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Abstract Background and objectives Migration, as an important social determinant in the field of health, plays a crucial role in the non-eradication of tuberculosis worldwide. Therefore, it is essential to identify the factors related to tuberculosis treatment in immigrants to effectively combat this disease. However no comprehensive study has focused on this issue. Therefore, this study was conducted using an ecological approach to identify the barriers and facilitators of tuberculosis treatment in immigrants. Methods This qualitative study utilized an integrative literature review. Studies were searched without time restrictions in database such as MEDLINE, Institute for Scientific Information (ISI), Google Scholar, Scopus, and EMBAS, as well as internal databases like Scientific Information Database and Magiran. The findings of 100 studies that met the inclusion criteria were analyzed using the conventional content analysis method based on the ecological approach. Results In general, the aforementioned codes were placed into four main categories, including individual factors (i.e., biological factors, psychological factors, behavioral factors, patient knowledge, factors related to tuberculosis, and economic factors), interpersonal factors (i.e., communication with the treatment team and family-related factors), factors related to health service provider centers (i.e., medical facilities), and extra-organizational factors (i.e., social factors and health policies). Conclusion The findings of the present study show that treating tuberculosis in immigrants is a complex phenomenon influenced by several factors. Therefore policymakers and healthcare providers should take a more comprehensive look at the factors affecting treatment in this group of patients to plan and implement more effective interventions.

Background: The objective is to assess lung compliance and identify the optimal positive end-expiratory pressure (PEEP) levels in patients with tuberculosis-associated Acute Respiratory Distress Syndrome (TB-ARDS) compared to non-TB-ARDS patients. Methods: This observational case–control study utilized electrical impedance tomography to evaluate lung mechanics in 20 TB-ARDS and 20 non-TB-ARDS patients. Participants underwent PEEP titration from 23 to 5 cm H2O in 2 cm H2O decrements. Lung compliance and the rates of hyperdistention and collapse were assessed at each PEEP level. Results: Delta impedance values showed higher amounts in a PEEP range of 11–17 cm H2O and in patients with TB-ARDS (P > 0.05). In addition, both hyperdistention and collapse rates were nonsignificantly higher in TB-ARDS patients (P > 0.05), and the compromised levels of hyperdistention and collapse rates were at 15–17 cm H2O, indicating the most favorable PEEP level. Conclusions: The observed patterns of hyperdistention and collapse rates across various PEEP levels provide valuable insights into the susceptibility of TB-ARDS patients to barotrauma. Notably, the identified optimal PEEP range between 15 and 17 cm H2O may guide ventilator management strategies in mitigating both hyperdistention and collapse; nonetheless, due to the high variability of lung compliances within groups, we strongly recommend individualized consideration for tailored respiratory support and evaluation.

Background: Coronavirus disease 2019 (COVID-19) vaccination has been shown to elicit both humoral (antibody) and cell-mediated (T-cell) immune responses. This study aimed to characterize and compare the QuantiFERON severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-SARS-CoV-2 antibody responses in vaccinated and unvaccinated COVID-19 patients, as well as vaccinated healthy controls (HCs). Methods: A total of 96 COVID-19 patients (68 vaccinated with Sinopharm and 15 with AstraZeneca), 13 unvaccinated COVID-19 patients, and 16 vaccinated HCs (8 Sinopharm and 8 AstraZeneca) were included. Serum antibodies against the SARS-CoV-2 spike (S1) protein and nucleocapsid (N) protein were measured by enzyme-linked immunosorbent assay. T-cell responses were evaluated using the QuantiFERON assay against three SARS-CoV-2 viral antigens (Ag1, Ag2, and Ag3). Results: There were no significant differences in S1 antibody levels between COVID-19 patients (vaccinated or unvaccinated) and HCs. However, 100% of unvaccinated COVID-19 patients had anti-N antibodies, which was significantly higher than the AstraZeneca-vaccinated group. T-cell responses did not differ significantly between vaccinated and unvaccinated patients or between vaccinated patients and HCs. Vaccination with Sinopharm induced higher levels of total N antibodies and greater interferon-gamma release against the viral antigens compared to the other groups. Conclusions: Vaccination, especially with Sinopharm, induced robust humoral (N antibodies) and cellular (T-cell) immune responses in COVID-19 patients. The findings highlight the importance of vaccination in eliciting a comprehensive immune response against SARS-CoV-2, even in the context of prior infection.

Background and Objective: The global incidence rate of tuberculosis and related death among the elderly are 3 times and 6 times more than that of non-elderly, respectively. Therefore, the successful treatment of tuberculosis in the elderly affects all national tuberculosis control programs. Given the fact that “medication adherence” is the main key to effective treatment, it is essential to identify the factors related to medication adherence in the elderly with tuberculosis and provide appropriate interventions. Family caregivers play a pivot role in the elderly care and treatment, and their characteristics can influence the medication adherence of the elderly with tuberculosis. The objective of present study was determining the medication adherence of the elderly with tuberculosis and the factors related to their family caregivers in Iran. Method: The present study was carried out through descriptive-analytical method and convenience sampling. 305 elderly patients with tuberculosis as well as their family caregivers who met the inclusion criteria were selected from those who referred to infectious diseases clinic of Masih Deneshvari Hospital in Tehran. Demographic and background data, 12-item standard general health questionnaire, Zarit Scale of Caregiver Burden questionnaire and Morisky Green Levine Medication Adherence questionnaire were used for the elderly with tuberculosis. The significance level for statistical tests was considered 0.05. Data analysis of the study was done using SPSS-25 software. Independent t-test, One-way ANOVA, Tukey’s test, Spearman’s correlation test and ordinal logistic regression model were also used for the analytical statistics. Findings: Out of the elderly with tuberculosis, 44.92 % had low medication adherence, 27.54 % had moderate medication adherence, and 27.54 % had full medication adherence. Medication adherence of married elderly was significantly better than single, widowed or lonely elderly (p 0.001 and r = 0.776) and no burden or low burden according to Zarit scale (p > 0.001 and F = 357/96). In addition, there was a significant relationship between general characteristics of the caregivers (age, gender, marital status, number of children, education, knowledge about tuberculosis, sources of information, relativity to the patient, number of caregivers, employment status, and affordability) and the medication adherence of the elderly with tuberculosis. The results of simultaneous regression test of ordinal logistic regression showed that variables predict medication adherence behavior to a very acceptable level. The coefficient of determination values obtained from McFadden (0.4), Nagelkerke (0.747) and Cox-Snell (0.714) statistics demonstrated high explanatory power of the model by predictor variables. Conclusion: The results of the present study suggested that the characteristics of family caregivers were associated with the medication adherence of the elderly patients. Therefore, policy making, providing treatment protocols emphasizing on the family role, investigating the characteristics of caregivers during patient visits and performing appropriate interventions will play vital roles in improving medication adherence of the elderly and controlling tuberculosis.

Background: The COVID-19 pandemic has affected millions globally, and still continues to do so. Regarding the cardiovascular influences of COVID-19, this study aimed to investigate the relationship between cardiac indices, particularly cardiac output (CO), and severity of disease. Methods: This retrospective cohort study was conducted on intubated COVID-19 patients admitted to the intensive care unit (ICU). The study involved analyzing data from mechanically ventilated patients, excluding those with preexisting cardiovascular or pulmonary comorbidities. Hemodynamic parameters were evaluated by ultrasonic cardiac output monitoring (USCOM), and the severity of disease was evaluated by acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scoring systems. Results: The study included 41 patients, predominantly male with an average age of 63.1 years. Hemodynamic parameters and scores were reported for 6 days. This showed significant changes in CO, SOFA, and APACHE II over time (with P = 0.02, 0.04, 0.03, respectively). A negative correlation was found between CO and both SOFA and APACHE II scores (P < 0.05), indicating that as CO increased, the severity scores decreased. Conclusion: This study emphasizes the importance of continuous hemodynamic monitoring in ICU settings for COVID-19 patients. The correlation between CO and severity scores suggests that USCOM, along with APACHE II and SOFA, can be crucial in assessing the dynamic clinical state of patients, contributing to better management and potentially improving outcomes.

Abstract Background In the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated. Methods Laboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day. Results The results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved. Conclusions In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS. Trial registration Iranian Registry of Clinical Trials RCT20170731035423N2 . Registered on June 12, 2020.

Abstract Background and aims The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients. Materials and methods COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention. Results A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041). Conclusion MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073 .

Abstract The pathogenesis of coronavirus disease 2019 (COVID-19) is not fully elucidated. COVID-19 is due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes severe illness and death in some people by causing immune dysregulation and blood T cell depletion. Increased numbers of myeloid-derived suppressor cells (MDSCs) play a diverse role in the pathogenesis of many infections and cancers but their function in COVID-19 remains unclear. To evaluate the function of MDSCs in relation with the severity of COVID-19. 26 PCR-confirmed COVID-19 patients including 12 moderate and 14 severe patients along with 11 healthy age- and sex-matched controls were enrolled. 10 ml whole blood was harvested for cell isolation, immunophenotyping and stimulation. The immunophenotype of MDSCs by flow cytometry and T cells proliferation in the presence of MDSCs was evaluated. Serum TGF-β was assessed by ELISA. High percentages of M-MDSCs in males and of P-MDSCs in female patients were found in severe and moderate affected patients. Isolated MDSCs of COVID-19 patients suppressed the proliferation and intracellular levels of IFN-γ in T cells despite significant suppression of T regulatory cells but up-regulation of precursor regulatory T cells. Serum analysis shows increased levels of TGF-β in severe patients compared to moderate and control subjects (HC) (P = 0.003, P

Background: Tocilizumab and baricitinib are considered standard treatments for hospitalized COVID-19 patients with an inflammatory status. However, the effects of co-administering these medications aiming for more rapid patient recovery are controversial among practitioners. The potential benefits include the rapid improvement of patients and regulation of the immune system, and the potential risks include the increased chance of serious adverse events, including infections. This study aimed to investigate the effects of co-administering these two medications on the 28-day mortality rate, other efficacy parameters, and safety issues.Methods: In this randomized open-label trial, 68 patients were recruited. The study was conducted at Dr. Masih Daneshvari Hospital during 6 months (from 21 March 2022 to 23 August 2022). Severely ill patients aged between 18 and 100 years old with confirmed COVID-19 were enrolled. The primary outcomes included the need for invasive mechanical ventilation and a 28-day mortality rate. Secondary outcomes included the need for non-invasive mechanical ventilation, the need for admission to the intensive care unit (ICU), the length of hospital stay, and the need for a second dose of tocilizumab. Safety assessments were also performed for 28 days. The data were collected from the patients’ medical records, which included age, gender, and comorbidities.Results: The 28-day mortality rate or the need for mechanical ventilation was not statistically different among the two groups (p-value = 0.49 for both outcomes). The need for non-invasive mechanical ventilation, the need for admission to the ICU, or the need for a second dose of tocilizumab and the length of hospital stay was not affected either (p-value = 1; 0.1; 0.49 and 0.9, respectively). One patient developed thrombosis in the combination group. No adverse events related to infectious complications were recorded in any groups.Conclusion: This study showed no beneficial effects of combining tocilizumab and baricitinib in managing severe COVID-19 cases. However, the need for ICU admission was meaningfully lower in the combination group. Studies with larger sample sizes are needed to confirm these results.Clinical Trial Registration: Identifier: RCT20151227025726N30M

Introduction: Most mortality in COVID-19 cases was due to the increased inflammatory cytokines and cytokine storm. As mesenchymal stem cells (MSCs) possess immunomodulatory properties, this study assessed the therapeutic effects of placental MSC-derived extracellular vesicles on the inflammation and pulmonary injury caused by COVID-19. Methods: The study was carried out in phases I (safety study, 101 patients) and II (efficacy study, 80 patients) in a randomized, double-blind study at four hospital centers from April 2021 to August 2021. In addition to standard treatments, 15 mL of normal saline solution containing 15×109 vesicles was injected intravenously for five consecutive days. Results: No reaction or adverse events were observed in any patients. In the intervention group, after 5 days of treatment, patients’ clinical status and oxygenation improved, and 75% of patients presented an increased SpO2 after 5 days. Besides, inflammatory parameters assessment indicated a 21% decrease in neutrophil-lymphocyte ratio and a 54% reduction in C-reactive protein after day five of the intervention. Conclusion: PMSC-derived extracellular vesicles were safe and well-tolerated, down-regulated cytokine storms, and restored oxygenation. Thus, they can be considered a promising therapeutic candidate for severe COVID-19.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Background: In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. Objective of study: To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. Materials and methods: In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. Results: Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p

IntroductionCOVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting.Materials and methodsA pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020–December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-β and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release.ResultsAll the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05).ConclusionOur study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.

The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran. Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry. COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8. A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39). COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSCs, lung, serum IL-8, and other inflammatory biomarkers should be measured.

Abstract Background This paper describes a case of antiphospholipid syndrome-like condition caused by coronavirus disease 2019. The medical community still faces many diagnostic and therapeutic challenges vis-à-vis coronavirus disease 2019. Ultimately, coronavirus disease 2019 is diagnosed on the basis of laboratory and radiological findings. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events. Case description The patient was a 56-year-old Iranian man who underwent coronary artery bypass graft surgery and mitral valve repair. During hospitalization, the patient showed an elevated level of anticardiolipin antibody (immunoglobulin G isotype), antiphospholipid antibodies, and thrombosis in the brachial artery of the left hand, based on which a differential diagnosis of antiphospholipid syndrome was made. However, ultimately, the coronavirus disease 2019 polymerase chain reaction test and computed tomography scan of the lungs showed that the patient had coronavirus disease 2019. Conclusion According to the few studies performed on coronavirus disease 2019 patients, elevated levels of the isotypes of antiphospholipid antibodies in coronavirus disease 2019 patients create conditions similar to antiphospholipid syndrome, which, in the absence of reliable coronavirus disease 2019 testing, can lead to misdiagnosis and consequently delayed or improper treatment. Therefore, to provide timely and appropriate treatment, it is important to pay attention to differential diagnosis.

Abstract Background Identification of molecular markers, such as miRNAs is promising for the diagnosis of asthma and its clinical phenotypes. The aim of this study was to examine the changes in the expression of selected microRNAs in plasma exosomal fractions of severe asthma patients. The expression of miRNAs was determined in relation to the changes in inflammatory markers. Method Severe asthma patients (n = 30) and healthy subjects (n = 30) were selected among the individuals referred to asthma and allergy clinic. Blood was collected from each participant to determine the serum high-sensitive C-reactive protein (hs-CRP) and total IgE. The exosomal fraction of plasma was isolated and processed for quantitation of miR-124, miR-125b, miR-133b, miR-130a and miR-125b-1-3p expression using quantitative real time-PCR (qRT-PCR). Results Serum hs-CRP and total IgE were significantly higher in asthma patients compared to controls. Expression of miR-124, miR-133b, and miR-130a was down-regulated in asthma patients as compared to controls (p

Abstract Background Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients. Methods A total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases). Findings There were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24–48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48–96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2–7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P

Background and aims: Over the past year, millions of people around the world have infected with the COVID-19 virus. The SARS-CoV-2 replicate efficiently in the human upper respiratory tract. Infected people produce large amounts of the virus in their upper respiratory tract during an introductory period, which leads to more spread of the virus to other people. The World Health Organization has suggested that acute respiratory syndrome SARS-CoV-2 is transmitted through person-to-person transmission and contact with contaminated surfaces. However, the rapid spread of the disease suggests that other routes, such as airborne transmission, may play a role. Several research studies have been performed to evaluate the possible transmission of the virus through the air. Although some studies have found no evidence of airborne transmission, recent work has confirmed the presence of SARS-CoV-2 even in public places. Past experience and knowledge of the mechanism of similar viruses such as SARS-CoV also support this hypothesis. During COVID-19 pandemic, while the hospitals can be one of the most important centers in providing health care services, due to the inappropriate air ventilation and purification system, high traffic of people; some of them have been introduced themselves as one of the most high-risk sources of SARS-CoV-2 transmission. The present study aimed to assess the SARS-CoV-2 in the air and surfaces of ICU ward in one of the designated hospitals in Tehran; so that in addition to determining the possibility of inhalation and contact exposure in ICU, which is the main ward for presenting special medical care to patients with severe acute respiratory infections, it aimed to assess a hypothesis of SARS-CoV-2 airborne transmission. Methods: This cross-sectional experimental study was performed on April 29, 2020 in the Covid-19 ICU ward in one of the designated hospitals, Tehran, Iran. The area of ward was 50 m2 and has seven beds, all of which were occupied at the time of sampling, and five medical staff were involving there. All patients were equipped with oxygen masks and all the staff used all conventional personal protective equipment such as Honeywell-75FFP100NL respirators. On average, surface disinfection was performed three times a day. The general ventilation system included the ceiling diffuser to supply fresh air into the room and wall-mounted exhaust vent and did not use natural ventilation (such as opening the window). It should be noted that the exhaust system didnchr(chr('39')39chr('39'))t work well at the time of sampling. This study was carried out in two phases including surface and air sampling. Impinger method was applied to air sampling. Thus, at a distance of 1.5 to 1.8 meters from the ground, the air of the ICU ward was passed through a sampling pump with an flow rate of 1.5 l/min into the porous midget impeller-30 ml containing 15 ml of virus transmission medium (PVTM) for 45 minutes. To reverse the presence of SARS-CoV-2 in air samples, the reverse polymerase chain reaction (RT-PCR) reaction method was used. Sampling of surfaces was done with the help of swabs impregnated with the solution of the Viral Transport Medium from a certain area (25 cm2) from the desired part and putting it inside the vial containing the transfer medium (protein stabilizer, antibiotic and buffer solution). They are also were analyzed by RT-PCR technique. Prior to sampling, all laboratory equipment used was sterilized and autoclaved using a 70% alcohol solution according to the US Centers for Disease Control and Prevention (CDC) protocol. The air sampling was done at a distance of 1.5 to 2 meters from the patientchr(chr('39')39chr('39'))s bed. The devices used to measure temperature, humidity and air velocity were multi-purpose anemometer (China BENETE, GM8910,) and air pressure, digital barometer (AIRFLOW, DB2, USA). The mean parameters of weather conditions included: air temperature 24 ° C, humidity 35%, air pressure 1005 mb and air velocity of 0.09 m / s. Results: Of the ten air samples, 6 were positive (60%), with the highest RNA concentrations observed at the point between beds 6 and 7 (3913 copies per ml). Most of the reported negative air samples were from the middle of the ward, which was further away from the patientschr(chr('39')39chr('39')) beds. The mean RNA concentration of the virus was obtained 820 ± 2601 copies per milliliter. Also, of ten samples taken from different surfaces of the ward, 4 samples were positive (40%) and the highest concentration (8318 copies per ml) was related to the table next to bed number 3. All positive samples were observed close to the patientchr(chr('39')39chr('39'))s bed, and the mean RNA concentration of the virus was 3227 ± 3674 copies per milliliter. Conclusion: The results of the study indicated that the virus was present in the inhaled air of the ward and its surfaces, especially in areas close to the bed of patients. These findings underscore the airborne transmission of the virus along with other ways of transmission, such as person-to-person contact and contact with contaminated surfaces. Due to the environmental pollution of the studied ICU ward to the SARS-CoV-2 virus, the effective implementation of air isolation methods such as the use of respiratory protection equipment (N95 mask) and powered air-purifying respirator as well as ensuring the correct function of hospital ventilation systems and improving it, is essential for the protection of health care staff. Health care workers need to be continuously monitored and screened from a COVID-19 perspective, and infection prevention and control protocols (IPCs), such as respiratory protection, regular cleaning of the environment, and effective disinfection of areas have been implemented. In the case of the virus, the spread of the disease through both direct methods (drops and person-to-person) as well as indirect contact (contaminated objects and airborne transmission) has almost been proven, which reaffirms the need for precautionary measures regarding airborne isolation against the virus. It has been suggested that in order to more accurately assess the transmission behavior of the virus, similar studies but longitudinal ones have been done from the admission to discharge of the patients in different wards of the hospitals, moreover, the role of natural and mechanical ventilation systems more comprehensively examined in the presence of airborne virus.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. Methods We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March–May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). Results The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. Conclusions This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.

Abstract Background Measurement of work of breathing (WOB) during mechanical ventilation is essential to assess the status and progress of intensive care patients. Increasing ventilator WOB is known as a risk factor for ventilator-induced lung injury (VILI). In addition, the minimization of WOB is crucial to facilitate the weaning process. Several studies have assessed the effects of varying inspiratory flow waveforms on the patient’s WOB during assisted ventilation, but there are few studies on the different effect of inspiratory flow waveforms on ventilator WOB during controlled ventilation. Methods In this paper, we analyze the ventilator WOB, termed mechanical work (MW) for three common inspiratory flow waveforms both in normal subjects and COPD patients. We use Rohrer’s equation for the resistance of the endotracheal tube (ETT) and lung airways. The resistance of pulmonary and chest wall tissue are also considered. Then, the resistive MW required to overcome each component of the respiratory resistance is computed for square and sinusoidal waveforms in volume-controlled ventilation (VCV), and decelerating waveform of flow in pressure-controlled ventilation (PCV). Results The results indicate that under the constant I:E ratio, a square flow profile best minimizes the MW both in normal subjects and COPD patients. Furthermore, the large I:E ratio may be used to lower MW. The comparison of results shows that ETT and lung airways have the main contribution to resistive MW in normals and COPDs, respectively. Conclusion These findings support that for lowering the MW especially in patients with obstructive lung diseases, flow with square waveforms in VCV, are more favorable than decelerating waveform of flow in PCV. Our analysis suggests the square profile is the best choice from the viewpoint of less MW.

Abstract Background The development of lung cancer is a multifactorial process that involves the environmental and genetic factors. The mortality rate of this cancer is higher than breast, colorectal, and prostate cancers. In this study, we try to analyze the proteome of patients with Non‐Small Cell Lung Cancer (NSCLC) and compare it with the healthy samples. Methods This study has compared 30 lung tissue samples from patients with NSCLC and 30 healthy samples using proteomics and RT‐PCR. Hence, tissue samples were obtained from the surgical ward in sterile conditions, and then, protein extraction applied to them. At the next stage, two‐dimensional electrophoresis and mass spectrometry LCMS/MS were performed for protein isolation and sequencing, respectively. Results The proteome analysis identified more than 40 differences in proteomic pattern of normal lung tissues compared to lung tissues with NSCLC. Peroxiredoxin, Haptoglobin, and Alpha‐1 antitrypsin proteins were identified. Molecularly, it has also been shown that the two main proteins of Peroxiredoxin‐2 and Alpha‐1 antitrypsin were upregulated, and the expression of Haptoglobin protein was downregulated in cancer tissue. Conclusion The results of this study showed that there are some differences in term of protein content between the normal and cancerous lung tissues. Further studies are needed to evaluate these proteins that investigate whether these proteins can candidate as biomarkers to use in the early diagnosis of patients with NSCLC.

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in white Caucasians. It affects many organs including the lung, pancreas, and liver. Whilst CF is a monogenic disease, several studies revealed a complex relationship between genotype and clinical phenotype of diseases. We examined the expression of human leukocyte antigen (HLA) class II alleles among Iranian CF patients with disease-related microbial infection. This study was conducted on 50 hospitalized CF patients (27 males, 23 females aged 15.5±6.5 years), and 50 healthy age- and gender-matched control subjects. 5ml whole blood was harvested and after isolation of genomic DNA, HLA-DRB1 subtypes were determined by single specific primer polymerase chain reaction methods. HLA-DRB1*10 was less frequent and HLA-DRB1*04 and HLA-DRB1*11 was the most frequent allele in CF patients, but none reached significance. HLA-DRB1*04 allele was frequently seen among16 CF patients with high serum IgE levels (430.25±219.7 IU/mL) and 27 CF patients that were positive for Pseudomonas aeruginosa colonization. A total of 31 CF patients had candida Albicans colonization in whom HLA-DRB1*11 was mostly seen. A total of 3 CF patients had allergic bronchopulmonary aspergillosis and two were diabetic. The DR4 and DR11 serotypes that recognize the HLA-DRB1*04 and HLA-DRB1*11 gene products respectively are not significantly enriched in the Iranian CF population. Further research should be conducted on DR4 and DR11 in CF patients to understand their possible role in infection and IgE expression.

Since the start of the COVID-19 pandemic, a large number of trials have examined the efficacy of various medications as potential treatments for COVID-19, but a promising therapeutic option is still missing and under investigation. Molnupiravir is an investigational oral antiviral medication and a nucleoside analogue that suppresses SARS-CoV-2 replication and has been found to be active against common virus variations (including the Delta variant). Several phase 2 and 3 clinical trials have shown high efficacy for direct antiviral activity of molnupiravir as well as its favorable safety and tolerability in mild to moderate Covid-19 patients. The current study was done on five hospitalized, severe COVID-19 patients. It seems that in combination with remdesivir, this novel antiviral could exert a synergistic effect on reducing the severity of symptoms as well as the duration of hospitalization. However, further clinical studies on the use of molnupiravir in the treatment of severe COVID-19 are warranted.

Coronavirus disease (COVID-19) pandemic has turned into one of the most considerable challenges worldwide. The optimal treatment strategy, particularly in severely ill patients, is still unrecognized. IgM-enriched immunoglobulin (Pentaglobin®, Biotest AG, Dreieich, Germany) contains IgM, IgA and IgG against a variety of pathogens representing passive immune protection for affected individuals and it may be effective in the treatment of COVID-19. On March 16, 2020, a 32-year-old woman presented to Masih Daneshvari Hospital, Tehran, Iran. On admission, the peripheral oxygen saturation (O2 Sat) was 84%. Spiral chest computed tomography (CT) scan revealed bilateral ground-glass opacification (GGO) involvement. On March 19, 2020, the clinical condition was deteriorated, and her O2 Sat decreased to 70% in ambient air. Treatment with IgM-enriched immunoglobulin was immediately initiated over the course of three days (total dose for the patient was calculated to be 1500 ml). On the seventh day of hospitalization, the patient was discharged with satisfactory general condition, without any complaints, and with stable vital signs and O2 Sat of 95% on room air. In conclusion, IgM-enriched immunoglobulin could be considered as a potential option for the treatment of severely ill patients with COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2)2, the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity. Objective: This pilot study followed the time-course of sACE2 levels in relation to systemic cytokines in severe and moderate COVID-19 patients treated with remdesivir/dexamethasone in combination. Methods: Peripheral blood was obtained upon admission from 30 patients (12 with moderate disease and 18 with severe disease) and 14 patients with PCR-confirmed mild COVID-19. Severe and moderate patients were treated with remdesivir (200mg/first day and 100mg/day for the remaining days) and dexamethasone (100mg/day). 6 healthy control subjects (HC) were also enrolled. Serum interleukin (IL)-6 and IL-8 and sACE2 levels were measured by ELISA at baseline and during treatment in severe and moderate patients and at baseline in mild and HCs. Results: Baseline sACE2 levels were lower in severe (p = 0.0005) and moderate (p = 0.0022) patients than in patients with mild COVID-19 and in HC (p = 0.0023 and p = 0.0012 respectively). Treatment significantly increased sACE2 levels in patients with moderate disease (p = 0.0156) but only 50% of patients with severe disease showed enhanced levels compared to baseline. Systemic IL-6 and IL-8 levels were higher in all patient groups compared with HC and were not significantly affected over time or by remdesivir/dexamethasone treatment for 5 days. Conclusion: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected. Future studies should link these results to clinical outcomes.

Background: A heterogeneous pattern was detected in COVID-19 severe acute respiratory distress syndrome (ARDS) patients. The aim of this study was to define special features and individualized treatment modalities for this fatal infectious disease. Methods: Thirty-six patients diagnosed as COVID-19 severe ARDS were chosen. Lung mechanics (compliance), the extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI), and serum concentrations of immunology markers (interleukin [IL]-1β, IL-6, IL-8, ferritin, and C-reactive protein) were measured. Accordingly, individualized treatment consisting of Actemra, hemoperfusion (HP), continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO) was implemented for each patient. Results: Patients were categorized according to the lung compliance: 18 in “L type” with compliance> 40 cc/cmH2O and 18 in “H type” with compliance ≤40 cc/cmH2O. In 16 patients, standard mechanical ventilation management and antiviral therapy were unsuccessful; therefore, hemodynamic and immunity responses were evaluated. Results of transpulmonary thermodilution in L-type patients surprisingly showed EVLWI = 8.8 ± 1.3 (6.9–9.7) and PVPI = 2.4 ± 0.1 (2.2–2.6). In the H-type patients, five cases showed EVLWI = 8.7 ± 0.8 (7.5–9.8) and PVPI = 2.6 ± 0.3 (2.1–2.8) which were subclassified as “Ha type” and five cases with EVLWI = 17.5 ± 1.9 (15.7–20.6) and PVPI = 3.9 ± 0.4 (3.5–4.5) were named “Hb type”. By measuring immunologic markers, these two groups were subdivided into high and low marker groups. Individualized treatment resulted in 2 survivals with Actemra, 1 with HP, 2 with HP + CRRT, and 1 with ECMO. Conclusion: According to the heterogeneity of COVID-19 severe ARDS presentation, which is due to various immunologic and hemodynamic responses, a systematic approach is an important and relatively successful strategy in choosing the appropriate treatment modality.

Abstract Background Hypertension is an emerging disease in children and adolescents resulting in future morbidities. Cigarette smoking is one of the most studied contributing factors in this regard; however, there are contradictory results among different studies. Therefore, the present meta-analysis tends to assess the relationship between passive exposure to cigarette smoke and blood pressure in children and adolescents. Method Medline, Embase, Scopus, EBSCO, and Web of Sciences were systematically reviewed for observational studies up to May, 2017, in which the relationship between cigarette smoking and hypertension were assessed in children and adolescents. The meta-analysis was performed with a fixed effect or random effects model according to the heterogeneity. Results Twenty-nine studies were included in present meta-analysis incorporating 192,067 children and adolescents. Active smoking (pooled OR = 0.92; 95% CI: 0.79 to 1.05) or passive exposure to cigarette smoke (pooled OR = 1.01; 95% CI: 0.93 to 1.10) were not associated with developing hypertension in the study population. Despite the fact that active cigarette smoking did not significantly affect absolute level of systolic and diastolic blood pressure, it was shown that passive exposure to cigarette smoke leads to a significant increase in absolute level of systolic blood pressure (pooled coefficient = 0.26; 95% CI: 0.12 to 0.39). Conclusion Both active and passive cigarette smoking were not associated with developing hypertension in children and adolescents. However, passive cigarette smoke was associated with higher level of systolic blood pressure in children and adolescents.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm.ObjectivesTo elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity.MethodsWe determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran.ResultsSerum levels of sTNFRI were significantly higher in ICU patients (P

Background: Coronavirus disease 2019 (COVID-19) pandemic has exposed nurses to a rapidly changing patient care practice. This study explored nurses’ experiences in caring for COVID-19 patients. Methods: Eighteen nurses, head nurses, and clinical supervisors employed in one of the hospitals affiliated to the Shahid Beheshti Medical University to participate in this qualitative content analysis study. Data were collected through interviews and field notes. The data were analyzed with conventional content analysis. Results: Data analysis of nurses’ experiences with respect to COVID-19 patients resulted in the extraction of information on 5 major categories: “security in care-giving,” “healing hands, empty hands,” “mental and physical problems,” “multiple feelings,” and “self-reassurance” and 11 subcategories. Conclusion: We found that giving care to COVID-19 patients entailed complex, intermingled, and interrelated physical, mental, and emotional aspects that underwent changes over time so that it can be called “journey of nursing in COVID-19 crisis.” The findings of this study further revealed that nurses’ experiences, feelings, and thoughts underwent modifications gradually, over time. They believed that they have undergone development in caregiving and experienced deeper aspects of nursing care.

In late December 2019, a vtiral pneumonia with an unknown agent was reported in Wuhan, China. A novel coronavirus was identified as the causative agent. Because of the human-to-human transmission and rapid spread; coronavirus disease 2019 (COVID-19) has rapidly increased to an epidemic scale and poses a severe threat to human health; it has been declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). This review aims to summarize the recent research progress of COVID-19 molecular features and immunopathogenesis to provide a reference for further research in prevention and treatment of SARS coronavirus2 (SARS-CoV-2) infection based on the knowledge from researches on SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV).

In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, affirmed to be the result of a novel coronavirus (later named Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)). Coronavirus disease-19, a kind of viral pneumonia, is caused by SARS-COV2. This virus infects angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) positive cells and causes influenza like symptoms ranging from mild disease to severe type with multi-organ involvement. In patients with more sever conditions, dysregulation of immune system, due to either virus activity or immune-based issues, leads to cytokine storm and unwanted inflammatory changes further followed by tissue damage. COVID-19 has spread rapidly by human-to-human transmission, caused an outbreak worldwide with considerable morbidity rates and mortality, which forced WHO to officially classified it as pandemic and a global concern on March 11. Without any signs of amelioration and with confirmed cases that are expected to increase further as they are updated daily as of May 8, the outbreak has stressed global socioeconomic and health systems and posed governments to clinical management challenges. Finding appropriate clinical strategy to control and even prevent is nowadays top priority issues globally. Recent studies and investigation considerably improve our understanding of disease pattern of distribution, pathology and immune-related changes in both mild and sever cases. Thus, many promising therapeutic approaches for clinical intervention and treatment of the disease are now under further investigations and their safety and efficiency are yet to be proved in clinical trials. One of these therapeutic approaches is cell therapy based interventions. Mesenchymal stem cells (MSCs) have commonly applied clinical trials and possess two positive roles, immunomodulatory effect and differentiation ability. MSCs immunomodulatory effects which mediated by anti-inflammatory cytokine release prevent or reduce the overactivation of the immune system and cytokine storm. So, MSCs therapy and other immune-based cell therapies can be promising in severe COVID-19 management and treatment. In this review the aim is investigation the impact of these kind of interventions in treatment of COVID-19 patients.

Aim Chronic obstructive pulmonary disease (COPD) is a chronic pulmonary inflammation that has various symptoms such as respiratory distress and severe cough. This disease has a global distribution; however, developed countries have the highest share in the number of people with this disease. Materials and methods As a developing country, Iran has included several cases of patients with COPD. The metropolis of Tehran, the capital of Iran, is the most industrialized city in the country. In this study, using geographic information system software, dispersion and factors influencing the distribution of patients with COPD referred to Masih Daneshvari Hospital in Tehran (2015–2017) were investigated. Results The results showed that distribution of patients in Tehran was nonuniform, and the accumulation of patients with COPD in the northern regions was more than other parts of Tehran. Conclusion Factors such as surface heights, opiate and cigarette consumption, and the presence of air pollutants in different areas can be cited as the cause of this heterogeneous distribution.

Background: Chronic obstructive pulmonary disease (COPD) is a global health burden that affects 300 million people worldwide. Globally, COPD was reported as the fourth leading cause of death in 2004 and is projected to occupy the third position in 2030. The goal of the present project is to describe the prevalence and determine the causes and risk factors of COPD in five provinces of Iran. Methods: This study followed a stratified cluster sampling strategy with proportional allocation within strata. The target population is all noninstitutionalized inhabitants, aged 18 and over, who inhabit in different provinces in Iran in the year 2017. The stratification of the sample according to the 31 provinces of Iran is incorporated in the sampling process. The core questionnaire was developed from preexisting validated questionnaires. The single most important outcome measure obtained as part of this protocol was spirometry before and after the administration of 200 mg (two puffs) of salbutamol. Results: The most commonly reported respiratory symptoms were as follows: wheezing (N=217, 20.4%, 95% confidence interval [CI]: 18%–22.8%), sputum production (N=173, 16.5%, 95% CI: 14.3%–18.8%), and dyspnea (N=131, 12.3%, 95% CI: 10.3%–14.3%). The overall COPD prevalence defined by the postbronchodilator spirometric Global Initiative for Chronic Obstructive Lung Disease criteria was 4.9%, higher in men (6.4%) than in women (3.9%). The prevalence of COPD was strongly dependent on smoking status, age, and sex. Conclusion: COPD is considered a preventable disease, and avoidance of exposure to major risk factors can prevent the vast majority of cases. The present study findings add to the literature on the prevalence of COPD in Iran and will help policy-makers, specialists, and all stakeholders to strategize and evaluate medical services required for reducing the prevalence of respiratory diseases. The data from our present study will serve as baseline information for future national and regional studies of COPD.

COVID-19 pneumonia has rapid development into a global pandemic. For the infected patients, it is an urgent matter to improve the cure rate and reduce the death rate, but there are no effective antiviral drugs for COVID-19 so far. There is an urgent need for effective treatment. The current focus has been on the development of novel therapeutics, including antivirals and vaccines. One of these drugs, Favipiravir (Avigan), an antiviral agent approved for use in influenza in Japan, is being studied for the treatment of COVID-19. Herein, we report a patient; a 53 Y/O man without any underlying disease, developed COVID19 pneumonia rapidly and well respond to combination treatment including Dexamethasone, Favipiravir, and IFN-β-1a.

Background: Anthracosis is a chronic pulmonary disease with black pigmentation of the bronchial mucosa, caused by carbon accumulation in the lungs, and in some cases, associated with pulmonary tuberculosis (TB). The purpose of this study is to evaluate the serum and bronchoalveolar lavage (BAL) fluid levels of the CD4/CD8 ratio and interleukin 8 (IL-8), as the potential diagnosis and prognosis biomarkers for anthracosis. Methods: Of 60 patients, referred to the Masih Daneshvari Hospital, 30 anthracosis patients, confirmed by bronchoscopy, were included as the case group. BAL sample and blood samples were collected from all individuals and sent to the immunology laboratory. Patients with no anthracosis on bronchoscopy, and suspected to have TB, were included in the control group. In addition, BAL samples were used for BK-polymerase chain reaction. Results: In this case–control study, 30 anthracosis patients and 30 controls were investigated. There were no significant differences in IL-8 of patients with anthracosis, compared to others. There were significant differences of the CD4/CD8 ratio in BAL fluid, between anthracosis cases and the control group (1.01 ± 0.77 vs. 2.41 ± 3.50; P = 0.04), and significant differences were seen in serum levels of two groups (P = 0.02). The rate of the confirmed pulmonary TB which was 88.9% in patients with anthracosis was significantly higher than the control group. Conclusion: These outcomes suggest that changes in the CD4/C8 levels in serum and BAL fluid may have a leading role in the diagnosis or prognosis of anthracosis. In addition, due to the strong association of anthracosis and pulmonary TB, TB should be considered in patients with anthracosis, which in turn can eventuate to the early distinguish and cure of the patients.

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high-throughput drug screening, require a small number of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. Many attempts have been made in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.

Cytokine release syndrome is prevalent in severe cases of COVID-19. In this syndrome, an uncontrolled response of immune system occurs. Extracorporeal blood purification has been proven to effectively remove the released inflammatory cytokines. Here, we reported a successful case to represent our experience of extracorporeal blood purification in a patient with severe COVID-19.

An amendment to this paper has been published and can be accessed via the original article.

Allergic rhinitis is a chronic inflammatory disease of the upper respiratory tract, which is associated with high incidence of anxiety symptom. There is evidence that medial prefrontal cortex modulates anxiety-related behaviors and receives projections from olfactory bulb. Since olfactory dysfunction has been reported in allergic rhinitis, we aimed to evaluate anxiety-like behavior and oscillations of olfactory bulb-medial prefrontal cortex circuit in an animal model of allergic rhinitis. The number of open arm entries in elevated zero maze was significantly reduced in sensitized rats exposed to intranasal ovalbumin compared to the control group, which was indicating the enhancement of anxiety-like behavior in allergic rhinitis animals. Analysis of local field potentials in olfactory bulb and medial prefrontal cortex during immobility and exploration state showed that anxiety-like behavior induced by allergic rhinitis was in association with increased activity of medial prefrontal cortex and enhancement of olfactory bulb-medial prefrontal cortex coupling in delta and theta bands. Moreover, in allergic rhinitis animals, theta strongly coordinates local gamma activity in olfactory bulb and medial prefrontal cortex, which means to have a strong local theta/gamma coupling. We suggested that disruption of olfactory bulb-medial prefrontal cortex circuit due to allergic reactions might have a governing role for inducing anxiety-like behavior in the allergic rhinitis experimental model.

Studies on the trend of air pollution in Tehran, Iran, as one of the most polluted metropolis in the world are scant, and today Tehran is known for its high levels of air pollutants. In this study, the trend of air pollution concentration was evaluated over the past 10 years (2004-2015). The data were collected from 22 stations of the Air Quality Control Company. Daily concentrations of CO, NO2, SO2, O3, PM10 were analyzed using SPSS 16 based on the statistical method, repeated measures, and intra-group test to determine the pattern of each pollutant changes. As a result of the 22 air pollution monitoring stations, NO2 and SO2 concentrations have been increasing over the period of 10 years. The highest anomaly is related to SO2. The CO concentrations represent a descending pattern over the period, although there was a slight increase in 2013 and 2014. The O3 concentrations declined in the following years. The average concentration of PM10 has been rising during the period. Also we evaluated changes of each pollutant in different months and calculated the number of clean, healthy, unhealthy days for sensitive, unhealthy, very unhealthy, and dangerous groups. The study findings illustrated the necessity for larger investment in air pollution abatement. Overall, trends have been progressed to worsening, the number of healthy days has been declined and the number of unhealthy days has been increased in recent years.

Background In spite of increasing prevalence of concomitant use of water pipe and cigarette there is no enough information in this field. So the concomitant use of water pipe and cigarette and its comparison to only cigarette smoking were evaluated in this study. Methods This cross-sectional study was carried out through stratified multistage sampling in several districts of Tehran. The trained interviewers collected the data about water pipe and cigarette smoking by going to the houses randomly. Results The study had 1830 participants among which 243 participants only consumed water pipe, 120 cases only smoked cigarette and 76 cases (4.2%) were dual users.There was no significant difference in both groups by sex. The mean age of dual users and exclusive cigarette smokers were 33.1±11.3 and 46±16.5 years respectively (p≤0.001). Comparing to cigarette smokers (35.2%), most of the dual users (64.7%) believed that water pipe is not addictive (p=0.001). 13.2% of dual users and 5.3% of cigarette users believed that water pipe smoking is safer than cigarette smoking(p< 000). While 54.1% of dual users and 78.5% of cigarette smokers believed that waterpipe consumption could cause serious diseases. Conclusions Younger age and misconception about safety of water-pipe in comparison to cigarette were significantly more in dual users than exclusive cigarette users. It is necessary to promote the knowledge about harms of water-pipe smoking in society especially among youth.

Good’s syndrome, the adult onset hypogammaglobulinemia associated with thymoma has been explained about six decades ago. It generally presents with recurrent infections and several paraneoplastic syndromes including myasthenia gravis, pure red cell aplasia, connective tissue disorders, superior vena cava, Horner’s syndrome, lichen planus and inflammatory bowel disease. Lack of B cell, dysfunction of T cell, CD4+ T cell lymphopenia, reversed CD4/CD8+ T cell ratio, autoantibodies against Th17 related cytokines have been respected as the pathogenesis of the immune dysregulation this syndrome. A 57-year-old man was admitted to our hospital with a history of thymectomy due to thymoma (Type A) 6 years ago. He developed weight loss and recurrent persistent diarrhea caused by isospora belli. His chest CT scan revealed bilateral bronchiectasis. His laboratory data showed hypogammaglobulinemia and he was treated by monthly IVIG with the diagnosis of good’s syndrome. Nevertheless he referred again with left sided loss of vision because of CMV retinitis and he also developed nail candidiasis. Good’s syndrome should be considered in every patient with a history of thymoma and recurrent infection. Immunologic evaluation of these patients including measurement of the serum level of immunoglobulin as well as B cell and T cell subgroups should be performed. Physicians must be aware and think about this entity in patients with adult onset immunodeficiency.

Background: In the era of well-developed site-specific treatment strategies in cancer, identification of occult primary is of paramount importance in CUP patients. Furthermore, exact determination of the extent of the disease may help in optimizing treatment planning. The aim of the present study was to investigate additional value of F-18 FDG PET/CT in patients with cancer of unknown primary (CUP) as an appropriate imaging tool in early phase of initial standard work up.Materials and Methods: Sixty-two newly diagnosed CUP patients with inconclusive diagnostic CT scan of chest, abdomen and pelvis referring for F-18 FDG PET/CT were enrolled in this study. Standard of reference was defined as histopathology, other diagnostic procedures and a 3-month formal clinical follow up. The results of PET/CT were categorized as suggestion for primary site and additional metastasis and classified as true positive, false positive, false negative and true negative. The impact of additional metastasis revealed by F-18 FDG PET/CT on treatment planning and the time contribution of F-18 FDG PET/CT in diagnostic pathway was investigated.Results: Sixty-two patients with mean age of 62 (30 men, 32 women), PET/CT correctly identified primary origin in 32% with false positive rate of 14.8%. No primary lesion was detected after negative PET/CT according to standard of reference. Sensitivity, Specificity and accuracy were 100%, 78% and 85%, respectively. Additional metastatic site was found in 56% with 22% impact on treatment planning. Time contribution for PET/CT was 10% of total diagnostic pathway.Conclusion: Providing higher detection rate of primary origin with excellent diagnostic performance, shortening the diagnostic pathway and improving treatment planning, F-18 FDG PET/CT may play a major role in diagnostic work up of CUP patients and may be recommended as an alternative imaging tool in early phase of investigation.

Background: Tuberculosis (TB) is a serpent disease with various pulmonary manifestations, and timely diagnosis of the disease is paramount, since delayed treatment is associated with severe morbidity, particularly in intensive care units (ICU). Therefore, it is imperative that intensivists understand the typical distribution, patterns, and imaging manifestations of TB. Aim: To describe different manifestations of pulmonary TB in patients in the ICU. Methods: In a retrospective study, all patients with a clinical and a laboratory-confirmed diagnosis of TB who were admitted to the ICU were entered in the study. All patients had a confirmatory laboratory diagnosis of TB including positive smears. The patterns of parenchymal lesions, involved segments and presence of cavity, bronchiectasis and bronchogenic spread of the lesions with computed tomography (CT) and chest/X-ray (CXR) were recorded and analyzed. Results: Data of 146 patients with TB were entered in the study. The most common finding in CT was acute respiratory distress syndrome (ARDS)-like radiologic manifestations (17.1%), followed by parenchymal nodular infiltration (13.6%) and cavitation (10.9%), consolidation (10.2%), interstitial involvement (9.5%), calcified parenchymal mass (8.3%), ground-glass opacities (7.5%), and pleural effusion or thickening (6.9%). Radiologic evidence of lymphadenopathy was seen in up to 43% of adults. Miliary TB was observed in 2.3% of patients, mostly in those older than 60 years of age. ARDS-like (64.5%) manifestations on CT and miliary TB (85.5%) had the highest mortality rates among other pulmonary manifestations. Conclusion: ARDS, interstitial involvement, and Parenchymal nodular infiltration are the most common manifestations of pulmonary TB. Various features of TB in ICU patients could be misleading for intensivists.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is globally known as one of the most important human pathogens. Mtb is estimated to infect nearly one third of the world's population with many subjects having a latent infection. Thus, from an estimated 2 billion people infected with Mtb, less than 10% may develop symptomatic TB. This indicates that the host immune system may constrain pathogen replication in most infected individuals. On entering the lungs of the host, Mtb initially encounters resident alveolar macrophages which can engulf and subsequently eliminate intracellular microbes via a plethora of bactericidal mechanisms including the generation of free radicals such as reactive oxygen and nitrogen species. Nitric oxide (NO), a key anti-mycobacterial molecule, is detected in the exhaled breath of patients infected with Mtb. Recent knowledge regarding the regulatory role of NO in airway function and Mtb proliferation paves the way of exploiting the beneficial effects of this molecule for the treatment of airway diseases. Here, we discuss the importance of NO in the pathogenesis of TB, the diagnostic use of exhaled and urinary NO in Mtb infection and the potential of NO-based treatments.

Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin. These overexpressed FLCs are co-localized to areas of mast cell infiltration. Importantly, FLC expression is associated with basal-like cancers with an aggressive phenotype. Moreover, FLC is expressed in areas of inflammatory cell infiltration and its expression is significantly associated with poor clinical outcome. In addition, serum and bronchoalveolar fluid FLC concentrations are increased in patients with idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) compared to control subjects. In this review, we provide an update on the role of FLC in the pathogenesis of several lung disorders and indicate how this may contribute to new therapeutic opportunities.

Background: Water-pipe smoking is increasing around the world. However, there is no comprehensive information on nicotine addiction in water-pipe smokers. This study was carried out to translate and validate the Lebanon Water-pipe Dependence Scale- into Persian language; besides, tobacco dependence was evaluated in Iranian water-pipe smokers. Methods: A forward-backward translation procedure was done to provide the Iranian version of the questionnaire. Our subjects were current water-pipe smokers who were known in prevalence study that conducted in Tehran. Psychometric properties of the instrument including validity (content, face and construct validity) and reliability (internal consistency and test-retest analysis), were evaluated. Results: A total of 465 participants took part in this study, of whom 298 (64%) were male. The mean age was 30 (standard deviation 10.2). Fifty three percent of subjects got score more than 10 on LWDS questionnaire that indicating dependence. The internal consistency of the LWDS (Persian Version) was 0.85. The physiologic dependence, psychological craving, and negative reinforcement domains had acceptable reliability (Cronbach's alpha was 0.94, 0.81, 0.77 respectively), but reliability was low (alpha = 0.45) in the positive reinforcement domain. External consistency of the LWDS was assessed by test retest. Intra class correlation (ICC) was calculated for all items (n = 20) and ICC for all of them was >0.7 and the mean ICC was 0.9. Content validity was acceptable; all of obtained content validity indexes (CVIs) were above 80%. The result of goodness of fit shows an adequate model (Comparative Fit Index (CFI = 0.94), Root Mean Square Error of approximation (RMSE) = 0.08). Conclusions: The study revealed strong documents for the reliability and validity of the LWDS for use in Iran. However, further study may be required to improve the reliability results in the positive reinforcement domain.

Background: Globally chronic obstructive pulmonary disease (COPD) was reported as the fourth leading cause of death (5.1%) in 2004 and is projected to occupy the third position (8.6%) in 2030. The goal of the present project is to describe the prevalence and risk factors of COPD in a province in the north of Iran. Methods: This study followed a stratified cluster sampling strategy with proportional allocation within strata. The stratification of the sample according to the 31 provinces of Iran is incorporated in the sampling process. The single most important outcome measure obtained as part of this protocol was spirometry before and after the administration of 200 mg (2 puffs) of salbutamol. The descriptive statistics for categorical variables included the number and percent and for continues variables included the mean ± SD. Results: A total of 1007 subjects were included in the study. Among all participants, 46 (5%) subjects had COPD on the basis of symptoms and 43 (8.3%) subjects had COPD on the basis of spirometry criteria. In univariate analysis, urban inhabitants in comparison with rural inhabitants had lower COPD risk (OR: 0.48; 95% CI: 0.24–0.95), smoker had higher risk compared with nonsmokers (OR: 1.97; 95% CI: 1.01–3.82), and subjects with exposure to dust (OR: 2.07; 95% CI: 1.09–3.94) had higher risk compared with contrary status. Conclusions: This study showed that occupational and environmental smoke exposure was associated with COPD. A new design of preventive measures must be taken to control cooking energy and cooking stoves, particularly in rural areas.

The objective of this study was to determine the prevalence and incidence of venous thromboembolism among critically ill medical surgical patients. In this cross sectional and retrospective study, we observed 243 patients who were first admitted at the intensive care unit. Patients who were diagnosed with deep venous thrombosis or embolism either by clinical or paraclinical methods were enrolled. Among 243 patients of ICU ward 12 cases of them were confirmed to have thromboembolism (prevalence of 9.4%).But the incidence of venous thromboembolism after 48 hour of ICU admission was 5.2%(6 cases). Among 6 VTE cases 3 of them didn’t receive any anticoagulant prophylaxis, 2 patients received LDUH 5000 unit twice a day and one patient received LMWH 60 mg daily but all developed VTE although receiving prophylaxis. We found that the prevalence of proximal lower limb DVT among medical-surgical critically ill patients remaining in the ICU for ≥3 days is about 9.4% and the incidence of that is about 5.2%. Further studies should be performed in order to assess the benefits and risks of venous thromboprophylaxis in Iranian patient

Introduction & Objective: Pulmonary Langerhans Cell Histiocytosis (PLCH) is an uncommon (5% ILD) interstitial tissue disorder with significant importance. It occurs predominantly in adult smokers. The organs involved in LCH include skin, bone, pituitary gland, thyroid, lymph node, and lungs. Materials & Methods: In this descriptive study all patients admitted to the Masih Daneshvari Hospital in Tehran from 1996 to 2007 diagnosed with LCH (recognized by clinical features, laboratory investigations, radiological manifestations, BAL and biopsy) were evaluated. Results: A total of 20 patients were studied mean age was 27.8 yrs. 40% were smokers 80% had pulmonary involvement while in 20% other organs were affected. On spirometry, a mixed pattern (50%) was the most common and on chest radiography (CXR) 77% of lung cysts were visible. The most frequent finding on CT- scan was diffuse lung cysts (80%). Conclusion: It is notable that ground glass opacity and consolidation occur in the early stages of disease. Since most of the patients refer with features of advanced disease, it is essential for the physicians to consider the early signs during the diagnostic stage. Also bronchoscopy and bronchial lavage are recommended in selected cases.