Study of PTPN22 1858C/T polymorphism in rheumatoid arthritis patients from Western India

BackgroundRheumatoid arthritis (RA) is an inflammatory autoimmune disorder with etiologies including genetic and environmental factors. Protein tyrosine phosphatase non-receptor type22 (PTPN22) 1858C/T polymorphism is widely suspected to be a susceptibility gene for RA in the non-HLA genes group.AimThis study aimed at determining whether PTPN22 1858C/T polymorphism is associated with RA patients from Western India and to evaluate its possible association with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.MethodsA total of 130 Indian RA patients and 100 age and sex matched normal controls were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) for the PTPN22 1858C/T polymorphism.ResultsRF positivity was seen among 73.8% RA patients studied and the overall incidence of anti-CCP antibodies was 86.2%. The homozygous genotype (T/T) was absent in both groups. Among RF positives, C/C homozygosity was 90.6% whereas 9.4% patients were C/T heterozygous. Among anti-CCP positives, 89.1% had C/C genotype while the remaining 10.9% have the C/T genotype. Statistically significant association was obtained between the polymorphism and anti-CCP positivity in RA patients (OR: 2.939, ‘p’ value = 0.0595).ConclusionOur study suggested that a positive autoantibody status may predispose an individual to RA. PTPN22 may act as a susceptibility gene only in certain ethnic groups and there is no direct association between PTPN22 C1858 polymorphism and RA patients from Western India. Still a larger study is needed to understand whether this polymorphism predisposes individual to disease-associated antibodies among Indian RA patients.     

Sorafenib and Mek inhibition is synergistic in medullary thyroid carcinoma in vitro

Clinical trials using kinase inhibitors have demonstrated transient partial responses and disease control in patients with progressive medullary thyroid cancer (MTC). The goal of this study was to identify potential combinatorial strategies to improve on these results using sorafenib, a multikinase inhibitor with activity in MTC, as a base compound to explore signaling that might predict synergystic interactions. Two human MTC cell lines, TT and MZ-CRC-1, which harbor endogenous C634W or M918T RET mutations, respectively, were exposed to sorafenib, everolimus, and AZD6244 alone and in combination. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) and poly (ADP-ribose) polymerase (PARP) cleavage assays were performed to measure cell survival and apoptosis. Western blots were performed to confirm activity of the compounds and to determine possible mechanisms of resistance and predictors of synergy. As a solitary agent, sorafenib was the most active compound on MTT assay. Western blots confirmed that sorafenib, everolimus, and AZD6244 inhibited their anticipated targets. At concentrations below its IC(50), sorafenib-treated TT and MZ-CRC-1 cells demonstrated transient inhibition and then re-activation of Erk over 6?h. In concordance, synergistic effects were only identified using sorafenib in combination with the Mek inhibitor AZD6244 (P<0.001 for each cell line). Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex-dependent and TORC2 complex-independent mechanisms respectively. Everolimus was neither additive nor syngergistic in combination with sorafenib or AZD6244. In conclusion, sorafenib combined with a Mek inhibitor demonstrated synergy in MTC cells in vitro. Mechanisms of resistance to everolimus in MTC cells likely involved TORC2-dependent and TORC2-independent pathways.     

Resuming eye bank services during the COVID-19 pandemic: Experience and inferences

Purpose:The aim of this study was to formulate a methodological approach for resuming eye bank services during COVID-19 pandemic.Methods:Eye bank operations were temporarily halted in March after the government-mandated “Lockdown” in response to COVID-19 pandemic. Before restarting eye bank operations in May, we studied sources of exposure, performed risk assessment, instituted additional process validations and redefined the Standard Operating Procedures (SOPs) in consultation with the guidelines published by the Eye bank Association of India and All India Ophthalmological Society. The eye bank staff were rigorously trained before and after operations were restarted. We conducted a survey at the end of July to gauge staff attitude and reaction.Results:Eye banks services resumed on 20^th May 2020. Since reopening till the end of July total 41 keratoplasties have been done. 91.75% of all keratoplasties done were therapeutic surgeries and 17% of the surgeries were done using glycerine preserved tissues. No staff had COVID-19 symptoms when the operations restarted and none developed symptoms up to the end of July. All eye bank staff were aware of COVID-19 pandemic and 86% said they felt safe working at the eye bank. 86% of the staff said that they received adequate training and 66% of the staff expressed that they always received proper PPE and kits. Overall, 93% of the staff expressed that the measures taken by the eye bank ensured their safety.Conclusion:Based on our experience we suggest the following activities for planned resumption of eye bank services during the pandemic: Exposure Risk Analysis, Personal Protective Equipment usage training, SOP Revision and staff training on modified SOPs. Criteria based selection of donor sources, participatory planning involving the staff and double-checking at critical process junctions helped us in managing a smooth transition.     

Neuro-ophthalmic presentation of COVID-19 disease: A case report

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery     

Role of Splenic Artery Embolization in Management of Traumatic Splenic Injuries: A Prospective Study

The objective of our study was to evaluate the role of splenic artery embolization (SAE) in the management of traumatic splenic injuries. From September 2008 to September 2010, a total of 67 patients underwent nonoperative management (NOM) for blunt splenic injuries. Twenty-two patients were excluded from the study because of associated significant other organ injuries. Twenty-five patients underwent SAE followed by NOM (group A) and 20 patients underwent standard NOM (group B). Improvement in clinical and laboratory parameters during hospital stay were compared between two groups using Chi-square test and Mann–Whitney test. SAE was always technically feasible. The mean length of the total hospital stay was lower in the group A patients (5.4 vs. 6.6 day, [P = 0.050]). There was significant increase in hemoglobin and hematocrit levels and systolic blood pressure (SBP) in group A patients after SAE, whereas in group B patients there was decrease in hemoglobin and hematocrit levels and only slight increase in SBP (pre- and early posttreatment relative change in hemoglobin [P = 0.002], hematocrit [P = 0.001], and SBP [P = 0.017]). Secondary splenectomy rate was lower in group A (4 % [1/25] vs. 15 % [3/20] [P = 0.309]). No procedure-related complications were encountered during the hospital stay and follow-up. Minor complications of pleural effusion, fever, pain, and insignificant splenic infarct noted in 9 (36 %) patients. SAE is a technically feasible, safe, and effective method in the management of splenic injuries. Use of SAE as an adjunct to NOM of splenic injuries results improvement in hemoglobin, hematocrit levels, and SBP. SAE also reduces secondary splenectomy rate and hospital stay.Keyword: Trauma, Splenic artery embolisation