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Objectives: To illustrate the clinical course and difficulties in early diagnosis of coronavirus disease 2019 in patients after thoracic surgery. Methods:We retrospectively analyzed the clinical course of the first 11 patients diagnosed with COVID-19 after thoracic surgery in early January 2020. Postoperative clinical, laboratory, and radiologic records and the time line of clinical course were summarized. Potential prognostic factors were evaluated.Results: In the 11 confirmed cases (3 female, 8 male), median days from symptom onset to case detection was 8. Insidious symptom onset and misinterpreted postoperative changes on chest computed tomography (CT) resulted in delay in diagnosis. There were 3 fatalities due to respiratory failure, whereas 4 severe and 4 mild cases recovered and were discharged. All patients had once experienced leukocytosis and eosinopenia. Remittent fever and resected lung segments !5 were associated with fatality. Conclusions:The case fatality rate of postsurgical patients subsequently diagnosed with COVID-19 was 27.3%. Insidious symptom onset, postoperative leukocytosis with lymphopenia, and postsurgical CT changes overshadowed the early signs of viral pneumonia. Dynamic symptom monitoring, serial chest CTs, and tests for viral RNA and serum antibody improve the chance for prompt detection of COVID-19. Consideration should be given to preadmission and preoperative screening and strict contact isolation during the postoperative period.

Key Points Question Are there differences in the antipyretic, analgesic, and safety profiles of acetaminophen (paracetamol) compared with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years? Findings In this meta-analysis of 19 studies with 241 138 participants, ibuprofen, compared with acetaminophen, was associated with reduced temperature at less than 4 hours and 4 to 24 hours and less pain at 4 to 24 hours. Adverse events were uncommon. Meaning In this study, use of ibuprofen vs acetaminophen for the treatment of fever or pain in children younger than 2 years was associated with reduced temperature and less pain within the first 24 hours of treatment, with equivalent safety.

Background: The Janus kinase (JAK) pathway mediates the activity of many asthma-relevant cytokines, including IL-4 and IL-13. GDC-0214 is a potent, inhaled, small-molecule JAK inhibitor being developed for the treatment of asthma. Objective: We sought to determine whether GDC-0214 reduces fractional exhaled nitric oxide (FENO), a JAK1-dependent biomarker of airway inflammation, in patients with mild asthma. Methods: We conducted a double-blind, randomized, placebocontrolled, phase 1 proof-of-activity study in adults with mild asthma and FENO higher than 40 parts per billion (ppb). Subjects were randomized 2:1 (GDC-0214:placebo) into 4 sequential ascending-dose cohorts (1 mg once daily [QD], 4 mg QD, 15 mg QD, or 15 mg twice daily). All subjects received 4 days of blinded placebo, then 10 days of either active drug or placebo. The primary outcome was placebo-corrected percent reduction in FENO from baseline to day 14. Baseline was defined as the average FENO during the blinded placebo period. Pharmacokinetics, safety, and tolerability were also assessed. Results: Thirty-six subjects (mean age, 28 years; 54% females) were enrolled. Mean FENO at baseline across all subjects was 93 6 43 ppb. At day 14, placebo-corrected difference in FENO was 223% (95% CI, 237.3 to 29) for 15 mg QD and 242% (95% CI, 257 to 227.4) for 15 mg twice daily. Higher plasma exposure was associated with greater FENO reduction. No doselimiting adverse events, serious adverse events, or treatment discontinuations occurred. There were no major imbalances in adverse events or laboratory findings, or evidence of systemic JAK inhibition. Conclusions: GDC-0214, an inhaled JAK inhibitor, caused dosedependent reductions in FENO in mild asthma and was well tolerated without evidence of systemic toxicity. (J Allergy Clin Immunol 2021;nnn:nnn-nnn.)

BackgroundFluticasone furoate/Vilanterol trifenatate (FF/VI) is an inhaled corticosteroid/long-acting beta-agonist combination with a prolonged bronchodilator duration of action. We characterised the time-course of onset and offset of airway anti-inflammatory action of FF/VI, as assessed by fraction of exhaled nitric oxide (FeNO), and compared this to the bronchodilator duration of action.MethodsA single-centre, randomised, double-blind, placebo-controlled, two-period, crossover study was undertaken in 28 steroid-naïve adults with asthma. Participants with an FEV1 ≥ 60% predicted, reversible airway disease, and FeNO > 40 ppb received FF/VI 100/25 mcg or placebo once daily for 14 days. FeNO and peak expiratory flow were measured twice-daily during treatment and during a 21-day washout period. FEV1 was measured for five days from treatment cessation. The primary outcome measure was FeNO change from baseline ratio for 21 days following treatment cessation.ResultsIn the 27 subjects who completed the study, median (range) baseline FeNO was 87 ppb (42–212). FF/VI 100/25 mcg reduced FeNO by day 3, ratio FF/VI versus placebo 0.72 (95% confidence interval 0.61–0.86) with the maximum reduction occurring at day 14, 0.32 (0.27–0.37). Following cessation of treatment FeNO remained suppressed for 18 days, ratio on day 18 0.77 (0.59–1.00), whereas improvements in FEV1 and peak flow were maintained for 3 to 4 days post-treatment.ConclusionsThe anti-inflammatory duration of action of FF/VI is consistent with the high glucocorticoid receptor affinity and long lung retention of fluticasone furoate. The anti-inflammatory effect of FF/VI was of greater duration than its bronchodilator effect in adults with mild asthma.Funding GlaxoSmithKline (201499).Trial registrationProspectively registered on ClinicalTrials.gov registry number NCT02712047.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0836-6) contains supplementary material, which is available to authorized users.