Search

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were 2 types) were found in 11/40 (27.5%) patients. Patients infected with non-16/18 genotypes, including the most common genotype, HPV 35, had significantly shorter DFS and OS. PD-L1 (p=0.003), MMR expression (p=0.01), clinical stage (p=0.048), histologic grade (p=0.015) and mixed HPV infection (p=0.026) were independent predictors of DFS. A remarkably high proportion of cervical cancer cells in our patients expressed PD-L1 which opens the possibility of the use of immune checkpoint inhibitors to treat these cancers. Exclusion of the common HPV genotypes from the vaccine exacerbates mortality from cervical cancer in underserved Black patients.

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were

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.

Background Distinguishing well-differentiated hepatocellular carcinoma (WD-HCC), hepatocellular adenoma (HA) and non-neoplastic liver tissue (NNLT) solely on morphology is often challenging. The purpose of this study was to evaluate the use of computational image analysis to distinguish WD-HCC, HA and NNLT. Methods Seventy-seven cases comprising of WD-HCC (n = 26), HA (n = 23) and NNLT (n = 28) were retrieved and reviewed. A total of 485 hematoxylin and eosin (H&E) photomicrographs (× 400, 0.09 µm2) of WD-HCC (n = 183), HA (n = 173), NNLT (n = 129) and nine whole-slide scans (three of each diagnosis) were obtained, color deconvoluted and digitally transformed. Quantitative data including nuclear density, nuclear sphericity, nuclear perimeter, and nuclear eccentricity from each image were acquired. The data were analyzed by one-way analysis of variance (ANOVA) with Tukey post hoc test, followed by unsupervised and supervised (Chi-square automatic interaction detection (CHAID)) cluster analysis. Results Unsupervised cluster analysis identified three well defined clusters of WD-HCC, HA and NNLT. Employing the four most discriminating nuclear features, supervised analysis was performed on a training set of 383 images, and validated on the remaining 102 test images. The analysis identified WD-HCC (sensitivity 100%, specificity 98%), HA (sensitivity 71%, specificity 85%) and NNLT (sensitivity 70%, specificity 86%). An analysis of whole-slide images identified WD-HCC with sensitivity and specificity of 100%. Conclusions We have successfully demonstrated that computational image analysis of nuclear features can differentiate WD-HCC from non-malignant liver with high accuracy, and can be used to assist in the histopathological diagnosis of hepatocellular carcinoma.

Pancreatic ductal carcinoma has a 5-year survival rate of 9%. This makes it the 4th leading cause of cancer-related death in the United States. Advanced-stage diagnosis and limited treatment options contribute to poor prognosis. Thus, there is an urgent need for new approaches to treatment. Enhancer of Zeste 2 (EZH2), a catalytic subunit of the multi-protein histone methyltransferase, known as the polycomb repressive complex, has been implicated in carcinogenesis. E2H2's downregulation has been shown to have a therapeutic effect in B cell lymphomas.We examined the effect of EZH2 downregulation in combination with irradiation on the proliferation and apoptosis of pancreatic cancer cells (PANC-1 and MIA PaCa-2)EZH2 downregulation resulted in the decreased proliferation of PANC-1 and MIA PaCa-2 cells within short-term assays with maximal reduction at 72 hr. Irradiation reduced cell proliferation beginning at 96 hr and continued over the long-term. Irradiation with EZH2 downregulation reduced cell proliferation between 48 and 72 hr. This combined treatment reduced cell proliferation by 3 to 14% as compared to those treated with irradiation alone at two weeks. PANC-1 and MIA PaCa-2 cells exhibited similar responses to EZH2 downregulation and irradiation, but to different degrees. siRNA or EPZ were equally effective in EZH2 downregulation.EZH2 downregulation in combination with irradiation reduces PANC-1 and MIA PaCa-2 cell proliferation more than irradiation alone. This study affirms the role of EZH2 downregulation for radiosensitization in pancreatic cancer treatment.

INTRODUCTION: Prone positioning is a cornerstone therapy in COVID-19 associated severe Acute Respiratory Distress Syndrome (ARDS) Ventilatory ratio (VR) calculates dead space ventilation, which is independently associated with an increased risk of mortality in ARDS patients However, no studies so far have demonstrated the changes in VR with proning in such patients We evaluated VR as a new tool to predict survival in prone positioned COVID -19 ARDS patients METHODS: This retrospective study included 24 COVID-19 positive ARDS patients admitted to SUNY Downstate Medical Center ICU between April 4, 2020 to May 15, 2020, who had PaO2/FiO2 (PF) ratio 2 The mortality rate for all patients included was 80% (20/24) CONCLUSIONS: COVID -19 ARDS patients demonstrate impaired ventilation and hypoxemia Commonly used PF ratio, in proning protocols, has limited prognostic value but deadspace fraction is a powerful predictor of mortality in ARDS Proning improved PF ratio and VR, however, the latter did not reach statistical significance PF ratio was not predictive of length of survival, however, VR > 2 before proning is a significant predictor for overall mortality Hence, VR can function as a new bedside predictive tool with proning in COVID-19 ARDS patients

Recombinant human TNFα (rhTNFα) has previously been shown to reduce fecundity in Schistosoma mansoni adult females maintained in vitro without males, and adversely affect the uptake of [14C]-tyrosine, an amino acid required for schistosome vitellogenesis. Here we report on the effect of rhTNFα on [14C]-methionine uptake in both separated and paired females, and the effect of three different preparations of rTNFα on schistosome oviposition in vitro. In the absence of rhTNFa, separated females incorporated only 30% of the [14C]-methionine incorporated by paired females in a dose and time-dependent manner, suggesting low metabolic activity of females in the absence of males. Separated females and worm-pairs were treated with increasing doses of rhTNFα for 2 or 4 hr and then incubated in RPMI 1640 containing 10% fetal calf serum (FCS) and 5 µCi ml-1[14C]-methionine for 1 hr. Separated females treated with rhTNFa for 4 hr incorporated less methionine than those treated for 2 hr. In contrast, paired females treated with rhTNFa incorporated significantly smaller amounts of [14C]-methionine in a TNFa dose-dependent but time-independent manner [2 hr (P = 0.001) or 4 hr (P = 0.027) One-Way ANOVA]. Worm-pairs maintained in RPMI 1640 containing 10% FCS and 100 ng ml-1 of any of the three rTNFa preparations laid significantly fewer eggs than the worms cultured without rTNFα(P = 0.001; Kruskal-Wallis Test). We also observed that among rTNFα-treated worm-pairs, females were sluggish and tended to separate from their male partners. These observations suggest that TNFa inhibits [14C]-methionine uptake and reduces fecundity in females paired with males. Since paired females incorporate substantially greater amounts of [14C]-methionine, the role of males in stimulating metabolic activity in females is affirmed. Reduced amino acid uptake, and possibly other nutrients, may contribute to the diminished fecundity observed in TNFa-treated females.

EZH2 is a polycomb group protein that is involved in the progression of multiple human cancers including prostatic, endometrial, and colonic adenocarcinomas. Its expression has been shown to increase from typical carcinoid to atypical carcinoid and further to small cell/large cell neuroendocrine carcinomas of the lung. Here we examine the EZH2 expression and the proliferation index (PI) by Ki-67 expression in neuroendocrine tumors of the gastrointestinal tract (GI) and pancreas. We retrieved 72 cases of GI and pancreatic neuroendocrine tumors of grades G1 (n = 56), G2 (n = 6) and G3 (n = 10) which were graded according to the WHO classification. Expression of EZH2 and Ki-67 was analyzed by immunohistochemistry using monoclonal antibodies (EZH2 at 1:200; Ki-67 at 1:70). Expression of EZH2 was determined to be low (10%), and was compared with the respective PI. All G1 tumors had low EZH2 expression and a low PI (20%). In G2 tumors, EZH2 expression was intermediate (1-10%) and PI was between 0-8%. One of the G2 tumors had a low PI of 0, however, the EZH2 expression was intermediate (3%). There was increased EZH2 expression relative to increasing tumor grade from G1 to G3 (p EZH2 expression increases incrementally from G1 neuroendocrine tumors to G2 and further to G3 tumors, suggesting an association or a role in progression of neuroendocrine tumors. There is strong correlation between the expression of EZH2 and PI in G1, G2 and G3 tumors. EZH2 appears to be a better predictor of tumor grade in G2 tumors as compared to PI. Thus, EZH2 could be used as an additional diagnostic marker in examining atypical GI neuroendocrine tumors. Citation Format: Jia Qin, Raag Agrawal, Miguel G. Echevarria, LAura A. Martello, M.A Haseeb, Raavi Gupta. Enhancer of zeste homolog 2 (EZH2) expression and proliferation index (Ki-67) in neuroendocrine tumors of the gastrointestinal tract and pancreas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3406. doi:10.1158/1538-7445.AM2015-3406