Bone metabolism and hand grip strength response to aerobic versus resistance exercise training in non-insulin dependent diabetic patients

Background: Diabetes mellitus has been shown in many studies to be associated with reduced bone mass and an increased risk of fracture. Currently, our understanding of how to use exercise effectively in diabetic patients in prevention of osteoporosis is incomplete and has prompted our interest to identify the type of effective osteogenic exercise.Objective: The aim of this study was to compare the changes in handgrip strength and bone metabolism after 6 months between aerobic and resistance exercise training in non-insulin dependent diabetic patients in Jeddah area.Materials and methods: One hundred non-insulin dependent diabetic male patients participated in this study and were divided into two equal groups; the first group (A) received aerobic exercise training, where the second group (B) received resistance exercise training. The program consisted of three sessions per week for six months.Results: The mean values of serum calcium and Hand grip strength were significantly increased, while the mean values of parathyroid hormone were significantly decreased in both groups .Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment.Conclusion: Aerobic exercise training on treadmill is appropriate to improve markers of bone  metabolism and hand grip strength in non-insulin dependent diabetic patients.Keywords: Aerobic exercise, resistance exercise, bone mineral density, non-insulin dependent diabetes

Markers of liver function and inflammatory cytokines modulation by aerobic versus resisted exercise training for nonalcoholic steatohepatitis patients

Background: Non-alcoholic steatohepatitis is a growing public health problem with no approved therapy; as cytokines and other pro-inflammatory mediators may each play a role in transition of steatosis to NASH which is projected to be the leading cause of liver transplantation in the United States by 2020.Objective: The aim of this study was to compare the impact of aerobic versus resisted exercise training on inflammatory cytokines and markers of liver function in patients with nonalcoholic steatohepatitis.Material and Methods: Fifty patients with NASH were included in the study and divided into two subgroups. Participants were included into 2 equal groups; the first group (A) received aerobic exercise training. The second group (B) received resisted exercise training three times a week for 3 months.Results: The mean values of TNF- α, IL6, IL8, ALT and AST were significantly decreased in group (A) and group (B).Also; there was a significant difference between both groups after treatment.Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic steatohepatitis.Keywords: Aerobic Exercise; Resisted Exercises; Inflammatory Cytokine; markers of liver function; Non-alcoholicsteatohepatitis

Liver enzymes and psychological well-being response to aerobic exercise training in patients with chronic hepatitis C

Background: Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person’s physical and psychological health.Objective: The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic exercise training in patients with CHC.Material and Methods: Fifty CHC patients were included in two equal  groups. The first group (A) received aerobic exercise training in addition to their regular medical treatment. The second group (B) received no training and only has their regular medical treatment. The program consisted of three sessions per week for three months.Results: There was a significant decrease in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate  Aminotransferase (AST), Gamma – Glutamyltransferase (GGT) , Beck  Depression Inventory (BDI ) & Profile of Mood States(POMS) and increase in Rosenberg Self-Esteem Scale (RSES) in group (A) after treatments, but the changes in group (B) were not significant. Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study.Conclusion: Aerobic exercise training improves hepatic enzymes and psychological well-being in patients with chronic hepatitis C.Key words: liver enzymes; psychological well-being; aerobic exercise; chronic hepatitis C

Plain language summary of the TOPAZ-1 study: Durvalumab and chemotherapy for advanced biliary tract cancer

WHAT IS THIS SUMMARY ABOUT?: This is a summary describing the results of a Phase III study called TOPAZ-1. The study looked at treatment with durvalumab (a type of immunotherapy) and chemotherapy to treat participants with advanced biliary tract cancer (BTC). Advanced BTC is usually diagnosed at late stages of disease, when it cannot be cured by surgery. This study included participants with advanced BTC who had not received previous treatment, or had their cancer come back at least 6 months after receiving treatment or surgery that aimed to cure their disease. Participants received treatment with durvalumab and chemotherapy or placebo and chemotherapy. The aim of this study was to find out if treatment with durvalumab and chemotherapy could increase the length of time that participants with advanced BTC lived, compared with placebo and chemotherapy. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took durvalumab and chemotherapy had a 20% lower chance of experiencing death at any point in the study compared with participants who received placebo and chemotherapy. The side effects experienced by participants were similar across treatment groups, and less than 12% of participants in either treatment group had to stop treatment due to treatment-related side effects. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, these results support durvalumab and chemotherapy as a new treatment option for people with advanced BTCs. Based on the results of this study, durvalumab is now approved for the treatment of adults with advanced BTCs in combination with chemotherapy by government organizations in Europe, the United States and several other countries

Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis

In patients with cytopenic myelofibrosis, treatment with the JAK2/IRAK1 inhibitor pacritinib was associated with anemia benefit in the phase 3 PERSIST-2 study. The impact of pacritinib on transfusion independence (TI) has not been previously described, nor has the mechanism by which pacritinib improves anemia been elucidated. Because it has been previously postulated that inhibition of activin A receptor, type 1 (ACVR1)/activin receptor-like kinase-2 improves anemia in patients with myelofibrosis via suppression of hepcidin production, we assessed the relative inhibitory potency of pacritinib compared with other JAK2 inhibitors against ACVR1. Pacritinib inhibited ACVR1 with greater potency (half-maximal inhibitory concentration [IC50] = 16.7 nM; Cmax:IC50 = 12.7) than momelotinib (IC50 = 52.5 nM; Cmax:IC50 = 3.2), fedratinib (IC50 = 273 nM; Cmax:IC50 = 1.0), or ruxolitinib (IC50 \u3e 1000; Cmax:IC50 \u3c 0.01). Pacritinib\u27s inhibitory activity against ACVR1 was corroborated via inhibition of downstream SMAD signaling in conjunction with marked suppression of hepcidin production. Among patients on PERSIST-2 who were not transfusion independent at baseline based on Gale criteria, a significantly greater proportion achieved TI on pacritinib compared with those treated on best available therapy (37% vs 7%, P = .001), and significantly more had a ≥50% reduction in transfusion burden (49% vs 9%, P \u3c .0001). These data indicate that the anemia benefit of the JAK2/IRAK1 inhibitor pacritinib may be a function of potent ACVR1 inhibition

Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis

Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR = 0.98 [0.59, 1.62]; LFS HR = 0.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR = 0.474, p = 0.0001; SIMPLIFY-2 HR = 0.226, p = 0.0005). Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR = 0.323; p \u3c 0.0001) and multivariate (HR = 0.311; p \u3c 0.0001) analyses. These findings underscore the importance of achieving or maintaining TI in myelofibrosis, supporting the clinical relevance of momelotinib\u27s pro-erythropoietic mechanism of action, and potentially informing treatment decision-making