The unique risk factor profile of triple negative breast cancer: a comprehensive meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. This systematic review and meta-analysis examines whether known risk factors for breast cancer are also associated with TNBC in adult females. METHODS: EMBASE, Medline, SCOPUS, and grey literature were queried with no limit on the date or language of publication. The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OC) use, duration of OC use, use of menopausal hormone therapy (MHT), family history, body mass index (BMI), alcohol use, smoking and breast density. The main outcome of interest was TNBC. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. We estimated weighted odds ratios from random effects models to study the exposure-outcome associations. Protocol was registered under the number: PROSPERO 2021 CRD42021254594. RESULTS: Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, whereas, later age at menarche, later age at first birth and breastfeeding were protective against TNBC. Parity, MHT, alcohol, smoking, and BMI were not significantly associated with TNBC overall, but higher parity was associated with higher risk among Black women. CONCLUSION: Our findings highlight that TNBC has a distinct risk-factor profile compared to overall breast cancer. This can be the foundational work in identification of actionable TNBC risk factors to improve prevention and early detection of these poor prognosis breast tumors.

Real world effectiveness of sotrovimab in preventing COVID-19-related hospitalisation or death in patients infected with Omicron BA.2.

BACKGROUND: Laboratory-based evidence indicates that neutralization of the BA.2 (Omicron) variant by sotrovimab is reduced versus previous SARS-CoV-2 variants. Since there is a lack of real-world data, we investigated whether sotrovimab has reduced clinical efficacy against the BA.2 variant. METHODS: We performed a prospective cohort study using real-world data from 1180 randomly-selected BA.2 variant-infected patients. Follow-up to study endpoints averaged 29 days. For mild cases (not requiring oxygen-supplementation), primary outcomes were requiring O2-supplementation, intensive care unit (ICU) admission or death. For moderate-to-severe COVID-19 cases (requiring oxygen-supplementation other than mechanical ventilation), the primary outcome was ICU admission or death. RESULTS: Patients in the sotrovimab group (n = 569) and control patients (n = 611) were included. Sotrovimab-treated patients versus controls had reduced risk of death (0.4% vs 6.4%, p < 0.001), need for oxygen supplementation (3.5% vs 12.8%, p < 0.001) and ICU admission (0.2% vs 4.9%, p < 0.001). The adjusted-odds ratio for developing any of these outcomes was 0.090 (95% CI 0.049-0.165, p < 0.001). Subgroup analysis of moderate-to-severe sotrovimab-treated patients versus controls revealed reduced mortality (17.7% vs 37.2%, p = 0.006) and ICU admission (0.0% vs 37.2%, p < 0.001). Adjusted-hazards ratio for death or ICU admission was 0.256 (95% CI 0.111-0.593, p < 0.001). CONCLUSION: Sotrovimab was effective in reducing COVID-19 progression risk in high-risk BA.2 variant-infected patients. This finding may alleviate concerns about its clinical efficacy.

The Role of Platelets in Hypoglycemia-Induced Cardiovascular Disease: A Review of the Literature.

Cardiovascular diseases (CVDs) are the leading cause of death globally as well as the leading cause of mortality and morbidity in type 2 diabetes (T2D) patients. Results from large interventional studies have suggested hyperglycemia and poor glycemic control to be largely responsible for the development of CVDs. However, the association between hypoglycemia and cardiovascular events is also a key pathophysiological factor in the development of CVDs. Hypoglycemia is especially prevalent in T2D patients treated with oral sulfonylurea agents or exogenous insulin, increasing the susceptibility of this population to cardiovascular events. The adverse cardiovascular risk of hypoglycemia can persist even after the blood glucose levels have been normalized. Hypoglycemia may lead to vascular disease through mechanisms such as enhanced coagulation, oxidative stress, vascular inflammation, endothelial dysfunction, and platelet activation. In the following review, we summarize the evidence for the role of hypoglycemia in platelet activation and the subsequent effects this may have on the development of CVD. In addition, we review current evidence for the effectiveness of therapies in reducing the risk of CVDs.

The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical manifestations. However, the pathophysiology of PCOS is still unclear. Heat shock proteins (HSPs) have recently been investigated for their role in the pathogenesis of PCOS. HSPs are a class of proteins that act as molecular chaperones and maintain cellular proteostasis. More recently, their actions beyond that of molecular chaperones have highlighted their pathogenic role in several diseases. In PCOS, different HSP family members show abnormal expression that affects the proliferation and apoptotic rates of ovarian cells as well as immunological processes. HSP dysregulation in the ovaries of PCOS subjects leads to a proliferation/apoptosis imbalance that mechanistically impacts follicle stage development, resulting in polycystic ovaries. Moreover, HSPs may play a role in the pathogenesis of PCOS-associated conditions. Recent studies on HSP activity during therapeutic interventions for PCOS suggest that modulating HSP activity may lead to novel treatment strategies. In this review, we summarize what is currently known regarding the role of HSPs in the pathogenesis of PCOS and their potential role in the treatment of PCOS, and we outline areas for future research.