Correction to: Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

[This corrects the article DOI: 10.1007/s12288-022-01602-5.].

Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18-65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP. Trial registration number and date of registration: CTRI/2019/04/018614.

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling.

INTRODUCTION: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are highly effective in treating insulin resistance. However, associated side effects such as weight gain due to increase in adipogenesis and lipogenesis hinder their clinical use. The aim of the study was to design and synthesize novel partial PPARγ agonists with weaker lipogenic effect in adipocytes and enhanced glucose transporter 4 (GLUT4) translocation stimulatory effect in skeletal muscle cells. METHODS: Novel partial PPARγ agonists (GS1, GS2, and GS3) were designed and screened to predict their binding interactions with PPARγ by molecular docking. The stability of the docked ligand-PPARγ complex was studied by molecular dynamics (MD) simulation. The cytotoxicity of synthesized compounds was tested in 3T3-L1 adipocytes and L6 myoblasts by MTT assay. The lipogenic effect was investigated in 3T3-L1 adipocytes using oil red O staining and GLUT4 translocation stimulatory effect in L6-GLUT4myc myotubes by an antibody-coupled colorimetric assay. RESULTS: The molecular docking showed the binding interactions between designed agonists and PPARγ. MD simulation demonstrated good stability between the GS2-PPARγ complex. GS2 and GS3 did not show any significant effect on cell viability up to 80 or 100 µM concentration. Pioglitazone treatment significantly increased intracellular lipid accumulation in adipocytes compared to control. However, this effect was significantly less in GS2- and GS3-treated conditions compared to pioglitazone at 10 µM concentration, indicating weaker lipogenic effect. Furthermore, GS2 significantly stimulated GLUT4 translocation to the plasma membrane in a dose-dependent manner via the AMPK-dependent signaling pathway in skeletal muscle cells. CONCLUSION: GS2 may be a promising therapeutic agent for the treatment of insulin resistance and type 2 diabetes mellitus without adiposity.

Computational investigations on the hemodynamic performance of a new swirl generator in bifurcated arteries.

Hemodynamic behaviour of blood in the bifurcated arteries are closely related to the development of cardiovascular disease. The secondary flows generated at the bifurcation zone promotes the deposition of atherogenic particles on the outer walls. The present study aims at suppressing the development of atherosclerosis plaque by inducing helical flow structure in the arterial passage. To realize this objective a novel swirl generator (stent like structure with an internal groove) has been developed to induce helicity in the bifurcated passage. The functional requirement of the swirl generator is to minimize the relative residence time (RRT) of the fluid layer near the endothelial wall without generating any additional pressure drop. Different configurations of the swirl generator have been tested computationally using large eddy simulation (LES) model. It is observed that the induced helical flow redistributes the kinetic energy from the centre to the periphery. A single rib swirl flow generator proximal to the stent treated passage can generate sufficient helicity to bring down the RRT by 36% without generating any additional pressure drop. The swirl flow adds azimuthal instability which increase vortex formations in the passage. The induced helical flow in the domain provokes more linked vortices, which may act as self-cleaning mechanism to the arterial wall.

Gastroduodenal intussusception due to pedunculated polypoid gastrointestinal stromal tumour (gist ): a rare case.

Gastrointestinal stromal tumours (GISTs) account for less than 3% of all gastrointestinal tract tumours and 5.7% of all sarcomas, and the majority of these tumours are gastric in origin. Patients commonly present with gastrointestinal bleeding or abdominal pain with 10-30% of patients presenting with symptoms of gastrointestinal obstruction. We report a rare case clinically presenting as gastric outlet obstruction, gastroscopy suspecting it to be organo-axial gastric volvulus, CECT(Contrast Enhanced Computerised Tomography) suggesting features of gastric malignancy (leiomyosarcoma) keeping the possibility of differential diagnosis of GIST. Eventually on exploratory laparotomy we discovered gastric outlet obstruction due to transpylorically herniated pedunculated polypoid GIST leading to gastroduodenal inussusception.

Prophyactic platelet transfusion in stable dengue Fever patients: is it really necessary?

Our hospital is a referral centre for Jehovah's Witnesses (JW) patients, who as a matter of religious belief refuse transfusions of blood/blood components. We have treated JW patients with dengue fever (DF) and thrombocytopenia without platelet transfusion, without any mortality or major morbidities. We retrospectively compared the duration needed for platelet recovery and duration of hospitalization of DF with thrombocytopenia in those treated with prophylactic platelet transfusion and JW patients who were managed without these. Among JW patients, platelet counts recovered to >50,000 in 2.57 days (Mean) as compared to those who received prophylactic platelet transfusion, who recovered in 4.43 days (P value < 0.0001). They also had significantly less number of days of hospitalization (3.68 days vs 5.13 days, P value < 0.0001). These differences persisted even when a subgroup analysis of patients who had nadir platelet count less than 10,000 were done. Most importantly, none of the patients in either group suffered any significant morbidity or mortality. Prophylactic platelet transfusion in clinically stable DF patients was associated with significant delay in platelet recovery and increased duration of hospitalization, even though was not harmful in terms of morbidity or mortality. Though number of subjects involved in the study was small, this brief report further adds to the current evidence that prophylactic platelet transfusion in clinically stable DF patients with a platelet count more than 10,000/cmm is not indicated.

Granulocytic sarcoma of colon in a patient with acute promyelocytic leukemia.

Granulocytic sarcoma in a patient with acute promyelocytic leukemia (APML) has been described often in the relapse setting, however primary presentation of APML as granulocytic sarcoma is rare. We present a case of a 29 year old male who was evaluated for thrombocytopenia with haematochezia and a diagnosis of acute promyelocytic leukemia was established after the colonic biopsy was reported as a granulocytic sarcoma.