A concurrent parallel study to compare the efficacy and safety of oral iron chelators, defrasirox and defriprone in patients of beta thalassaemia major

Background: This study was planned to evaluate all the cases of β thalassaemia major, already receiving one of the oral iron chelators for a comparison among the efficacy, safety and economy of deferasirox and deferiprone to establish the better option in an Indian scenario.Methods: We identified two groups of patients: 38 treated with deferasirox and 35 treated with deferiprone. Laboratory parameters such as serum ferritin, creatinine, SGPT, Hb, CBC and urine were recorded at the time of inclusion and at 1, 3 and 6 months after the inclusion. The primary outcome variable was serum Ferritin level at the start and at the end of study. Serum ferritin level was carried out by microparticle enzyme linked immunoassay.Results: Before the study, the mean hemoglobin level was 7.32±1.50mg/dL ranged from 4 to 10.8 in deferasirox group and 7.54±1.15mg/dL ranged from 5.5 to 8.8 in deferiprone group. At the time of inclusion, study population was characterized by a mean serum ferritin value of 4735.11±450.01 SE in deferasirox and 4315.97±340.75 SE in deferiprone group. After one month the mean serum ferritin increases to 4578.66±371.96 in deferasirox and 4388.82±316.16 in deferiprone group. After three month the mean serum ferritin reduces to 4295.60±377.37 in deferasirox and 3988.88±349.84 in Deferiprone group.Conclusions: Thus, we conclude that deferasirox and deferiprone are well tolerated, have few adverse effects and almost have a comparable effect in lowering of the patient's serum ferritin level. Deferiprone is more cost effective but needs a strict control on compliance owing to requirement in three divided doses per day

A concurrent parallel study to compare the efficacy and safety of oral iron chelators, defrasirox and defriprone in patients of beta thalassaemia major

Background: This study was planned to evaluate all the cases of β thalassaemia major, already receiving one of the oral iron chelators for a comparison among the efficacy, safety and economy of deferasirox and deferiprone to establish the better option in an Indian scenario.Methods: We identified two groups of patients: 38 treated with deferasirox and 35 treated with deferiprone. Laboratory parameters such as serum ferritin, creatinine, SGPT, Hb, CBC and urine were recorded at the time of inclusion and at 1, 3 and 6 months after the inclusion. The primary outcome variable was serum Ferritin level at the start and at the end of study. Serum ferritin level was carried out by microparticle enzyme linked immunoassay.Results: Before the study, the mean hemoglobin level was 7.32±1.50mg/dL ranged from 4 to 10.8 in deferasirox group and 7.54±1.15mg/dL ranged from 5.5 to 8.8 in deferiprone group. At the time of inclusion, study population was characterized by a mean serum ferritin value of 4735.11±450.01 SE in deferasirox and 4315.97±340.75 SE in deferiprone group. After one month the mean serum ferritin increases to 4578.66±371.96 in deferasirox and 4388.82±316.16 in deferiprone group. After three month the mean serum ferritin reduces to 4295.60±377.37 in deferasirox and 3988.88±349.84 in Deferiprone group.Conclusions: Thus, we conclude that deferasirox and deferiprone are well tolerated, have few adverse effects and almost have a comparable effect in lowering of the patient's serum ferritin level. Deferiprone is more cost effective but needs a strict control on compliance owing to requirement in three divided doses per day

Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis.

We have previously described hypomorphic reelin (Reln) mutant mice, RelnCTRdel, in which the morphology of the dentate gyrus is distinct from that seen in reeler mice. In the RelnCTRdel mutant, the infrapyramidal blade of the dentate gyrus fails to extend, while the suprapyramidal blade forms with a relatively compact granule neuron layer. Underlying this defect, we now report several developmental anomalies in the RelnCTRdel dentate gyrus. Most strikingly, the distribution of Cajal-Retzius cells was aberrant; Cajal-Retzius neurons were increased in the suprapyramidal blade, but were greatly reduced along the subpial surface of the prospective infrapyramidal blade. We also observed multiple abnormalities of the fimbriodentate junction. Firstly, progenitor cells were distributed abnormally; the "neurogenic cluster" at the fimbriodentate junction was absent, lacking the normal accumulation of Tbr2-positive intermediate progenitors. However, the number of dividing cells in the dentate gyrus was not generally decreased. Secondly, a defect of secondary glial scaffold formation, limited to the infrapyramidal blade, was observed. The densely radiating glial fibers characteristic of the normal fimbriodentate junction were absent in mutants. These fibers might be required for migration of progenitors, which may account for the failure of neurogenic cluster formation. These findings suggest the importance of the secondary scaffold and neurogenic cluster of the fimbriodentate junction in morphogenesis of the mammalian dentate gyrus. Our study provides direct genetic evidence showing that normal RELN function is required for Cajal-Retzius cell positioning in the dentate gyrus, and for formation of the fimbriodentate junction to promote infrapyramidal blade extension

Carbon microelectromechanical systems as a substratum for cell growth

The study of the biocompatible properties of carbon microelectromechanical systems (carbon-MEMS) shows that this new microfabrication technique is a promising approach to create novel platforms for the study of cell physiology. Four different types of substrates were tested, namely, carbon-MEMS on silicon and quartz wafers, indium tin oxide (ITO) coated glass and oxygen-plasma-treated carbon thin films. Two cell lines, murine dermal fibroblasts and neuroblastoma spinal cord hybrid cells (NSC-34) were plated onto the substrates. Both cell lines showed preferential adhesion to the selectively plasma-treated regions in carbon films. Atomic force microscopy and Fourier transform infrared spectroscopy analyses demonstrated that the oxygen-plasma treatment modifies the physical and chemical properties of carbon, thereby enhancing the adsorption of extracellular matrix-forming proteins on its surface. This accounts for the differential adhesion of cells on the plasma-treated areas. As compared to the methods reported to date, this technique achieves alignment of the cells on the carbon electrodes without relying on direct patterning of surface molecules. The results will be used in the future design of novel biochemical sensors, drug screening systems and basic cell physiology research devices

The "Woundosome" Concept and Its Impact on Procedural Outcomes in Patients With Chronic Limb-Threatening Ischemia

This editorial assembles endovascular specialists from diverse clinical backgrounds and nationalities with a global call to address key challenges to enhance revascularization in chronic limb-threatening ischemia (CLTI) patients.- Dedicated below-the-ankle (BTA) angiography and revascularization is underutilized in ischemic foot treatment. Existing guidelines do not address comprehensive BTA vessel analysis. CLTI trials also often lack data on in-line arterial flow to the ischemic lesion and BTA vessel evaluation, hindering outcome assessment.- Dedicated multi-planar angiographic evaluation of the distal microcirculation is key: Direct arterial flow or good-quality collaterals are crucial in influencing wound healing and need to be assessed diligently to the level of the distal ischemic wound territory, termed “woundosome.”- An important primary emphasis of future trials should be on validating technologies and strategies for assessing tissue perfusion before, during, and after revascularization undertaken to heal tissue loss in CLTI patients. This will allow determination of a potentially significant delta in tissue perfusion prior to and following intervention at the “woundosome” level. Once changes in arterial perfusion have been identified as positively correlated to wound healing, these could serve as a much-needed novel primary technical outcome measure for patients with tissue loss undergoing surgical, hybrid, or endovascular revascularization

Congenital rubella syndrome surveillance in India, 2016–21: Analysis of five years surveillance data

Background: In India, facility-based surveillance for congenital rubella syndrome (CRS) was initiated in 2016 to estimate the burden and monitor the progress made in rubella control. We analyzed the surveillance data for 2016–2021 from 14 sentinel sites to describe the epidemiology of CRS. Method: We analyzed the surveillance data to describe the distribution of suspected and laboratory confirmed CRS patients by time, place and person characteristics. We compared clinical signs of laboratory confirmed CRS and discarded case-patients to find independent predictors of CRS using logistic regression analysis and developed a risk prediction model. Results: During 2016–21, surveillance sites enrolled 3940 suspected CRS case-patients (Age 3.5 months, SD: 3.5). About one-fifth (n = 813, 20.6%) were enrolled during newborn examination. Of the suspected CRS patients, 493 (12.5%) had laboratory evidence of rubella infection. The proportion of laboratory confirmed CRS cases declined from 26% in 2017 to 8.7% in 2021. Laboratory confirmed patients had higher odds of having hearing impairment (Odds ratio [OR] = 9.5, 95% confidence interval [CI]: 5.6–16.2), cataract (OR = 7.8, 95% CI: 5.4–11.2), pigmentary retinopathy (OR = 6.7, 95 CI: 3.3–13.6), structural heart defect with hearing impairment (OR = 3.8, 95% CI: 1.2–12.2) and glaucoma (OR = 3.1, 95% CI: 1.2–8.1). Nomogram, along with a web version, was developed. Conclusions: Rubella continues to be a significant public health issue in India. The declining trend of test positivity among suspected CRS case-patients needs to be monitored through continued surveillance in these sentinel sites