Background: High-flow nasal cannula oxygen therapy (HFNC) has been shown to be a useful therapy in the treatment of patients with Acute Respiratory Distress Syndrome (ARDS), but its efficacy is still unknown in patients with COVID-19. Our objective is to describe its utility as therapy for the treatment of ARDS caused by SARS-CoV-2. Methods: A retrospective, observational study was performed at a single centre, evaluating patients with ARDS secondary to COVID-19 treated with HFNC. The main outcome was the intubation rate at day 30, which defined failure of therapy. We also analysed the role of the ROX index to predict the need for intubation.Results: In the study period, 196 patients with bilateral pneumonia were admitted to our pulmonology unit, 40 of whom were treated with HFNC due to the presence of ARDS. The intubation rate at day 30 was 52.5%, and overall mortality was 22.5%. After initiating HFNC, the SpO2/FiO2 ratio was significantly better in the group that did not require intubation (113.4±6.6 vs 93.7±6.7, p=0.020), as was the ROX index (5.0±1.6 vs 4.0±1.0, p=0.018). A ROX index less than 4.94 measured 2 to 6 h after the start of therapy was associated with increased risk of intubation (HR 4.03 [95% CI 1.18 – 13.7]; p=0.026).Conclusion: High-flow therapy is a useful treatment in ARDS in order to avoid intubation or as a bridge therapy, and no increased mortality was observed secondary to the delay in intubation. After initiating HFNC, a ROX index below 4.94 predicts the need for intubation.
Syntheses of the cyclic tripeptides OF4949-III 1 and K-13 2 are reported, in which the key steps are intermolecular and intramolecular Negishi cross-coupling reactions, respectively. In addition, the synthesis of a protected isomer of K-13 25 is reported. The synthesis of K-13 features a tripeptidic organozinc reagent 11, one of the most highly functionalized such reagents to be described. An O-aryltyrosine derivative 15, prepared by S(N)Ar reaction between Boc-tyrosine and 2-fluorobenzaldehyde, followed by Dakin reaction, iodination, and methylation, is used as a common intermediate for all of the syntheses described. The routes to this class of cyclic tripeptide are among the shortest reported to date and demonstrate the high functional group tolerance of the carbon-zinc bond toward peptide derivatives.
Diels−Alder reactions of a range of
(R)-4-hydroxy-4-[(p-tolylsulfinyl)methyl]-2,5-cyclohexadienones
with cyclopentadiene and 1,3-pentadiene proceed in a total π-facial
diastereoselective manner from
the C-4 OH side. Ab initio calculations at the
RHF/6-31G* theory level provide data on transition-state energies for cycloadditions with cyclopentadiene in full agreement
with the experimental
results.
Introduction
Tocilizumab is an interleukin 6 receptor antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome (ARDS). However, there is no data about the best moment for its administration along the course of the disease.
Methods
We provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020.
Findings
A total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. At baseline, 114 (61%) required oxygen support with FiO2 >0.5 % and 72 (39%) <0.5%. Early administration of tocilizumab, when the need of oxygen support was still below FiO2 <0.5%, was significantly more effective than given it in advanced stages (FiO2 >0.5 %), achieving lower rates of intubation or death (13% vs 37% repectively, p<0.001).
Interpretation
The benefit of tocilizumab in severe SARS-Cov-2 pneumonia is only expected when it is administrated before the need of high oxygen support.
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