Background: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS-CoV-2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS-CoV-2 clinical outcomes. Objectives: To estimate the association between T level and SARS-CoV-2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU). Materials and methods: A consecutive series of 31 male patients affected by SARS-CoV-2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the "Carlo Poma" Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D-dimer, fibrinogen, interleukin 6 (IL-6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. Results: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT < 5 nmol/L or cFT < 100 pmol/L. How to cite this article: RastrelliG, Di Stasi V, Inglese F, et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients.
Background and aim: Various low triiodothyronine (T3) states have been described in severe nonthyroidal diseases and associated with a poor prognosis in cardiovascular disease patients. We assessed thyroid function in patients with severe respiratory failure from pulmonary disorders, and needing invasive or noninvasive mechanical ventilation, in order to evaluate the prognostic value of nonthyroidal illness syndrome. Methods: We studied 32 consecutive patients with acute or acute-on-chronic respiratory failure. Measured variables upon admission included APACHE II score, the ratio of the partial pressure of oxygen in arterial blood to the fraction of oxygen in inspired gas (PaO 2 /FiO 2 ), and plasma levels of free T3 (fT3) and free thyroxine (fT4), and TSH levels. Thyroid function was further evaluated at discharge. Results: Plasma levels of fT3 were below normal in 17 patients (53%). Plasma fT3 was correlated with PaO 2 /FiO 2 (P , 0.001), and with APACHE II score (P ¼ 0.003). In four patients (12.5%) who died, fT3 levels were significantly lower (P ¼ 0.002) than in patients who survived. In univariate logistic regression analysis, fT3 was the only factor significantly associated with an increased risk of death (odds ratio, 64.23; 95% confidence interval, 1.78 -2316.86, P ¼ 0.023). Normalization of thyroid function was observed at discharge with a significant correlation between the percent increase in both fT3 and PaO 2 /FiO 2 (P ¼ 0.015). P values were calculated using Spearman's Correlation Coefficient. Conclusion: Our preliminary data suggest that the low T3 state is a predictor of outcome in pulmonary patients with respiratory failure.
The contribution of human alveolar macrophages (AM) from normal subjects in Cryptococcus neoformans infection was investigated. AM were able to efficiently phagocytize the fungus after opsonization, but killing activity did not occur at an effector-to-target ratio of 10:1 in a 6-h incubation since there was an inhibition of phagosome-lysosome fusion. Moreover, the role of AM as antigen-presenting cells was investigated. Cryptococcus-laden AM were co-cultured with autologous T lymphocytes and lymphoproliferation was determined; a massive blastogenic response of alpha/beta TCR-bearing T lymphocytes was observed. The response started after 1 day of co-culture and was triggered and regulated by IL-1 produced by AM in response to C. neoformans. Finally, the antigen-presentation process was associated with HLA class II DR molecules. This finding suggests that AM play a key role in the lung as antigen-presenting cells and, through the secretion of IL-1, regulate proliferation and activation of T lymphocytes, which are important in mediating pulmonary clearance. We speculate that in immunodepressive conditions, the impairment of AM functions could contribute to the spread of C. neoformans infection from the lung.
Pulmonary function of 31 heavy smokers with laryngeal cancer was evaluated before and during the 1st year after total (n = 21) and conservative (n = 10) laryngectomy. 2 of them died because of recurrences, 1 for bronchopulmonary complications. Long-lasting hoarseness was the only presenting symptom in all patients. Preoperative lung function data and mucociliary clearance were consistent with a coexisting chronic obstructive lung disease in most subjects and was probably due to smoking. No differences were observed comparing pre- and postoperative data in the 10 conservative laryngectomy patients. On the contrary, the total-laryngectomy patients showed a progressive impairment of bronchial obstruction and bacteriological infection of the trachea during the 1st year after the operation. An impressive increase in mucociliary clearance rates has been observed 2 months after total laryngectomy during the postoperative hypersecretory phase. The obtained data allow us to hypothesize that when clinical conditions of laryngectomized patients in whom local or distant recurrences have been excluded deteriorate, this is related to a progressive bronchial obstruction at any level of the bronchial tree due to descending bacterial infection of the airways. To our knowledge this is the only work demonstrating that total laryngectomized patients need a complete pre- and postoperative evaluation of lung function, airway dynamics, mucociliary function and tracheal bacteriology for long-term prognosis and treatment.
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