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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.

Highlights • Approximately one-fifth of uterine serous carcinomas (USC) will express WT-1. • WT-1 expression is associated with a significant improvement in platinum sensitivity. • Improved platinum sensitivity among WT-1 positive tumors contributes to a superior PFS vs. WT-1 negative tumors., Background Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), historically thought to rarely express WT1. However, more recent data indicates a significant percentage of USC may express WT1. The clinical implications of WT1 positivity in USC remain unclear. Methods A multicenter retrospective analysis of patients with USC was conducted from 2000 to 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Chemosensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. 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 WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. There was no difference in the stage (p = 0.158), race (p = 0.227) or distribution of recurrence sites (p = 0.581) between WT1 positive and WT1 negative tumors. The majority of patients were chemosensitive (63%). Chemosensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p = 0.016). We observed a trend towards improved PFS among WT1 positive tumors (21 vs. 16-months, respectively) (p = 0.544). On MVA, stage (p

BackgroundAfrican-Americans/Blacks have suffered higher morbidity and mortality from COVID-19 than all other racial groups. This study aims to identify the causes of this health disparity, determine prognostic indicators, and assess efficacy of treatment interventions.MethodWe performed a retrospective cohort study of clinical features and laboratory data of COVID-19 patients admitted over a five-week period at the height of the pandemic in the United States. This study was performed at an urban academic medical center in New York City, declared a COVID-only facility, serving a majority Black populationResultOf the 1,070 consecutive patients who tested positive for COVID-19, 496 critically ill patients were hospitalized and included in the study. 88% of patients were Black; and a majority (53%) were 61-80 years old with a mean body mass index in the “obese” range. 97% had one or more comorbidities. Hypertension was the most common (84%) pre-existing condition followed by diabetes mellitus (57%) and chronic kidney disease (24%). Patients with chronic kidney disease and end-stage renal disease who received hemodialysis were found to have significantly lower mortality, then those who did not receive it, suggesting benefit from hemodialysis (11%, OR, 0.35, CI, 0.17 - 0.69 P=0.001). Age >60 years and coronary artery disease were independent predictors of mortality in multivariate analysis. Cox Proportional Hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. CRP (180, 283 mg/L), LDH (551, 638 U/L), glucose (182, 163 mg/dL), procalcitonin (1.03, 1.68 ng/mL), and neutrophil / lymphocyte ratio (8.5, 10.0) were predictive of mortality on admission and at 48-96 hrs. Of the 496 inpatients, 48% died, one third of patients died within the first three days of admission. 54/488 patients received invasive mechanical ventilation, of which 87% died and of the remaining patients, 32% died.CONCLUSIONSCOVID-19 patients in our predominantly Black neighborhood had higher mortality, likely due to higher prevalence of comorbidities. Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes. Early escalation of care based on comorbidities and key laboratory indicators is critical for improving outcomes in African-American patients.

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.

Objectives: Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma (OSC) and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), traditionally thought to rarely express WT1. However, recent data indicates a significant percentage of USC may express WT1, limiting its use as a differentiating marker between these two tumors. Additionally, the clinical implications of WT1 positivity in USC remain unclear. Methods: A multicenter retrospective analysis of patients with USC was conducted from 2000 - 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Platinum-sensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. 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: WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Of these 61 patients, 56 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 (97%). Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. The majority of patients were designated as platinum-sensitive (63%). 36 (64%) patients recurred during the study period, 8 (62%) of the WT1 positive and 28 (65%) of the WT1 negative cohort. 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=0.158), race (p=0.227) or distribution of recurrence sites (p=0.581) between WT1 positive and WT1 negative tumors. Platinum-sensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p=0.016). For the entire cohort, the median PFS was 20 months and the median OS was 29 months. The median PFS and OS did not differ significantly based on WT1 status (p=0.544 and p=0.759, respectively). However, we did observe a trend towards improved PFS among WT1 positive tumors (21 vs. 16 months, respectively). On MVA, stage (p Download : Download high-res image (147KB) Download : Download full-size image Conclusions: WT1 positivity is observed in over 20% of USC, limiting its utility to differentiating OSC and USC. Additionally, WT1 status holds prognostic significance as expression was associated with improved platinum-sensitivity and a clinically significant 5-month improvement in PFS.

Objective We assessed the prognostic value of histomorphologic features of lymph node (LN) metastases in patients with prostate cancer treated with radical prostatectomy Materials and Methods We evaluated the effect of the features of LN metastasis on the risk of biochemical recurrence (BCR) in 280 LN-positive patients who underwent radical prostatectomy between 2006 to 2018. LN specific parameters recorded included number of metastatic LNs, size of the largest metastatic focus, Gleason Grade (GG) of the metastatic focus, and extranodal extension (ENE). Results A solitary positive LN was found in 166/280 (59%), 95/280 (34%) patients had 2-4 positive LNs, and 19/280 (7%) had 5 or more positive LNs. The size of the largest metastatic focus > 2 mm (macrometastasis) in 154/261 (59%). GG of the metastatic focus was as follows: GG 1-2: 29/224 (13%); GG 3: 27/224 (12%); and GG 4-5: 168/224 (75%). ENE was identified in 99/244 (41%). We found the number of LNs positive (2-4 vs. 1 Hazard ratio (HR) = 1.60; 95% CI: 1.02 to 2.5; P = 0.04) and GG of the metastatic focus (GG 4&5 vs. 1-3 HR = 1.90; 95% CI: 1.14-3.2; P= 0.014) to be independent predictors of the risk of BCR after surgery on multivariate analysis. Conclusions Our study showed the number of LNs positive and GG of the LN metastatic focus to be significant independent predictors of BCR after radical prostatectomy. We recommend reporting histomorphologic parameters of LN metastasis as they may help in defining BCR risk categorization.

Introduction/Objective Recent reports suggest that though COVID-19 is predominantly a respiratory pathogen, one of its presenting features can be gastrointestinal symptoms. We hereby present a case of a female with COVID-19 infection whose hospital course was complicated by colonic pseudo-obstruction caused by pseudomembranous colitis resulting in an emergent hemicolectomy. Methods A 59-Year-old female with history of hypertension, diabetes, and breast cancer post mastectomy presented with pneumonia and was confirmed to be COVID-19 positive. She was admitted to the hospital and was treated with Azithromycin for 6 days. Patient developed constipation on day six of hospitalization and started having abdominal pain on day eight with elevated WBC count. Imaging showed distension of cecum and proximal colon. She underwent exploratory laparotomy which revealed a necrotic appearing cecum that was massively dilated and had a serosal tear. These findings prompted emergent hemicolectomy with loop ileostomy. Grossly cecum was black/green, dilated, thin walled with a 5 x 5 cm yellow green raised plaques. Microscopy of the plaques revealed focal erosion of colonic mucosa with overlying acute inflammatory cells, fibrin deposits, mucus, and necrotic epithelial cells consistent with pseudomembranous colitis. Conclusion Review of literature shows no reported cases of intestinal pseudo-obstruction due to pseudomembranous colitis in a COVID-19 patient. Not only this, but there are also only a limited number of case studies of pseudomembranous colitis presenting as intestinal pseudo-obstruction without diarrhea. Though this patient’s presentation could be from Clostridium difficile infection secondary to Azithromycin, it is not a common antibiotic to cause this. Also, one of the known causes of pseudomembranous colitis is ischemia. Given that COVID-19 infection is a pro-thrombotic condition, possible ischemia secondary to COVID-19 infection related coagulopathy should also be a consideration.

Rationale: Lung cancer is a leading cause of cancer-related deaths. Smoking is major risk factor for initial and subsequent lung cancer especially in active smokers. Treatment of subsequent lung cancer depends on whether it is synchronous or metachronous. We report a rare case of triple metachronous lung cancer and review of literature of patients with triple metachronous cancers. This will be the second case reported of triple metachronous lung cancer. Patient concerns: A 60-year-old male, active smoker with diabetes mellitus, chronic obstructive pulmonary disease (COPD) and peripheral arterial disease presented with cough and hemoptysis. Initial computed tomography (CT) scan showed right upper lobe spiculated mass. Diagnosis: He underwent transthoracic needle biopsy for right upper lobe mass, showing primary lung adenocarcinoma (ADC)-Stage-IIIA. He continued to smoke and 9-years later had new left upper lobe spiculated nodule, which on surgical resection showed squamous cell carcinoma (SCC)-Stage-IA1. Despite counselling on smoking cessation, he was unable to quit. Six months later, he presented with shortness of breath and CT chest showing right hilar adenopathy in right upper and lower lobes. He underwent transbronchial biopsies of lesion which showed small cell lung carcinoma (SCLC). Interventions: His initial lung ADC-Stage-IIIA, was treated with chemotherapy, weekly thoracic radiation and additional chemotherapy cycles. Nine years later, his left upper lobe mass showing SCC-Stage-IA1 was deemed curative after apical resection and he was kept on surveillance. Six months later, after diagnosis of SCLC in right upper and lower lobe, patient was not a candidate for systemic chemotherapy due to poor performance status and opted for hospice care. Outcomes: His initial lung ADC-Stage-IIIA showed complete radiological response with chemotherapy and radiation. Subsequent SCC-Stage-IA1 was deemed curative after resection. Due to his poor performance status, he was not a candidate for chemotherapy for SCLC and patient opted for hospice care. Lessons: Smoking is a major risk factor for developing lung cancer and with continued smoking, patients are at higher risk for developing subsequent primary lung cancers. We recommend, patients with lung cancer must quit smoking, and those who do not, should remain on long-term surveillance.

INTRODUCTION AND OBJECTIVES:To determine the association between the number of positive lymph nodes (LN), extranodal extension (ENE), size and Grade Group (GG) of metastatic focus (MET) in in the L...

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.