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  • Thomson posted an update 7 months, 2 weeks ago

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human erythroenzymopathy affecting around 10% of the world population. India is endemic for malaria and antimalarial drugs are known to induce haemolysis in G6PD deficient individuals. Here we report the prevalence as well as the molecular diversity of G6PD deficiency in geographical regions of India.

    A total of 20,896 individuals (11,838 males and 9058 females) were screened by DPIP dye decolorisation method followed by quantitation of G6PD enzyme activity on the suspected samples. Molecular analysis was undertaken in a total of 350 G6PD deficient individuals by PCR-RFLP and DNA sequencing. A structural characteristic of the novel variant was deduced by using DynaMut web-server. The prevalence rate of G6PD deficiency varied between 0.8 and 6.3% with an overall prevalence of 1.9%. A total of twelve mutations were identified. Of the total deleterious alleles detected G6PD Orissa (56.5%) was found to be the most predominant variant followed by G6PD Mediterranean (23.6%). G6PD Mediterranean, G6PD Kaiping and G6PD Mahidol were found to be severely deficient variant and 14.1% of them showed undetectable activity. A novel mutation c.544C➔G (R182G) in exon 6 was identified in one tribal male where substitution of arginine by glycine, likely causes the alteration in the alpha helix leading to disruption of secondary structure of the protein.

    There are large differences in the distribution of G6PD causal variants between Indian states, and this may have implications for the treatment in the malaria endemic areas.

    There are large differences in the distribution of G6PD causal variants between Indian states, and this may have implications for the treatment in the malaria endemic areas.

    In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.

    Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 11 to receive open-label pemetrexed 500 mg/m

    plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks. Eligible patients could crossover from the chemotherapy arm to pembrolizumab monotherapy after progression. Responses were assessed per the Response Evaluation Criteria in Solid Tumors version 1.1.

    After the median time of 49.4 months from randomization to data cutoff, objective response rate (58% versus 33%) and progrw-up.

    First-line pembrolizumab plus pemetrexed-carboplatin continued to show improved response and survival versus chemotherapy alone in advanced nonsquamous NSCLC, with durable clinical benefit in patients who completed 2 years of therapy. No new safety signals were observed with longer follow-up.The introduction of specific humanized monoclonal antibodies over the past 20 years has dramatically changed the treatment of allergic diseases. At present, 5 mAbs are licensed for treating moderate to severe allergic and eosinophilic asthma, atopic dermatitis, chronic spontaneous urticaria, chronic sinusitis with nasal polyps, and eosinophilic granulomatosis with polyangiitis. AG-120 Given the high costs of biologics, understanding their cost-effectiveness is critical. As new biologics are developed and new indications are approved for existing biologics, the use of biologics for allergic diseases will increase. Conducting cost-effectiveness evaluations in parallel to efficacy and effectiveness trials will help patients, providers, payers, and policymakers in decision making.

    Patients with severe eosinophilic asthma show different responses to various anti-IL-5 biologics, ranging from super response to nonresponse. Residual disease manifestations observed in partial responders may prompt physicians to switch between biologics. More data on response, switches, and residual disease manifestations are needed to improve personalized treatment.

    To assess (1) prevalences and predictors of super, partial, and nonresponders to long-term anti-IL-5 treatment, (2) frequency and reasons for switches between anti-IL-5 biologics, and (3) nature of residual disease manifestations.

    In this 2-year follow-up study, patients with severe asthma were included who initiated an anti-IL-5 biologic (mepolizumab, reslizumab, benralizumab) (n= 114). Patient characteristics (clinical, functional, inflammatory) and comorbidities were collected at baseline and 2-year follow-up. “Super responders” showed no residual disease manifestations at 2-year follow-up, “partial responders” experienced residual disend in 83% of patients with severe asthma, including a super response in 14%. Most partial responders show impaired lung function or uncontrolled sinonasal disease, causing physicians to switch between biologics.

    To establish whether deep learning methods are able to improve the signal-to-noise ratio of time-domain (TD) OCT images to approach that of spectral-domain (SD) OCT images.

    Method agreement study and progression detection in a randomized, double-masked, placebo-controlled, multicenter trial for open-angle glaucoma (OAG), the United Kingdom Glaucoma Treatment Study (UKGTS).

    The training and validation cohort comprised 77 stable OAG participants with TD OCT and SD OCT imaging at up to 11 visits within 3 months. The testing cohort comprised 284 newly diagnosed OAG patients with TD OCT images from a cohort of 516 recruited at 10 United Kingdom centers between 2007 and2010.

    An ensemble of generative adversarial networks (GANs) was trained on TD OCT and SD OCT image pairs from the training dataset and applied to TD OCT images from the testing dataset. Time-domain OCT images were converted to synthesized SD OCT images and segmented via Bayesian fusion on the output of the GANs.

    Bland-Altman analysis assessed agreement between TD OCT and synthesized SD OCT average retinal nerve fiber layer thickness (RNFLT) measurements and the SD OCT RNFLT.

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