Imaging characteristics of interval cancers detected on Full Field Digital Mammography (FFDM) versus Digital Breast Tomosynthesis (DBT).

OBJECTIVE: To compare imaging features of interval cancers detected in patients screened with full field digital mammography (FFDM) versus digital breast tomosynthesis (DBT). MATERIALS/METHODS: This retrospective observational study consisted of female patients undergoing screening DM or FFDM at an academic medical center and two outpatient imaging facilities between January 2012 and June 2017. A natural language processing algorithm queried breast imaging reports for breast density and BI-RADS category. This was cross-referenced to an institutional breast cancer registry to identify interval cancers. Retrospective consensus review of the cases was done to categorize imaging features of interval cancers on FFDM vs DBT. RESULTS: The rate of interval cancers was comparable in patients screened with FFDM (30/39793) and DBT (29/32180) (p = 0.58). There was no significant difference in the rate, histopathology, or imaging features of interval cancers in patients screened with FFDM versus DBT. The most common mammographic features on diagnostic imaging across both groups was the presence of a mass (13/47). Almost equally common was negative diagnostic mammogram with mass detected only on ultrasound (11/47). The rate of interval cancers detected by high-risk surveillance breast MRI was increased in patients who previously had screening with DBT relative to those who had screening with FFDM (p = 0.0419). CONCLUSION: There is no significant difference in rate of detection, histopathology, or imaging features of interval cancers in patients screened with FFDM versus DBT. However, across both cohorts, the most common features on diagnostic mammogram were either the presence of a mass or a negative mammogram.

Pod-based e-liquids impair human vascular endothelial cell function.

Pod-based electronic (e-) cigarettes more efficiently deliver nicotine using a protonated formulation. The cardiovascular effects associated with these devices are poorly understood. We evaluated whether pod-based e-liquids and their individual components impair endothelial cell function. We isolated endothelial cells from people who are pod users (n = 10), tobacco never users (n = 7), and combustible cigarette users (n = 6). After a structured use, pod users had lower acetylcholine-mediated endothelial nitric oxide synthase (eNOS) activation compared with never users and was similar to levels from combustible cigarette users (overall P = 0.008, P = 0.01 pod vs never; P = 0.96 pod vs combustible cigarette). The effects of pod-based e-cigarettes and their constituents on vascular cell function were further studied in commercially available human aortic endothelial cells (HAECs) incubated with flavored JUUL e-liquids or propylene glycol (PG):vegetable glycerol (VG) at 30:70 ratio with or without 60 mg/mL nicotine salt for 90 min. A progressive increase in cell death with JUUL e-liquid exposure was observed across 0.0001-1% dilutions; PG:VG vehicle with and without nicotine salt induced cell death. A23187-stimulated nitric oxide production was decreased with all JUUL e-liquid flavors, PG:VG and nicotine salt exposures. Aerosols generated by JUUL e-liquid heating similarly decreased stimulated nitric oxide production. Only mint flavored e-liquids increased inflammation and menthol flavored e-liquids enhanced oxidative stress in HAECs. In conclusion, pod e-liquids and their individual components appear to impair endothelial cell function. These findings indicate the potential harm of pod-based devices on endothelial cell function and thus may be relevant to cardiovascular injury in pod type e-cigarette users.

Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury.

BACKGROUND: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. METHODS: We analyzed CAC levels in 324 healthy participants aged 21-45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users (n = 65), sole e-cigarette users (n = 19), sole combustible cigarette users (n = 212), and dual users (n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. RESULTS: The cohort was 47% female, 51% Black/African American, with a mean (± SD) age of 31 ± 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q ⩽ 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q ⩽ 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q ⩽ 0.05). CONCLUSION: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Breast Malignancies After Mastectomy With Autologous or Implant Reconstruction.

There are multiple indications for mastectomy for breast cancer, including extent of tumor, inability to achieve negative margins after re-excision, patient preference, or prevention in women with a high lifetime risk of breast cancer. Multiple types of autologous or implant reconstruction options are available for cosmesis. Although rare, breast cancers after mastectomy can occur, and it is important for both surgeons and radiologists to be aware of the associated risk factors, common locations, and classic imaging features of these malignancies. This article reviews the types of mastectomies, reconstruction options, and information about the location, presentation, and prognosis of cancers in the reconstructed breast.

Lipid profiles in users of combustible and electronic cigarettes.

Electronic cigarette use has especially risen among adolescents and young adults. The aim of this study was to investigate fasting blood glucose and lipid profiles in chronic combustible cigarette and electronic cigarette users. We evaluated participants aged 21 to 45 (n = 525, mean age 31 ± 7 years, 45% women) without established cardiovascular disease or risk factors who were combustible cigarette users (n = 290), electronic cigarette users (n = 131; 65 sole users and 66 dual users), or never users (n = 104). In the first wave of enrollment (2014-2017), electronic cigarette users reported their products as first, second and third generation devices (e-cig users) and were all largely current (i.e., dual) or former (sole) combustible cigarette users, whereas in the second wave of enrollment (2019-2020), electronic cigarette users all reported pod-based device use (pod users) and included more sole users who were never smokers. In multivariable-adjusted analyses comparing to never users, both sole e-cig users and combustible cigarette users had higher glucose and triglycerides and lower high-density lipoprotein (HDL) cholesterol levels. Dual e-cig users showed higher triglycerides and very-low-density lipoprotein cholesterol, and lower HDL cholesterol compared to never users. In contrast, pod users (both sole and dual) had lipid profiles and glucose levels similar to never users. Overall, users of early generation electronic cigarettes display adverse metabolic profiles. In contrast, pod-based electronic cigarette users have similar lipid profiles to never users. Future studies are needed to understand the cumulative effects of electronic cigarette use on cardiometabolic health.

Alterations in Vascular Function Associated With the Use of Combustible and Electronic Cigarettes.

Background Electronic cigarettes (e-cigarettes) have been proposed as a potential harm reduction tool for combustible cigarette smokers. The majority of adult e-cigarette users continue to smoke combustible cigarettes and are considered dual users. The vascular impact of e-cigarettes remains incompletely defined. Methods and Results We examined the association of e-cigarette use with measures of vascular function and tonometry, preclinical measures of cardiovascular injury. As part of the CITU (Cardiovascular Injury due to Tobacco Use) study, we performed noninvasive vascular function testing in individuals without known cardiovascular disease or cardiovascular disease risk factors who were nonsmokers (n=94), users of combustible cigarettes (n=285), users of e-cigarettes (n=36), or dual users (n=52). In unadjusted analyses, measures of arterial stiffness including carotid-femoral pulse wave velocity, augmentation index, carotid-radial pulse wave velocity, and central blood pressures differed across the use groups. In multivariable models adjusted for age, sex, race, and study site, combustible cigarette smokers had higher augmentation index compared with nonusers (129.8±1.5 versus 118.8±2.7, P=0.003). The augmentation index was similar between combustible cigarette smokers compared with sole e-cigarette users (129.8±1.5 versus 126.2±5.9, P=1.0) and dual users (129.8±1.5 versus 134.9±4.0, P=1.0). Endothelial cells from combustible cigarette smokers and sole e-cigarette users produced less nitric oxide in response to A23187 stimulation compared with nonsmokers, suggestive of impaired endothelial nitric oxide synthase signaling. Conclusions Our findings suggest that e-cigarette use is not associated with a more favorable vascular profile. Future longitudinal studies are needed to evaluate the long-term risks of sustained e-cigarette use.

Diesel exhaust particles dysregulate multiple immunological pathways in murine macrophages: Lessons from microarray and scRNA-seq technologies.

Exposure to ambient particulate matter has been shown to promote a variety of disorders, including cardiovascular diseases predominantly of ischemic etiology. However, the mechanisms linking inhaled particulates with systemic vascular effects, resulting in worsened atherosclerosis, are not well defined. We assessed the potential role of macrophages in translating these effects by analyzing gene expression patterns in response to diesel exhaust particles (DEP) at the average cell level, using Affymetrix microarrays in peritoneal macrophages in culture (in vitro), and at the individual cell level, using single-cell RNA sequencing (scRNA-seq) in alveolar macrophages collected from exposed mice (in vivo). Peritoneal macrophages were harvested from C57BL/6J mice and treated with 25 µg/mL of a DEP methanol extract (DEPe). These cells exhibited significant (FDR < 0.05) differential expression of a large number of genes and enrichment in pathways, especially engaged in immune responses and antioxidant defense. DEPe led to marked upregulation of heme oxygenase 1 (Hmox1), the most significantly upregulated gene (FDR = 1.75E-06), and several other antioxidant genes. For the in vivo work, C57BL/6J mice were subjected to oropharyngeal aspiration of 200 µg of whole DEP. The gene expression profiles of the alveolar macrophages harvested from these mice were analyzed at the single-cell level using scRNA-seq, which showed significant dysregulation of a broad number of genes enriched in immune system pathways as well, but with a large heterogeneity in how individual alveolar macrophages responded to DEP exposures. Altogether, DEP pollutants dysregulated immunological pathways in macrophages that may mediate the development of pulmonary and systemic vascular effects.

Evaluation of Hormone Receptor Status (ER/PR/HER2-neu) in Breast Cancer in Pakistan.

OBJECTIVE: To evaluate the biological markers that are commonly assessed in breast cancer to estimate a patient's response to endocrine therapy and their prognosis for better clinical outcomes. METHODS: The retrospective study was conducted at Bahawalpur Institute of Nuclear Oncology and comprised record of early breast cancer patients who gave positive diagnostic tests for hormone receptors status i.e. immunohistochemical test and were treated during 2007-2013. Data of oestrogen, progesterone and human epidermal growth factor receptor 2 expression status was analysed. SPSS 12 was used for statistical analysis. RESULTS: Overall record of 345 patients was studied of whom 149(43%) were identified to have positive hormone receptor status.. The age of the patients ranged from 24 to 86 years with 97(65%) in 25-50 years, 46(30.8%) 51-75 years and 6(4.08%)in 76-100 years. Besides, 76(51%) patients had carcinoma of right breast; 86(58%) were diagnosed as Stage III, 55(37%) Stage II and 8(5.3%) Stage IV. Those diagnosed with oestrogen receptor (positive status) were 16(10.7%), human epidermal growth factor receptor 2 over-expression 13(8.7%), oestrogen/progesterone hormone receptor positivity (or luminal A) 76(51%) and 35(23.4%) patients were positive for all the three receptors. CONCLUSIONS: About half of the patients were diagnosed with a positive hormone status and it was observed that in most of the cases disease was metastasised to distant organs.