Thrombotic and Hemorrhagic Outcomes After Elective Surgery in Preoperatively Anticoagulated Patients.

OBJECTIVE: To better understand the incidence and timing of thrombotic and hemorrhagic complications in anticoagulated patients undergoing elective surgery. METHODS: Using institutional American College of Surgeons National Surgical Quality Improvement Program data, we identified patients receiving preoperative anticoagulation undergoing elective surgery between 2011 and 2021. Medical records review supplemented National Surgical Quality Improvement Program data to detail complication and anticoagulation type and timing. Outcomes for postoperative hemorrhage, acute venous thromboembolism (VTE), and cerebrovascular accident (CVA) were collected. RESULTS: A total of 1442 patients met inclusion criteria, and 84 patients (5.8%) experienced 1 or more complications. There were 4 CVA (0.3%), 16 VTE (1.1%), and 68 bleeding (4.7%) events postoperatively. Three patients (75%) with CVA, 10 patients (62.5%) with VTE, and 18 patients (26.5%) with postoperative bleeding had resumed therapeutic anticoagulation before the complication. In terms of long-term sequelae in the CVA cohort, there was 1 mortality (25%), and an additional patient (25%) continues to experience long-term physical and mild cognitive impairments. Patients who experienced postoperative VTE required only anticoagulation adjustments. In patients who experienced bleeding complications, 6 (8.8%) required intensive care unit admissions, and there was 1 mortality (1.5%). CONCLUSION: Despite the increased use of anticoagulation over time, balancing postoperative bleeding and thrombotic risks remains challenging. Bleeding complications were most common in preoperatively anticoagulated patients undergoing elective surgery. Earlier postoperative resumption of anticoagulation is unlikely to prevent thrombotic events as 65% of patients had already resumed therapeutic anticoagulation.

Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results.

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and ß chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy. In a phase 2 single-arm study, we treated seven patients with metastatic, mismatch repair-proficient colorectal cancers who had progressive disease following multiple previous therapies. The primary end point of the study was the objective response rate as measured using RECIST 1.1, and the secondary end points were safety and tolerability. There was no prespecified interim analysis defined in this study. Three patients had objective clinical responses by RECIST criteria including regressions of metastases to the liver, lungs and lymph nodes lasting 4 to 7 months. All patients received T cell populations containing ≥50% TCR-transduced cells, and all T cell populations were polyfunctional in that they secreted IFNγ, GM-CSF, IL-2 and granzyme B specifically in response to mutant peptides compared with wild-type counterparts. TCR-transduced cells were detected in the peripheral blood of five patients, including the three responders, at levels ≥10% of CD3+ cells 1 month post-ACT. In one patient who responded to therapy, ~20% of CD3+ peripheral blood lymphocytes expressed transduced TCRs more than 2 years after treatment. This study provides early results suggesting that ACT with T cells genetically modified to express personalized neoantigen-reactive TCRs can be tolerated and can mediate tumor regression in patients with metastatic colorectal cancers. ClinicalTrials.gov registration: NCT03412877 .