Systematic review and meta-analysis of the susceptibility of ABO blood group to COVID-19 infection.

BACKGROUND: Numerous studies investigate the association between the ABO blood groups and the occurrence of COVID-19 infection; discordant findings were reported. Therefore, the purpose of this meta-analysis was to evaluate the existing evidence on the susceptibility of the ABO blood group to COVID-19 infection. METHODS: Systematically searched published articles in PubMed, Google Scholar, Scopus, and EMBASE between 1 st January 2020 and 21 st March 2021. After quality control and the exclusion of irrelevant studies, 16 studies were included in the final analysis. RESULTS: Although the random-effect meta-analysis revealed a large heterogeneity among studies, I 2 = 99.197 %. The pooled event rates and (95 % CIs) for A, O, B, and AB blood group were 0.459 (95 %CI: 0.358-0.441), 0.342 (95 %CI: 0.298-0.374), 0.180 (95 %CI: 0.150-0.214), and 0.076 (95 %CI: 0.055-0.127), respectively. These results indicated that the COVID-19 infection rate was higher in persons with blood group A > O > B > AB. Overall, the ABO blood group's vulnerability to COVID-19 infection was statistically significant (pooled p -value<0.001). CONCLUSION: This meta-analysis offers a further indication of blood group A individuals' vulnerability to COVID-19 infection, and blood type AB are linked to a lower risk of COVID-19 infection.

Perceptions, Attitudes, and Barriers towards the Use of Central Board for Accreditation of Healthcare Institutions (CBAHI) Standards among Saudi Healthcare Providers.

BACKGROUND: Quality improvement is a strategic priority for all healthcare systems. However, the engagement of healthcare providers in pursuing accreditation plays a critical role in integrating standards into routine practice. Therefore, the current study assessed the perceptions, attitudes, and barriers towards using the Central Board for Accreditation of Healthcare Institutions (CBAHI) standards among Saudi healthcare providers. METHOD: This cross-sectional study was conducted in 2023 among a representative sample (364) of Saudi healthcare providers (both genders, aged 20-60) working at twenty governmental CBAHI-accredited hospitals in Saudi Arabia. The study participants were selected using a cluster random sampling method. Data regarding the perceptions, attitudes, and barriers toward using CBAHI standards among Saudi healthcare providers were evaluated using a validated questionnaire. Additional information regarding demographic-socioeconomic variables was obtained with an interview-based questionnaire. Statistical analysis was performed using SPSS version 28. RESULTS: A total of 364 healthcare providers participated in the current study. Of them, 54.4% were males, and 45.6% were females. Almost half (48.6%) of the study participants held bachelor's degrees. For the variables of age group, marital status, monthly income, and years of work experience, statistically significant associations were found between males and females (p-value < 0.05). The means of overall item agreement percentage of the participating healthcare providers for perceptions and attitudes towards using CBAHI standards and attitudes towards using CBAHI standards as a tool for quality improvement were 80.1%, 76.4%, and 72.0%, respectively. The highest item agreement percentage of the participating healthcare providers regarding the barriers that inhibit the hospital from obtaining the full benefit from the CBAHI accreditation was for the inexpedient IT tools (59.6%). CONCLUSION: The current study's results demonstrated accepted perceptions and attitudes toward using CBAHI standards among Saudi healthcare providers. In addition, the identified barriers should be alleviated to improve the quality, effectiveness, and efficiency of the hospitals in Saudi Arabia. The findings also help clarify the accreditation operating process, which may be helpful to policymakers and stakeholders in making informed decisions on integrating accreditation standards.

Overdiagnosis Due to Screening Mammography for Breast Cancer among Women Aged 40 Years and Over: A Systematic Review and Meta-Analysis.

The current systematic review and meta-analysis was conducted to estimate the incidence of overdiagnosis due to screening mammography for breast cancer among women aged 40 years and older. A PRISMA systematic search appraisal and meta-analysis were conducted. A systematic literature search of English publications in PubMed, Web of Science, EMBASE, Scopus, and Google Scholar was conducted without regard to the region or time period. Generic, methodological, and statistical data were extracted from the eligible studies. A meta-analysis was completed by utilizing comprehensive meta-analysis software. The effect size estimates were calculated using the fail-safe N test. The funnel plot and the Begg and Mazumdar rank correlation tests were employed to find any potential bias among the included articles. The strength of the association between two variables was assessed using Kendall's tau. Heterogeneity was measured using the I-squared (I2) test. The literature search in the five databases yielded a total of 4214 studies. Of those, 30 articles were included in the final analysis, with sample sizes ranging from 451 to 1,429,890 women. The vast majority of the articles were retrospective cohort designs (24 articles). The age of the recruited women ranged between 40 and 89 years old. The incidence of overdiagnosis due to screening mammography for breast cancer among women aged 40 years and older was 12.6%. There was high heterogeneity among the study articles (I2 = 99.993), and the pooled event rate was 0.126 (95% CI: 15 0.101-0.156). Despite the random-effects meta-analysis showing a high degree of heterogeneity among the articles, the screening tests have to allow for a certain degree of overdiagnosis (12.6%) due to screening mammography for breast cancer among women aged 40 years and older. Furthermore, efforts should be directed toward controlling and minimizing the harmful consequences associated with breast cancer screening.

Patterns of Thyroid Cancer Mortality and Incidence in Saudi Arabia: A 30-Year Study.

Thyroid cancer is the most prevalent endocrine cancer among the female population in the Kingdom of Saudi Arabia (KSA) and the ninth most common in the male population in Saudi Arabia. Over the past years, an increasing incidence of thyroid cancer has been reported in Saudi Arabia. However, the etiology of thyroid cancer is still not clear. Therefore, this study aimed to estimate thyroid cancer incidence and mortality trends in Saudi Arabia from 1990 to 2019. The current study utilized the Global Burden of Disease and the Institute for Health Metrics and Evaluation databases to extract prevalence data of thyroid cancer in Saudi Arabia from 1990 to 2019. Moreover, the current project utilizes Global Burden of Disease (GBD) web-based tools to visualize these data. In total, 23,846 cases (17,220 females and 6626 males) were diagnosed with thyroid cancer in Saudi Arabia from 1990 to 2019. The incidence is higher in females than in males. Over these 30 years, women's incidence steadily increased by 15-fold versus a 22-fold increase in men. Moreover, there were 2056 deaths in total caused by thyroid cancer in KSA. The mortality rate in women steadily increased by threefold in the same period. However, the increase in mortality was higher in males (sixfold). A high percentage of YLLs was observed in males, with around 24.8% ranging from 30 to 34 and 40 to 45 years. Thyroid cancer incidence rates have increased exponentially between 1990 and 2019. The expansion of the incidence of thyroid cancer in Saudi Arabia could be due to the increased development in detection and diagnosis. The current study provided evidence of the need to increase awareness and diagnosis in the male population.

The Association between Colorectal Cancer and Colonoscopic Conditions in Saudi Patients: A 10-Year Cross-Sectional-Retrospective Study.

Background: In Saudi Arabia, colorectal cancer (CRC) is the most common cancer in males and the third most common cancer in females. The current gold standard for colorectal cancer diagnosis is colonoscopy. Several concerns regarding the balance of ordering colonoscopy procedures for patients presenting with signs and symptoms. There are also several concerns regarding over-ordering the procedure when unnecessary. The current study aimed to evaluate the association between colorectal cancer and colonoscopic conditions in Saudi patients. Methods: A 10-year cross-sectional study was conducted at Alnoor Specialty Hospital, Makkah, over the last ten years. Colonoscopy reports of patients were evaluated to identify the colonoscopy manifestations associated with mass, polyps, and bleeding. Results: The current study evaluated 2158 cases admitted to the hospital for colonoscopic diagnosis. Results indicated that most of the patients were males (55.4%). Additionally, results showed a significant statistical association between tumor and bleeding, polyp, and hemorrhage. Moreover, it highlighted the association between polyps and bleeding, inflammation, and diverticulosis. Conclusion: CRC screening in Saudi Arabia is comprehensive; however, there are a few areas for improvement, including standardization of colorectal cancer pathology reporting to improve the health system's quality. Also, the current study identified conditions that are significantly associated with reported colon polyps and tumors, which could aid in stratifying patients selected for screening via colonoscopy.

Differential expression of the BCAT isoforms between breast cancer subtypes.

BACKGROUND: Biological characterisation of breast cancer subtypes is essential as it informs treatment regimens especially as different subtypes have distinct locoregional patterns. This is related to metabolic phenotype, where altered cellular metabolism is a fundamental adaptation of cancer cells during rapid proliferation. In this context, the metabolism of the essential branched-chain amino acids (BCAAs), catalysed by the human branched-chain aminotransferase proteins (hBCAT), offers multiple benefits for tumour growth. Upregulation of the cytosolic isoform of hBCAT (hBCATc), regulated by c-Myc, has been demonstrated to increase cell migration, tumour aggressiveness and proliferation in gliomas, ovarian and colorectal cancer but the importance of the mitochondrial isoform, hBCATm has not been fully investigated. METHODS: Using immunohistochemistry, the expression profile of metabolic proteins (hBCAT, IDH) was assessed between breast cancer subtypes, HER2 + , luminal A, luminal B and TNBC. Correlations between the percentage and the intensity of protein expression/co-expression with clinical parameters, such as hormone receptor status, tumour stage, lymph-node metastasis and survival, were determined. RESULTS: We show that hBCATc expression was found to be significantly associated with the more aggressive HER2 + and luminal B subtypes, whilst hBCATm and IDH1 associated with luminal A subtype. This was concomitant with better prognosis indicating a differential metabolic reliance between these two subtypes, in which enhanced expression of IDH1 may replenish the α-ketoglutarate pool in cells with increased hBCATm expression. CONCLUSION: The cytosolic isoform of BCAT is associated with tumours that express HER2 receptors, whereas the mitochondrial isoform is highly expressed in tumours that are ER + , indicating that the BCAT proteins are regulated through different signalling pathways, which may lead to the identification of novel targets for therapeutic applications targeting dysregulated cancer metabolism.

Susceptibility of ABO blood group to COVID-19 infections: clinico-hematological, radiological, and complications analysis.

ABSTRACT: In the wake of the COVID-19 pandemic, research indicates that the COVID-19 disease susceptibility varies among individuals depending on their ABO blood groups. Researchers globally commenced investigating potential methods to stratify cases according to prognosis depending on several clinical parameters. Since there is evidence of a link between ABO blood groups and disease susceptibility, it could be argued that there is a link between blood groups and disease manifestation and progression. The current study investigates whether clinical manifestation, laboratory, and imaging findings vary among ABO blood groups of hospitalized confirmed COVID-19 patients.This retrospective cohort study was conducted between March 1, 2020 and March 31, 2021 in King Faisal Specialist Hospital and Research Centre Riyadh and Jeddah, Saudi Arabia. Demographic information, clinical information, laboratory findings, and imaging investigations were extracted from the data warehouse for all confirmed COVID-19 patients.A total of 285 admitted patients were included in the study. Of these, 81 (28.4%) were blood group A, 43 (15.1%) were blood group B, 11 (3.9%) were blood group AB, and 150 (52.6%) were blood group O. This was almost consistent with the distribution of blood groups among the Saudi Arabia community. The majority of the study participants (79.6% [n = 227]) were asymptomatic. The upper respiratory tract infection (P = .014) and shortness of breath showed statistically significant differences between the ABO blood group (P = .009). Moreover, the incidence of the symptoms was highly observed in blood group O followed by A then B except for pharyngeal exudate observed in blood group A. The one-way ANOVA test indicated that among the studied hematological parameters, glucose (P = .004), absolute lymphocyte count (P = .001), and IgA (P = .036) showed statistically significant differences between the means of the ABO blood group. The differences in both X-ray and computed tomography scan findings were statistically nonsignificant among the ABO age group. Only 86 (30.3%) patients were admitted to an intensive care unit, and the majority of them were blood groups O 28.7% (n = 43) and A 37.0% (n = 30). However, the differences in complications' outcomes were statistically nonsignificant among the ABO age group.ABO blood groups among hospitalized COVID-19 patients are not associated with clinical, hematological, radiological, and complications abnormality.

BCATc modulates crosstalk between the PI3K/Akt and the Ras/ERK pathway regulating proliferation in triple negative breast cancer.

The cytosolic branched chain aminotransferase (BCATc) protein has been found to be highly expressed in breast cancer subtypes, including triple negative breast cancer (TNBC), compared with normal breast tissue. The catabolism of branched-chain amino acids (BCAAs) by BCATc leads to the production of glutamate and key metabolites which further drive the TCA cycle, important for cellular metabolism and growth. Upregulation of BCATc has been associated with increased cell proliferation, cell cycle progression and metastasis in several malignancies including breast, gliomas, ovarian and colorectal cancer but the underlying mechanisms are unclear. As nutrient levels of BCAAs, substrates of BCATc, regulate the PI3K/Akt pathway we hypothesized that increased expression of BCATc would contribute to tumour cell growth through upregulation of the insulin/IGF-1 signalling pathway. This pathway is known to potentiate proliferation and metastasis of malignant cells through the activation of PI3K/Akt and the RAS/ERK signalling cascades. Here we show that knockdown of BCATc significantly reduced insulin and IGF-1-mediated proliferation, migration and invasion of TNBC cells. An analysis of this pathway showed that when overexpressed BCATc regulates proliferation through the PI3K/Akt axis, whilst simultaneously attenuating the Ras/Erk pathway indicating that BCATc acts as a conduit between these two pathways. This ultimately led to an increase in FOXO3a, a key regulator of cell proliferation and Nrf2, which mediates redox homeostasis. Together this data indicates that BCATc regulates TNBC cell proliferation, migration and invasion through the IGF-1/insulin PI3K/Akt pathway, culminating in the upregulation of FOXO3a and Nrf2, pointing to a novel therapeutic target for breast cancer treatment.

Hypoxia modulates the stem cell population and induces EMT in the MCF-10A breast epithelial cell line.

A common feature among pre-malignant lesions is the induction of hypoxia through increased cell propagation and reduced access to blood flow. Hypoxia in breast cancer has been associated with poor patient prognosis, resistance to chemotherapy and increased metastasis. Although hypoxia has been correlated with factors associated with the latter stages of cancer progression, it is not well documented how hypoxia influences cells in the earliest stages of transformation. Using the immortalized MCF-10A breast epithelial cell line, we used hypoxic culture conditions to mimic reduced O2 levels found within early pre-malignant lesions and assessed various cellular parameters. In this non-transformed mammary cell line, O2 deprivation led to some changes not immediately associated with cancer progression, such as decreased proliferation, cell cycle arrest and increased apoptosis. In contrast, hypoxia did induce other changes more consistent with an increased metastatic potential. A rise in the CD44+CD24-/low-labeled cell sub-population along with increased colony forming capability indicated an expanded stem cell population. Hypoxia also induced cellular and molecular changes consistent with an epithelial-to-mesenchymal transition (EMT). Furthermore, these cells now exhibited increased migratory and invasive abilities. These results underscore the contribution of the hypoxic tumour microenvironment in cancer progression and dissemination.

The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis.

The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.