Dual antiplatelet therapy (DAPT) is a cornerstone of antithrombotic treatment in patients undergoing percutaneous coronary intervention. The optimal duration of DAPT, i.e. the minimal period needed to ensure the best safety and efficacy, to prevent ischemic complications, including stent thrombosis, has been extensively explored in multiple randomized controlled trials over the last years. Accumulating evidence is supporting a clinical approach where there is a prevailing role of the risk of bleeding in patients at high bleeding risk (HBR) it is generally advisable to reduce the duration of DAPT irrespective of their risk of thrombosis. In addition, among HBR patients, (i) new recommendations prefer direct oral anticoagulants (DOAC) over vitamin K antagonists in DOAC-eligible patients with atrial fibrillation and coronary artery disease; (ii) measures to minimize bleedings while on DAPT should be pursued, including de-escalation of P2Y12 receptor inhibitor therapy; and (iii) new studies are testing reversal strategies for short DAPT regimens, with early discontinuation of aspirin.  https://www.selleckchem.com/products/protac-tubulin-degrader-1.html  In the present review, we discuss the rationale and decision-making considerations to reduce safely DAPT duration in HBR patients.A significant proportion of patients undergoing percutaneous coronary intervention (PCI) is deemed at high bleeding risk. Definition and identification of high bleeding risk patients at the time of PCI is extremely important to inform decision-making regarding antithrombotic treatment selection and optimize the balance between ischemic and bleeding risk. The recent introduction of standardized definitions and tools to identify and treat patients at high bleeding risk is promising to improve evidence-based care in this subgroup of patients.HLH (hemophagocytic lymphohistiocytosis; hemophagocytic syndrome) occurs when inflammatory reaction cannot stop on its own, but continues to self-accelerate with positive feedback loops. If not interrupted, this pathomechanism leads to death. HLH in adults is usually diagnosed based on HLH-2004 criteria, but its confirmation should not stop the diagnostic process. Finding the triggering factor (especially malignancy) is of utmost importance. Treatment strongly depends on the established trigger; based on etoposide HLH-94 protocol (adjusted for adults) is used in many instances. Diagnostic process should not unnecessarily delay the treatment, patients in severe or quickly deteriorating clinical condition require its fast initiation. Provided progressive character of HLH, time is extremely important. Prompt diagnosis and treatment, frequently made by an internal medicine specialist, is life-saving. Aim of this review is to raise HLH awareness among internal medicine specialists and to provide advice on HLH management tailored for this group of physicians. Suggested approach is based on the latest recommendations by the Histiocyte Society and include novel insights based on the Authors' experience.Aims of this population-based cohort study was to compare the overall and site-specific cancer incidence in individuals with alcohol or drug use disorders with incidence of the general population, and to estimate excess cancer risk in a subgroup of individuals who have hepatitis C virus or HIV infection. The study included 4373 residents of Reggio Emilia province diagnosed with alcohol or drug use disorders during the period from 1 January 1985 to 31 December 2014. All newly diagnosed cancers registered from 1 January 1996 to 31 December 2014 were taken into account to calculate the standardised incidence ratio (SIR) of cancers of any site and of site-specific cancers. SIR of cancer at any site was 1.54 (95% confidence interval [CI] 1.31-1.81). Oropharyngeal and nasopharyngeal cancers were associated with the highest excess risk (SIR=21.3; 95% CI 8.0-56.6), followed by anogenital (SIR=37.4; 95% CI 15.6-89.7) and oesophageal cancer (SIR=12.9; 95% CI 4.8-34.3). Excess risk of cancer of larynx, oropharynx, oesophagus, non-Hodgkin lymphoma, lung and bronchus, liver and anus were observed among alcohol use disorders individuals and of bronchus and lungs, pancreas, liver, colon and anus among drug use disorders individuals. Among hepatitis C virus-positive individuals, cancer at any site risk was 1.59 (95% CI 0.99-2.56) and among HIV-infected individuals it was 2.84 (95% CI 1.61-5.0). Individuals with alcohol and drug use disorders face a higher risk of various cancers. Effective interventions to prevent or reduce the harm of substance abuse and risky behaviours in this population are warranted.To identify neurons that specifically increase blood glucose from among the diversely-functioning cell types in the ventromedial hypothalamic nucleus (VMN), we studied the cholecystokinin (CCK) receptor-B (CCKBR)-expressing VMN targets of glucose-elevating parabrachial nucleus neurons. Activating these VMNCCKBR neurons increased blood glucose. Furthermore, while silencing the broader VMN decreased energy expenditure and promoted weight gain without altering blood glucose, silencing VMNCCKBR neurons decreased hepatic glucose production (HGP), insulin-independently decreasing blood glucose without altering energy balance. Silencing VMNCCKBR neurons also impaired the counter-regulatory response (CRR) to insulin-induced hypoglycemia and glucoprivation and replicated hypoglycemia-associated autonomic failure (HAAF). Hence, VMNCCKBR cells represent a specialized subset of VMN cells that function to elevate glucose. These cells not only mediate the allostatic response to hypoglycemia, but also insulin-independently modulate the homeostatic setpoint for blood glucose, consistent with a role for the brain in the insulin-independent control of glucose homeostasis.SGLT2 inhibitors are beneficial in halting diabetic kidney disease; complete mechanisms is unknown. The epithelial to mesenchymal transition (EMT) is associated with Sirt3 suppression and aberrant glycolysis. Here, we hypothesized that the SGLT2 inhibitor restores normal kidney histology/function associated with the inhibition of aberrant glycolysis in diabetic kidneys. CD-1 mice with streptozotocin-induced diabetes displayed kidney fibrosis associated with the EMT at 4-months after diabetes induction. Empagliflozin intervention for one month restored all changes; adjustment of blood glucose by insulin did not. Empagliflozin normalized suppressed Sirt3 levels and aberrant glycolysis (characterized by hypoxia-inducible factor-1α accumulation, hexokinase 2 induction and pyruvate kinase isozyme M2 dimer formation) in diabetic kidneys. Empagliflozin also suppressed the accumulation of glycolysis byproducts in diabetic kidneys. Another SGLT2 inhibitor, canagliflozin, demonstrated similar in vivo effects. High-glucose media induced the EMT, which was associated with Sirt3 suppression and aberrant glycolysis induction, in the HK2 proximal tubule cell line; SGLT2 knockdown suppressed the EMT with restoration of all aberrant functions.