Cross-cultural adaptation and validation of Leicester Cough Questionnaire in sarcoidosis: the persian version.

BACKGROUND AND AIM: Cough is a common symptom among patients with sarcoidosis, and the Leicester Cough Questionnaire, a cough-specific quality-of-life measure, evaluates the impact of cough across physical, psychological, and social domains in patients with chronic cough. The aim of this study was cross-cultural adaptation and validation of Persian version of Leicester Cough Questionnaire (LCQ) in pulmonary sarcoidosis in Iran. METHODS: Psychometric analyses included translation and back translation of the questionnaire, face validity, content validity, construct validity, criterion-related validity, internal consistency, and test -retest reliability were performed. RESULTS: Twenty-five participants demonstrated no major language barriers or difficulties in completing the questionnaire and adequate face validity of ≥1.5. Twelve experts confirmed the content validity was good (CVR˃0.56, I-CVI≤0.79, S-CVI/Ave˃0.80). Totally, 190 patients were included in the study. The Pearson's coefficients and their significance's (P<0.05) showed an acceptable agreement between the LCQ and the SF-36 questionnaire. The goodness-of-fit of the conceptual model including psychological, physical, and social domains, obtained from EFA, was confirmed throughout the RMSEA of 0.09 (<0.1), NFI of 0.9, NNFI of 0.91, and CFI of 0.92 which all were ≥0.9. The Persian LCQ showed an excellent internal consistency regarding Cronbach's alpha of 0.974 and ICC (95%CI) value of 0.983 (0.977, 0.987). CONCLUSIONS: The psychometric properties showed that the Persian version of LCQ is a valid and reliable measure to evaluate cough-specific quality of life and is a fit-for-purpose measure for use in patients with pulmonary sarcoidosis and the results can guide clinicians in treatment decisions.

Time-Dependent Changes in COVID-19 Severity Based on the Information of Patients Referring to Masih Daneshvari Hospital, Tehran, Iran.

Background: Coronavirus disease 2019 (COVID-19) is a newly emerged disease with many unknown facets, so both the treatment and the cause of spreading this disease have remained mysterious so far. Materials and Methods: Based on the information of 4372 patients with COVID-19 referring to Dr. Masih Daneshvari Hospital in Tehran, the time-dependent changes in COVID-19 severity were investigated in this study using correlation analysis. Results: According to the results of this study, on average 154.80 patients were infected with mild to moderate COVID-19, and 39.06 were infected with severe COVID-19. The results of this study also indicated a descending trend in the number of patients with mild to moderate COVID-19 (r=-0.40, P-value=0.004) and an ascending trend in the number of patients with severe COVID-19 (r=0.43, P-value=0.003) overtime on a daily basis so that almost two patients were removed from those with mild to moderate COVID-19 and one was added to the patients with severe COVID-19 on average per day. Conclusion: Based on the current study results, it is concluded that COVID-19 severity will not be constant over time, and there is a probability of COVID-19 becoming more aggressive. Therefore, by the lack of timely control of the disease over time, we will witness an increased number of patients with severe COVID-19 and an increased number of hospitalizations in the intensive care unit (ICU) ward.

Safety and feasibility study of ex vivo expanded allogeneic-NK cells infusion in patients with acute pneumonia caused by COVID-19.

BACKGROUND: NK cells are the most active innate immune cells in antiviral immunity, which are impaired by SARS-COV2 infection. Infusion of allogeneic NK cells might be a complementary treatment to boost immune system function in COVID-19 patients. In this project, we focused on COVID-19 patients with low inspiratory capacity (LIC). This project aims to evaluate the feasibility and safety of allogeneic NK cell infusion as an intervention for respiratory viral disease. METHODS: A non-blind two arms pilot study was designed and conducted after signing the consent form. Ten matched patients, in terms of vital signs and clinical features, were enrolled in the control and intervention groups. Approximately 2 × 10^6 cells/kg of NK cells were prepared under GCP (good clinical practice) conditions for each patient in the intervention group. The control group was under the same conditions and drug regimen except for the treatment with the prepared cells. Then, infused intravenously during 20 min in the ICU ward of Masih Daneshvari Hospital. The clinical signs, serological parameters, and CTCAE (Common Terminology Criteria for Adverse Events) were recorded for safety evaluation and the feasibility of project management were evaluated via designed checklist based on CONSORT. RESULTS: There were no symptoms of anaphylaxis, hypersensitivity, significant changes in blood pressure, cardiovascular complications, and fever from injection time up to 48 h after cell infusion. The mean hospitalization period in the control and intervention groups was 10 and 8 days, respectively. The blood O2 saturation level was raised after cell infusion, and a significantly lower mean level of inflammatory enzymes was observed in the intervention group following discharge compared to the control group (p < 0.05). The inflammatory parameters differences at the discharge date in cell therapy group were highly negative. CONCLUSION: Intravenous infusion of ex vivo-expanded allogeneic NK cells was safe and feasible. However, the efficacy of this approach to reducing the severity of disease in COVID-19 patients with LIC could not be determined. TRIAL REGISTRATION: Name of the registry: NKCTC. IRCT20200621047859N2. December 29, 2020. URL of trial registry record: https://www.irct.ir/trial/49382.

Serial SOFA-score trends in ICU-admitted COVID-19 patients as predictor of 28-day mortality: A prospective cohort study.

Background and Aim: The efficacy of Sequential Organ Failure Assessment (SOFA) score as predictor of clinical outcomes among ICU-admitted COVID-19 patients is still controversial. We aimed to assess whether SOFA-score in different time intervals could predict 28-day mortality compared with other well-acknowledged risk factors of COVID-19 mortality. Methods: This observational prospective cohort was conducted on 1057 patients from March 2020 to March 2022 at Masih Daneshvari Hospital, Iran. The univariate and multivariate Cox proportional analysis were performed to assess the hazards of SOFA-score models. Receiver operating characteristic (ROC) curves were designed to estimate the predictive values. Results: Mean SOFA-score during first 96 h (HR: 3.82 [CI: 2.75-5.31]), highest SOFA-score (HR: 2.70 [CI: 1.93-3.78]), and initial SOFA-score (HR: 1.65 [CI: 1.30-2.11]) had strongest association with 28-day mortality (p < .0001). In contrast, SOFA scores at 48 and 96 h as well as Δ-SOFA: 48-0 h and Δ-SOFA: 96-0 h did not show significant correlations. Among them, merely mean SOFA-score (HR: 2.28 [CI: 2.21-3.51]; p < .001) remained as independent prognosticator on multivariate regression analysis; though having less odds of predicting value compared with age (HR: 3.81 [CI: 1.98-5.21]), hypertension (HR: 3.11 [CI: 1.26-3.81]), coronary artery disease [CAD] (HR: 2.82 [CI: 1.51-4.8]), and diabetes mellitus (HR: 2.45 [CI: 1.36-2.99]). The area under ROC (AUROC) for mean SOFA-score (0.77) and highest SOFA-score (0.71) were larger than other SOFA intervals. Calculating the first 96 h of SOFA trends, it was obtained that fatality rate was <12.3% if the score dropped, between 28.8% and 46.29% if the score remained unchanged, and >50.45% if the score increased. Conclusion: To predict the 28-day mortality among ICU-admitted COVID-19 patients, mean SOFA upon first 96 h of ICU stay is reliable; while having inadequate accuracy comparing with well-acknowledged COVID-19 mortality predictors (age, diabetes mellitus, hypertension, CAD). Notably, increased SOFA levels in the course of first 96 h of ICU-admission, prognosticate at least 50% fatality regardless of initial SOFA score.

Association of Upon-Diagnosis Blood Eosinophilic Count with Frequency and Severity of Annual Exacerbation in Chronic Obstructive Pulmonary Disease: A Prospective Longitudinal Analysis.

Introduction: There is a controversy regarding the relationship between blood eosinophil count and COPD exacerbation. We aimed to determine whether peripheral eosinophils upon COPD diagnosis could affect the frequency and severity of annual acute exacerbation of COPD (AECOPD). Methods: This prospective study was conducted on 973 newly diagnosed COPD patients who were under 1-year follow-up in a pulmonology center in Iran. The Cox proportional model, polynomial regression, and receiver operator characteristic curves were conducted to evaluate the impact of the eosinophil levels on AECOPD. A linear regression model was conducted to evaluate the continuous association of eosinophilic count with AECOPDs. Results: Patients with eosinophil >200 cells/microliter were higher pack-year smokers with more pulmonary hypertension prevalence compared to COPD patients with <200 cells/microliter. There was a positive correlation between the eosinophilic count and the frequency of AECOPDs. Eosinophil >900 cells/microliter and eosinophil >600 cells/microliter had a sensitivity of 71.1% and 64.3%, respectively, in predicting the occurrence of more than one AECOPD. Eosinophilic count cutoff of 800 cells/microliter had the highest Youden index with sensitivity and specificity of 80.2% and 76.6%, respectively, for incident AECOPD in newly diagnosed patients. Using a linear model, increasing 180 cells/microliter in serum eosinophils was associated with further exacerbation. Evaluating gender, BMI, smoking pack-year, FEV1/FVC, CAT score, GOLD score, pulmonary hypertension, annual influenza, pneumococcal vaccinations, leukocytosis, and blood eosinophils, only blood eosinophils (hazard ratio (HR) = 1.44; 95% confidence interval = 1.33-2.15; p value = 0.03) and GOLD score (HR = 1.19; 95% CI = 1.30-1.52; p value = 0.03) were found as independent risk factors of AECOPD >3 episodes/year. Requirement for ICU admission, invasive ventilation, and mortality rate due to AECOPDs was similar between eosinophilic and noneosinophilic groups. Conclusion: Eosinophilia upon COPD diagnosis is a factor of recurrent AECOPDs. To reduce the risk of AECOPDs and the burden of disease, clinicians may consider inhaler corticosteroids and domiciliary oxygen with a lower threshold for eosinophilic-COPD patients regardless of their clinical status.

Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via phosphoinositide-dependent kinase 1 (PDK1) upregulation. Androgen also increases inflammatory M1 macrophage abundance, but reduces anti-inflammatory M2 polarization in rat antral and preovulatory follicles. However, the role of small extracellular vesicles (sEVs; also known as exosomes) secretion in determining the cellular content and function of miRNAs in exosome-receiving cells is largely unknown. Our objectives were to determine: 1) the regulatory role of granulosa cells (GC)-derived exosomal miR379 on macrophage polarization and ovarian inflammation; 2) whether miR379-induced M1 polarization regulates GC proliferation; and 3) if this regulated process is follicular stage-specific. Compared with non-PCOS subjects, PCOS subjects had a higher M1/M2 ratio, supporting the concept that PCOS is an inflammatory condition. Ovarian overexpression of miR379 increased the number of M1 macrophages and the M1/M2 ratio in preantral follicles specifically. Transfection of macrophages with a miR379 mimic reduced the cellular content of PDK1 and induced M0→M1 polarization; whereas its inhibitor polarized M0→M2. Conditioned media from macrophages transfected with miR379 mimic and follicular fluid from PCOS subjects had higher galectin-3 content, a pro-inflammatory cytokine which specifically suppresses human antral follicle GC proliferation. These results indicate that miR379 inhibits M2 macrophage polarization, a condition which suppresses GC proliferation in a follicle stage-dependent manner, as exhibited in PCOS.

Androgen-induced exosomal miR-379-5p release determines granulosa cell fate: cellular mechanism involved in polycystic ovaries.

Polycystic ovarian syndrome (PCOS) is a complex multi-factorial syndrome associated with androgen excess and anovulatory infertility. In the current study, we investigated the role of dihydrotestosterone-induced exosomal miR-379-5p release in determining the destiny of the developing follicles. Our hypothesis was that androgen regulates granulosa cell miR-379-5p content by facilitating its exosomal release in a follicular-stage dependent manner, a process which determines granulosa cell fate. Compared to human non-PCOS subjects, individuals with PCOS exhibit higher follicular fluid free testosterone levels, lower exosomal miR-379-5p content and granulosa cell proliferation. Androgenized rats exhibited lower granulosa cell miR-379-5p but higher phosphoinositide-dependent kinase-1 (PDK1; a miR-379-5p target) content and proliferation. Androgen reduced granulosa cell miR-379-5p content by increasing its exosomal release in preantral follicles, but not in antral follicles in vitro. Studies with an exosomal release inhibitor confirmed that androgen-induced exosomal miR-379-5p release decreased granulosa cell miR-379-5p content and proliferation. Ovarian overexpression of miR-379-5p suppressed granulosa cell proliferation, and basal and androgen-induced preantral follicle growth in vivo. These findings suggest that increased exosomal miR-379-5p release in granulosa cells is a proliferative response to androgenic stimulation specific for the preantral stage of follicle development and that dysregulation of this response at the antral stage is associated with follicular growth arrest, as observed in human PCOS.

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial.

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508).

Missed bronchial web in a 4-year-old boy with foreign body aspiration: A case report.

Congenital bronchial webs are extremely rare and usually remain undiagnosed due to nonspecific symptoms. Herein, we reported a 4-year-old case of the bronchial web who was initially undiagnosed upon bronchoscopy following foreign body aspiration and afterward misdiagnosed as childhood asthma through his consistent cough and exertional dyspnea for several months.

SWI/SNF chromatin remodeling subunit Smarca4/BRG1 is essential for female fertility†.

Mammalian folliculogenesis is a complex process that involves the regulation of chromatin structure for gene expression and oocyte meiotic resumption. The SWI/SNF complex is a chromatin remodeler using either Brahma-regulated gene 1 (BRG1) or BRM (encoded by Smarca4 and Smarca2, respectively) as its catalytic subunit. SMARCA4 loss of expression is associated with a rare type of ovarian cancer; however, its function during folliculogenesis remains poorly understood. In this study, we describe the phenotype of BRG1 mutant mice to better understand its role in female fertility. Although no tumor emerged from BRG1 mutant mice, conditional depletion of Brg1 in the granulosa cells (GCs) of Brg1fl/fl;Amhr2-Cre mice caused sterility, whereas conditional depletion of Brg1 in the oocytes of Brg1fl/fl;Gdf9-Cre mice resulted in subfertility. Recovery of cumulus-oocyte complexes after natural mating or superovulation showed no significant difference in the Brg1fl/fl;Amhr2-Cre mutant mice and significantly fewer oocytes in the Brg1fl/fl;Gdf9-Cre mutant mice compared with controls, which may account for the subfertility. Interestingly, the evaluation of oocyte developmental competence by in vitro culture of retrieved two-cell embryos indicated that oocytes originating from the Brg1fl/fl;Amhr2-Cre mice did not reach the blastocyst stage and had higher rates of mitotic defects, including micronuclei. Together, these results indicate that BRG1 plays an important role in female fertility by regulating granulosa and oocyte functions during follicle growth and is needed for the acquisition of oocyte developmental competence.

Automated prediction of COVID-19 mortality outcome using clinical and laboratory data based on hierarchical feature selection and random forest classifier.

Early prediction of COVID-19 mortality outcome can decrease expiration risk by alerting healthcare personnel to assure efficient resource allocation and treatment planning. This study introduces a machine learning framework for the prediction of COVID-19 mortality using demographics, vital signs, and laboratory blood tests (complete blood count (CBC), coagulation, kidney, liver, blood gas, and general). 41 features from 244 COVID-19 patients were recorded on the first day of admission. In this study, first, the features in each of the eight categories were investigated. Afterward, features that have an area under the receiver operating characteristic curve (AUC) above 0.6 and the p-value criterion from the Wilcoxon rank-sum test below 0.005 were used as selected features for further analysis. Then five feature reduction methods, Forward Feature selection, minimum Redundancy Maximum Relevance, Relieff, Linear Discriminant Analysis, and Neighborhood Component Analysis were utilized to select the best combination of features. Finally, seven classifiers frameworks, random forest (RF), support vector machine, logistic regression (LR), K nearest neighbors, Artifical neural network, bagging, and boosting were used to predict the mortality outcome of COVID-19 patients. The results revealed that the combination of features in CBC and then vital signs had the highest mortality classification parameters, respectively. Furthermore, the RF classifier with hierarchical feature selection algorithms via Forward Feature selection had the highest classification power with an accuracy of 92.08 ± 2.56. Therefore, our proposed method can be confidently used as a valuable assistant prognostic tool to sieve patients with high mortality risks.

Evaluation of the Tracheal Stenosis Effects on Airway Resistance and Work of Breathing Using Computational Fluid Dynamics.

Background: Bronchoscopy is one of the most accurate procedures to diagnose airway stenosis which is an invasive procedure. However, a quick and noninvasive estimation of the percent area of obstruction (%AO) of the lumen is helpful in decision-making before performing a bronchoscopy procedure. We hypothesized that there is a relationship between %AO and tracheal resistance against fluid flow. Materials and Methods: By measuring airway resistance, %AO could be estimated before the procedure. Using computational fluid dynamics (CFD), this study simulates the fluid flow through trachea models with web-liked stenosis using CFD. A cylindrical segment was inserted into the trachea to represent cross-sectional areas corresponding to 20%, 40%, 60%, and 80% AO. The fluid flow and pressure distribution in these models were studied. Our CFD simulations revealed that the tracheal resistance is exponentially increased by %AO. Results: The results showed a 130% and 55% increase in lung airway resistance and resistive work of breathing for an 80% AO, respectively. Moreover, a curve-fitted relationship was obtained to estimate %AO based on the measured airway resistance by body plethysmography or forced oscillation technique. Conclusion: This pre-estimation is very useful in diagnostic evaluation and treatment planning in patients with tracheal stenosis.

Impact of Using Educational Multimedia on Knowledge, Skill, and Reduction of Medical Error Following Bronchoscopy.

Background: Achieving procedural skills is one of the pillars of health higher education which is in line with the social responsibility of medical education. Since it is not possible to encounter important cases in bronchoscopy during the training course, the common cases that the students encounter in their future work environment were prepared as an educational video. Therefore, the purpose of this study was to find out the impact of using bronchoscopy educational video intervention on medical assistants' knowledge, skill, and medical error comparing it with the traditional method at Dr. Masih Daneshvari Hospital. Materials and Methods: In this experimental study, two groups were randomly assigned: the experimental and the control. Each one consists of 15 participants. The first group used mannequins (traditional method) and the second used multimedia as the experimental group. Both groups were evaluated by pre and post-tests. Multiple choices (MCQs) were given to evaluate the knowledge and a checklist for skills. A comparison of the impact of intervention before and after education in both groups was statistically analyzed using the independent t-test. Results: There were statistically significant differences between the experimental group and the control group at a significance level of 0.042 for the skill. An average increase of 3 points was observed in the experiment group, while the control group increased by 1.4 points. No significant difference was seen for knowledge. The number of patients with pneumothorax was also decreased. Conclusion: Results showed that the multimedia training method effectively promotes the assistants' skills and reduces medical errors following bronchoscopy Administration. It is recommended to use educational videos (multimedia) to improve assistants' skills. It is suggested to apply the new model of education rather than sticking to the traditional one.

Investigating the Coronavirus Disease 2019 Process and its Related Occurrences during the Treatment Course.

Background: The disease process involves the occurrences happening during the disease and treatment course for the patient. Investigating this process is a significant and necessary issue for all diseases, including coronavirus disease 2019 (COVID-19). Materials and Methods: Using the information of 4372 patients with COVID-19 referring to Dr. Masih Daneshvari Hospital in Tehran during the COVID-19 epidemic, being hospitalized, cared for, and home quarantined due to having mild symptoms, the COVID-19 process and its related occurrences were investigated during the treatment course. Results: In the COVID-19 course, considering the disease severity, the likelihood of hospitalization in the general ward or the intensive care unit (ICU) ward, the likelihood of isolation or home quarantine, and the likelihood of occurrences such as recovery or death at the end of the disease course were taken into consideration. Based on the results of this study, the likelihood of hospitalization in the general ward, the ICU ward, and isolation or home quarantine was determined to be approximately 49.54%, 14.73%, and 35.73%, respectively. Also, for patients hospitalized in the general ward, the ICU ward, and isolated or home quarantined, the likelihood of recovery was estimated at approximately 64.79%, 10.82%, and 96.31%, respectively, and the likelihood of death was also estimated at about 35.21%, 89.18%, and 3.69% respectively. Conclusion: Investigating the COVID-19 process and estimating the likelihood of incidence of its related occurrences during the treatment course both create an accurate prognosis and provide the possibility of achieving an efficient treatment for these patients.

The role of electrolyte imbalances in predicting the severity of COVID-19 in the hospitalized patients: a cross-sectional study.

Coronavirus disease 2019 (COVID-19) can be fatal in severe cases. Accordingly, predicting the severity and prognosis of the disease is valuable. This study examined the role of electrolyte imbalances in predicting the severity of COVID-19. In this cross-sectional study, 169 hospitalized patients with COVID-19 were included and categorized into three groups based on the severity of the disease (moderate, severe, and critical). Serum levels of electrolytes (calcium [Ca], phosphorus [P], sodium [Na], potassium [k], and magnesium [Mg]), inflammatory markers (D-dimer, C-reactive protein [CRP], ferritin, and lactate dehydrogenase [LDH]), and 25OHVitamin D were measured. The mean age of patients was 53 years, and 54% were male. They had moderate, severe, and critical illnesses in 22%, 47%, and 31%, respectively. CRP, D-dimer, and ferritin increased with the severity of the disease. The lower median values of Mg, Na, 25OHVitamin D, Ca, LDH, and higher median lymphocyte counts were observed in the moderate vs. the severe group (P < 0.05). These parameters have acceptable sensitivity and specificity at the suggested cut-off level to discriminate the moderate and critical cases. Serum parameters introduced in this study are appropriate for differentiating between critical and moderate cases. The electrolyte imbalance can predict critical patients.

Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .

National Research Institute of Tuberculosis and Lung Disease (NRITLD) Protocol for the Treatment of Patients with COVID-19.

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized patients.

Allergic shiners in a patient with cough-variant asthma: a case report.

BACKGROUND: Chronic cough, with a duration of coughing of more than 8 weeks in adults, affects 5-10% of the general population. One of the most common causes of chronic cough is cough-variant asthma, which accounts for approximately one-third of cases. This phenotype of asthma is characterized by extreme sensitivity of the neuronal pathways mediating cough to environmental irritants, which results in an urge to cough. This case is an example of cough-variant asthma presenting with allergic shiners due to her severe cough. CASE PRESENTATION: A 38-year-old Iranian woman, who was well before the start of the coronavirus disease 2019 pandemic, presented with a nonproductive hacking cough that had begun after excessive use of antiseptic solutions. The only positive finding on physical examination was a reddish-purple rash on and around the eyelids mimicking a heliotrope rash, which had probably evolved due to the severity of the cough. The results of the pulmonary function test were within normal limits. Methacholine challenge test and chest x-ray were both normal. Chest high-resolution computed tomography revealed hyperinflation and tree-in-bud opacities. All other laboratory tests were normal. Because of the reversibility in her pulmonary function test, despite normal baseline parameters, asthma treatment was initiated, resulting in disappearance of the cough and the eye discoloration, being indicative of the correct diagnosis and proper treatment. CONCLUSION: Patients with cough-variant asthma may often have no other classic symptoms of asthma other than cough.

Efficacy and safety of colchicine treatment in patients with COVID-19: A prospective, multicenter, randomized clinical trial.

Colchicine has shown clinical benefits in the management of COVID-19 via its anti-inflammatory effect. However, the exact role of colchicine in COVID-19 patients is unknown. The current clinical trial was performed on 202 patients with moderate to severe COVID-19. Patients were randomly assigned in a 1:1 ratio to receive up to a 3-day course of 0.5 mg colchicine followed by a 12-day course of 1 mg colchicine in combination with standard care or a 15-day course of standard care. Among 202 randomized patients, 153 completed the study and received colchicine/standard care or continued standard care (M age, 54.72 [SD, 15.03] years; 93 [63.1%] men). On day 14, patients in the colchicine/standard care group had significantly higher odds of a better clinical status distribution on chest CT evaluation (p = .048). Based on NYHA classification, the percentage change of dyspnea on day 14 between groups was statistically significant (p = .026), indicating a mean of 31.94% change in the intervention group when compared with 19.95% in the control group. According to this study, colchicine can improve clinical outcomes and reduce pulmonary infiltration in COVID-19 patients if contraindications and precautions are considered and it is prescribed at the right time and in appropriate cases.

DNA sequencing validation by PCR-RFLP for evaluating butyrophilin-like 2 rs2076530 polymorphism in Iranian patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a multifactorial immune disorder with an uncertain origin. A single nucleotide polymorphism (G→A, rs2076530) in the butyrophilin-like 2 (BTNL2) gene results in the formation of truncating protein. This study aimed to genotype the predisposition of the BTNL2 rs2076530 polymorphism in Iranian patients with sarcoidosis using the RFLP technique. MATERIALS AND METHODS: In this study, 80 patients with sarcoidosis and 80 healthy individuals were included. The rs2076530 polymorphism of the BTNL2 gene was genotyped using the PCR-RFLP method by AvrII restriction enzyme and confirmed by DNA sequencing (Capillary electrophoresis 3130, ABI). RESULTS: There was a statistically significant difference between proportions of patients with AA (47,5%) and controls (27.5%) (OR=2.38, 95%CI:1.23-4.61, P=0.009). In addition, a significant difference was observed in the frequency of the A allele (62.5%) in sarcoidosis (OR=2.14, 95%CI:1.37-3.35, P=0.001). A Bonferroni correction with P<0.0038 indicates a statistical difference for genotype AA (P=0.009). In an effective model, binary logistic regression analysis indicates a statistical association between AA genotype and sarcoidosis (P=0.018 with 60% prediction). Based on the gene analysis study using DNA sequencing, all of the mentioned mutations were seen via RFLP. CONCLUSION: According to our findings, the BTNL2 rs2076530 A allele in the Iranian population is associated with susceptibility to sarcoidosis. This designed PCR-RFLP method for detecting SNPs is effective as DNA sequencing.