The efficacy of corticosteroids therapy in patients with moderate to severe SARS-CoV-2 infection: a multicenter, randomized, open-label trial.

BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.

Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia.

BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.

Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in IRAN: A single center study.

BACKGROUND: An outbreak of COVID-19 in Iran has spread throughout the country. Identifying the epidemiological characteristics of this disease will help to make appropriate decisions and thus control the epidemic. The aim of this study was characterization of the epidemiological features of COVID-19 in Iran. METHODS: In this retrospective study, data related to the epidemiological characteristics of COVID-19 patients admitted to Baqiyatallah Hospital in Tehran, Iran, from 19 February 2020 to 15 April 2020 have been analyzed and reported. Patient characteristics including age, gender and underlying diseases were investigated. Data were collected through patient records. Sex ratio, Case Fatality Rate (CFR) and daily trend of cases were also determined. A multiple logistic regression analysis was also performed to assess affecting factors on mortality. RESULTS: From February 19, 2020 to April 15, 2020, 12870 patients referred to the hospital emergency department, of which 2968 were hospitalized with COVID-19 diagnosis. The majority of cases were in the age group of 50 to 60 years of old. The male-to-female ratio was 1.93:1. A total of 239 deaths occurred among all cases for an overall CFR of 1.85% based on the total number of patients (both outpatient and inpatient) and 8.06% among hospitalized patients. Out of all patients 10.89% had comorbidity. Diabetes, chronic respiratory diseases, hypertension, cardiovascular diseases, chronic Kidney diseases and cancer were the most common comorbidities with 3.81, 2.02 , 1.99 , 1.25, 0.60 and 0.57 %, respectively. Male gender (OR=1.45, 95% CI: 1.08-1.96), older age (OR=1.05, 95% CI: 1.04-1.06) and having underlying diseases (OR=1.53, 95% CI: 1.04-2.24) were significantly associated with mortality. CONCLUSIONS: The results of this study showed that Male gender, older age and having comorbidities were significantly associated with the risk of death among COVID-19 patients. It is important to pay special attention to male elderly patients with underlying diseases.

Electrochemical biosensors for the detection of lung cancer biomarkers: A review.

Cancer is one of the most widespread challenges and important diseases, which has the highest mortality rate. Lung cancer is the most common type of cancer, so that about 25% of all cancer deaths are related to the lung cancer. The lung cancer is classified as two different types with different treatment methodology: the small cell lung carcinoma and nonsmall cell lung carcinoma are two categories of the lung cancer. Since the lung cancer is often in the latent period in its early stages, therefore, early diagnosis of lung cancer has many challenges. Hence, there is a need for sensitive and reliable tools for preclinical diagnosis of lung cancer. Therefore, many detection methods have been employed for early detection of lung cancer. As lung cancer tumors growth in the body, the cancerous cells release numerous DNA, proteins, and metabolites as special biomarkers of the lung cancer. The levels of these biomarkers show the stages of the lung cancer. Therefore, detection of the biomarkers can be used for screening and clinical diagnosis of the lung cancer. There are numerous biomarkers for the lung cancer such as EGFR, CEA, CYFRA 21-1, ENO1, NSE, CA 19-9, CA 125 and VEGF. Nowadays, electrochemical methods are very attractive and useful in the lung cancer detections. So, in this paper, the recent advances and improvements (2010-2018) in the electrochemical detection of the lung cancer biomarkers have been reviewed.

Curcumin Mitigates Radiation-induced Lung Pneumonitis and Fibrosis in Rats.

Radiation-induced lung injury is one of the most prominent factors that interfere with chest cancer radiotherapy, and poses a great threat to patients exposed to total body irradiation. Upregulation of pro-oxidant enzymes is one of the main mechanisms through which the late effects of ionizing radiation on lung injury can be exerted. Interleukin (IL)-4 and IL-13 are two important cytokines that have been proposed to be involved in this process. Through stimulation of dual oxidase 1 and 2 (DUOX 1 & 2), they induce chronic oxidative stress in irradiated tissues. In this study, we evaluated the effects of curcumin treatment on the regulation of IL-4 and IL-13, DUOX1 & 2 genes as well as the pathological changes developed by this treatment. Twenty male Wistar rats were divided into four groups: radiation only; curcumin only; radiation +curcumin; and control group with neither pharmacotherapy nor radiation. Curcumin was administered for 4 and 6 consecutive days before and after irradiation, respectively. Also, the chest area was irradiated with 15 Gy using a cobalt-60 gamma rays source. All rats were sacrificed 67 days after irradiation, followed by the assessment of the levels of IL-4 and IL-13; the expression of IL- 4 receptor-a1 (IL4Ra1), IL13Ra2, DUOX1 and DUOX2, and finally the histopathological changes were evaluated. Radiation led to the increased level of IL-4, while the level of IL-13 showed no change. QPCR results showed the upregulation of IL4Ra1, DUOX1 and DUOX2 following lung irradiation. Histopathological evaluation also showed a remarkable increase in pneumonitis and fibrosis. Treatment with curcumin downregulated the expression of IL-4, IL4Ra1, DUOX1 & 2. Furthermore, it could mitigate pneumonitis and fibrosis following lung irradiation. The late effects of radiation- induced lung injury may be due to the upregulation of DUOX1 & 2 genes. Curcumin, through modulation of these genes, may contribute to the protection against ionizing radiation.

Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard.

Sulfur mustard (SM) is a potent alkylating agent that targets several organs, especially lung tissue. Although pathological effects of SM on mustard lung have been widely considered, molecular and cellular mechanisms for these pathologies are poorly understood. We investigated changes in expression of genes related to oxidative stress (OS) and antioxidant defense caused by SM in lung tissue of patients. We performed gene expression profiling of OS and antioxidant defense in lung tissue samples from healthy controls (n=5) and SM-exposed patients (n=6). Changes in gene expression were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in cellular OS response. 47 (55.95%) genes were found to be significantly upregulated in patients with mustard lung compared with controls (p<0.05), whereas 7 (8.33%) genes were significantly downregulated (p<0.05). Among the most upregulated genes were OS responsive-1 (OXSR1), forkhead box M1 (FOXM1), and glutathione peroxidase-2 (GPX2), while metallothionein-3 (MT3) and glutathione reductase (GSR) were the most downregulated genes. Expression of hypoxia-induced genes (CYGB and MB), antioxidants and reactive oxygen species (ROS)-producing genes were significantly altered, suggesting an increased oxidative damage in mustard lungs. Mustard lungs were characterized by hypoxia, massive production of ROS, OS, disruption of epithelial cells, surfactant dysfunction, as well as increased risk of lung cancer and pulmonary fibrosis. Oxidative stress induced by ROS is the major mechanism for direct effect of SM exposure on respiratory system. Antioxidant treatment may improve the main features of mustard lungs.

Efficacy of Tiotropium Bromide and Rehabilitation Treatment on Pulmonary Function of Patients With Sulfur Mustard Lung Injury.

BACKGROUND: Chronic pulmonary complication is the most common delayed toxic effect of sulfur mustard (SM) and it has no treatment so far. OBJECTIVES: To evaluate short-term therapeutic effects of inhaled tiotropium bromide and pulmonary rehabilitation on pulmonary function of patients with SM induced lung injury. PATIENTS AND METHODS: In a randomized clinical trial, using convenient sampling method, 54 patients with chronic lung disease due to SM exposure were recruited in Baqiyatallah General Hospital, Tehran, Iran for a period of 2-month study. They were randomly divided into 3 groups of 18 participants each. Group 1 received routine drugs (Serevent, Flixotide), pulmonary rehabilitation 30 minutes/2 times a week, and tiotropium bromide 18 µg/day. Group 2 was treated with routine drugs and pulmonary rehabilitation and group 3 was only on the routine drugs. cardiopulmonary exercise test (CPET), plethysmographic measurements, and respiratory symptoms evaluation were performed before and after medical intervention. RESULTS: In group 1, compared to group 3, significant differences were found with regard to symptoms of cough ([difference between the first and last visit in group 1: Diff 1] = -1.6, Diff 3 = -0.3, P = 0.01) and nocturnal dyspnea (Diff 1 = -1.9, Diff 3 = 0.0, P = 0.01), likewise, compared to group 2, significant differences were found with regard to lung function parameters of forced vital capacity (Diff 1 = 3.0, Diff 2 = -3.5, P = 0.03), forced expiratory volume in one second (Diff 1 = 3.9, Diff 2 = -5.6, P = 0.009), maximal mid-expiratory flow rate 25% - 75% (Diff 1 = 1.5, Diff 2 = -3.2, P = 0.007) and peak expiratory flow (Diff 1 = -2.06, Diff 2 = -4.3, P = 0.04). Total lung capacity (Diff 2 = 9.28, Diff 3 = -12.07, P = 0.02) and residual volume (Diff2 = 32.1, Diff3 = -27.6, P = 0.04) were increased in group 2 compared to group 3. There were no significant differences with regard to CPET results among all groups (P > 0.05). CONCLUSIONS: Inhalation of tiotropium bromide in combination with pulmonary rehabilitation could improve some plethysmographic lung volumes and clinical outcomes in patients with chronic pulmonary disease due to SM. Short-term prescription of pulmonary rehabilitation has no effect on CPET of patients.