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Olfactory dysfunction (hyposmia, anosmia) is a well-recognized symptom in patients with coronavirus disease-19 (COVID-19). Studies of olfactory dysfunction in asymptomatic patients have not been reported. We conducted a study looking for the presence of olfactory dysfunction with an objective assessment tool in asymptomatic Covid 19 and compared it with patients with mild COVID-19 and age-matched controls. We recruited 57 male patients each of Mild COVID-19, asymptomatic Covid 19, and healthy controls for the study. All participants underwent evaluation of smell threshold by Butanol Threshold test (BTT) and ability to distinguish common odors by Smell identification test. The scores of each test were recorded on a numerical scale. The participants in all three arms were matched for age, history of smoking, and pre-existing medical conditions. The mean scores of the Butanol Threshold test in Mild COVID-19, asymptomatic Covid 19 and controls were 2.95 ± 2.25 (0-7.5), 3.42 ± 2.23 (0-7.5), and 4.82 ± 1.86 (0-8), respectively. A one-way ANOVA showed a significant difference between groups (df 2, MS 53.78, F 11.94, p  < 0.005). Intergroup differences using the student T-test showed significantly low BTT scores in Mild COVID-19 ( p  < 0.005) and asymptomatic ( p  < 0.005) as compared to control. BTT scores could not distinguish between asymptomatic patients and control. The smell threshold was impaired in asymptomatic Covid 19 and Mild COVID-19. Butanol Threshold Test score could not differentiate between asymptomatic Covid 19 and controls., Competing Interests: Conflicts of interestAll the authors declare that there is no conflict of interest., (© Association of Otolaryngologists of India 2021.)

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE., Methods: We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation., Results: At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P = .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P = .0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection., Conclusions: In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Symptomatic intervertebral disc degeneration is being recently reported in younger population, questions the basis of its degenerative etiology. Latest evidences show that genetics play a significant role. Collagen IX, an important constituent of disc, is found to be altered in genetically predisposed individuals. Mutations have been reported in COL9A2 and COL9A3 genes, which encode Collagen IX, in Finnish and various other populations. The purpose of the present study is to test the significance of these genes in the Indian population., Materials and Methods: One hundred proven cases of intervertebral disc disease (IDD) of various regions of spine were selected for the study, along with matched controls. They were tested for the above mentioned alleles by allelic discrimination method with real-time polymerase chain reaction (PCR) study after isolation of DNA from blood sample. Each blood sample was classified into one of the three types - homozygous, heterozygous, and wild (normal) type allele - separately for COL9A2 and COL9A3 genes., Results: Homozygosity for COL9A2 allelic variation was associated with 100% occurrence of the disease. Heterozygous allele of COL9A2 was significantly higher in the study group (42%) as compared to the control group (17%). In contrast, allelic variation in COL9A3 gene was found to have no significant correlation with disc disease. There was no single patient with homozygous allelic variation for COL9A3, suggesting predominance of COL9A2 variation in the Indian population., Conclusion: This candidate gene strategy approach adds considerably to our knowledge of genetic makeup of Indian populations in relation with disc disease. This study highlights importance of COL9A2 gene variation especially of homozygous variety in contrast to COL9A3 variation in causing disc disease in Indian population.

Background & Aims: The efficacy of abatacept, a selective costimulation modulator, in Crohn's disease (CD) and ulcerative colitis (UC) is unknown., Methods: Four placebo-controlled trials evaluated the efficacy and safety of abatacept as induction (IP) and maintenance (MP) therapy in adults with active, moderate-to-severe CD (CD-IP; CD-MP) and UC (UC-IP1; UC-MP). In CD-IP and UC-IP1, 451 patients with CD and 490 patients with UC were randomized to abatacept 30, 10, or 3 mg/kg (according to body weight) or placebo, and dosed at weeks 0, 2, 4, and 8. In MP, 90 patients with CD and 131 patients with UC who responded to abatacept at week 12 in the induction trials were randomized to abatacept 10 mg/kg or placebo every 4 weeks through week 52., Results: In CD-IP, 17.2%, 10.2%, and 15.5% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at weeks 8 and 12, vs 14.4% receiving placebo (P = .611, P = .311, and P = .812, respectively). In UC-IP1, 21.4%, 19.0%, and 20.3% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at week 12, vs 29.5% receiving placebo (P = .124, P = .043, and P = .158, respectively). In CD-MP, 23.8% vs 11.1% of abatacept vs placebo patients were in remission at week 52. In UC-MP, 12.5% vs 14.1% of patients receiving abatacept vs placebo were in remission at week 52. Safety generally was comparable between groups., Conclusions: The studies showed that abatacept is not efficacious for the treatment of moderate-to-severe CD or UC., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute rejection and protection of renal function in kidney transplant recipients demonstrated similar efficacy and significantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lymphoproliferative disorder was higher. Here, we present the results for the extension of this trial, which aimed to assess long-term safety and efficacy of belatacept. Seventy-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA completed the long-term extension period. GFR remained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graft loss or acute rejection were low. The frequencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12% of each group. No patients who were treated with belatacept and one patient who was treated with CsA developed posttransplantation lymphoproliferative disorder during the follow-up period. Serious gastrointestinal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders occurred more frequently with CsA (2% belatacept versus 12% CsA). Pharmacokinetic analyses showed consistent exposure to belatacept over time. CD86 receptor saturation was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 weeks (56%). In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years.

Objective: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was studied in a first-in-human trial in rheumatoid arthritis (RA) patients receiving concomitant methotrexate (MTX)., Methods: The ACTION trial was a combined phase I/II study of placebo plus MTX versus ocrelizumab plus MTX in 237 RA patients (intent-to-treat population). During phase I, 45 patients were treated with 1 of 5 escalating doses of study drug (infusions on days 1 and 15, 10-1,000 mg per each infusion). An additional 192 patients were randomized during phase II. Eligible patients had active disease, an inadequate response to treatment with at least MTX, rheumatoid factor positivity, and elevated levels of acute-phase reactants. The total study duration was 72 weeks. B cell pharmacodynamics over time was investigated., Results: Baseline demographics were similar among the treatment groups. Based on the entire 72-week data set, the incidence of serious adverse events in the ocrelizumab-treated patients was 17.9%, as compared with 14.6% in placebo-treated patients. The incidence of serious infections was 2.0% in all ocrelizumab-treated patients and 4.9% in placebo-treated patients. Infusion-associated adverse events were mostly grade 1 or grade 2 and were more frequent around the time of the first infusion. No serious infusion-associated adverse events were reported in the ocrelizumab group. Evidence of clinical activity was observed at all doses evaluated. Peripheral B cell depletion after infusion was rapid at all doses, with earlier repletion of B cells at doses of 10 mg and 50 mg. Human anti-human antibodies were detected in 19% and 10%, respectively, of those receiving 10 mg and 50 mg of ocrelizumab, compared with 0-5% of those receiving 200, 500, and 1,000 mg., Conclusion: Ocrelizumab therapy in combination with MTX was well tolerated. Doses of 200 mg (2 infusions) and higher showed better clinical responses, better reduction of C-reactive protein levels, and very low immunogenicity.

The aim of the present study was to predict which patients with severe or difficult-to-treat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management. Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline. Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index > or =35 kg x m(-2); post-bronchodilator per cent predicted forced vital capacity <70%; history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0-18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12- to 18-months follow-up among the same cohort (c-index: 0.77). The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.

Transitioning to a filmless department is no easy task, especially at a large academic medical center. At the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, a phased modality integration schedule was implemented to allow the technical and clinical staff to gradually absorb all of the changes to workflow. One-on-one training sessions were designed to prepare radiologists and referring clinicians to access and navigate the in-house picture archiving and communication system (PACS) workstations as well as to view images over the Internet via the PACS Web server. An interdepartmental steering committee was formed to plan deployment of the in-house workstations. A planning committee met on a weekly basis to outline placement of workstations within the Radiology Department, and to redesign the reading room. A user group was created to discuss specific user problems. Of particular interest was the challenge of outfitting a dozen conference rooms with projection systems capable of displaying radiologic images. We distinguished between regular and working conferences. At regular conferences only a few cases are reviewed over the course of an hour and only after the diagnosis has been made at a PACS workstation. In contrast, the surgical and medical intensive care units conduct daily working conferences. At those sessions the images of 20 to 30 patients are reviewed, many of them for the first time, and for each case a definitive diagnosis is expected. During the implementation process, a range of issues came up that limited access of certain studies to radiologists and referring clinicians alike. Even after the initial PACS installation, many studies went unread because of a lack of worklists. Other problems included image ordering for head computed tomography and magnetic resonance imaging. A few of our modalities were not DICOM compliant and needed image capture devices in order to be integrated with the PACS. To our dismay, this was also true of one of our modalities that was supposed to be DICOM compliant. These problems, and the solutions we discovered, are discussed in this paper.