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.

Lats1 and Lats2 are required for the maintenance of multipotency in the Müllerian duct mesenchyme.

WNT signaling plays essential roles in the development and function of the female reproductive tract. Although crosstalk with the Hippo pathway is a key regulator of WNT signaling, whether Hippo itself plays a role in female reproductive biology remains largely unknown. Here, we show that conditional deletion of the key Hippo kinases Lats1 and Lats2 in mouse Müllerian duct mesenchyme cells caused them to adopt the myofibroblast cell fate, resulting in profound reproductive tract developmental defects and sterility. Myofibroblast differentiation was attributed to increased YAP and TAZ expression (but not to altered WNT signaling), leading to the direct transcriptional upregulation of Ctgf and the activation of the myofibroblast genetic program. Müllerian duct mesenchyme cells also became myofibroblasts in male mutant embryos, which impeded the development of the male reproductive tract and resulted in cryptorchidism. The inactivation of Lats1/2 in differentiated uterine stromal cells in vitro did not compromise their ability to decidualize, suggesting that Hippo is dispensable during implantation. We conclude that Hippo signaling is required to suppress the myofibroblast genetic program and maintain multipotency in Müllerian mesenchyme cells.

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.

Lung ultrasound for the diagnosis of cystic fibrosis pulmonary exacerbation.

BACKGROUND: High-resolution computed tomography (HRCT) is the gold standard for the evaluation of cystic fibrosis (CF) lung disease; however, lung ultrasound (LUS) is being increasingly used for the assessment of lung in these patients due to its lower cost, availability, and lack of irradiation. We aimed to determine the diagnostic performance of LUS for the evaluation of CF pulmonary exacerbation. METHODS: This cross-sectional study included patients with CF pulmonary exacerbation admitted to Masih Daneshvari Hospital, Tehran, Iran, from March 21, 2020 to March 20, 2021. Age, gender, and body mass index (BMI) of the patients were recorded. All patients underwent chest X-ray (CXR), HRCT, and LUS on admission. Pleural thickening, atelectasis, air bronchogram, B-line, and consolidation were noted in LUS and then compared with the corresponding findings in CXR and HRCT. Taking HRCT findings as reference, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA) of LUS and CXR for the detection of each pulmonary abnormality were determined. RESULTS: Of the 30 patients included in this study, with a mean age of 19.62 ± 5.53 years, 14 (46.7%) were male. Of the 15 patients aged 2-20 years, BMI was below the 5th percentile in 10 (66.7%), within the 5-10 percentiles in 1 (6.7%), 10-25 percentiles in 3 (20%), and 25-50 percentiles in 1 (6.7%). The mean BMI for 15 patients > 20 years was 18.03 ± 2.53 kg/m2. LUS had better diagnostic performance compared to CXR for the detection of air bronchogram, consolidation, and pleural thickening (area under the receiver operating characteristic curve [AUROC]: 0.966 vs. 0.483, 0.900 vs. 0.575, and 0.656 vs. 0.531, respectively). Also, LUS was 100% and 96.7% specific for the diagnosis of pleural effusion and atelectasis, respectively. CONCLUSIONS: LUS appears to be superior to CXR and comparable with HRCT for the evaluation of CF pulmonary exacerbation, especially in terms of air bronchogram and consolidation detection. LUS can be used to lengthen the HRCT evaluation intervals in this regard or utilized along with HRCT for better evaluation of CF pulmonary exacerbation.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Evaluating the relationship between high-resolution computed tomography findings and their extent in eosinophilic lung diseases with peripheral blood eosinophil level.

PURPOSE: Eosinophilic lung diseases are a group of pulmonary disorders associated with peripheral or tissue eosinophilia. They can be classified into primary (idiopathic) and secondary groups based on their aetiology. On the other hand, blood eosinophilia is a common clinical problem with various causes. In many cases the lung infiltrations in patients with peripheral eosinophilia are non-eosinophilic. Herein, we aim to assess the relationship between blood eosinophilia and abnormal high-resolution computed tomography (HRCT) features and their extent in idiopathic chronic eosinophilic pneumonia (ICEP) (the most common form of idiopathic eosinophilic lung disease). This can help in differentiating eosinophilic from non-eosinophilic lung infiltrations in patients with blood eosinophilia. MATERIAL AND METHODS: In this descriptive-correlational study, all patients with proven ICEP, who were referred to Masih Daneshvari Hospital, Tehran, Iran from 2012 to 2019, were included. The ICEP diagnosis was based on lung infiltrations on imaging, in addition to increased numbers of eosinophils in bronchoalveolar lavage fluid, blood or lung biopsy samples, and rapid response to corticosteroids. Patients with known aetiologies for eosinophilic lung diseases were excluded. The HRCT findings and their extent in each patient were compared with the blood eosinophil level. RESULTS: Positive correlation was found only between blood eosinophil level and frequency and extent of consolidation, and with frequency of lymphadenopathy. CONCLUSIONS: HRCT can help to differentiate eosinophilic from non-eosinophilic lung infiltrations in patients with blood eosinophilia by comparing the extent of consolidation with the blood eosinophil level.

Extracorporeal membrane oxygenation and COVID-19: The causes of failure.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapeutic strategy for the coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). There are inconclusive data in this regard and causes of VV-ECMO failure are not yet understood well. CASE SERIES: Here, seven patients with COVID-19-induced ARDS who underwent VV-ECMO introduced and causes of VV-ECMO failure discussed. Medical records of seven COVID-19 patients treated with VV-ECMO were retrospectively evaluated to determine the clinical outcomes of VV-ECMO. Oxygenator failure occurred in four patients whom needed to oxygenator replacement. Successful VV-ECMO decannulation was done in three patients, however finally one patient survived. CONCLUSIONS: Hypercoagulability state and oxygenator failure were the most main etiologies for VV-ECMO failure in our study. All patients with COVID-19 undergoing VV-ECMO should be monitored for such problems and highly specialized healthcare team should monitor the patients during VV-ECMO.

The evaluation of interleukin-4 and interleukin-13 in the serum of pulmonary sarcoidosis and tuberculosis patients.

BACKGROUND: Sarcoidosis and tuberculosis (TB) are two granulomatous inflammatory diseases with several common symptoms. The aim of the present study was to compare the serum levels of biomarkers including interleukin-4 (IL-4) and IL-13, calcium (Ca), hemoglobin, sedimentation rate, and lymphocyte-to-neutrophil ratio between patients with pulmonary TB, patients with sarcoidosis, and control group. MATERIALS AND METHODS: This case-control study was performed on patients referred to the Masih Daneshvari Hospital, Tehran, from April 2017 to 2018. In this study, 24 newly diagnosed patients with active pulmonary TB, 34 patients with pulmonary sarcoidosis, and 30 healthy individuals as the control group were enrolled. Demographic data, erythrocyte sedimentation rate (ESR), the ratio of neutrophil-to-lymphocyte (NLR), serum Ca level, hemoglobin (Hb), and IL-4 and IL-13 were compared between the study groups. Receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity were also calculated using SPSS 16.0 software. RESULTS: The mean age was 47.71 ± 10.88 and 55.25 ± 21.58 years in the sarcoidosis and TB. The mean ESR in sarcoidosis patients was 21.45 ± 13.37 mm/h and 41.4 ± 17 mm/h in the TB group. The percentage of peripheral blood lymphocytes in sarcoidosis and TB patients was 28.02 ± 12.20 and 21.41 ± 12.49, respectively, which was significantly higher among patients with sarcoidosis. NLR was also 2.4 ± 1.6 and 4.4 ± 2.9 in sarcoidosis and TB patients, respectively, which showed a significant difference among the groups. Regarding the evaluation of the level of IL-4 and IL-13 in patients, it is worth noting that IL-4 in patients with sarcoidosis was 90 pg/ml compared to 20 pg/ml for TB patients (P < 0.001). There was no significant difference in the levels of IL-13 in the TB and control groups, which varied between 20 and 80 pg/ml (P = 0.35). However, its value was significantly higher in patients with sarcoidosis (P = 0.01) than in the healthy control group and TB (P = 0.01). The ROC curves showed that the diagnostic cutoff of ESR level, Ca, NLR, and Hb could be valuable due to the area under the curves. The cutpoint of 34 mm/h for ESR had a sensitivity of 86% as well as 80% specificity to distinguish TB from the sarcoidosis. CONCLUSION: Serum levels of the biomarkers indicated a stronger immunological background in sarcoidosis using NLR, Ca, ESR, and Hb.

The diagnostic accuracy of endobronchial ultrasound and spiral chest computed tomography scan in the prediction of infiltrating and non-infiltrating lymph nodes in patients undergoing endobronchial ultrasound.

PURPOSE: Endobronchial ultrasound (EBUS) and spiral chest computed tomography (CT) scan are important methods in the prediction of infiltrating and non-infiltrating lymph nodes, and the determination of their diagnostic accuracy would result in a reduction of the burden of problems and an improvement in prognosis. The purpose in this study was to determine the diagnostic accuracy of endobronchial ultrasound and spiral chest CT scan in the prediction of infiltrating and non-infiltrating lymph nodes in patients undergoing endobronchial ultrasound. MATERIAL AND METHODS: In this observational prospective study, 40 consecutive patients with infiltrating and non-infiltrating lymph nodes in Masih-Daneshvari Hospital in 2017 and 2018 were enrolled, and the sensitivity, specificity, and accuracy of EBUS and CT-scan versus fine needle aspiration pathology results were determined in them. RESULTS: The results in this study demonstrated that the congruence between EBUS and CT scan was 80.5% (p = 0.0001). The sensitivity, specificity, and accuracy for CT scan were 100%, 22.6%, and 40%, respectively, and the sensitivity, specificity, and accuracy for EBUS were 100%, 16.1%, and 35%, respectively. CONCLUSION: According to the obtained results, it may be concluded that CT scan and EBUS results have good congruence and high sensitivity to differentiate infiltrating and non-infiltrating lymph nodes. Hence, these methods are useful for screening methods, but due to their low specificity and accuracy the use of them for a confirmative approach is not beneficial. However, regarding the accessibility and less invasive nature, use of chest CT scan is more rational and is recommended in these patients.

Human endogenous retrovirus env genes: Potential blood biomarkers in lung cancer.

Lung cancer, the leading cause of cancer mortality, needs urgent development of newly qualified diagnostic and therapeutic biomarkers. Recently, Human Endogenous Retroviruses (HERVs) have been introduced for cancer diagnosis. In this case-control study, we have collected blood samples from 60 lung cancer patients and 20 healthy controls. Quantitative gene expression analysis of various HERV env genes, including HERV-R, HERV-H, HERV-K, and HERV-P was performed by real-time PCR. Results indicate that expression of all four HERV env mRNAs is significantly increased in the blood of lung cancer patients than healthy controls (P-values<0.01). Furthermore, we have observed a positive and significant pairwise correlation between the expressions of four HERV env genes. The level of HERV env transcript in the blood of adenocarcinoma patients was generally much higher than squamous cell carcinoma (SCC) and small-cell lung cancer (SCLC) patients. Also, the expression of three HERV P, HERV H, and HERV K in the blood of lung cancer patients could significantly differentiate between adenocarcinoma and other types of lung cancer. In conclusion, these four HERV families could be considered as promising non-invasive blood-based biomarkers for prognosis, early detection, and monitoring of lung cancer.

WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.

Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in granulosa cells (GCs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. Using conditional gene targeting, we found that GC-specific inactivation ofWnt5a(but notWnt11) results in the female subfertility associated with increased follicular atresia and decreased rates of ovulation. Microarray analyses have revealed that WNT5a acts to down-regulate the expression of FSH-responsive genesin vitro, and corresponding increases in the expression of these genes have been found in the GCs of conditional knockout mice. Unexpectedly, we found that WNT5a regulates its target genes not by signalingviathe WNT/Ca(2+)or planar cell polarity pathways, but rather by inhibiting the canonical pathway, causing both ß-catenin (CTNNB1) and cAMP responsive element binding (CREB) protein levels to decreaseviaa glycogen synthase kinase-3ß-dependent mechanism. We further found that WNT5a prevents follicle-stimulating hormone and luteinizing protein from up-regulating the CTNNB1 and CREB proteins and their target genes, indicating that WNT5a functions as a physiologic inhibitor of gonadotropin signaling. Together, these findings identify WNT5a as a key regulator of follicle development and gonadotropin responsiveness.-Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., Boerboom, D. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.

Serum ACE Level in Sarcoidosis Patients with Typical and Atypical HRCT Manifestation.

BACKGROUND: Sarcoidosis is an inflammatory disease that affects multiple organs. Before widespread use of computed tomography (CT), the severity of sarcoidosis was assessed based on chest X-ray abnormalities. HRCT can distinguish between active inflammatory changes and irreversible fibrosis. In this study, we analyzed different ACE levels in 148 patients diagnosed with sarcoidosis. MATERIAL/METHODS: We categorized these patients based on their HRCT results into four groups: 1) patients diagnosed with chronic disease; 2) patients diagnosed with non-chronic disease; 3) patients who exhibited typical HRCT changes; and 4) patients who exhibited atypical HRCT changes. Afterward the mean ACE level of each group was calculated and compared. RESULT: The HRCT scans of chronic sarcoidosis patients tended to show more atypical sarcoidosis patterns. Moreover, there was a reverse correlation between chronicity and ACE level (P-value <0.05). CONCLUSIONS: HRCT is another modality which would be useful when the diagnosis of sarcoidosis is not definite.

Prevalence, antimicrobial susceptibility and virulotyping of Listeria species and Listeria monocytogenes isolated from open-air fish markets.

BACKGROUND: The aim of this study was to investigate the prevalence and characterization of Listeria species and Listeria monocytogenes isolated from raw fish and open-air fish market environments. Eight hundred and sixty two samples including raw fish and fish market environments (samples from workers' hands, workers' knives, containers and work surface) were collected from the open-air fish markets in the Northern region of Iran. RESULTS: Listeria spp. was isolated from 104/488 (21.3%) raw fish and 29/374 (7.8%) of samples from open-air fish market environment. The isolates of Listeria spp. included L. innocua (35.3%), L. monocytogenes (32.3%), L. seeligeri (18%), and L. ivanovii (14.3%). Of the 43 L. monocytogenes isolates, 31 (72.1%), 10 (23.3%) and 2 (4.7%) belonged to serovars 1/2a, 4b, and 1/2b, respectively. The inlA, inlB, inlC, inlJ, actA, hlyA, iap, plcA, and prfA virulence-associated genes were detected in almost all of the L. monocytogenes isolates. The Listeria spp. isolates showed high resistance against tetracycline (23.3%), penicillin G, and cephalothin (each 16.5%). Besides, we observed significant resistance level to tetracycline (27.9%), ampicillin (20.9%), cephalothin, penicillin G, and streptomycin (each 16.3%) in the L. monocytogenes isolates. All of the isolates were susceptible to cefotaxime, gentamicin, kanamycin, and pefloxacin. We found that tetM (25.6%), tetA (23.3%), ampC (14%), and penA (11.6%) were the most prevalent antibiotic resistance genes in the L. monocytogenes isolates. CONCLUSIONS: Recovery of potentially pathogenic L. monocytogenes from raw fish and environment of open-air fish market samples in this study is a convincing evidence for the zoonotic potential of listeriosis.

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.

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.

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.

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.

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.

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.