Efficacy of Various Treatment Modalities on Patientrelated Outcome in Hospitalized COVID-19 Patients –A Retrospective Study

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in China, in December 2019, and was declared a pandemic by WHO on March 11, 2020. The treatment is evolving and is mostly supportive in nature. Material and methods: This was a single-center retrospective study that included confirmed COVID-19 cases treated at our institute (a tertiary care hospital in Jammu and Kashmir, India), between March 2020 and December 2020. Patients with age more than 18 years were included in the study. Results: On evaluating the effect of various drug therapies used in management of COVID-19 patients of all severity, use of remdesivir and famotidine was associated with significantly higher odds of survival. In subgroup of patients with severe disease, use of systemic steroids was associated with significantly higher odds of survival in addition to remdesivir and famotidine. In patients with severe COVID-19 illness, likelihood of survival was significantly higher in those who received combination of systemic steroids plus remdesivir compared to steroids and remdesivir alone. Conclusion: Steroids were effective in severe COVID-19 illness and the combination of steroids and remdesivir was more effective in severe illness. There is a need to undertake more large scale prospective randomized trials to determine the most effective drug therapies to treat the sick patients and prevent worsening of mild cases

Molecular typing of HLA-class II alleles reveals an association with autoantibodies and disease subsets of systemic sclerosis in a North Indian (Kashmir) population

Aim of the work: To identify specific human leukocyte antigen (HLA)-Class II (DRB/DQB1/DPB1) alleles associated with systemic sclerosis (SSc) and to explore their relation with SSc autoantibodies, clinical manifestations, and disease subsets. Patients and methods: HLA-class II alleles (DRB1/DRB3/DRB4/DRB5/DQB1) were determined by DNA typing in 80 SSc cases and 60 matched controls and HLA-DPB1 in 40 SSc patients and 30 controls by allele-specific-polymerase chain reaction with sequence-specific primers (PCR-SSP). Results: The mean age of SSc patients was 36.9 ± 9.4 years; 76 females and 4 males (F:M 19:1) and a disease duration of 5.3 ± 3.3 years, they were 43(53.7%) limited and 37(46.2%) diffuse subtypes. SSc was significantly associated with DRB1*11, DRB1*01, DQB1*04, and DQB1*03*03 in a >4-fold manner, whereas DPB1*04 had a >7-fold increased risk compared to controls. There was a strong association between DRB1*11 (p = 0.04), DQB1*03*03 (p = 0.005), and DPB1*13 (p = 0.009) with anti-topoisomerase I (anti-topoI) whereas the frequency of DRB1*01 (p < 0.0001) was increased in patients with anti-centromere (ACA) positive SSc compared those negative (56% vs 25%; p < 0.0001). DRB1*03, DRB1*15, and DQB1*03*01 were SSc protective alleles in patients with positive ACA. Anti-topo I was associated with interstitial lung disease (ILD) (p < 0.01), whereas ACA with pulmonary arterial hypertension (PAH) (p = 0.01) and protection against ILD (p < 0.001). In addition, HLA-DRB1*03, DQB1*03*01and DPB1*03 were more frequent in patients with ILD than in patients without. Conclusion: Associations between specific HLA-class II alleles with certain SSc-specific autoantibodies (anti-topo I and ACA) were identified. Specific HLA associations with clinical and serological subtypes could serve as biomarkers of disease severity and progression in SSc

Isolation, cytotoxicity evaluation and HPLC-quantification of the chemical constituents from Prangos pabularia.

Phytochemical analysis of the dichloromethane:methanol (1:1) extract of root parts of Prangos pabularia led to the isolation of twelve cytotoxic constituents, viz., 6-hydroxycoumarin (1), 7-hydroxycoumarin (2), heraclenol-glycoside (3), xanthotoxol (4), heraclenol (5), oxypeucedanin hydrate (6), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (7), oxypeucedanin hydrate monoacetate (8), xanthotoxin (9), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (10), imperatorin (11) and osthol (12). The isolates were identified using spectral techniques in the light of literature. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity screening of the isolated constituents was carried out against six human cancer cell lines including lung (A549 and NCI-H322), epidermoid carcinoma (A431), melanoma (A375), prostate (PC-3) and Colon (HCT-116) cell lines. Osthol (12) exhibited the highest cytotoxicity with IC50 values of 3.2, 6.2, 10.9, 14.5, 24.8, and 30.2 µM against epidermoid carcinoma (A431), melanoma (A375), lung (NCI-H322), lung (A549), prostate (PC-3) and colon (HCT-116) cell lines respectively. Epidermoid carcinoma cell line A431 was sensitive to most of the compounds followed by lung (A549) cancer cell line. Finally a simple and reliable HPLC method was developed (RP-HPLC-DAD) and validated for the simultaneous quantification of these cytotoxic constituents in Prangos pabularia. The extract was analyzed using a reversed-phase Agilent ZORBAX eclipse plus column C18 (4.6×250 mm, 5 µm) at 250 nm wavelength using a gradient water-methanol solvent system at a flow rate of 0.8 ml/min. The RP-HPLC method is validated in terms of recovery, linearity, accuracy and precision (intra and inter-day validation). This method, because of shorter analysis time, makes it valuable for the commercial quality control of Prangos pabularia extracts and its future pharmaceutical preparations

Limits of detection (LOD) and quantification (LOQ) of marker compounds <b>1–12</b>.

<p>a) The calibration curves were constructed by plotting the peak areas versus the concentration of each analyte.</p><p>b) LOD refers to the limit of detection.</p><p>c) LOQ refers to the limit of quantification.</p><p>Limits of detection (LOD) and quantification (LOQ) of marker compounds <b>1–12</b>.</p

Intra and inter-day precisions area of HPLC method of marker compounds <b>1–12</b>.

<p>Intra and inter-day precisions area of HPLC method of marker compounds <b>1–12</b>.</p

Chemical structure of marker compounds isolated from plant Prangos pabularia.

<p>(<b>1</b>), 6-hydroxo-coumarin (<b>2</b>), Umbelliferone (<b>3</b>), Heraclenol glycoside (<b>4</b>), Xanthotoxol (<b>5</b>), Heraclenol (<b>6</b>), Oxypeucedanin hydrate (<b>7</b>), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (Merangin) (<b>8</b>), Oxypeucedanin hydrate monoacetate (<b>9</b>), Xanthotoxin (<b>10</b>), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (<b>11</b>), Imperatorin (<b>12</b>), Osthol.</p

Recovery percentage of marker compounds <b>1–12</b>.

<p>Recovery percentage of marker compounds <b>1–12</b>.</p