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Background & Aims: Despite several recent international guidelines, no consensus exists on the bleeding risk nor haemostatic parameter thresholds that define the safety of invasive procedures in patients with cirrhosis. The aim of this study was to establish a position paper on the bleeding risk associated with invasive procedures in patients with cirrhosis among the experts involved in various guidelines. Methods: All experts involved in recent guidelines on the management of invasive procedures in patients with cirrhosis were invited to classify 80 procedures as ''high risk'' or ''low risk'' with respect to bleeding. Procedures were considered high risk when the estimated risk of major bleeding was 1.5% or more, or when even minor bleeding might lead to significant morbidity or death. The experts were also asked to choose safety thresholds for laboratory test values at which elective invasive procedures could be safely performed. The predetermined threshold considered as “consensus” was ≥75% agreement. Results: Fifty-two experts participated in the study. Out of 80 procedures, a consensus opinion was reached for 52 procedures (65%): 17 procedures were classified as “high risk”, primarily interventional endoscopic procedures, percutaneous organ biopsies, or procedures involving the central nervous system; and 35 as “low risk”, primarily “diagnostic” procedures. The lowest platelet counts at which performance of a low-risk procedure or a high-risk procedure/surgery were deemed acceptable were 30 × 109/L and 50 × 109/L, respectively. Experts did not believe that international normalised ratio should be considered before performing low-risk procedures; 71% also indicated that it should not be considered before performing high-risk procedures. Conclusions: This experience-based classification may be helpful to refine future study designs and to guide clinical decision making regarding invasive procedures in patients with cirrhosis. Impact and implications: Several risk classifications and management guidelines for invasive procedures in patients with cirrhosis have been proposed, but with conflicting recommendations. By providing a position paper, based on the opinion of a broad panel of experts, on the bleeding risk associated with 52 invasive procedures in patients with cirrhosis, this survey will help to provide a framework for future study design. The consensus on platelet count, international normalised ratio, fibrinogen and activated partial thromboplastin time identified in this survey will inform physicians regarding the laboratory test values considered acceptable by the experts prior to the performance of an elective invasive procedure in patients with cirrhosis.

Objective The aim of this study was to evaluate overdilation of 10-mm standard and 8–10 mm controlled-expansion Viatorr stents to 12 mm during transjugular intrahepatic portosystemic shunt (TIPS) placement when insufficient reduction (<50%) in portosystemic gradient (PSG) is achieved with standard 10 mm dilation. Materials and Methods It is a single-institution, institutional review board-approved, retrospective review of TIPS (2013–2022) to identify patients in the overdilation group (12 mm dilation of a 10-mm stent) and a control group (10 mm dilation of a 10-mm stent) matched for age, indication, stent type, Model for End-Stage Liver Disease (MELD) score, pre-TIPS PSG, and variceal embolization. Stent diameter, technical success, clinical outcomes, and adverse events were assessed for both groups. Results TIPS was created for the overdilation group (n = 35, 57 ± 11 years, 69% male; MELD: 14 ± 5) and control group (n = 35, 57 ± 11 years, 83% male; MELD: 14 ± 5). Overdilation to 12 mm adequately reduced PSG by more than 50% (55 vs. 65% in the control group, p = 0.11). The stent diameter was larger in the overdilation group on cross-sectional imaging (9.8 ± 0.2 vs. 9.5 ± 0.4 mm, p < 0.001), with an estimated 57% higher volume flow rate (p = 0.002). Patients were followed for a median of 11.3 months (range: 0.03–75) and 15.6 months (range: 0.03–106) in the overdilation and control groups, respectively. There was an equivalent rate of ascites resolution (56 vs. 63%, p = 0.68) and rebleeding (13 vs. 17%, p = 0.82) in the overdilation and control groups, with a similar risk of new-onset hepatic encephalopathy (41 vs. 33%, p = 0.51) and TIPS occlusion (11 vs. 9%, p = 0.69). Overdilation did not result in any instance of stent fracture. Conclusion Overdilation of 10-mm Viatorr stents with 12 mm balloons may provide benefit by potentially reducing PSG further for patients initially having inadequate PSG reduction with short-term safety. [ABSTRACT FROM AUTHOR]

Aim: The present study was aimed to highlight the current prescribing pattern of oral hypoglycemia in type 2 diabetes mellitus and to evaluate the therapeutic effectiveness of these therapeutic categories in achieving target glycemic control. Methods: This is a prospective, cross-sectional, observational study of 6 months' duration conducted in a tertiary care hospital of Lahore, Pakistan. Results: The current research recruited 145 patients presented in diabetes management center of a tertiary care hospital in Lahore, Pakistan. Mean age of the participants was 50.2 (± 8.5) years. Out of the 145 patients, 63% were females and 37% were males. Most patients were diagnosed to have diabetes within the past 5 years. Diabetes-induced neuropathy was the most common complication (71.7%) among the patients. A large proportion of these patients (70.3%) were also suffering from other comorbidities among which the most common one is hypertension. The average number of prescribed medications was 1.31. Metformin was prescribed to a majority of patients (64%) as monotherapy while 28.96% received combination therapy. Mean glycated hemoglobin (HBA1c) before and after 3 months of treatment was 8.5 (± 2.3) and 8.04 (± 2.1), respectively. Inferential statistics show a strong association between HBA1c and life style modifications and adherence to medication therapy (P = 0.05). However, the correlation between HBA1c and Morisky score and duration of disease was inverse and weak (P = 0.6, 0.4). The t-test values show a small difference between HBA1c values before and after 3 months (t = 0.440 and 0.466, respectively). Conclusion: Optimization of medication regimen and continuous patient education regarding life style modification and adherence to medication therapy are necessitated to bring HBA1c values near to target. [ABSTRACT FROM AUTHOR]

Background: Vorinostat (SAHA) is a histone deacetylase inhibitor that has shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, only a subset of patients with CTCL (30-35%) respond to SAHA and the response is not always sustainable. Thus, understanding the mechanisms underlying evasive resistance in this cancer is an unmet medical need to improve the efficacy of current therapies., Purpose: This study aims to identify factors contributing to resistance against SAHA in CTCL and ways to mitigate it., Methods and Results: In this study, we demonstrated that attenuated reactive oxygen species (ROS) induces the expression of interleukin (IL)-2Rα, one of the IL-2 receptors, which drives resistance to SAHA in CTCL. We also determined that cantharidin could overcome SAHA resistance to CTCL by blocking IL-2Rα-related signaling via ROS-dependent manner. Mechanistically, accelerated translation of IL-2Rα contributes to excessive IL-2Rα protein formation as a result of reduced ROS levels in SAHA-resistant CTCL. At the same time, amplified IL-2R signals are evidenced by strengthened interaction of IL-2Rβ with IL-2Rγ and Janus kinase/signal transducer and activator of transcription molecules, and by increased expression of protein kinase B (AKT)/mTOR and mitogen-activated protein kinase signaling. Moreover, cantharidin, an active constituent of Mylabris used in traditional Chinese medicine, markedly increased ROS levels, and thereby restrained IL-2Rα translation, resulting in suppression of downstream pathways in SAHA-resistant cells. Cantharidin is also found to synergize with SAHA and triggers SAHA-resistant cell death via IL-2R signaling both in vitro and in vivo., Conclusion: Our study uncovers a novel molecular mechanism of acquired SAHA resistance and also suggests that using cantharidin is a potential approach to overcome CTCL therapy resistance. Our findings underlie the therapeutic potential of cantharidin in treating CTCL., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)