Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.

PURPOSE: Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities. EXPERIMENTAL DESIGN: We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs. RESULTS: These studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurrence. Analyses of clinical databases revealed significant association of this transcriptional profile with worse overall survival and upregulation at recurrence. Notably, gene expression analyses identified upregulation of TGFß signaling, and more than one-hundred-fold increase in THY1 levels at recurrence. Furthermore, THY1-positive cells represented <10% of cells in treatment-naïve tumors, compared to 75-96% in recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples and determined that they were inherently resistant to chemoradiation in orthotopic models. Additionally, using image-guided biopsies from treatment-naïve human GBM, we conducted spatial transcriptomic analyses. This revealed rare THY1+ regions characterized by mesenchymal/stem-like gene expression, analogous to our recurrent mouse model, which co-localized with macrophages within the perivascular niche. We then inhibited TGFBRI activity in vivo which decreased mesenchymal/stem-like protein levels, including THY1, and restored sensitivity to TMZ/IR in recurrent tumors. CONCLUSIONS: These findings reveal that GBM recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive, mesenchymal cells within the perivascular niche.

Estrogen receptor status has no prognostic relevance in metaplastic breast carcinoma.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histologic variant of breast cancer characterized by the presence of glandular and non-glandular components. The prognostic significance of estrogen receptor (ER) status has been scarcely studied in these tumors. We therefore investigated the prognostic relevance of ER status in MBC within our patient population. DESIGN: We reviewed MBC cases (n = 125) between January 2000 and September 2019. Histologic slides were reviewed for variables including tumor morphology and hormonal status. Additional clinical information was obtained from the electronic medical records. RESULTS: Of the 125 patients, 15 (12%) had ER positive tumors and 110 (88%) had ER negative tumors. Eleven (73%) ER positive tumors had ER positivity > 10% and 4 (27%) had ER positivity ≤ 10%. ER positive tumors had a smaller median tumor size of 2.5 cm, compared with ER negative tumors with median tumor size 3.05 cm, however this difference was not statistically significant (P = 0.82). There were no statistical differences between ER positive and ER negative tumors in terms of histologic grade (P = 0.34), histologic subtype (P = 0.65), clinical stage (P>0.99) or human epidermal growth factor receptor 2 (HER2) expression (P = 0.29). There was also no difference in overall survival (OS) between ER positive and ER negative metaplastic breast cancers (HR = 0.35, 95% CI, 0.003-2.67, P = 0.39). CONCLUSION: Our experience suggests that ER positivity has no prognostic relevance in MBC. Regardless of ER expression status, there were no statistically significant differences in overall survival between ER positive and ER negative MBC.

COVID-19 Vaccine Hesitancy among Arab Americans.

(1) Background: Coronavirus disease-2019 (COVID-19) vaccines have a significant impact on reducing morbidity and mortality from infection. However, vaccine hesitancy remains an obstacle in combating the pandemic. The Arab American (AA) population is understudied; thus, we aimed to explore COVID-19 attitudes within this community. (2) Methods: This was a cross-sectional study. An anonymous online survey was distributed to members of different AA associations and to the community through the snowball method. (3) Results: A total of 1746 participants completed the survey. A total of 92% of respondents reported having received at least one dose of a COVID-19 vaccine. A total of 73% reported willingness to receive a booster, and 72% plan to give their children the vaccine. On multivariate analysis, respondents were more likely to be vaccine-hesitant if they were hesitant about receiving any vaccine in general. They were less likely to be vaccine-hesitant if they were immigrants, over the age of 40, up to date on their general vaccination and if they believed that COVID-19 vaccines are safe and effective in preventing an infection. The belief that all vaccines are effective at preventing diseases was also associated with lower hesitancy. (4) Conclusions: This sample of AAs have higher vaccination rates and are more willing to vaccinate their children against COVID-19 when compared to the rest of the population. However, a reemergence of hesitancy might be arising towards the boosters.

Clinicopathologic Characteristics and Outcome Descriptors of Metaplastic Breast Carcinoma.

CONTEXT.­: Metaplastic breast carcinoma is an aggressive form of breast cancer that accounts for 0.5% to 3% of all breast cancers. OBJECTIVE.­: To study the clinicopathologic characteristics and outcomes of this rare disease. DESIGN.­: Retrospective study of patients with a diagnosis of metaplastic breast carcinoma between 2000 and 2019. Hematoxylin-eosin-stained slides were reviewed and additional clinical data were obtained from electronic medical records. Univariable and multivariable Cox proportional hazard regression analyses were used to determine associations between overall survival and several clinicopathologic variables. RESULTS.­: Of the 125 patients with metaplastic breast carcinoma identified, only patients with high-grade disease (N = 115) were included in the data analysis. A total of 38 participants (33%) were white, 66 (57%) were African American, and 11 (10%) belonged to other ethnicities. The median age at diagnosis was 57 years. The median tumor size was 3 cm. Heterologous histology was seen in 30% of cases. Multivariable analyses showed that patients with a larger tumor size had worse overall survival (hazard ratio [HR], 1.25; 95% CI, 1.10-1.44; P < .001). Distant metastatic disease was also associated with worse overall survival on multivariable analysis (HR, 10.27; 95% CI, 2.03-55.54; P = .005). In addition to treatment with either partial or complete mastectomies, 84 patients (73%) received chemotherapy. Multivariable analyses showed that chemotherapy had no effect on overall survival (HR, 0.53; 95% CI, 0.09-6.05; P = .55). CONCLUSIONS.­: A larger tumor size and distant metastatic disease are associated with worse overall survival in patients with metaplastic breast carcinoma. Additional studies are needed to further characterize our findings.

Evaluation of COVID-19 Vaccine Attitudes among Arab American Healthcare Professionals Living in the United States.

BACKGROUND: Vaccine hesitancy is the next great barrier for public health. Arab Americans are a rapidly growing demographic in the United States with limited information on the prevalence of vaccine hesitancy. We therefore sought to study the attitudes towards the coronavirus disease 2019 (COVID-19) vaccine amongst Arab American health professionals living in the United States. METHODS: This was a cross sectional study utilizing an anonymous online survey. The survey was distributed via e-mail to National Arab American Medical Association members and Arab-American Center for Economic and Social Services healthcare employees. Respondents were considered vaccine hesitant if they selected responses other than a willingness to receive the COVID-19 vaccine. RESULTS: A total of 4000 surveys were sent via e-mail from 28 December 2020 to 31 January 2021, and 513 responses were received. The highest group of respondents were between the ages of 18-29 years and physicians constituted 48% of the respondents. On multivariable analysis, we found that respondents who had declined an influenza vaccine in the preceding 5 years (p < 0.001) and allied health professionals (medical assistants, hospital administrators, case managers, researchers, scribes, pharmacists, dieticians and social workers) were more likely to be vaccine hesitant (p = 0.025). In addition, respondents earning over $150,000 US dollars annually were less likely to be vaccine hesitant and this finding was significant on multivariable analysis (p = 0.011). CONCLUSIONS: Vaccine hesitancy among health care providers could have substantial impact on vaccine attitudes of the general population, and such data may help inform vaccine advocacy efforts.

Human Papillomavirus Infection and Cervical Dysplasia in a Subset of Arab American Women.

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women. Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing. Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as "negative for intraepithelial lesion," the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01-338.62; p < 0.001). One hundred twenty-five (29%) women were tested for high-risk HPV serotypes; 106 (91%) had negative results, 4 (3%) were positive for HPV-16, 7 (6%) were positive for other high-risk serotypes, and 8 results were not recorded. A negative HPV screen was significantly associated with a negative Pap smear (Fisher's exact test p = 0.006). There was no significant association between abnormal cervical cytology and evaluated socioeconomic factors. Conclusions: Additional population based-studies to determine cervical dysplasia/cancer and HPV prevalence in women of Middle Eastern descent are needed.

Characteristics and distribution of obesity in the Arab-American population of southeastern Michigan.

BACKGROUND: Arab-Americans constitute ~ 5% of Michigan's population. Estimates of obesity in Arab-Americans are not up-to-date. We aim to describe the distribution of and factors associated with obesity in an Arab-American population in Southeastern Michigan (SE MI). METHODS: Retrospective medical record review identified n = 2363 Arab-American patients seeking care at an Arab-American serving clinic in SE MI, located in a city which is home to a large proportion of Arab-Americans in the United States (US). Body mass index (BMI) was the primary outcome of interest. Distribution of BMI was described using percentages, and logistic regression models were constructed to examine the association between obesity, other comorbid conditions and health behaviors. This cohort was compared to Michigan's Behavioral Risk Factor Surveillance System (BRFSS) data from 2018 (n = 9589) and to a cohort seeking care between 2013 and 2019 from a free clinic (FC) located in another city in SE MI (n = 1033). RESULTS: Of the 2363 Arab-American patients, those who were older or with HTN, DM or HLD had a higher prevalence of obesity than patients who were younger or without these comorbidities (all p-value < 0.001). Patients with HTN were 3 times as likely to be obese than those without HTN (95% CI: 2.41-3.93; p < 0.001). Similarly, the odds of being obese were 2.5 times higher if the patient was diabetic (95% CI: 1.92-3.16; p < 0.001) and 2.2 times higher if the patient had HLD (95% CI: 1.75-2.83; p < 0.001). There was no significant difference in obesity rates between Arab-Americans (31%) and the BRFSS population (32.6%). Compared to Arab-Americans, patients seen at the FC had a higher obesity rate (52.6%; p < 0.001) as well as significantly higher rates of HTN, DM and HLD (all p < 0.001). CONCLUSION: Overall obesity rates in Arab-Americans were comparable to the population-based BRFSS rates, and lower than the patients seen at the FC. Further studies are required to understand the impact of obesity and the association of comorbidities in Arab-Americans.