Michael Sheu

Background: Circulating tumor DNA is a promising biomarker for molecular residual disease and recurrence surveillance in biliary tract cancers. We evaluated the association between postoperative tumor-informed ctDNA and recurrence-free survival (RFS) and assessed the performance of initial and longitudinal ctDNA surveillance. Methods: We performed a single-institution retrospective cohort study of 51 patients with resected non-metastatic biliary tract cancers who underwent postoperative ctDNA testing. Kaplan–Meier, log-rank, univariable Cox regression, and limited multivariable Cox regression analyses were used to evaluate associations between ctDNA status and RFS. A 3-month landmark sensitivity analysis was performed to address time-related bias. Results: Twenty-five patients (49.0%) developed recurrence. Recurrence occurred in 18 of 20 patients (90.0%) with postoperative ctDNA positivity compared with 7 of 31 patients (22.6%) without ctDNA positivity. Median RFS was 10.8 versus 47.4 months, respectively. Postoperative ctDNA positivity was associated with shorter RFS (HR, 7.85; 95% CI, 3.03–20.29; p < 0.001). In a pre-specified multivariable Cox model adjusting for stage III/IV disease and CA 19-9 > 37 U/mL, postoperative ctDNA positivity remained associated with shorter RFS (adjusted HR, 5.09; 95% CI, 1.82–14.26; p = 0.002). Longitudinal ctDNA surveillance demonstrated a sensitivity of 72.0%, specificity of 92.3%, PPV of 90.0%, and NPV of 77.4% for recurrence. Median lead time to recurrence was 69.5 days. In a 3-month landmark cohort of 37 evaluable patients, postoperative ctDNA positivity was associated with shorter subsequent RFS after exploratory adjustment for stage and CA 19-9 (adjusted HR, 6.45; 95% CI, 1.47–28.34; p = 0.014). Conclusions: Postoperative ctDNA positivity was associated with recurrence and shorter RFS. Longitudinal ctDNA surveillance improved recurrence detection and frequently preceded clinically documented recurrence.

Introduction: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. Results: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. Conclusion: Among bacteremic AML patients in the post‐HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low. image

Introduction: Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration. Methods: This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days. Results: 43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780 mL vs. 850 mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively. Conclusion: There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT.

This study explored the efficacy of intravenous immunoglobulin (IVIG) prophylaxis in reducing infection-related hospitalizations (IRHs) in MM patients. This was a retrospective study of MM patients who received IVIG at Taussig Cancer Center between July 2009 and July 2021. The primary endpoint was rate of IRHs per patient-year on-IVIG versus off-IVIG. 108 patients were included. There was a significant difference in the primary endpoint of rate of IRHs per patient-year on-IVIG versus off-IVIG in the overall study population (0.81 vs. 1.08; Mean Difference [MD], -0.27; 95% Confidence Interval [CI], -0.57 to 0.03; p value [P] = 0.04). The subgroup of patients with a 1-year period of continuous IVIG (49, 45.3%), the subgroup with standard-risk cytogenetics (54, 50.0%) and the subgroup with 2 or more IRHs (67, 62.0%) all showed a significant reduction in IRHs while on-IVIG versus off-IVIG (0.48 vs. 0.78; MD, -0.30; 95% CI, -0.59 to 0.002; p = 0.03) and (0.65 vs. 1.01; MD, -0.36; 95% CI, -0.71 to -0.01; p = 0.02) and (1.04 vs. 1.43; MD, -0.39; 95% CI, -0.82 to 0.05; p = 0.04) respectively. IVIG showed significant benefit in reducing IRHs in the overall population and in multiple subgroups.