Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.

BACKGROUND: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial. METHODS: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment. RESULTS: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013). CONCLUSION: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.

Vitamin D Levels as a Marker of Severe SARS-CoV-2 Infection.

The SARS-CoV-2 virus may cause severe infection, which is associated with diverse clinical manifestations. Vitamin D has immunomodulating properties and may enhance the body's defense system against invading pathogenic organisms. The aim was to assess 25(OH)D3 levels in patients hospitalized for severe infection from the SARS-CoV-2 virus and explore the relationship between 25(OH)D3 and outcomes. In a group of 88 patients hospitalized for severe infection from the SARS-CoV-2 virus and a control group matched for age and sex, the levels of 25(OH)D3 were analyzed. Levels of 25(OH)D3 were 17.36 ± 8.80 ng/mL (mean ± SD) compared with 24.34 ± 10.34 ng/mL in patients with severe SARS-CoV-2 infection and the control group, respectively, p < 0.001 (Student's t-test). 25(OH)D3 levels were significantly related to outcomes, i.e., survival as opposed to non-survival, as more patients with 25(OH)D3 deficiency (0-10 ng/mL) and insufficiency (10-20 ng/mL) had a fatal outcome as compared with those with vitamin D sufficiency (p < 0.001, chi-square test, p < 0.001, Fisher's exact test). Levels of 25(OH)D3 were inversely related to C-reactive protein (CRP), ferritin, d-dimer, and fibrinogen levels (p < 0.001, linear regression analysis, beta coefficient of variation, -0.176, -0.160, -0.178, and -0.158, respectively). Vitamin D deficiency observed in severe SARS-CoV-2 infection was related to disease outcomes.

Results of transoral laser microsurgery in 102 patients with squamous cell carcinoma of the tonsil.

The objective of this study is to assess the feasibility of transoral laser microsurgery (TLM) in the treatment of squamous cell cancer of the tonsil and to report the oncological and functional outcomes, using retrospective chart review in the setting of single-institute, academic tertiary referral center. Between October 1987 and December 2006, 102 patients were eligible for this study, mostly suffering from advanced disease: 13% presented with stage I and II (UICC/AJCC 2002) tumors and 87% with stages III and IVa. The median follow-up was 63 months. All patients were treated by TLM with (or without) neck dissection (95%) and with (66%) postoperative radiotherapy. Overall survival, recurrence-free survival, disease-free survival, local control and loco-regional control were analyzed as end points. Rate of tracheotomies, postoperative complications and swallowing function were also analyzed. 5-year Kaplan-Meier local and loco-regional control was 78% for pT1 and pT2 and 75 % for pT3 and pT4a tumors. 5-year Kaplan-Meier disease-free survival, recurrence-free survival, and overall survival and was 74, 64 and 59% for stage I and II, 68, 60 and 56 % for stage III and IVa, respectively. Our data supports the conclusion, that TLM should be considered as a therapeutic option for the treatment of cancer of the tonsil. The oncological and functional results are comparable to any other treatment regimen, while the morbidity and complications tend to be lower.