Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Medical Students' Perception of Pathology in Saudi Arabia.

Pathology is the bridge between basic science and clinical practice. An inadequate perception of pathology leads to an incomplete understanding of diseases, which consequently affects its management. This study aims to identify medical students' perceptions of pathology in medical colleges around Saudi Arabia and use their feedback to improve teaching strategies. A validated online self-structured questionnaire form was distributed to medical students in basic and clinical years, including private and governmental universities in all regions of Saudi Arabia. The study comprised a total of 476 medical students. It revealed that n = 226 (48%) of the participants were not aware of pathologists' roles, and n = 262 (55%) of students reported that the main reason was insufficient exposure to actual pathology practice. A total of n = 209 (44%) students believed the current teaching methods in the basic years were insufficient to provide clear perceptions of pathology. The majority of participants n = 366 (77%) chose practical sessions as the most effective strategy in teaching pathology. Our study demonstrated that medical students require more engagement in laboratories to improve their perception. We suggest that Saudi medical schools need to deliver more comprehensive and practical teaching methods that reflect the actual practice of pathology.

Course and predictors of excellent response to therapy in patients with differentiated thyroid cancer at long-term follow-up.

OBJECTIVES: To investigate the long-term outcomes of differentiated thyroid cancer (DTC) and the predictive factors for excellent and incomplete responses to therapy on long-term follow-up of patients. METHODS: A retrospective chart review and analysis was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Demographic, histological, and therapeutic data were collected from patients older than 13 years at the time of diagnosis, with a minimum follow-up of 18 months. Outcomes were divided into excellent, indeterminate, biochemically incomplete, and structurally incomplete responses. Odds ratios (ORs) for predictors of incomplete response at the last visit were determined. We first tested associations univariately with incomplete responses, and then variables with significant associations were included in a multivariable logistic model. RESULTS: Among 230 patients with DTC, 61.7% had excellent responses to therapy on long-term follow-up, and 24.3% had incomplete biochemical and structural responses. The median follow-up was 4.6 years. Factors significantly associated with incomplete response to therapy in the multivariate analysis (p<0.05) were age >55 years (OR=5) and lymph node (OR=3.4) and distant metastases (OR=29). Older age did not affect the outcome in low-risk patients with DTC but was significantly associated with incomplete responses in those with intermediate risk (p=0.04) and high risk (p=0.003). CONCLUSION: We strongly advocate incorporating age into recurrence risk assessment for patients with DTC.

Prognostic value of glucose transporter proteins-1 (GLUT1) in breast carcinoma.

Several studies have reported increased glucose transporters (GLUT) expression in different cancer types, including breast cancer. The primary purpose of this study is to examine GLUT1 immunoexpression in breast cancer patients in Saudi Arabia and to determine its significance. The study examined the association between GLUT1 immunophenotype and the clinicopathological characteristics in breast cancer. GLUT1 expression was analyzed in retrospectively collected tissue samples (n = 578) from breast cancer patients using immunohistochemistry. A total of 311 (54%) of the cases expressed GLUT1 cytoplasmic immunohistochemical staining. In univariate analysis, we found a significant association between GLUT1 expression and high-grade tumors (p < 0.0001). Positive estrogen and progesterone receptor results predicted lower GLUT1 immunoexpression (p < 0.0001 for both). Vascular invasion showed a significant association with GLUT1 immunoexpression (p = 0.045). Our findings support that GLUT1 immunohistochemistry can be used as a marker to determine the grade and hormonal receptor status in breast cancer.

Physicians' Attitude and Perception Towards Social Media Medical Consultation.

AIM: Social media plays a major role in modern healthcare. However, little is known about physicians' experience as related to medical consultation through social media, such as Twitter. This study aims to characterize physicians' attitudes and perceptions toward medical consultations through social media and estimate the use of social media for medical consultation purposes. MATERIALS AND METHODS: The study was conducted through the distribution of electronic questionnaires to physicians from different specialities. A total of 242 healthcare providers responded to the questionnaire. RESULTS: Our results demonstrated that 79% of the healthcare providers received consultations through social media at least "sometimes" and that 56% of them agreed that it is appropriate to have personal social media platforms that can be accessible by patients. They also agreed (87%) that it is appropriate to interact with patients on social media; however, most of them do not find social media platforms appropriate for diagnosis or treatment. CONCLUSION: Physicians think positively of social media consults, but do not consider it a proper method to manage medical conditions.

ChromoEnhancer: An Artificial-Intelligence-Based Tool to Enhance Neoplastic Karyograms as an Aid for Effective Analysis.

Cytogenetics laboratory tests are among the most important procedures for the diagnosis of genetic diseases, especially in the area of hematological malignancies. Manual chromosomal karyotyping methods are time consuming and labor intensive and, hence, expensive. Therefore, to alleviate the process of analysis, several attempts have been made to enhance karyograms. The current chromosomal image enhancement is based on classical image processing. This approach has its limitations, one of which is that it has a mandatory application to all chromosomes, where customized application to each chromosome is ideal. Moreover, each chromosome needs a different level of enhancement, depending on whether a given area is from the chromosome itself or it is just an artifact from staining. The analysis of poor-quality karyograms, which is a difficulty faced often in preparations from cancer samples, is time consuming and might result in missing the abnormality or difficulty in reporting the exact breakpoint within the chromosome. We developed ChromoEnhancer, a novel artificial-intelligence-based method to enhance neoplastic karyogram images. The method is based on Generative Adversarial Networks (GANs) with a data-centric approach. GANs are known for the conversion of one image domain to another. We used GANs to convert poor-quality karyograms into good-quality images. Our method of karyogram enhancement led to robust routine cytogenetic analysis and, therefore, to accurate detection of cryptic chromosomal abnormalities. To evaluate ChromoEnahancer, we randomly assigned a subset of the enhanced images and their corresponding original (unenhanced) images to two independent cytogeneticists to measure the karyogram quality and the elapsed time to complete the analysis, using four rating criteria, each scaled from 1 to 5. Furthermore, we compared the enhanced images with our method to the original ones, using quantitative measures (PSNR and SSIM metrics).

Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

BACKGROUND: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures. METHODS: Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. RESULTS: The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. CONCLUSIONS: Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.

Abdominal visceral adipose tissue over the menopause transition and carotid atherosclerosis: the SWAN heart study.

OBJECTIVES: To characterize abdominal visceral adipose tissue (VAT) trajectory relative to the final menstrual period (FMP), and to test whether menopause-related VAT accumulation is associated with greater average, common carotid artery intima-media thickness (cIMT) and/or internal carotid artery intima-media thickness (ICA-IMT). METHODS: Participants were 362 women (at baseline: age was (mean ±â€ŠSD) 51.1 ±â€Š2.8 y; 61% White, 39% Black) with no cardiovascular disease from the Study of Women's Health Across the Nation Heart study. Women had up to two measurements of VAT and cIMT over time. Splines revealed a nonlinear trajectory of VAT with two inflection points demarcating three time segments: segment 1: >2 years before FMP; segment 2: 2 years before FMP to FMP; and segment 3: after FMP. Piecewise-linear random-effects models estimated changes in VAT. Random-effects models tested associations of menopause-related VAT with each cIMT measure separately. Estimates were adjusted for age at FMP, body mass index, and sociodemographic, lifestyle, and cardiovascular disease risk factors. RESULTS: VAT increased significantly by 8.2% (95% CI: 4.1%-12.5%) and 5.8% (3.7%-7.9%) per year in segments 2 and 3, respectively, with no significant change in VAT within segment 1. VAT predicted greater ICA-IMT in segment 2, such that a 20% greater VAT was associated with a 2.0% (0.8%-3.1%) greater ICA-IMT. VAT was not an independent predictor of ICA-IMT in the other segments or of the other cIMT measures after adjusting for covariates. CONCLUSIONS: Women experience an accelerated increase in VAT starting 2 years before menopause. This menopause-related increase in VAT is associated with greater risk of subclinical atherosclerosis in the internal carotid artery.

Video Summary:http://links.lww.com/MENO/A722 .

Arterial Stiffness Accelerates Within 1 Year of the Final Menstrual Period: The SWAN Heart Study.

OBJECTIVE: Menopause may augment age-dependent increases in arterial stiffness, with black women having greater progression in midlife compared with white women. We sought to determine whether and when women experience changes in arterial stiffness relative to the final menstrual period (FMP) and whether these changes differ between black and white midlife women. Approach and Results: We evaluated 339 participants from the SWAN (Study of Women's Health Across the Nation) Heart Ancillary study (Study of Women's Health Across the Nation). Women had ≤2 carotid-femoral pulse-wave velocity (cfPWV) exams over a mean±SD of 2.3±0.5 years of follow-up. Annual percentage changes in cfPWV were estimated in 3 time segments relative to FMP and compared using piecewise linear mixed-effects models. At baseline, women were 51.1±2.8 years of age and 36% black. Annual percentage change (95% CI) in cfPWV varied by time segments: 0.9% (-0.6% to 2.3%) for >1 year before FMP, 7.5% (4.1% to 11.1%) within 1 year of FMP, and -1.0% (-2.8% to 0.8%) for >1 year after FMP. Annual percentage change in cfPWV within 1 year of FMP was significantly greater than the other 2 time segments; P<0.05 for both comparisons. Adjusting for concurrent cardiovascular disease risk factors explained part of the change estimates but did not eliminate the difference. Black women had greater increase in cfPWV compared with white women in the first segment; P for interaction, 0.04. CONCLUSIONS: The interval within 1 year of FMP is a critical period for women when vascular functional alterations occur. These findings underscore the importance of more intensive lifestyle modifications in women transitioning through menopause.

Serum 25-hydroxyvitamin-D and nonalcoholic fatty liver disease: Does race/ethnicity matter? Findings from the MESA cohort.

BACKGROUND AND AIMS: Low serum 25-hydroxyvitamin D (25(OH)D) is associated with higher nonalcoholic fatty liver disease (NAFLD) risk in studies of mainly white participants. Significant racial/ethnic differences exist in serum 25(OH)D and NAFLD prevalence questioning extending this association to other racial/ethnic groups. We tested whether the association between serum 25(OH)D and NAFLD vary by race/ethnicity. METHODS AND RESULTS: This was a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) that included 3484 participants (44% male; 38.4% Whites, 27.8% African-Americans, 23.5% Hispanics, and 10.3% Chinese-Americans) who had serum 25(OH)D and upper abdominal CT images available at baseline. Serum 25(OH)D was measured by high-performance liquid chromatography-tandem mass spectrometry. NAFLD was identified if liver-to-spleen Hounsfield-Unit ratio was <1. Whites had the highest 25(OH)D level and African-Americans had the lowest level (mean ± SD: 29.5 ± 10.4 vs.19.9 ± 9.1, respectively). Six hundred and eleven (17.5%) participants had NAFLD; Hispanics had the highest prevalence (26.2%) followed by Chinese-Americans (19.8%), Whites (15.8%) and African-Americans (11.7%), P < 0.0001. In adjusted model, the association of 25(OH)D with NAFLD differed by race/ethnicity (P < 0.0001). Negative association was only evident in Causations (OR (95% CI):1.23 (1.03, 1.47) per 1 SD lower serum 25(OH)D). For other racial/ethnic groups, BMI, triglycerides, diabetic status and/or smoking, but not serum 25(OH)D, were common independent risk factors for NAFLD. CONCLUSIONS: The negative association between serum 25(OH)D and NAFLD in Whites may not be broadly generalizable to other racial/ethnic groups. Modifiable risk factors including BMI, triglycerides, diabetic status and/or smoking associate with NAFLD risk in non-white racial/ethnic groups beyond 25(OH)D.

HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women.

Objective- HDL-C (high-density lipoprotein cholesterol) may not always be cardioprotective in postmenopausal women. HDL particles (HDL-P) via ion-mobility may better reflect the antiatherogenicity of HDL. Objectives were (1) to evaluate associations of HDL-C and ion-mobility HDL-P with carotid intima-media thickness (cIMT) and carotid plaque separately and jointly in women; and (2) to assess interactions by age at and time since menopause. Approach and Results- Analysis included 1380 females from the MESA (Multi-Ethnic Study of Atherosclerosis; age: 61.8±10.3; 61% natural-, 21% surgical-, and 18% peri-menopause). Women with unknown or early menopause (age at nonsurgical menopause ≤45 years) were excluded. Adjusting for each other, higher HDL-P but not HDL-C was associated with lower cIMT ( P=0.001), whereas higher HDL-C but not HDL-P was associated with greater risk of carotid plaque presence ( P=0.04). Time since menopause significantly modified the association of large but not small HDL-P with cIMT; higher large HDL-P was associated with higher cIMT close to menopause but with lower cIMT later in life. The proatherogenic association reported for HDL-C with carotid plaque was most evident in women with later age at menopause who were >10 years postmenopausal. Conclusions- Elevated HDL-C may not always be cardioprotective in postmenopausal women. The cardioprotective capacity of large HDL-P may adversely compromise close to menopause supporting the importance of assessing how the menopause transition might impact HDL quality and related cardiovascular disease risk later in life.