Publications

BACKGROUND: To measure the impact of the COVID-19 pandemic on the management of patients with carotid artery stenosis.

METHODS: We prospectively collected data from 25 centers (19 centers in the United States and 6 centers internationally) on postponed carotid artery operations between March 2020 and January 2022. We describe the characteristics of these patients and their planned operations, along with outcomes including mortality and neurological deterioration during the period of operative delay due to the COVID-19 pandemic.

RESULTS: A total of 1,220 vascular operations were postponed during the pandemic, of them 96 patients presented with significant carotid stenosis (median stenosis of 71%; interquartile range; 70-80) and 80% of them were planned for carotid endarterectomy. Most patients were asymptomatic (69%), and 31% of patients were symptomatic (16% of patients had a stroke, 15% of patients had a transient ischemic attack, and 1% of patients experienced amaurosis fugax). The median length of surgical delay was 71 days (interquartile range: 45.5, 115.5). At the data entry time, 62% of patients had their carotid operations postponed and successfully completed. Most postponements (72%) were due to institutional policies aimed at resource conservation. During the delay, no patient decompensated or required an urgent operation. A total of 5 patients (5%) with carotid stenosis died while awaiting operations due to COVID-19.

CONCLUSIONS: Our study of a cohort of patients with carotid artery stenosis who underwent a median delay of 71 days during the COVID-19 pandemic showed a disparate operation delay between US regions and internationally, most postponements were due to hospital policy, and none of the patients deteriorated or required an emergency surgery during the delay.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is a morbid complication with suboptimal treatment. We aimed to evaluate the biomarker profile and functional outcomes in patients with submassive PE (sPE) treated with catheter-directed thrombolysis (CDT) compared with anticoagulation alone (ACA). We performed a secondary biomarker and survey analysis of the SUNSET sPE (standard vs ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism) randomized trial comparing standard CDT to ultrasound-assisted thrombolysis in patients with sPE.

METHODS: As a part of the SUNSET sPE study, patients who did not receive an intervention were enrolled in the medical (ACA) arm. The biomarkers associated with CTEPH in the literature (ie, CCL2, CXCL10, PTX3, GDF-15, RAGE, BCA-1, TFPI) were collected and measured using a multiplex assay at diagnosis, discharge, and 3-month follow-up. Patients underwent a 6-minute walk test and answered quality-of-life questionnaires (pulmonary embolism quality of life; University of California, San Diego, shortness of breath questionnaire; 36-item short-form survey) at 3 months after diagnosis. Comparisons were made using the Student t test. Nonparametric tests were used when the distributions were not normal. Significance was set at P ≤ .05.

RESULTS: A total of 72 patients (age, 56 ± 15 years; 40.3% women) were included in the present analysis. Of these 72 patients, 53 underwent CDT and 19 were included in the ACA arm. The baseline right ventricle/left ventricle ratios were similar between the two groups (CST, 1.8; ACA, 1.7). The survival and complication rates were similar between the two groups. At discharge, CXCL10 (768.9 ± 148.6 pg/mL vs 3032.0 ± 1201.0 pg/mL; P = .018) and PTX3 (3203.5 ± 1298.0 pg/mL vs 12,716.2 ± 6961.5 pg/mL; P = .029) were lower in the CDT group and displayed a quicker return to baseline than in the ACA group. This trend, although not significant, was also seen with the other biomarkers. At 3 months, the 6-minute walking distance and quality-of-life scores were similar between both groups.

CONCLUSIONS: In patients with sPE, the biomarkers of CTEPH were lower with CDT compared with ACA. At 3 months, both groups demonstrated similar biomarker levels, 6-minute walking distances, and quality-of-life scores.

BACKGROUND: Pulmonary embolism (PE) is a major cause of mortality with presentation varying between few or no symptoms to sudden death. This makes timely and appropriate treatment extremely important. Multidisciplinary PE response teams (PERT) have emerged to improve the management of acute PE. This study aims to describe the experience of a large multihospital single-network institution with PERT.

METHODS: A retrospective cohort study of patients admitted for submassive and massive PE between 2012 and 2019 was conducted. The cohort was divided based on time of diagnosis and hospital into two groups: non-PERT included patients treated at hospitals that did not initiate PERT and patients diagnosed before the introduction of PERT (June 1, 2014); and the PERT group included those admitted after June 1, 2014, to a hospital with PERT. Patients with low-risk PE and those who had admissions in both time periods were excluded. Primary outcomes included all-cause mortality at 30, 60, and 90 days. Secondary outcomes included causes of death, intensive care unit (ICU) admission, ICU length of stay (LOS), total hospital LOS, type of treatment, and specialty consultations.

RESULTS: We analyzed 5190 patients, with 819 (15.8%) being in the PERT group. Patients in the PERT group were more likely to receive extensive workup that included troponin-I (66.3% vs 42.3%; P < .001) and brain natriuretic peptide (50.4% vs 20.3%; P < .001). They also more often received catheter-directed interventions (12% vs 6.2%; P < .001) rather than anticoagulation monotherapy. Mortality outcomes were similar between both groups at all measured timepoints. Rates of ICU admission (65.2% vs 29.7%; P < .001), ICU LOS (median, 64.7 hours; interquartile range [IQR], 41.9-89.1 hours vs median, 38 hours; IQR, 22-66.4 hours; P < .001), and total hospital LOS (median, 5 days; IQR, 3-8 days vs median, 4 days; IQR, 2-6 days; P < .001) were all higher among the PERT group. Patients in the PERT group were more likely to receive vascular surgery consultation (5.3% vs 0.8%; P < .001) and the consultation occurred earlier in the admission when compared with the non-PERT group (median, 0 days; IQR, 0-1 days vs median, 1 day; IQR, 0-1; P = .04).

CONCLUSIONS: The data presented here showed that there was no difference in mortality after PERT implementation. These results suggest that the presence of PERT increases the number of patients receiving a full PE workup with cardiac biomarkers. PERT also leads to more specialty consultations and more advanced therapies such as catheter-directed interventions. Further research is needed to assess the effect of PERT on long-term survival of patients with massive and submassive PE.

OBJECTIVE: Hypercoagulability is common in severe acute respiratory syndrome coronavirus 2 and has been associated with arterial thrombosis leading to acute limb ischemia (ALI). Our objective was to determine the outcomes of concurrent coronavirus disease 2019 (COVID-19) infection and ALI, particularly during the Delta variant surge and the impact of vaccination status.

METHODS: A retrospective review was performed of patients treated at a single health care system between March 2020 and December 2021 for ALI and recent (<14 days) COVID-19 infection or who developed ALI during hospitalization for the same disease. Patients were grouped by year as well as by pre and post Delta variant emergence in 2021 based on the World Health Organization timeline (January to May vs June to December). Baseline demographics, imaging, interventions, and outcomes were evaluated. A control cohort of all patients with ALI requiring surgical intervention for a 2-year period prior to the pandemic was used for comparison. Primary outcomes were in-hospital mortality and amputation-free survival. Kaplan-Meier survival and Cox proportional hazards analysis were performed.

RESULTS: Forty acutely ischemic limbs were identified in 36 patients with COVID-19, the majority during the Delta surge (52.8%) and after the wide availability of vaccines. The rate of COVID-19-associated ALI, although low overall, nearly doubled during the Delta surge (0.37% vs 0.20%; P = .09). Intervention (open or endovascular revascularization vs primary amputation) was performed on 31 limbs in 28 individuals, with the remaining eight treated with systemic anti-coagulation. Postoperative mortality was 48%, and overall mortality was 50%. Major amputation following revascularization was significantly higher with COVID-19 ALI (25% vs 3%; P = .006) compared with the pre-pandemic group. Thirty-day amputation-free survival was significantly lower (log-rank P < .001). COVID-19 infection (adjusted hazard ratio, 6.2; P < .001) and age (hazard ratio, 1.1; P = .006) were associated with 30-day amputation in multivariate analysis. Severity of COVID-19 infection, defined as vasopressor usage, was not associated with post-revascularization amputation. There was a higher incidence of re-thrombosis in the latter half of 2021 with the Delta surge, as reintervention for recurrent ischemia of the same limb was more common than our previous experience (21% vs 0%; P = .55). COVID-19-associated limb ischemia occurred almost exclusively in non-vaccinated patients (92%).

CONCLUSIONS: ALI observed with Delta appears more resistant to standard therapy. Unvaccinated status correlated highly with ALI occurrence in the setting of COVID-19 infection. Information of limb loss as a COVID-19 complication among non-vaccinated patients may help to increase compliance.

OBJECTIVE: Gender bias, which contributes to burnout and attrition of female medical trainees, may manifest as disparate workplace evaluations. Here, we explore gender-based differences in perceived competence and professionalism as described in an institutional electronic risk management reporting system.

DESIGN: In this retrospective qualitative study, recurring themes were identified from anonymous entries reported to an electronic institutional risk management database from July 2014 to July 2015, and from July 2019 to July 2020 using inductive methods. This electronic system is often used by hospital staff to document complaints against physicians under the pretext of poor patient care, regardless of whether an adverse event occurred. Two individuals independently coded entries. Themes were determined from event indicator codes (EIC) using Delphi methodology and compared between gender and specialty using bivariate statistics.

SETTING: A multi-center integrated healthcare delivery system.

PARTICIPANTS: Risk management entries pertaining to physician trainees by hospital staff as written submissions to the institution's electronic risk management reporting system. Main outcomes included themes defined as: (1) lack of professionalism (i.e., delay in response, attitude, lack of communication), (2) perceived medical error, (3) breach of institutional protocol.

RESULTS: Of the 207 entries included for analysis, 52 entries identified men (25%) and 31 entries identified women (15%). The gender was not available in 124 entries and, therefore, categorized as ambiguous. The most common complaint about men involved a physician-related EIC (n = 12, 23%, EIC TX39) and the most common complaint about women involved a communication-related EIC (n = 7, 23%, EIC TX55). Eighty-eight (43%) entries involved medical trainees; 82 (40%) involved surgical trainees. Women were more often identified by their name only (n = 8, 26% vs. n = 3, 6%; p < 0.001). This finding was consistent in both medical (n = 0, 0% vs. n = 5, 31%; p < 0.001) and surgical (n = 2, 7% vs. n = 3, 25%; p = 0.006) specialties. In entries involving women, a lack of professionalism was most frequently cited (n = 29, 94%). Entries identifying medical errors more frequently involved men (n = 25, 48% vs. n = 7, 23%; p = 0.02).

CONCLUSIONS: Gender-based differences exist in how hospital staff interpret trainees' actions and attitudes. These differences have consequences for training paradigms, perceptions of clinical competence, physician burnout, and ultimately, patient outcomes.

INTRODUCTION: Thromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype.

METHODS: We treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing.

RESULTS: We found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression.

DISCUSSION: Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.

BACKGROUND: The use of low-titer group O whole blood is increasing. To reduce wastage, unused units can be converted to packed red blood cells. Supernatant is currently discarded post-conversion; however, it could be a valuable transfusable product. The aim of this study was to evaluate supernatant prepared from late-storage low-titer group O whole blood being converted to red blood cells, hypothesizing it will have higher hemostatic activity compared to fresh never-frozen liquid plasma.

METHODS: Low-titer group O whole blood supernatant (n = 12) prepared on storage day 15 was tested on days 15, 21, and 26 and liquid plasma (n = 12) on 3, 15, 21, and 26. Same-day assays included cell counts, rotational thromboelastometry, and thrombin generation. Centrifuged plasma from units was banked for microparticle characterization, conventional coagulation, clot structure, hemoglobin, and additional thrombin generation assays.

RESULTS: Low-titer group O whole blood supernatant contained more residual platelets and microparticles compared to liquid plasma. At day 15, low-titer group O whole blood supernatant elicited a faster intrinsic clotting time compared to liquid plasma (257 ± 41 vs. 299 ± 36 s, P = 0.044), and increased clot firmness (49 ± 9 vs. 28 ± 5 mm, P < 0.0001). Low-titer group O whole blood supernatant showed more significant thrombin generation compared to liquid plasma (day 15 endogenous thrombin potential 1,071 ± 315 vs. 285 ± 221 nM·min, P < 0.0001). Flow cytometry demonstrated low-titer group O whole blood supernatant contained significantly more phosphatidylserine and CD41+ microparticles. However, thrombin generation in isolated plasma suggested residual platelets in low-titer group O whole blood supernatant were a greater contributor than microparticles. Additionally, low-titer group O whole blood supernatant and liquid plasma showed no difference in clot structure, despite higher CD61+ microparticle presence.

CONCLUSIONS: Plasma supernatant produced from late-storage low-titer group O whole blood shows comparable, if not enhanced, in vitro hemostatic efficacy to liquid plasma.

BACKGROUND: Platelet concentrates (PLT) can be manufactured using a combination of apheresis collection devices and suspension media (plasma or platelet additive solution (PAS)). It is unclear how platelet quality and hemostatic function differ across the current in-use manufacturing methods in the United States. The objective of this study was therefore to compare baseline function of PLT collected using different apheresis collection platforms and storage media.

STUDY DESIGN AND METHODS: PLT were collected at two sites with identical protocols (N = 5 per site, N = 10 total per group) on the MCS® + 9000 (Haemonetics; "MCS"), the Trima Accel® 7 (Terumo; "Trima"), and the Amicus Cell Separator (Fresenius Kabi, "Amicus"). MCS PLT were collected into plasma while Trima and Amicus PLT were collected into plasma or PAS (Trima into Isoplate and Amicus into InterSol; yielding groups "TP", "TI" and "AP", "AI", respectively). PLT units were sampled 1 h after collection and assayed to compare cellular counts, biochemistry, and hemostatic function.

RESULTS: Differences in biochemistry were most evident between plasma and PAS groups, as anticipated. MCS and TP had the highest clot strength as assessed by viscoelastometry. AI had the lowest thrombin generation capacity. Both TP and TI had the highest responses on platelet aggregometry. AI had the greatest number of microparticles.

DISCUSSION: Platelet quality and function differ among collection platforms at baseline. MCS and Trima platelets overall appear to trend toward higher hemostatic function. Future investigations will assess how these differences change throughout storage, and if these in vitro measures are clinically relevant.

BACKGROUND: The use of low-titer group O whole blood is increasing. To reduce wastage, unused units can be converted to packed red blood cells. Supernatant is currently discarded post-conversion; however, it could be a valuable transfusable product. The aim of this study was to evaluate supernatant prepared from late-storage low-titer group O whole blood being converted to red blood cells, hypothesizing it will have higher hemostatic activity compared to fresh never-frozen liquid plasma.

METHODS: Low-titer group O whole blood supernatant (n = 12) prepared on storage day 15 was tested on days 15, 21, and 26 and liquid plasma (n = 12) on 3, 15, 21, and 26. Same-day assays included cell counts, rotational thromboelastometry, and thrombin generation. Centrifuged plasma from units was banked for microparticle characterization, conventional coagulation, clot structure, hemoglobin, and additional thrombin generation assays.

RESULTS: Low-titer group O whole blood supernatant contained more residual platelets and microparticles compared to liquid plasma. At day 15, low-titer group O whole blood supernatant elicited a faster intrinsic clotting time compared to liquid plasma (257 ± 41 vs. 299 ± 36 s, P = 0.044), and increased clot firmness (49 ± 9 vs. 28 ± 5 mm, P < 0.0001). Low-titer group O whole blood supernatant showed more significant thrombin generation compared to liquid plasma (day 15 endogenous thrombin potential 1,071 ± 315 vs. 285 ± 221 nM·min, P < 0.0001). Flow cytometry demonstrated low-titer group O whole blood supernatant contained significantly more phosphatidylserine and CD41+ microparticles. However, thrombin generation in isolated plasma suggested residual platelets in low-titer group O whole blood supernatant were a greater contributor than microparticles. Additionally, low-titer group O whole blood supernatant and liquid plasma showed no difference in clot structure, despite higher CD61+ microparticle presence.

CONCLUSIONS: Plasma supernatant produced from late-storage low-titer group O whole blood shows comparable, if not enhanced, in vitro hemostatic efficacy to liquid plasma.

BACKGROUND: The rapid provision of blood products is life-saving for patients with massive hemorrhage. Ideally, RhD-negative blood products would be supplied to a woman of childbearing potential whose Rh type is unknown due to the risk of D-alloimmunization and the potential for hemolytic disease of the fetus and newborn to occur if RhD-positive blood products are transfused. Therefore, there is a need for a test that rapidly determines her RhD type. This study compared the RhD type determined using a rapid ABO and RhD test to the RhD type determined by an immunohematology reference laboratory.

METHODS: After receiving ethics review board approval, 200 random, unique, deidentified patient samples that had undergone routine pretransfusion testing in an immunohematology reference laboratory using column agglutination technology were collected and tested using a rapid ABO and RhD test (Eldoncard Home kit 2511). The RhD typing results from these two methods were compared to determine the accuracy of the rapid ABO and RhD test.

RESULTS: The rapid ABO and RhD test produced results that were concordant with the transfusion service's results in 199/200 (99.5%) of cases, with a negative predictive value of 98.2% and 99.3% sensitivity. The single outlier was likely an RhD variant due to its serological characteristics.

DISCUSSION: These data indicate that this rapid ABO and RhD test could be used for the rapid determination of a patient's RhD type, perhaps even in the emergency department, which could guide the selection of blood products provided during their resuscitation.