Search

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.

Objectives: Uterine serous (USC) and clear cell carcinoma (CC) are aggressive variants of endometrial cancer (EC), comprising only 20% of all cases, but accounting for a disproportionately high number of EC related deaths. The molecular profile of USC and CC is distinct from that of other EC, displaying alternations in TP53 and HER2/neu. Human epidermal growth factor receptor 2/neu (HER2) is a key player in singling for cancer cell growth, survival and proliferation. Recent data demonstrates a survival benefit with the use of trastuzumab, a monoclonal antibody against HER2, in combination with chemotherapy for HER2 expressing USC. However, the clinical implications of HER2 status on prognosis remain unclear. Methods: A multicenter retrospective analysis of patients with USC and CC was conducted from 2000 - 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for HER2 assessment via immunohistochemistry (IHC). HER2 positive was defined as IHC score of 3+. Platinum sensitivity was defined as recurrence >6 months from last platinum-based therapy. Differences in the frequencies of stage, race, chemosensitivity and sites of disease recurrence were identified using Pearson's chi-square test. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: HER2 status was evaluated in 56 patients. Histology included 44 (79%) USC, 9 (16%) CC and 3 (6%) mixed serous-clear cell. 11 (19.6%) were positive for HER2; 18.2% USC, 22.2% CC and 33.3% mixed histology. Of these 56 patients, 50 had follow-up information available for review and were included in final analysis. The mean age was 67-years and the majority of patients were African American (88%). Stage distribution included 38% stage I, 8% stage II, 18% stage III and 36% stage IV. 29 (58%) patients recurred during the study period, 7 (70%) of the HER2 positive and 22 (55%) of the HER2 negative cohort (p=0.390). The most common location of recurrence was the abdomen followed by the pelvis and extra-abdominopelvic sites. There was no difference in the stage (p=0.471), race (p=0.323) or distribution of recurrence sites (p=0.813) between HER2 positive and negative tumors. Platinum sensitivity was significantly improved in HER negative (65%) vs. HER2 positive tumors (30%) (p=0.044). For the entire cohort, the median PFS was 21 months and the median OS was 29 months. The median PFS and OS did not differ significantly based on HER2 status (p=0.229 and p=0.255, respectively). However, there was a clinically relevant trend towards improved PFS (26 vs. 7 months) and OS (35 vs. 14 months) in HER2 negative vs. positive tumors. On MVA, platinum sensitivity (p Download : Download high-res image (140KB) Download : Download full-size image Conclusions: In addition to being a tool to guide targeted therapy, HER2 is a valuable prognostic marker in USC and CC. Expression is associated with significantly lower platinum sensitivity and inferior survival compared to tumors not expressing HER2.

INTRODUCTION Von Willebrand Disease (vWD) is the most common hereditary hemorrhagic disorder with diverse clinical and genetic characteristics. Transmitted as an autosomal dominant trait (except Type III), it is caused primarily by the quantitative or qualitative deficiency of von Willebrand factor (vWF). ABO blood group types can affect the pathology, severity and hence the presentation of this clinically heterogeneous entity as the genes responsible for ABO blood groups also affects vWF levels in the plasma. We conducted a study to analyze and compare different clinico-demographic aspects among O and non-O blood group patients with Von Willebrand Disease. Our primary aim was to determine the relationship of different blood groups with venous thromboembolism (VTE) in patient with vWD. Our secondary aim was to determine the association of blood groups with different comorbid conditions such as coronary artery disease, cerebrovascular disease, peripheral vascular disease, chronic liver disease, chronic kidney disease etc. in patients with vWD. METHODS A retrospective review was carried out to include all patients diagnosed with Von Willebrand Disease from year 2002 to 2012. Patient population was obtained by using International Classification of Diseases, 9th revision (ICD9) codes. Data was collected with the help of electronic medical records. Multiple clinical variables and demographic characteristics of Von Willebrand Disease patients (n=381) were analyzed and compared between those with type O blood group (205 patients; 54%) and those with type non-O blood groups (176 patients; 46%). Univariate logistic regression was used to obtain crude odds ratios. Predictors with statistically significant p-values were included in a multivariable logistic regression model in order to yield adjusted odds ratio. Statistical significance was set at p RESULTS Patients with O blood groups were less likely to develop VTE (OR 0.29, 95% CI 0.16-0.52, p < 0.001) as compared to Non-O blood groups in which the prevalence of VTE was much higher (25% vs. 9%). Additionally, patients with O blood groups had relatively lower factor 8 activity (125.9±90.8%; OR 0.99, 95% CI 0.99-1.00, p = 0.018) when compared with Non-O blood groups (168.5±120.6%). Patients with O-blood group had significant, life threatening bleeds at an early age (40.4±20.8 years; OR 0.99, 95% CI 0.97-1.00, p = 0.008) when compared with patients with type non-O blood group (Age 47.1±21.9 years). Additionally, O-Blood groups were related to a lesser prevalence of cerebrovascular disease (OR 0.48, 95% CI 0.29-0.79, p = 0.004) and peripheral vascular disease (OR 0.47, 95% CI 0.25-0.87, p = 0.015) as compared to Non-O blood groups. DISCUSSION Our study consolidates the fact that vWD patients with O blood group have a lesser risk of developing VTE as compared to non-O blood group patients. Additionally, strokes and peripheral vascular disease is also seen less frequently in O blood groups in patients with Von Willebrand disease. These results suggest that the genes responsible for ABO blood groups also have a significant effect on clinical outcomes in patients with vWD. There are multiple proposed mechanisms to explain this association including presence of ABO antigens on several platelet glycoproteins and glycosphingolipids as well as on the surface of vascular endothelium. More sophisticated, large-scale studies are needed to strengthen the associations we observed in our retrospective study. Disclosures Kuriakose: Kedrion: Speakers Bureau.