Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial.

Objectives: To estimate thresholds for defining meaningful within-patient improvement from baseline to weeks 13-24 and interpreting meaningfulness of between-group difference for the non-transfusion-dependent beta-thalassaemia patient-reported outcome (NTDT-PRO) tiredness/weakness (T/W) and shortness of breath (SoB) scores. A secondary objective was to determine the symptom severity threshold for the NTDT-PRO T/W domain to identify patients with symptomatic T/W.

Design: Pooled blinded data from the phase 2, double-blind, placebo-controlled, randomised BEYOND trial in NTDT (NCT03342404) were used.

Barriers and Enablers for Physical Activity Engagement Among Individuals From India With Type 2 Diabetes Mellitus: A Mixed-Method Study.

Background: Type 2 diabetes mellitus (T2DM) is a complex, chronic condition that can cause multiple complications due to poor glycemic control. Self-management plays a crucial role in the management of T2DM. Lifestyle modifications, including physical activity (PA), are fundamental for self-management.

Luspatercept stimulates erythropoiesis, increases iron utilization, and redistributes body iron in transfusion-dependent thalassemia.

Luspatercept, a ligand-trapping fusion protein, binds select TGF-β superfamily ligands implicated in thalassemic erythropoiesis, promoting late-stage erythroid maturation. Luspatercept reduced transfusion burden in the BELIEVE trial (NCT02604433) of 336 adults with transfusion-dependent thalassemia (TDT). Analysis of biomarkers in BELIEVE offers novel physiological and clinical insights into benefits offered by luspatercept.

Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial.

Background: Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.

Long-term safety and erythroid response with luspatercept treatment in patients with β-thalassemia.

Background: β-thalassemia is a hereditary blood disorder resulting in ineffective erythropoiesis and anemia. Management of anemia with regular blood transfusions is associated with complications including iron overload. Here, we report long-term safety and efficacy results of the first clinical study of luspatercept in β-thalassemia, initiated in 2013, enrolling adults with both nontransfusion-dependent (NTD) and transfusion-dependent (TD) β-thalassemia.

Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke.

Diabetes mellitus, a well-established risk factor for stroke, is related to higher mortality and poorer outcomes following the stroke event. Advanced glycation end products(AGEs), their receptors RAGEs, other ligands, and several other processes contribute to the cerebrovascular pathomechanism interaction in the diabetes-ischemic stroke combination. Critical reappraisal of molecular targets and therapeutic agents to mitigate them is required to identify key elements for therapeutic interventions that may improve patient outcomes.

Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial.

Background: In patients with non-transfusion-dependent β-thalassaemia, haemoglobin concentrations lower than 10 g/dL are associated with a higher risk of morbidity, mortality, and impaired quality of life. No drugs are specifically approved for anaemia management in patients with non-transfusion-dependent β-thalassaemia, other than transfusion therapy administered infrequently in accordance with patients' needs. We assessed the efficacy and safety of luspatercept versus placebo in patients with non-transfusion-dependent β-thalassaemia.

Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study.

JCO Luspatercept has high clinical activity in patients with transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS) and ring sideroblasts (RS) relapsed or refractory to erythropoietin. We report long-term luspatercept safety and efficacy in 108 patients with LR-MDS in the PACE-MDS study, including 44 non-RS and 34 non-transfusion-dependent or previously untreated patients. The primary end point was safety.

Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts.

Luspatercept is an approved therapy for selected patients with lower risk myelodysplasia requiring transfusion despite erythropoiesis-stimulating agents, based on the early results of a randomized trial against placebo. Zeidan and colleagues report that after a median of 26 months follow-up, 27% of patients commencing luspatercept were continuing therapy. Their updated analyses confirm that a significant minority (45%) of eligible patients can achieve transfusion independence, with a median durability of 30 weeks.

Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the MEDALIST Phase 3 Trial.

Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk MDS who had ring sideroblasts and were refractory to, intolerant to, or ineligible for prior treatment with erythropoiesis-stimulating agents. We evaluated the effect of luspatercept on HRQoL in patients enrolled in MEDALIST using the EORTC QLQ-C30 and the QOL-E questionnaire.

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia.

Background: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.

Methods: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.

Crestal Bone Loss around Dental Implants: Platform Switching vs Platform Matching-A Retrospective Study.

Aim: The objective of this study was to determine the vertical and horizontal marginal bone levels in platform-switched and platform-matched dental implants.

Materials And Methods: In the present study, 50 dental implants were placed in 50 patients over a 1-year period. Measurement was performed from the implant shoulder to the most apical and horizontal marginal defect by periapical radiographs to examine the changes of peri-implant alveolar bone before and 12 months after prosthodontic restoration delivery.

Bisalbuminemia in a Hypothyroid Patient with Diabetes: A Case Report.

Bisalbuminemia is a rarely encountered anomaly characterized by presence of bifid albumin bands or a single widened albumin band in electrophoretogram. Inherited bisalbuminemia is quite rare and inherited as an autosomal dominant form. The acquired form of bisalbuminemia is usually transient and may be observed during long term beta lactam antibiotic therapy, acute pancreatitis, myeloma and nephrotic syndrome.

Urinary protein thiols in different grades of proteinuria.

Total thiol status of plasma, especially thiol groups over protein contributes maximum to the plasma antioxidant status of the body. Serum protein thiols were found to be decreased in various disease conditions including chronic renal failure patients. Only few studies determined the levels of urinary protein thiols in disease conditions.

Phenotypic detection of inducible clindamycin resistance among Staphylococcus aureus isolates by using the lower limit of recommended inter-disk distance.

Context: Clindamycin is one of the important alternative antibiotics in the therapy of Staphylococcus aureus, particularly in methicillin-resistant S. aureus (MRSA) infections. Inducible clindamycin resistance (iMLS B--inducible Macrolide-Lincosamide-Streptogramin B resistance) is a critical factor in antimicrobial susceptibility testing.

Iron supplementation and oxidative stress in patients with uremia.

The existence of oxidative stress in uremia is well proved but the relative importance of uremic status versus the role of free iron in exacerbating oxidative stress in patients with uremia is not been clarified. Serum creatinine, free iron both in ferrous and ferric state, protein thiols, lipid hydroperoxides levels were estimated by spectrophotometric methods. The study groups comprised of patients with chronic kidney disease on conservative management, on hemodialysis with and without iron supplementation, and compared with healthy controls.

Relationship between free iron and glycated hemoglobin in uncontrolled type 2 diabetes patients associated with complications.

Free iron in serum has been found in several disease conditions including diabetes. In the present work, we studied the relationship between free iron, fasting blood glucose (FBG) and glycated haemoglobin (HbA(1c)). Study was carried out on 50 type 2 diabetes cases under poor glycemic control associated with complications, 53 type 2 diabetes cases under good glycemic control and 40 healthy controls.