Citations

Abstract Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

AbstractInfection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient‐ and surgeon‐dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9–54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5–149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR.

The coronavirus disease 2019 (COVID-19) pandemic currently gripping the globe is impacting the entire health care system with rapidly escalating morbidities and mortality. Although the infectious risk to the pediatric population appears low, the effects on children with congenital heart disease (CHD) remain poorly understood. The closure of congenital heart surgery programs worldwide to address the growing number of infected individuals could have an unintended impact on future health for COVID-19-negative patients with CHD. Pediatric and congenital heart surgeons, given their small numbers and close relationships, are uniquely positioned to collectively assess the impact of the pandemic on surgical practice and care of children with CHD. We present the results of an international survey sent to pediatric and congenital heart surgeons characterizing the early impact of COVID-19 on the care of patients with CHD.

Background Trans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis and limited response to PD-(L)1 checkpoint inhibitors in cancer. To our knowledge, no clinical intervention has reduced any of these circulating forms of extracellular PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment to reduce circulating extracellular PD-L1. Results In patients with melanoma, sPD-L1 levels above 0.277 ng/mL predicted inferior overall survival. In patients undergoing TPE for non-malignant indications, each TPE session removed a mean 70.8% sPD-L1 and 73.1% evPD-L1 detectable in plasma. TPE also reduced total and ADAM10-positive extracellular vesicles. Conclusion Here, we report the first known clinical intervention to remove either sPD-L1 or evPD-L1 from plasma in vivo. TPE reduces plasma sPD-L1 and evPD-L1 in vivo and may have a role in treatment with immunotherapy. TPE may also prove useful in patients with other extracellular vesicle-related conditions.

AbstractBackgroundA new protocol has been developed on the Amicus Separator that enables the device to perform online extracorporeal photopheresis (ECP) procedures when used in conjunction with the Phelix photoactivation device and associated disposable kit. The objective of this study was to evaluate the safety and performance of the Amicus ECP System in adult subjects with steroid‐refractory or dependent chronic graft vs host disease (cGVHD).Study Design and MethodsEight subjects with mild to severe cGVHD underwent 31 procedures. Subject safety evaluations were performed pre and post procedure and adverse events (AEs) were recorded during treatment and 24 hours after the last procedure. In vitro evaluations of the treated cells included hematology counts and lymphocyte apoptosis, viability and proliferation as measures for ECP procedure validation.ResultsFor n = 23 evaluable procedures, median (range) procedure time was 88 (78‐110) minutes, during which 2.9 (0.6‐4.7) × 109 TNCs (approximately 90% MNCs) were treated and reinfused to the subjects. All subject safety evaluations (vitals, cell counts, plasma hemoglobin and bacterial and endotoxin testing) were within expected ranges. All device or procedure related AEs were mild in nature. After 24 hours in culture, 86 (52‐98)% of treated lymphocytes were apoptotic compared to 27 (15‐51)% in controls. Inhibition of lymphocyte proliferation was >91% in all procedures.ConclusionECP procedures were safely completed in adult subjects with SR‐cGVHD treated using the new online Amicus ECP system.

The rate of ulcerative colitis (UC), an inflammatory bowel disease, has been on the rise in the United States for the last several decades. Colectomy can be performed when other treatment options cannot provide a reasonable quality of life to patients with UC. Frailty has been shown to be a strong tool for evaluating preoperative risk factors for poor postoperative outcomes. The National Surgical Quality and Improvement Program cross-institutional database was used for this study. Data from 943 patients who underwent colectomy for UC between 2005 and 2012 were evaluated. Modified frailty index (mFI) is a previously described and validated 11-variable frailty measure used in the National Surgical Quality and Improvement Program to assess frailty. Outcome measures included serious morbidity; overall morbidity; cardiopulmonary, septic, and wound complications; and Clavien class IV (requiring ICU) and V (mortality) complications. Median age was 46 years and median body mass index was 25.5 Kg/m 2 . In all, 54.3 per cent of patients were male and 39.38 per cent of patients were American Society of Anesthesiologists Class lll or higher. The median mFI was 0 (0–0.54). As the mFI increased from 0 (nonfrail) to 0.18 and above, the overall morbidity increased from 25.40 to 52.1 per cent ( P < 0.05), serious morbidity increased from 14.9 to 42.1 per cent ( P < 0.05), septic complications increased from 9.87 to 21.49 per cent ( P < 0.05), cardiopulmonary complications increased from 2.98 to 23.14 per cent ( P < 0.05), Clavien class IV complications increased from 3.5 to 26.5 per cent ( P < 0.05), and Clavien V complications increased from 0.16 to 6.61 per cent ( P < 0.05). On multivariate analysis, mFI was an independent predictor of septic complications [Adjusted Odds Ratio (AOR): 31.26; P = 0.006], cardiopulmonary complications (AOR: 216.3; P ≤ 0.001), serious morbidity(AOR: 66.8; P ≤ 0.001), overall morbidity (AOR: 25.5; P ≤ 0.001), Clavien class IV (AOR: 204.9; P ≤ 0.001) complications, and return to the operating room (AOR: 14.29; P = 0.048). Frailty is associated with an increase in morbidity and mortality after colectomy in patients with UC. mFI is an easy-to-use tool and can play an important role in the risk stratification of these patients.

Frailty has been noted as a powerful predictive preoperative tool for 30-day postoperative complications. We sought to evaluate the association between frailty and postoperative outcomes after colectomy for Clostridium difficile colitis. The National Surgical Quality and Improvement Program cross-institutional database was used for this study. Data from 470 patients with a diagnosis of C. difficile colitis were used in the study. Modified frailty index (mFI) is a previously described and validated 11-variable frailty measure used with the National Surgical Quality and Improvement Program to assess frailty. Outcome measures included serious morbidity, overall morbidity, and Clavien IV (requiring ICU) and Clavien V (mortality) complications. The median age was 70 years and body mass index was 26.9 kg/m 2 . 55.6 per cent of patients were females. 98.5 per cent of patients were assigned American Society of Anesthesiologists Class III or higher. The median mFI was 0.27 (0–0.63). Because mFI increased from 0 (non-frail) to 0.55 and above, the overall morbidity increased from 53.3 per cent to 84.4 per cent and serious morbidity increased from 43.3 per cent to 78.1 per cent. The Clavien IV complication rate increased from 30.0 per cent to 75.0 per cent. The mortality rate increased from 6.7 per cent to 56.2 per cent. On a multivariate analysis, mFI was an independent predictor ofoverall morbidity (AOR: 13.0; P < 0.05), mortality (AOR: 8.8; P = 0.018), cardiopulmonary complications (AOR: 6.8; P = 0.026), and prolonged length of hospital stay (AOR: 6.6; P = 0.045). Frailty is associated with increased risk of complications in C. difficile colitis patients undergoing colectomy. mFI is an easy-to-use tool and can play an important role in the risk stratification of these patients who generally have significant morbidity and mortality to begin with.