IgE regulates airway smooth muscle phenotype: Future perspectives in allergic asthma

The purpose of this commentary is to highlight the emerging role of IgE on airway smooth muscle (ASM) cells function through activation of the high-affinity Fc receptor for IgE. We discuss the potential implications of IgE-mediated ASM sensitization in airway inflammation and remodeling, the hallmark features of allergic asthma.     

A novel LC-MS/MS method for simultaneous estimation of acalabrutinib and its active metabolite acalabrutinib M27 in human plasma and application to a human pharmacokinetic study

A simple, specific, selective and accurate bioanalytical method was developed and validated for simultaneous estimation of acalabrutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Deuterated analogs of both the analytes were used as internal standards. The extraction of analytes and internal standards were evaluated from the human plasma by liquid–liquid extraction technique using methyl tertiary butyl ether (TBME). The separation of the analytes was carried out on Zorbax Eclipse XDB-C_{18 (}150 × 4.6 mm, 5 μm) column with a mixture of acetonitrile and 10 mM ammonium formate in 0.1% formic acid buffer (65 : 35, v/v) as mobile phase at a flow rate of 1 mL min⁻¹. The method linearity was determined in the widen concentration range from 5.000 ng mL⁻¹ to 1600 ng mL⁻¹ with r² > 0.99. The entire method validation was carried out as per the USFDA guidelines on bioanalytical method validation and all validation experiment results were found within acceptable limits. Clinical pharmacokinetic study of both the parent drug and its active metabolite was successfully performed on six healthy volunteers under fasting conditions by applying the present method.

A simple, specific, selective and accurate bioanalytical method was developed and validated for simultaneous estimation of acalabrutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS).     

Coats’ disease – Prognostic factors for globe and vision salvage in children,a long-term experience

Purpose:Coats’ disease is associated with poor outcomes, and there are limited studies on long-term outcomes of Coats’ disease. The purpose of our study is to identify various predictive factors to help in prognosticating the treatment outcomes in advanced Coats’ disease in children.Methods:This is a retrospective case series from a single tertiary eye care center of children (<18 years) diagnosed with coat’s disease. Sixty-seven patients with Coat’s disease were identified from the medical records from 2009 to 2020. Patients’ demographic data, clinical presentation, stage, extent of involvement, detailed treatment history, clinical sequelae post-treatment (including complications and anatomical and functional outcomes) were noted. Binary logistic regression was performed to correlate the predictive factors for anatomical and functional improvement.Results:Of the 67 patients, 51 eyes of 51 patients were included in the study. The male to female proportion was 2.2. Mean age at presentation was 4.98 ± 3.55 years (range: 2 months–15 years). Mean duration of follow-up was 31.53 ± 26.38 months. Overall, our globe salvage rate was 92.2%. We found that vitreoretinal fibrosis (P < 0.001), subretinal gliosis (P < 0.001), vitreous hemorrhage (P = 0.02), tractional or combined retinal detachment (P < 0.001), foveal scar (P < 0.006), and cataract (P < 0.001) to be important factors to affect the outcome.Conclusion:Advanced stage of presentation (stage 3B and above), diffuse involvement, cataract, vitreoretinal fibrosis (preretinal and subretinal), vitreous hemorrhage, tractional or combined retinal detachment, and anterior hyaloid proliferation are poor prognostic factors for globe salvage in advanced disease. Subretinal gliotic nodule or scar and lack of visual rehabilitation suggest poor functional outcomes.     

Metformin extended‐release versus immediate‐release: An international,randomized, double‐blind,head‐to‐head trial in pharmacotherapy‐naïve patients with type 2 diabetes

This international, randomized, double‐blind trial (NCT01864174) compared the efficacy and safety of metformin extended‐release (XR) and immediate‐release (IR) in patients with type 2 diabetes. After a 4‐week placebo lead‐in, pharmacotherapy‐naïve adults with glycated haemoglobin (HbA1c) at 7.0% to 9.2% were randomized (1:1) to receive once‐daily metformin XR 2000 mg or twice‐daily metformin IR 1000 mg for 24 weeks. The primary endpoint was change in HbA1c after 24 weeks. Secondary endpoints were change in fasting plasma glucose (FPG), mean daily glucose (MDG) and patients (%) with HbA1c <7.0% after 24 weeks. Overall, 539 patients were randomized (metformin XR, N = 268; metformin IR, N = 271). Adjusted mean changes in HbA1c, FPG, MDG and patients (%) with HbA1c <7.0% after 24 weeks were similar for XR and IR: ?0.93% vs ?0.96%; ?21.1 vs ?20.6 mg/dL (?1.2 vs ?1.1 mmol/L); ?24.7 vs ?27.1 mg/dL (?1.4 vs ?1.5 mmol/L); and 70.9% vs 72.0%, respectively. Adverse events were similar between groups and consistent with previous studies. Overall, metformin XR demonstrated efficacy and safety similar to that of metformin IR over 24 weeks, with the advantage of once‐daily dosing.     

An epitope-specific PCR test for diagnosis of Leishmania donovani infections

The carboxy-terminal region of recombinant heat shock protein 70 of Leishmania donovani has been shown to have an immunodominant epitope. We designed a PCR assay using a new set of primers encompassing the gene sequence from 457bp to 927bp, which amplified a segment of the L. donovani genome in a species-specific manner. The assay was sensitive enough to detect 0.5pg of parasite DNA, which increased 10-fold (0.05pg) when an internal probe (583-609bp) was used in the Southern blot. The assay was able to detect parasite DNA from the liver and spleen of L. donovani-infected hamsters as well as lesion aspirates from parasitologically confirmed post-kala-azar dermal leishmaniasis (PKDL) and bone marrow aspirates from visceral leishmaniasis (VL) patients. No amplification was seen with axenically cultured promastigotes of L. infantum, L. tropica, L. major, L. mexicana, L. aethiopica or other intracellular organisms such as Entamoeba histolytica, Mycobacterium tuberculosis, Plasmodium vivax or human peripheral blood mononuclear cells. This PCR provides a specific tool for the diagnosis of VL and PKDL with simultaneous species identification.