TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type.

BACKGROUND: Telomerase reverse transcriptase (TERT) gene promoter mutations have been explored, as biomarkers of improved survival for patients with cancer receiving immune checkpoint inhibitors. We sought to investigate their prevalence by race and sex across different cancer types to inform patient selection in clinical trials. RESULTS: In this observational study, 31 925 patients with cancer underwent next-generation sequencing of their tumors with 88% (27 970) patients self-reported being Whites, 7.1% (2273) Asians, and 5.3% (1682) Blacks. Examining the distribution of TERT promoter mutations by race, White patients with melanoma harbored more TERT promoter mutations than Asian and Black patients (OR = 25.83; 95%CI, 6.84-217.42; P < .001). In contrast, Asian patients with head and neck cancer (HNC) harbored more TERT promoter mutations compared to White patients (OR = 2.47; 95%CI, 1.39-4.37; P = .004). In addition, the distribution of TERT promoter mutations differed by sex. Males were enriched for TERT gene promoter mutations compared to females with melanoma (OR = 1.82; 95%CI, 1.53-2.16; P < .001), cancer of unknown primary (OR = 1.96; 95%CI, 1.43-2.69; P < .001), hepatobiliary (OR = 3.89; 95%CI, 2.65-5.69; P < .001), and thyroid cancers (OR = 1.42; 95%CI, 1.10-1.84; P = .0087), while females were more enriched for TERT promoter mutations compared to males for HNC (OR = 0.56; 95%CI, 0.39-0.81; P = .0021). CONCLUSIONS: The prevalence of TERT gene promoter mutations varies among patients with cancer based on race and sex. These findings inform our understanding of cancer biology and can assist in the design of future clinical trials that leverage drugs targeting TERT promoter dependencies.

Acceptance and attitude of Lebanese lawyers and medical students toward surrogate pregnancy: a cross-sectional study.

BACKGROUND: Little is known about the acceptance of specific populations of decision makers in Lebanon regarding surrogacy. This study aimed to explore the acceptance and attitude of Lebanese Lawyers and Medical Students regarding surrogacy. METHODS: In total 248 medical students and 204 lawyers completed a questionnaire to assess socio-demographic data, attitude toward surrogacy, and three different clinical scenarios to assess patterns of thinking. Finally, we validated a scale to assess the acceptance of surrogacy in these two populations. RESULTS: Concerning medical students, 54.8% reported they were supportive of surrogacy, 35.1% were neutral and 10.1% were against. For lawyers, 52.9% were supportive, 25% were neutral and 22.1% were against. Lawyers were more likely to be against surrogacy (p = 0.001). After conducting a multivariate analysis on the whole studied population to find predictors of acceptance of surrogacy, the best predictors were being single (OR 0.415; 95% CI 0.228, 0.753; p < 0.01), a supportive reported attitude regarding surrogacy (OR 5.464; 95% CI 3.65, 8.13; p < 0.001) and believing that surrogacy is a solution worth discussing in Lebanon (OR 4.186; 95% CI 1.709, 10.256; p < 0.01). Concerning the clinical scenarios, they showed that lawyers were more likely to oppose abortion regardless of the reason (p < 0.01). Also, in a case of gestational surrogacy, lawyers were more likely to give the right to the gestational carrier to keep the baby compared to medical students (p < 0.001). CONCLUSION: In conclusion, this study shows that only a minority of medical students and lawyers in Lebanon oppose surrogate pregnancy which warrants exploration of the perspective of other populations of decision makers in Lebanon to better guide legislations.

SGLT2 Inhibitor-Dapagliflozin Attenuates Diabetes-Induced Renal Injury by Regulating Inflammation through a CYP4A/20-HETE Signaling Mechanism.

Diabetic kidney disease (DKD) is a serious complication of diabetes, affecting millions of people worldwide. Inflammation and oxidative stress are key contributors to the development and progression of DKD, making them potential targets for therapeutic interventions. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a promising class of drugs, with evidence demonstrating that they can improve renal outcomes in people with diabetes. However, the exact mechanism by which SGLT2i exert their renoprotective effects is not yet fully understood. This study demonstrates that dapagliflozin treatment attenuates renal injury observed in type 2 diabetic mice. This is evidenced by the reduction in renal hypertrophy and proteinuria. Furthermore, dapagliflozin decreases tubulointerstitial fibrosis and glomerulosclerosis by mitigating the generation of reactive oxygen species and inflammation, which are activated through the production of CYP4A-induced 20-HETE. Our findings provide insights onto a novel mechanistic pathway by which SGLT2i exerts their renoprotective effects. Overall, and to our knowledge, the study provides critical insights into the pathophysiology of DKD and represents an important step towards improving outcomes for people with this devastating condition.

Social media medical misinformation: impact on mental health and vaccination decision among university students.

BACKGROUND: The COVID-19 pandemic highlighted the need of social media as a medium for gathering health-related information. Simultaneously, a slew of false information, primarily about COVID-19's origin, dissemination, prevention, treatment, and fatality surfaced, making it difficult to distinguish fake from genuine material. However, the possible effects on mental health and the extent to which this influences our decisions, particularly regarding vaccination, are unknown. AIM: The purpose of this questionnaire-based cross-sectional study was to examine Lebanese University students' perceptions of social media influence during the COVID-19 pandemic, as well as to measure the impact of misinformation on respondents' mental health and vaccination decisions. METHODS: In total, 440 students took part and were asked to complete an online survey that included questions on social media trust, the "general health questionnaire index" (GHQ-12), and a scale measuring "attitude towards vaccination". RESULTS: Our data demonstrated a low frequency of mental health disorders among Lebanese University students, which was correlated to frequent social media exposure during the COVID-19 pandemic. These findings suggested that students are more aware of misinformation and had lower rates of despair and anxiety than the general population. Furthermore, Facebook use was associated with worse attitude and behaviour towards vaccination (p = 0.001), but a better mental health. Twitter had the inverse effect (p = 0.002). CONCLUSION: It is a necessity to use social media correctly in health-related topics, to push governments and platforms towards making decisions about false and invalidated posts.

Intestinal microbiota regulates diabetes and cancer progression by IL-1ß and NOX4 dependent signaling cascades.

Diabetes changes the host microbiota, a condition known as dysbiosis. Dysbiosis is an important factor for the pathogenesis of diabetes and colorectal cancer (CRC). We aimed at identifying the microbial signature associated with diabetes and CRC; and identifying the signaling mechanism altered by dysbiosis and leading to CRC progression in diabetes. MKR mice that can spontaneously develop type 2 diabetes were used. For CRC induction, another subset of mice was treated with azoxymethane and dextran sulfate sodium. To identify the role of microbiota, microbiota-depleted mice were inoculated with fecal microbial transplant from diabetic and CRC mice. Further, a mouse group was treated with probiotics. At the end of the treatment, 16S rRNA sequencing was performed to identify microbiota in the fecal samples. Blood was collected, and colons were harvested for molecular, anatomical, and histological analysis. Our results show that diabetes is associated with a microbial signature characterized by reduction of butyrate-forming bacteria. This dysbiosis is associated with gastrointestinal complications reflected by a reduction in colon lengths. These changes are reversed upon treatment with probiotics, which rectified the observed dysbiosis. Inoculation of control mice with diabetic or cancer microbiota resulted in the development of increased number of polyps. Our data also show that inflammatory cytokines (mainly interleukin (IL)-1ß) and NADPH oxidase (NOX)4 are over-expressed in the colon tissues of diabetic mice. Collectively our data suggest that diabetes is associated with dysbiosis characterized by lower abundance of butyrate-forming bacteria leading to over-expression of IL-1ß and NOX4 leading to gastrointestinal complications and CRC.

Utility of hematological and inflammatory biomarkers in predicting recovery in critical Covid-19 patients: Our experience in the largest Covid-19 treating center in Lebanon.

BACKGROUND: COVID-19 pandemic has led to a catastrophic shortage of ICU beds. This has resulted in the need to identify patients that can be discharged early before full clinical recovery. We designed this study to determine if in changes routine tests like CBCD and CRP can be a useful complement to clinical status when deciding to discharge patients from ICU. METHODS: This retrospective study was conducted in Rafic Hariri University Hospital. Levels of biomarkers measured at admission (T1) and within 3 days of outcome (T2) were collected and ratios (T2/T1) were calculated. The Odds Ratios of association between the changes in these biomarkers and outcome were estimated. Multivariate analysis and AUC for the performance of these biomarkers were also conducted. RESULTS: We found on multivariate analysis that reduction in counts of lymphocyte and platelets and elevation in counts of neutrophils and level of CRP (T2/T1 ratio > 1) are strongly associated with mortality with respective ORs estimated at 6.74, 3.26, 5.65 and 4.34 [p-values < 0.001]. AUCs were found to lie in a range of 0.68 to 0.81 indicating fair to good performance. Other factors found to impact survival were AKI, AF and ACS [p-values < 0.01]. In contrast to other studies, risk factors didn't show an association with survival when adjusted for effects of complications and changes in biomarker levels. CONCLUSIONS: Our results confirm that inexpensive tests like lymphocyte count and CRP can be reliably used to follow COVID-19 patients in ICU and to support the decision to discharge patients.

Overcoming Therapy Resistance in Colon Cancer by Drug Repurposing.

Colorectal cancer (CRC) is the third most common cancer in the world. Despite improvement in standardized screening methods and the development of promising therapies, the 5-year survival rates are as low as 10% in the metastatic setting. The increasing life expectancy of the general population, higher rates of obesity, poor diet, and comorbidities contribute to the increasing trends in incidence. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC with the advantage of treating underlying comorbidities and decreasing chemotherapy toxicity. This review elaborates on the current data that supports drug repurposing as a feasible option for patients with CRC with a focus on the evidence and mechanism of action promising repurposed candidates that are widely used, including but not limited to anti-malarial, anti-helminthic, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic agents.

Challenges and perspective of cancer patients during the COVID-19 pandemic and the Lebanese financial crisis: a multicentric cross-sectional study.

Lebanese cancer patients are facing a war on two fronts, between the COVID-19 pandemic and one of the most severe financial crises globally in recent times. This multicentric cross-sectional study was conducted, aiming to analyse challenges and perspective of this particularly vulnerable population. A questionnaire was prepared to assess socio-demographic data, challenges faced during the pandemic, perspectives concerning cancer and COVID-19, a scale was also validated to assess knowledge level regarding COVID-19 in this population. Patients were interviewed in chemotherapy units from four different private and public hospitals in Lebanon during December 2020 and March-June 2021. In total, 272 patients were interviewed (median age, 57 years, range, 22-90 years). Concerning salary during the pandemic, it changed negatively (45.6%), or did not change (7.7%), while 46.7% of participants did not work. Some challenges such as transportation problems (39%), inability to reach their physician by phone (16.9%), deferral of chemotherapy dates (31.6%), difficulty finding chemotherapy medications (49.6%) were more likely to be reported by patients receiving chemotherapy in public compared to private hospitals (p < 0.01 for each). Other challenges include not being able to find non-cancer-related medications (71.3%), this challenge being increased when comparing December 2020 with March-June 2021 (p < 0.02). Using a multivariate analysis, the best predictor for increased knowledge about COVID-19 was higher levels of education (p < 0.001). In conclusion, this study shows that cancer patients in Lebanon are facing many challenges that complicate different aspects of health. Perspective and challenges of these patients must be taken into consideration in order to deliver better care to our patients in these unprecedented times.