Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). It is well known that novel Coronavirus disease 2019 (COVID-19) pneumonia progresses to ARDS and even multiple organ failure. High blood neutrophil levels are an early indicator of COVID-19 and predict severe respiratory diseases. Also it is reported that mucus structure of COVID-19 is very similar to cystic fibrosis due to the accumulation of excessive NET in the lungs. In this study, we showed the recovery of three COVID-19 patients after including Dornase alfa in their treatment. We followed clinical improvement in the radiological analysis (2-of-3 cases), oxygen saturation (SpO 2 ), respiratory rate, disappearing of dyspnea, coughing and a decrease in NET formation and SARS-CoV-2 viral load after the treatment. Also here, we share our preliminary results suggesting that Dornase alfa has an anti-viral effect against SARS-CoV-2 infection in a green monkey kidney cell line, Vero, and a bovine kidney cell line, MDBK without determined cytotoxicity on healthy peripheral blood mononuclear cells.
The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3 rd -5 th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.
Effective palliative treatment in malignant pleural effusion can only be carried out when the lung is fully expanded after drainage of effusion. We investigated the efficacy of intrapleural fibrinolytics for lysing fibrin deposits and improving lung reexpansion in patients with malignant pleural effusion. We randomly allocated 47 patients with malignant pleural effusion into 2 groups: a fibrinolytic group of 24 were given 3 cycles of 250,000 U intrapleural streptokinase; the control group of 23 received pleural drainage only. Pleurodesis with 5 mg of talc slurry was performed in all patients who had lung reexpansion after drainage. Patient characteristics, pleural drainage, lung expansion assessed by chest radiography, and pleurodesis outcomes were compared between the 2 groups. Patient characteristics were similar in both groups. Lung reexpansion was adequate for performing talc pleurodesis in 96% of patients in the fibrinolytic group and 74% in the control group. In the fibrinolytic group, the mean volume of daily pleural drainage before streptokinase administration was 425 mL, and it increased significantly to 737 mL after streptokinase infusion. Intrapleural administration of streptokinase is advisable for patients with malignant pleural effusion.
The results of this study revealed that both OSA and non-apneic, nocturnal desaturated COPD patients showed increased levels of lipid peroxidation and decreased PON activity despite the differences in nocturnal hypoxia pattern.
The cardiovascular complications that frequently accompany obstructive sleep apnea syndrome (OSAS) are thought to develop as a result of inflammatory stress associated with cytokines such as IL-6 and TNF-α. We conducted the current study to compare levels of these cytokines in OSAS patients (n = 33) and nonapneic controls (n = 24). Furthermore, we investigated the impact of a three-month regime of continuous positive airway pressure (CPAP) on serum levels of IL-6 and TNF-α only in the OSAS patients. There were no significant differences in serum levels of either IL-6 (P = 0.782) or TNF- α (P = 0.722) or TNF-α (P = 0.722) between OSAS patients and nonapneic controls. Serum IL-6 levels correlated significantly with neck circumference in OSAS patients (P = 0.006). In OSAS patients, reduced levels of TNF-α and IL-6 correlated with increases in mean SaO2 after CPAP treatment (P = 0.020 and P = 0.051, resp.). However, neither of cytokine levels was significantly impacted by CPAP therapy (both P > 0.137). We have demonstrated that plasma cytokine levels are similar in both otherwise healthy subjects with OSAS and in nonapneic control, and we conclude that OSAS-related parameters and CPAP treatment do not play a significant role in altering cytokine levels.
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