Alpelisib is an α-selective phosphatidylinositol 3-kinase inhibitor used for treating hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2–), PIK3CA-mutated locally advanced or metastatic breast cancer following disease progression on or after endocrine therapy. Hyperglycemia is an on-target effect of alpelisib affecting approximately 60% of treated patients, and sometimes necessitating dose reductions, treatment interruptions, or discontinuation of alpelisib. Early detection of hyperglycemia and timely intervention have a key role in achieving optimal glycemic control and maintaining alpelisib dose intensity to optimize the benefit of this drug. A glycemic support program implemented by an endocrinology–oncology collaborative team may be very useful in this regard. Lifestyle modifications, mainly comprising a reduced-carbohydrate diet, and a designated stepwise, personalized antihyperglycemic regimen, based on metformin, sodium–glucose co-transporter 2 inhibitors, and pioglitazone, are the main tools required to address the insulin-resistant hyperglycemia induced by alpelisib. In this report, based on the consensus of 14 oncologists and seven endocrinologists, we provide guidance for hyperglycemia management strategies before, during, and after alpelisib therapy for HR+, HER2–, PIK3CA-mutated breast cancer, with a focus on a proactive, multidisciplinary approach.

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.

Metabolomics, the research area studying chemical processes involving metabolites, finds its utility in inflammasome biomarker discovery, thus representing a novel approach for cardiometabolic syndrome pathogeny acknowledgements. Metabolite biomarkers discovery is expected to improve the disease evolution and outcome. The activation of abundantly expressed NLRP3 inflammasome represents the background process of the diabetes mellitus disturbances like hyperglycemia and insulin resistance, as well as for myocardial cell death and fibrosis, all of them being features characteristic for cardiometabolic syndrome. Many molecules like troponins, brain natriuretic protein (BNP), ST2/IL-33, C-reactive protein (CRP), TNF, IL-1β, and IL-18 cytokines have been already examined as molecular markers for diagnosing or predicting different cardiac disturbances like myocardial infarction, heart failure, or myocarditis. In addition, metabolomics research comes with new findings arguing that NLRP3 inflammasome becomes a promising molecular tool to use for clinical and therapeutical management providing new targets for therapies in cardiometabolic syndrome. Inflammasome markers analyses, along with other molecular or genetic biomarkers, will result in a better understanding of cardiometabolic syndrome pathogenesis and therapeutic targets. Screening, diagnostic, and prognostic biomarkers resulted from inflammasome biomarker research will become standard of care in cardiometabolic syndrome management, their utility becoming the first magnitude.

Gut microbiota plays a major role in the process of food absorption and low grade inflammation, two key steps in obesity and diabetes mellitus occurrence. Gut microbiota metabolites, such as short chain fatty acids (SCFA), have an important impact over the metabolic pathways like insulin signalling, incretin production and inflammation. [1-3] We aimed to study the microbiota patterns in obese and T2D patients from Black Sea Coast region, considering the ethnic mixture, environmental and geographical particularities, involving diet or various habits in this area. 100 patients and 100 controls matched by age, gender and ethnicity were studied regarding feaces predominance of Lactobacillus and Bifidobacterium species. We compared the results of microbiota patterns from patients to those obtained in a similar control group of healthy subjects. The standard pour plate 0.05% L-cystine enriched method was used to obtain the bacterial cultures and anaerobic conditions. Morphological and biochemical tests were used to identify the Lactobacillus and Bifidobacterium spp. Fecal organic acid concentrations were explored in frozen samples. The association between bacterial counts/organic acid concentrations and independent variables, including age, diet, ethnicity and other risk factors were calculated using multivariable linear regression analysis. Pearson�s correlation coefficients were calculated to detect associations between fecal bacteria counts/organic acid concentrations and laboratory variables (serum biomarkers, body mass index, age, and severity of obesity/T2D according to international scales). Junk and sweet diets, lack of physical activity and familial aggregation of hypercholesterolemia and diabetes were significantly more often present in our T2D/obese patients than in controls. The bacterial counts of the L. acidophilus, L plantarum and L. reuteri subgroups of Lactobacillus sp were significantly lower among patients with T2D and obesity than in controls. The counting of Bifidobacterium spp revealed a higher presence of B. bifidum in controls than in obese or T2D patients. Diet type (junk food and sweets), BMI (]25) and personal history of metabolic disorders were associated with decreased counts of L acidophilus and increased counts of L. fermentum and B. adolescentis in T2D patients. Ethnicity, metabolic disorders history and junk and sweet diet were associated with low counts of L. acidophilus and L. reuteri and low counts of B. longum. Junk and sweet diet was associated with low counts of B. bifidum. Romanian ethnicity and metabolic disorders were associated with low counts of B. choerinum at obese patients, independent of age or previous antidiabetic treatments. The concentrations of acetic and butyric acids were significantly lower in all patients groups, while the concentrations of valeric acid were significantly higher in patients with untreated T2D and obese patients compared to the controls. Low counts of L. acidophilus and L. reuteri were positively correlated with the increased levels of HbA1c, LDL cholesterol, TG and inflammatory markers such as CRP, ESR and IL-6, no matter of diet, age, ethnicity or metabolic disorders history. Also, low counts of B. bifidum and B. infantis were positively correlated with high levels of CRP, IL-6 and TG. In obese patients, statistic analysis results showed that low counts of L. acidophilus, L. plantarum, L. johnsonii and L. reuteri were positively associated with increased levels of CPR, IL-6 and TG, while low counts of B. bifidum, B infantis and B. breve were positively correlated with higher counts of CPR, LDL cholesterol and TG. Low counts of B. bifidum and B choerinum were positively correlated with low counts of HDL cholesterol in Romanian ethnicity patients and in those with previous metabolic disorders. Low bacterial counts of some particular strains of Lactobacillus spp and Bifidobacterium spp were positively correlated with diet type, BMI, Romanian ethnicity and personal history of metabolic disorders obese and T2D patients from Romanian Black Sea Coast Region.

Balneotherapy, a branch of physical and rehabilitation medicine using the natural factors of balneal resorts for therapeutical purposes to modulate the symptoms of numerous diseases, represents a non‑pharmaceutical therapeutic alternative, easily accepted by patients and used both preventively and curatively. Crenotherapy, a branch of balneotherapy, is the method in which mineral waters are used as a therapeutic internal cure by ingestion. This procedure is performed in spa resorts (where these natural resources exist), and the ingestion of mineral water takes place at the source (spring), in the quantities recommended by the medical rehabilitation physician, according to specific regimens for the condition to be treated. Depending on their physical and chemical composition, the therapeutic mineral waters fall into several categories, having clear indications for certain pathologies. Hypotonic, isotonic, or slightly hypertonic mineral waters are recommended in diseases of the digestive tract and hepatobiliary conditions. Over time, studies have been conducted to determine the effect of these types of treatments, highlighting the complex influence of crenotherapy on the gastrointestinal tract, with favorable results, therefore the use of mineral water intake in various pathologies being recommended. The current review focuses on the existing literature data and refers to the main progress made in understanding the benefit, indications, and crenotherapy procedures in the management of gastrointestinal disorders.

Background: Secondary prevention of thromboembolic disease in cancer patients with oral anticoagulants is a challenging issue, due to the particular liver biology in this high-risk category of subjects. Aim: To compare novel oral anticoagulant dabigatran vs acenocumarol administered in patients with malignant disease and deep vein thrombosis. Method. We randomized 46 patients with paraneoplastic deep vein thrombosis in two groups, matched by age, sex, cancer type and Khorana score in 2 groups: first group (n=23) assigned to bid fixed-dose dabigatran (according to individual creatinine clearance), and second group (n= 23) assigned to qd adjusted-dose acenocumarol (according to individual INR determined monthly). Patients were followed-up 6 months. Results: 6 patients from the dabigatran group (13.95%) experienced an adverse outcome (major bleeding or recurrent thrombosis), vs. 12 patients (52.817%) from acenocumarol group, showing a significant difference (P=0.0349; 95%CI=0.2266-1.103). No patient developed pulmonary thromboembolism.There was one death due to major bleeding in the acenocumarol group vs. none in dabigatran group. No difference in the progression of underlying cancer was noticed between the two studied groups (4 deaths in dabigatran group vs 5 deaths in acenocumarol group, OR= 0.7579; 95% CI= 0.1752-3.279; P=0.3551). Patients in the dabigatran group reported a better QOL due to the fact that there was no need for monthly blood tests as in acenocumarol group. Conclusion: In our study dabigatran was associated with a smaller rate of complications and may be safer in cancer patients with venous thromboembolism. Larger studies are needed, but difficult to be performed in this specific class of patients.