifactor Xa levels to guide dosing. Respondents at academic institutions were more likely to use guideline-directed dosing (based on the Eastern Association of the Surgery of Trauma and the Western Trauma Association guidelines) of VTE chemoprophylaxis compared with those at non-academic centers (86.2% vs 62.5%; p=0.0158) and guideline-directed dosing was reported more often if the trauma team included a clinical pharmacist (88.2% vs 69.0%; p=0.0142). Wide variability in initial timing of VTE chemoprophylaxis after traumatic brain injury, solid organ injury, and spinal cord injuries was found. Conclusions: A high degree of variability exists in prescribing and monitoring practices for the prevention of VTE in trauma patients. Clinical pharmacists may be helpful on trauma teams to optimize dosing and increase prescribing of guideline-concordant VTE chemoprophylaxis.

Racial, Gender, and Neighborhood-Level Disparities in Pediatric Trauma Care.

BACKGROUND: Disparities in trauma outcomes and care are well established for adults, but the extent to which similar disparities are observed in pediatric trauma patients requires further investigation. The objective of this study was to evaluate the unique contributions of social determinants (race, gender, insurance status, community distress, rurality/urbanicity) on trauma outcomes after controlling for specific injury-related risk factors. STUDY DESIGN: All pediatric (age < 18) trauma patients admitted to a single level 1 trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed (n = 14,398). Primary outcomes were receipt of opioids in the emergency department, post-discharge rehabilitation referrals, and mortality. Multivariate logistic regressions evaluated demographic, socioeconomic, and injury characteristics. Multilevel logistic regressions evaluated area-level indicators, which were derived from abstracted home addresses. RESULTS: Analyses adjusting for demographic and injury characteristics revealed that Black children (n = 6255) had significantly lower odds (OR = 0.87) of being prescribed opioid medications in the emergency department compared to White children (n = 5883). Children living in more distressed and rural communities had greater odds of receiving opioid medications. Girls had significantly lower odds (OR = 0.61) of being referred for rehabilitation services than boys. Post hoc analyses revealed that Black girls had the lowest odds of receiving rehabilitation referrals compared to Black boys and White children. CONCLUSION: Results highlight the need to examine both main and interactive effects of social determinants on trauma care and outcomes. Findings reinforce and expand into the pediatric population the growing notion that traumatic injury care is not immune to disparities.

Population Density and Triage of Pediatric Firearm Injuries in a Rural Trauma System.

BACKGROUND: Rural pediatric firearm injuries require regional pediatric and trauma expertise. We evaluated county-level population density associations with transport, hospital interventions, and patient outcomes at a Level I pediatric trauma center serving a rural, statewide catchment area. MATERIAL AND METHODS: The trauma registry of the only in-state pediatric trauma center was reviewed for firearm injuries in patients < 18 between 1/2013 and 3/2020. County-level population density was classified according to the United States Office of Management and Budget definitions for rural, micropolitan, and metropolitan areas. RESULTS: 364 patients were identified, including 7 patients who were re-injured. Mean age was 11.3 ± 4.5 y and patients were 79.4% male. 59.3% were transferred from a referring hospital. Median injury severity score was 5 (IQR 1-10); 88.0% required trauma center admission, and 48.2% required operative intervention. 7.4% were injured in a rural county, 46.4% in a micropolitan county, and 46.2% in a metropolitan county. Patients from rural counties were more likely to be unintentionally injured (72.0%) than those from micropolitan (54.4%) or metropolitan counties (44.0%, P = .04). While need for inpatient admission and length of stay were similar, those transported from rural counties had significantly longer transport times (P < .01) and less frequent need for operative intervention (P = .03), as well as trends toward lower injury severity (P = .08) and mortality (P = .06). CONCLUSION: Management of pediatric firearm injury is a unique challenge with significant regional variability. Opportunities exist for outreach, telehealth, and decision support to ensure equitable distribution of resources in rural trauma systems. LEVEL OF EVIDENCE: Epidemiological, Level III.

Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Viscoelastic Hemostatic Assays for Orthopedic Trauma and Elective Procedures.

The application of viscoelastic hemostatic assays (VHAs) (e.g., thromboelastography (TEG) and rotational thromboelastometry (ROTEM)) in orthopedics is in its relative infancy when compared with other surgical fields. Fortunately, several recent studies describe the emerging use of VHAs to quickly and reliably analyze the real-time coagulation and fibrinolytic status in both orthopedic trauma and elective orthopedic surgery. Trauma-induced coagulopathy-a spectrum of abnormal coagulation phenotypes including clotting factor depletion, inadequate thrombin generation, platelet dysfunction, and dysregulated fibrinolysis-remains a potentially fatal complication in severely injured and/or hemorrhaging patients whose timely diagnosis and management are aided by the use of VHAs. Furthermore, VHAs are an invaluable compliment to common coagulation tests by facilitating the detection of hypercoagulable states commonly associated with orthopedic injury and postoperative status. The use of VHAs to identify hypercoagulability allows for an accurate venous thromboembolism (VTE) risk assessment and monitoring of VTE prophylaxis. Until now, the data have been insufficient to permit an individualized approach with regard to dosing and duration for VTE thromboprophylaxis. By incorporating VHAs into routine practice, orthopedic surgeons will be better equipped to diagnose and treat the complete spectrum of coagulation abnormalities faced by orthopedic patients. This work serves as an educational primer and up-to-date review of the current literature on the use of VHAs in orthopedic surgery.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Weight Bias: Examining Achalasia Therapy in the Obese Patient.

We hypothesize that obesity is a common diagnosis in those with achalasia at our institution but time to diagnosis and treatment is longer compared to normal weight counterparts due to implicit bias. We retrospectively reviewed all adult patients between 1/1/2013 and 6/31/2020 with a diagnosis of achalasia. Demographics, comorbidities, Eckardt scores, interventions, complications, time to consult, duration of symptoms, and follow-up were evaluated. More than half of the patients were seen in the most recent 2 years following POEM introduction and 138 had available BMI data. 46 were obese (33%) and 92 were non-obese (67%). Obese patients reported a shorter duration of symptoms prior to seeking treatment 12 versus 24 months. There was no difference in time to intervention or procedure offered. There was a non-significant trend toward higher leak (11 vs 5%) and overall complication rate (19 vs 17%) in obese patients. In follow-up 98 patients had BMI data. There was a a significant difference in mean BMI change -1.2 +/- 4.2 kg/m2 in obese patients and +0.1 +/- 2.1 kg/m2 in normal weight patients. One year follow-up was available in 16 (47%) obese and 25 (33%) non-obese patients and showed a non-significant trend toward greater weight gain in the normal/overweight group (+3.2 +/- 1.1 kg/m2) compared to obese (+2.0 +/- 3.5 kg/m2). Obese patients with achalasia have unique considerations. Duration of symptoms may be shorter in the obese patient with esophageal dysphagia. We noted trends toward greater weight gain following interventions in non-obese patients with equivalent complication rates.

Self-selection vs Randomized Assignment of Treatment for Appendicitis.

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ. Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment. Design, Setting, and Participants: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, 2020; all participants were eligible for at least 1 year of follow-up, with all follow-up ending in 2021. The randomized cohort included 1094 adults with appendicitis; the self-selection cohort included patients who declined participation in the randomized group, of whom 253 selected appendectomy and 257 selected antibiotics. In this secondary analysis, characteristics and outcomes in both self-selection and randomized cohorts are described with an exploratory analysis of cohort status and receipt of appendectomy. Interventions: Appendectomy vs antibiotics. Main Outcomes and Measures: Characteristics among participants randomized to either appendectomy or antibiotics were compared with those of participants who selected their own treatment. Results: Clinical characteristics were similar across the self-selection cohort (510 patients; mean age, 35.8 years [95% CI, 34.5-37.1]; 218 female [43%; 95% CI, 39%-47%]) and the randomized group (1094 patients; mean age, 38.2 years [95% CI, 37.4-39.0]; 386 female [35%; 95% CI, 33%-38%]). Compared with the randomized group, those in the self-selection cohort were less often Spanish speaking (n = 99 [19%; 95% CI, 16%-23%] vs n = 336 [31%; 95% CI, 28%-34%]), reported more formal education (some college or more, n = 355 [72%; 95% CI, 68%-76%] vs n = 674 [63%; 95% CI, 60%-65%]), and more often had commercial insurance (n = 259 [53%; 95% CI, 48%-57%] vs n = 486 [45%; 95% CI, 42%-48%]). Most outcomes were similar between the self-selection and randomized cohorts. The number of patients undergoing appendectomy by 30 days was 38 (15.3%; 95% CI, 10.7%-19.7%) among those selecting antibiotics and 155 (19.2%; 95% CI, 15.9%-22.5%) in those who were randomized to antibiotics (difference, 3.9%; 95% CI, -1.7% to 9.5%). Differences in the rate of appendectomy were primarily observed in the non-appendicolith subgroup. Conclusions and Relevance: This secondary analysis of the CODA RCT found substantially similar outcomes across the randomized and self-selection cohorts, suggesting that the randomized trial results are generalizable to the community at large. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Thromboelastography-Based Evaluation of Gender-Associated Hypercoagulability.

BACKGROUND: Age, race, and gender differences in coagulation status of healthy volunteers have been reported in previous case series; however, rigorous multivariate analysis adjusting for these factors is lacking. We aimed to investigate the effects of age, race, and gender on baseline coagulation status in healthy volunteers. METHODS: Thirty healthy volunteer controls with no history of bleeding or thrombotic events and no previous anticoagulant or antiplatelet use were recruited. Citrated and heparinized blood samples were drawn, and kaolin and platelet-mapping thromboelastography (TEG) assays performed. RESULTS: Thirty participants had a mean age of 37, mean body mass index of 29 kg/m2, and were 47% African-American and 70% female. Women were significantly older than men (40 ± 11 y vs 28 ± 7 y, P = .002); there were no significant differences in demographics by race. Multivariate analysis of variance for the effect of age, race, and gender across TEG parameters yielded evidence for gender differences in hypercoagulability (Pillai's trace P = .02), which appear to be driven by differences in K-time, alpha angle, maximal amplitude, and G parameter. Women were hypercoagulable compared to men, as manifested by shorter K-time, steeper alpha angle, higher maximal amplitude, and larger G parameter. DISCUSSION: Women at baseline have relatively hypercoagulable fibrin deposition kinetics, platelet contributions to clot formation, and overall clot strength compared to men, even when adjusted for age and race. Additional research is needed to specifically detail the key patient-level factors, clinical implications, and opportunities for tailored therapy related to gender-associated hypercoagulability.

Impedance Planimetry and the Changing Paradigm of Esophageal Dysphagia.

OBJECTIVES: Patients presenting with dysphagia can encounter a pathway to therapy and relief that is expensive and frustrating. High resolution impedance planimetry (HRIP) is a new mechanism for enhancing and possibly hastening that process. A balloon with integrated pressure sensors is utilized to measure luminal geometry and pressure by volume-controlled distention. Esophagogastric junction (EGJ) distensibility and body contractility are assessed at the time of other endoscopic procedures. Here we describe a single-center experience utilizing HRIP in the endoscopic evaluation of patients presenting with dysphagia. METHODS: A prospectively maintained registry of patients undergoing impedance planimetry assessments at an academic medical center was queried for demographics, procedural details, and patient-reported outcomes. RESULTS: Data was reviewed for 122 procedures performed by two providers. HRIP was performed in 63 (52%) patients for initial dysphagia assessment, 36 (30%) for follow-up assessment, and 20 (16%) as a procedural adjunct at the time of other planned procedures. HRIP contractile response was characterized as normal in 36%, absent in 32%, and diminished/disorganized in 14%. These results motivated clinical planning for surgical referral in 7 (5%) patients, 31 (26%) additional testing, and 82 (68%) continued medical management and follow-up. DISCUSSION: HRIP is an emerging endoscopic modality which can streamline diagnostic work-up and therapeutic planning for patients with symptomatic dysphagia. Using functional esophageal assessment at the time of other diagnostic and therapeutic procedures, HRIP may expedite care and lead to improved patient satisfaction and clinical outcomes.