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Nontuberculous mycobacteria (NTM) are opportunistic pathogens that are widely distributed in the environment. There is a lack of data on species distribution of these organisms from Iran. This study consists of a review of NTM articles published in Iran between the years 1992 and 2014. In this review, 20 articles and 14 case reports were identified. Among the 20 articles, 13 (65%) studies focused on NTM isolates from clinical specimens, 6 (30%) studies examined NTM isolates from environmental samples, and one (5%) article included both clinical and environmental isolates. M. fortuitum (229/997; 23%) was recorded as the most prevalent and rapid growing mycobacteria (RGM) species in both clinical (28%) and environmental (19%) isolated samples (P < 0.05). Among slow growing mycobacteria (SGM), M. simiae (103/494; 21%) demonstrated a higher frequency in clinical samples whereas in environmental samples it was M. flavescens (44/503; 9%). These data represent information from 14 provinces out of 31 provinces of Iran. No information is available in current published data on clinical or environmental NTM from the remaining 17 provinces in Iran. These results emphasize the potential importance of NTM as well as the underestimation of NTM frequency in Iran. NTM is an important clinical problem associated with significant morbidity and mortality in Iran. Continued research is needed from both clinical and environmental sources to help clinicians and researchers better understand and address NTM treatment and prevention. [ABSTRACT FROM AUTHOR]

Background: Brucellosis remains the most common zoonotic disease throughout the world and especially in Iran. Several clinical trials have tested different therapeutic regimens for brucellosis, but few have assessed the optimal duration of treatment. Methods: We performed a randomized controlled trial to compare a triple-drug regimen of doxycycline plus rifampicin for 6 weeks and streptomycin for the first 7 days with doxycycline plus rifampicin for 8 weeks and streptomycin for 7 days in patients with uncomplicated brucellosis in Arak, Iran. The primary outcome measure for the treatment groups was the relapse rate measured at 1, 3, 6, 12, and 24 months after cessation of therapy. Results: Eligible patients were randomized to one of the 2 groups with 72 per arm. We found no significant difference in the relapse rate for the 8-week treatment group compared to the 6-week group (9.7% vs 13.9%). There were no significant differences between the 6-week and 8-week groups regarding the relapse rate, period between clinical presentation and beginning of treatment, and time of relapse. Symptom resolution was achieved in all cases at a median 9.5 days and no cases experienced continuing symptoms after treatment. Conclusions: Our trial found no significant difference between 6-week and 8-week regimens of doxycycline and rifampicin plus streptomycin for the first 7 days. Further comparative studies with a large sample size should be implemented to achieve a consistent therapeutic regimen for uncomplicated brucellosis, to help identify those who may benefit from longer treatment, and to minimize adverse effects and unnecessary continuation of treatment. [ABSTRACT FROM AUTHOR]

The ultrastructure of the cell wall of extensively drug-resistant (XDR), multidrug-resistant (MDR) and susceptible tuberculosis (TB) bacilli was viewed under transmission electron microscopy (TEM). Under the TEM, marked differences were observed in the thickness of their cell wall: 20.2 ±1.5 and 17.1 ±1.03 nm for the XDR and MDR TB bacilli, respectively, and 15.6 ± 1.3 nm for the susceptible isolates (p < 0.05). In MDR bacilli, thickening of the cell wall was observed in the intermediate electron-transparent layer (ETL) and outer electron-opaque layer, whereas in XDR TB cells the basal peptidoglycan layer was denser and almost fused with the ETL. Five to seven percent of XDR TB bacilli had the appearance of the stationary phase with cell wall thickness ranging from 21 to 26 nm (p < 0.001). Information provided in this study is of significant importance in terms of drug selection for effective treatment of resistant strains. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a study of the emergence of totally drug-resistant (TDR) tuberculosis (TB) strain from multidrug-resistant (MDR) TB patients. Methods used in the study include testing the drug susceptibility of TB strains from patients, sputum smear tests, and analysis of cultured mycobacterium specimens from those patients. The study concludes that TDR strains are isolated geographically in Iran from MDR-TB strains and could possibly disseminate in Asian nations.

Summary: Background: Lamivudine is used for the treatment of chronic hepatitis B patients. Recent studies show that the YMDD motif mutants (resistant hepatitis B virus) occur as natural genome variability in lamivudine-untreated chronic hepatitis B patients. In this study we aimed to determine the rate of YMDD motif mutants in lamivudine-untreated chronic hepatitis B patients in Iran. Patients and methods: A total of 77 chronic hepatitis B patients who had not been treated with lamivudine were included in the study. Serum samples from patients were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detection of YMDD motif mutants. All patients were also tested for liver enzymes, anti-HCV, HBeAg, and anti-HBe. Results: Of the 77 patients enrolled in the study, 73% were male and 27% were female. Mean ALT and AST levels were 124.4±73.4 and 103.1±81IU/l, respectively. HBeAg was positive in 40% and anti-HBe in 60% of the patients. Anti-HCV was negative in all of them. YMDD motif mutants were not detected in any of the patients despite the liver enzyme levels and the presence of HBeAg or anti-HBe. Conclusion: Although the natural occurrence of YMDD motif mutants in lamivudine-untreated patients with chronic hepatitis B has been reported, these mutants were not detected in Iranian lamivudine-untreated chronic hepatitis B patients. [Copyright &y& Elsevier]

This survey identified the spoligopatterns of Mycobacterium tuberculosis strains with an international designation responsible for transmission and prevalence of TB (2000 to 2005) among native and immigrant populations of Tehran. The spacer oligonucleotides typing was performed on 1742 Mycobacterium tuberculosis strains isolated from verified cases of TB. Clinical and demographic data of patients were collected using traditional methods. A total of 133 distinct spoligopatterns was observed. 1679 clinical isolates were clustered in 70 clusters (52.5%) and 63 isolates were defined as orphans pattern (47.3%). Based on an international spoligotype database, the east African-Indian (EAI, 24%), central Asian (CAS, 20.8%), T clade (20.7%), Haarlem I (4.4%), Beijing (3.2%) and shared type 253 (3.1%) were the major identified M. tuberculosis superfamilies. Our results showed that the intra-community TB transmission was 13.7%, whereas the inter-community transmission was 39.3% for Afghanis and 20.3% for Iranians. The study highlighted the epidemic potential of specific genotypes (EAI, CAS, T clades) among tuberculosis cases in the Tehran territory. We also confirmed that the impact of transmission through immigration is low. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article by M. Aloosh and A. Aloosh in volume 520 of the journal which discusses the impact of economic sanctions on public health in Iran.

Objectives: The aim of this study was to evaluate the frequency and genotype of human parvovirus B19 and its relation with anemia among Iranian patients under dialysis. Methods: Fifty hemodialysis (HD) and 33 peritoneal dialysis (PD) patients were enrolled. B19 IgG and IgM antibodies were assessed by ELISA, and the presence of B19 DNA was evaluated by nested PCR. PCR products were sequenced directly and phylogenetic analysis was performed. Results: In the HD group, the prevalence of B19 antibodies was 54% for IgG and 4% for IgM. B19 DNA was detected in 10% of the cases, and 10% showed B19 IgG and viremia simultaneously. In the PD group, the prevalence of B19 IgG and IgM was 57.6 and 0% respectively, whereas B19 DNA was found in 12.1% of the group. A total of 9.1% showed B19 IgG and viremia concurrently. There was no significant difference regarding anemia and B19 infection in either group. All B19 isolates were clustered in genotype 1A. Conclusion: Our findings indicate that B19 infection plays no role in leading chronic anemia in dialysis patients. However, persistent B19 viremia and the circulation of the same strains in dialysis patients may indicate a potential risk for the contamination of dialysis equipment and nosocomial spread of B19 infection within dialysis units. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis is a chronic and progressive genetic disease with a worldwide prevalence. As the disease progresses, symptoms develop, and make its management more challenging. Accumulating evidence suggests that early diagnosis of CF can significantly contribute to preventing reported nutritional problems including anemia, vitamin deficiencies, and hypoalbuminemia. This cross-sectional study was conducted to assess disease severity in cystic fibrosis patients using the Shwachman-Kulczycki score, as well as to determine its relation with anemia and vitamin D deficiency. Materials and Methods: Clinical and CF-related laboratory data were collected from the medical records of 57 CF patients with a definitive diagnosis. At the time of diagnosis, physicians performed simultaneous, blood sampling and scoring of patients using the Shwachman scoring system. Results: The mean age of patients was 16.12±6.48 years. Total scores of 86-100, 71-85, 56-70, 41-55, and <40, were reported in 5.4%, 7.1%, 14.3%, 14.3%, and 58.9% of CF patients, respectively. A significant correlation was found between disease severity and patients' age (P=0.02). The analysis also showed that the disease severity was significantly higher in anemic patients when compared to non-anemics (p =0.006). Based on the results, 33 patients with normochromic, 11 patients with microcytic, and 6 patients with macrocytic anemia were diagnosed in this study. We did not find a significant difference between disease severity and vitamin D levels (P=0.150). Conclusion: The scoring system used in the current study could reflect properly the clinical status of CF patients. However, simultaneous use of various methods using a larger sample size for comparison of results is suggested to improve the accuracy of findings. [ABSTRACT FROM AUTHOR]

Background: Mendelian susceptibility to mycobacterial disease (MSMD) is an uncommon disorder with increased susceptibility to less virulent mycobacteria including bacillus Calmette-Guérin (BCG). Fibrosing mediastinitis (FM) is also a rare condition defined by excessive fibrotic reactions in the mediastinum. So far, some infectious organisms and autoimmune diseases have been introduced as possible etiologies of FM. However, no study has ever discussed the possible association of BCG infection and FM. Case presentation: In this study, we report a 3-year-old female presenting with persistent fever, weakness, and bloody diarrhea in addition to mediastinal lymphadenopathy, hepatosplenomegaly, and pleural and pericardial effusion. Further examinations established a diagnosis of MSMD based on her clinical condition, immunologic data, positive tests for mycobacterial species, positive family history, and genetic study (IL12RB1 gene, c.G1193C, p.W398S). A year and a half later, she was referred with submandibular lymphadenitis and underwent immunologic work-up which revealed high inflammatory indices, a slight reduction in numbers of CD3 + and CD4 + cells as well as elevated CD16/56 + cell count and hyperimmunoglobulinemia. Purified protein derivative (PPD), QuantiFERON, and gastric washing test were all negative. Her chest computed tomography (CT) scan revealed suspicious para-aortic soft tissue and her echocardiography was indicative of strictures in superior vena cava and pulmonary veins. She further underwent chest CT angiography which confirmed FM development. Meanwhile, she has been treated with anti-mycobacterial agents and subcutaneous IFN-γ. Conclusion: In summary, we described a novel case of MSMD in a child presenting with granulomatous FM possibly following BCG infection. This is the first report introducing aberrant BCG infection as the underlying cause of FM. This result could assist physicians in identifying early-onset FM in suspicious cases with MSMD. However, more studies are required to support this matter. [ABSTRACT FROM AUTHOR]

Hydatidosis is one of the most important parasitic and zoonotic endemic infections caused by the larvae of cestode Echinococcus granulosus. Co-infection of hydatid cyst with the coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been previously reported. The mortality rate of hydatidosis is reported to be 2-4% and the liver and lungs are the two most commonly involved organs, respectively. In the present study, we have reported two recovered pulmonary hydatidosis patients who were infected with SARS-CoV-2 after thoracotomy in the hospital. In general, current cases suggest that patients with thoracic surgery are more likely to develop severe infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The patients presented COVID-19 symptoms shortly after thoracotomy and their viral tests were confirmed with the positive result of SARS-CoV-2 RT-PCR. In conclusion, possible differential diagnoses should be considered in similar cases and adequate attention should be paid to intraoperative and postoperative care. [ABSTRACT FROM AUTHOR]

Background and Aim: The COVID-19 disease is an emerging infectious disease that appeared in December 2019 in Wuhan, China. An uncontrolled systemic inflammatory response is one of the primary mechanisms causing death in this disease. In this study, the expression levels of some inflammatory cytokines, vitamin D, and some hematological and biochemical parameters were compared in patients with severe COVID-19 and mild types. Materials and Methods: In this cross-sectional study, 60 blood samples were taken from 30 severe coronavirus patients and 30 mild coronavirus patients. The expression levels of cytokines such as IL (interleukin)-6, interferon (IFN)-α, IL-12, transforming growth factor (TGF) β, IL-8 and tumor necrosis factor (TNF)-α were evaluated using Real-time PCR. A T-test was used for Statistical Analysis. Results: IL-6, IFN-α, IL-12, TGF-β, IL-8, and TNF-α cytokines in the peripheral blood of severe patients, were positive in 28/30 (93.33%), 27/30 (90%), 24/30 (80%), 25/30 (83.33%), 26/30 (86.66%), and 27/30 (90%) respectively. The positive rate of these cytokines in the mild patients were 20/30 (66.67%), 21/30 (70%), 18/30 (60%), 17/30 (56.67%), 19/30 (63.33%), 18/30 (60%), respectively. There was a statistically significant difference between these two groups in terms of cytokines biomarkers. A significant difference was found between both groups in terms of the serum level of lactate dehydrogenase (LDH), the mean number of lymphocytes and neutrophils as well as the mean percentage of neutrophils/ lymphocytes ratio (NLR). Conclusion: The expression of cytokine genes and their release into the peripheral blood was increased in both severe and mild patients with COVID-19. However, they were more intense in patients with severe symptoms than those with mild symptoms and can cause inflammatory and even destructive reactions. Vitamin D deficiency plays no role in causing severe COVID-19 in patients without risk factors. Severe COVID-19 is characterized by elevated serum levels of LDH and NLR≥3.45. [ABSTRACT FROM AUTHOR]

Background: Although many aspects of the COVID-19 disease have not yet been clarified, dysregulation of the immune system may play a crucial role in the progression of the disease. In this study, the lymphocyte subsets were evaluated in patients with different severities of COVID-19. Materials and Methods: In this prospective study, the frequencies of peripheral lymphocyte subsets (CD3+, CD4+, and CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were evaluated in 67 patients with confirmed COVID-19 on the first day of their admission. Results: The mean age of patients was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases, and 11 (16.4%) were categorized as critical. The frequencies of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells, and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+56+ lymphocytes were lower in more severe cases compared to the milder patients. The percentages of lymphocytes, T cells, and NK cells were significantly lower in the deceased patients. (p= 0.002 and p= 0.042, p=0.006, respectively). Conclusion: Findings of this cohort study demonstrated that the frequencies of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells differed in the severe cases of COVID-19. Moreover, lower frequency of T cells and NK cells could be predictors of mortality in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the leading causes of morbidity and mortality around the world. Caregivers of these patients are affected by various physical, emotional, social, spiritual, and financial factors that can affect their quality of life (QoL). This study aimed to compare the QoL and general health status of thoracic cancer patients with their family caregivers in Iranian population. Materials and Methods: Using the City of Hope-Quality of Life (COH-QOL) questionnaire and the General Health Status (GHQ) questionnaire, this crosssectional study compared the QoL and general health status in 71 thoracic cancer patients with their family members as the primary caregivers. The study was conducted in Masih Daneshvari Hospital of Tehran, Iran from 2017 to 2018. Demographic data and results of the questionnaires were analyzed using the Statistical Package for the Social Sciences (SPSS v.20). Student’s t-test, Chi square test, and Pearson’s correlation were used to compare the results. Results: In patients and their caregivers, 53.5% (N=38) and 36.6% (N=26) were male, respectively (P=0.043). While the average score of physical wellbeing was 6.12 ± 1.95 in caregivers, it was 5.32 ± 2.08 in patients (P=0.021). In case of psychological wellbeing, the average score in caregivers was 4.14 ± 1.50 and in patients was 5.7 ± 1.54 (P=0.000). We observed no significant difference between caregivers and patients regarding social concerns (4.62 ± 1.50 vs. 4.90 ± 1.74) and spiritual wellbeing (7.03 ± 1.17 vs. 7.2 ± 1.53). Also, the mean scores of GHQ-12 were 5.06 ± 2.5 and 4.17 ± 2.53 in caregivers and patients, respectively (P=0.04). A significant negative correlation was observed between GHQ-12 and QoL scores (r=-0.593, P<0.001). The probability of acquiring mental disorders in female caregivers was two times higher than male caregivers (P=0.05). Conclusion: Our findings demonstrated that family caregivers of thoracic cancer patients suffer from physical and psychological distress, sometimes even more than the patients. This highlights the important role of family caregivers in the process of approaching a patient with thoracic cancer. [ABSTRACT FROM AUTHOR]

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant autoinflammatory disorder caused by mutations in the PSTPIP1/CD2BP1 gene. We systematically reviewed 93 patients with PAPA and PAPA-like syndrome. Most patients were male (65.9%) mainly born to non-consanguineous parents. The median (IQR) age at the onset of symptoms and diagnosis was 6.0 (2.0-8.0) and 25.0 (7.0-32.0) years, respectively. 62.5% of patients were presented with arthropathies and septic arthritis was the most common (54.2%) initial diagnosis. Joint disorders were the most common findings (n=71, 78.9%) starting at the median (IQR) age of 4.0 (2.0-8.0) years, mainly in the knee (56.5%), ankle (36.9%), and elbow (47.8%). Skin involvement (62 (66.7%)) initially presented at a median (IQR) age of 12.0 (20.-10.0) years and included pyoderma gangrenosum (n=41, 44.1%), acne (n=43, 46.2%), and nodulocystic acne (n=19, 20.4%). There was a stronger association between skin manifestations and the development of the classic triad (P<0.001) compared to joint disorders (P=0.05) and patients with lower age of onset were more prone to the progression of the complete triad (P=0.18). Corticosteroids (n=45, 50.0%) with or without anakinra (33.3%) were the treatments applied in the majority of patients. PAPA/PAPA-like syndromes involve mainly non-axial joints in early childhood and later skin in the second decade of life. Only 26.4% of the patients manifested the classical triad of PAPA syndrome. There is no clear genotype-phenotype association in these disorders. More studies are required to investigate the therapeutic options in PAPA/PAPA-like syndromes. [ABSTRACT FROM AUTHOR]

Background: It is widely accepted that concerns have been recently raised regarding the impact of air pollution on the health of children with cystic fibrosis (CF). Air pollution probably affects the exacerbation of CF and its laboratory findings. On the other hand, the World Health Organization (WHO) has asked all countries to update their data and reports on the distribution and prevalence of CF in different areas. The purpose of the present study was to investigate the distribution and prevalence of CF based on the levels of atmospheric pollutants, such as PM10, PM2.5, SO2, NO2, CO, and O3 in 22 zones of Tehran, and to report the abnormal laboratory findings that might indicate the exacerbation of CF. Materials and Methods: The studied statistical population included children with CF referred to Masih Daneshvari Hospital from 2003 to 2020. Demographic data, location of living area, and laboratory findings were extracted from patient records. The geographic information system (GIS) was applied to indicate the distribution and dispersion of the disease. The information related to air pollutants was collected from all stations in Tehran during the studied period by the Department of Environment of Tehran Province, and the average levels were used for final reporting. Results: The analysis results on 287 CF patients demonstrated that the risk of disease exacerbation significantly increased by the presence of air pollutants. In areas with multiple air pollutants, more laboratory findings were observed to be abnormal, and the lower survival rate for patients with CF was recorded. Investigating the CF distribution pattern based on climatic layers and above mean sea level (AMSL) indicated that distribution of the disease was higher in dry areas with lower AMSL and the higher volume of the atmospheric pollutants, which were primarily centralized in southern and central Tehran. Conclusion: Environmental factors, such as air pollution, can be considered vital parameters, along with high-risk factors, such as pure and integrated race, migration, and mutation, influencing the prevalence and exacerbation of CF symptoms. Considering the higher prevalence of CF in deprived areas of Tehran, households' cultural and economic level appears to be a factor in the lack of diagnostic screening and prevention of CF in these areas. On the other hand, continuous monitoring of the air pollution caused by traffic and giving warnings to CF patients and their parents is particularly important. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is the cause of tuberculosis in humans and is responsible for more than 2 million deaths per year. Despite the development of anti-tuberculosis drugs (Isoniazid, Rifampicin, Ethambutol, pyrazinamide, streptomycin, etc.) and the TB vaccine, this disease has claimed the lives of many people around the world. Drug resistance in this disease is increasing day by day. Conventional methods for discovering and developing drugs are usually time-consuming and expensive. Therefore, a better method is needed to identify, design, and manufacture TB drugs without drug resistance. Bioinformatics applications in obtaining new drugs at the structural level include studies of the mechanism of drug resistance, detection of drug interactions, and prediction of mutant protein structure. In the present study, computer-based approaches including molecular dynamics simulation and molecular docking as a novel and efficient method for the identification and investigation of new cases as well as the investigation of mutated proteins and compounds will be examined. [ABSTRACT FROM AUTHOR]

Summary: Background: Brucellosis is a zoonotic disease of worldwide distribution. Despite its control in many countries, it remains endemic in Iran. The aim of this study was to determine the risk factors for brucellosis acquisition in the central province of Iran. Methods: A matched case–control study was conducted in the central part of Iran. A total of 300 subjects (150 cases and 150 controls) were enrolled in the investigation. Brucellosis cases were defined on the basis of epidemiologic, clinical, and laboratory criteria. Subjects were interviewed using a questionnaire to obtain risk factor information. We used odds ratios and conditional logistic regression models to explore the association between the disease and the variables studied. Result: Significant risk factors for infection were related to the existence of another case of brucellosis in the home (OR=7.55, p =0.0001) and consumption of unpasteurized dairy products (OR=3.7, p =0.014). Keeping cattle and cattle vaccination were also important risk factors. Conclusions: Pasteurization of dairy products and education regarding fresh cheese must be pursued for eradication of brucellosis. A major risk factor for acquiring brucellosis is the existence of another infected family member. Therefore screening family members of an index case of brucellosis may lead to the detection of additional cases. [Copyright &y& Elsevier]

Background: Pulmonary Alveolar Proteinosis (PAP) is an uncommon pulmonary disease characterized by the accumulation of surfactant composed of proteins and lipids due to disruption of surfactant clearance by alveolar macrophages. The current standard treatment is lung lavage. There are no specific criteria for lavage, but in case of observing these signs it is recommended to perform lavage for the patient: progressive respiratory failure, no labored breathing at rest, and drop in oxygen level during activity (>5%). Materials and Methods: In this study, patients with PAP admitted to Pediatric ward of Masih Daneshvari Hospital were studied. The required data were collected including the patient's demographic data, clinical signs and radiographic data, the number of admissions, the age of diagnosis, detection and treatment methods, number of lavage, current condition of the patient, and in case of death, the cause of death. Results: In this study, 17 patients with PAP who were admitted during the past 15 years were examined; among which 7 patients were boys (41.2%) and 10 were girls (58.8%). The mean age of population was 11.79±7.21 years. Transbronchial Lung Biopsy (TBLB) (47.1%) and open lung biopsy (52.9%) were used for diagnosis of patients. Lung lavage was used to treat patients, 15 of whom were treated by this method. Five of the patients died because of their serious conditions. Conclusion: Therapy method in the present study was lavage for both lungs, and it was performed for all patients except for two patients due to their anatomical complications. This method is still considered as the gold standard for PAP. Considering the findings from previous studies and the present study, it seems that Whole Lung Lavage (WLL) was fruitful for patients who had the indication for using this therapy and it played a significant role in improving the prognosis of patients. Besides, it is recommended to do follow-up regularly in order to have more therapeutic efficacy and increased patient longevity. [ABSTRACT FROM AUTHOR]

Background: It is known that inflammatory responses occur in the airways of patients with non-cystic fibrosis bronchiectasis during respiratory exacerbations but the role of these cytokines is not clear in this condition. Herein we evaluated the levels of interleukin-1ß (IL-1ß), IL-8 and tumor necrosis factor a (TNF-a) in the serum and bronchoalveolar lavage among children with non-cystic fibrosis bronchiectasis. Materials and Methods: This cross-sectional study was performed on all children with non-cystic fibrosis bronchiectasis who were admitted with respiratory exacerbation in the pediatric pulmonology ward of Masih Daneshvari Hospital, Tehran-Iran. All patients underwent fiberoptic bronchoscopy and spirometry before and after the bronchoscopy. IL-1ß, IL-8, and TNF-a levels were measured in the serum and bronchoalveolar lavage. Results: Patients included 10 (59%) female and 7 (41%) male subjects with mean age of 13.8 years (range, 5-18). Mean values for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were below the normal range before and after bronchoscopy. Mean value for FVC (from 55% to 63%, P= 0.01) and FEV1 (from 60% to 64%, P= 0.26) increased after bronchoscopy compared to before that. IL-1ß and IL-8 levels were increased and TNF-a level was decreased in the serum and bronchoalveolar lavage but no significant correlation was found between spirometry and these cytokines levels. Conclusion: Changes in inflammatory cytokines levels in serum and bronchoalveolar lavage during respiratory exacerbation in patients with noncystic fibrosis bronchiectasis have no significant correlation with spirometry and cannot be used in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Mendelian susceptibility to mycobacterial disease (MSMD) is an inborn error of immunity, resulting in susceptibility to weakly virulent mycobacteria and other intramacrophagic pathogens. Rheumatologic manifestations and vasculitis are considered rare manifestations in MSMD patients. Case presentation: In this study, we reported a 20-year-old female who was presented with recurrent lymphadenitis following bacillus Calmette-Guérin (BCG) vaccination and a history of recurrent disseminated rash diagnosed as leukocytoclastic vasculitis (LCV). A slight reduction in lymphocyte subsets including CD4+, CD19+, and CD 16 + 56 T-cell count, as well as an elevation in immunoglobulins level (IgG, IgA, IgM, IgE), were observed in the patient. Whole exome sequencing revealed a homozygous Indel-frameshift mutation, c.527_528delCT (p. S176Cfs*12), at the exon 5 of the IL12B gene. She experienced symptom resolution after treatment with anti-mycobacterial agents and subcutaneous IFN-γ. We conducted a manual literature search for MSMD patients reported with vasculitis in PubMed, Web of Science, and Scopus databases. A total of 18 MSMD patients were found to be affected by a variety of vasculitis phenotypes mainly including LCV and Henoch-Schönlein purpura (HSP) with often skin involvement. Patients were all involved with vasculitis at the median age of 6.8 (2.6–7.7) years, nearly 6.1 years after the initial presentations. Sixteen patients (88.9%) had IL12RB1 defects and concurrent Salmonella infection was reported in 15 (88.2%) patients. Conclusion: The lack of IL-12 and IL-23 signaling/activity/function and salmonella infection may be triggering factors for the development of leukocytoclastic vasculitis. IL12B or IL12RB1 deficiency and salmonellosis should be considered in MSMD patients with vasculitis. [ABSTRACT FROM AUTHOR]

Despite the fact that about two years have passed since the onset of the COVID-19 pandemic, there is still no curative treatment for the disease. Most cases of COVID-19 have mild or moderate illness and do not require hospitalization. This guideline released by the National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital COVID-19 Expert Group to provide a treatment guide for outpatient management of COVID-19. [ABSTRACT FROM AUTHOR]

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare group of genetic disorders characterized by infections with weakly virulent environmental mycobacteria (EM) or Mycobacterium bovis bacillus Calmette-Guérin (BCG). Herein, we described the case of a 4.5-year-old boy with protein-losing enteropathy, lymphoproliferation, and candidiasis, who was found to have disseminated Mycobacterium simiae infection. A homozygous mutation in the IL12B gene, c.527_528delCT (p.S176Cfs*12) was identified, responsible for the complete IL-12p40 deficiency. He was resistant to anti-mycobacterial treatment and finally died due to sepsis-related complications. [ABSTRACT FROM AUTHOR]

Mycobacterium simiae is an emerging nontuberculous mycobacterium (NTM) and an opportunistic pathogen which is described mainly in Asia and presents in the environment that can cause pulmonary infection. The objective of this study is to characterize M. simiae clinical isolates using mycobacterial interspersed repetitive unit variable-number tandem repeats (MIRU-VNTR) typing for the differentiation of the strains. A total of 169 clinical isolates of NTM were recovered from patients suspected of having tuberculosis (TB)-like and related infections. After isolation and identification of mycobacterial strains by conventional biochemical and PCR-based tests, M. simiae strains were confirmed using restriction fragment length polymorphism (RFLP)-based identification assay. Furthermore, drug susceptibility and MIRU-VNTR typing was performed using on the clinical isolates of M. simiae. Out of 169 NTM strains, 92 (54.4%) isolates were identified as M. simiae. Antibiotic susceptibility experiments indicated that all 92 M. simiae isolates were resistant to first line antimycobacterial agents. Moreover, 8 (8.6%) M. simiae isolates were resistant to ciprofloxacin; and 6 (6.5%) were resistant to both amikacin and kanamycin, while the remaining were susceptible to second line antimycobacterial agents. MIRU-VNTR analysis showed that the M. simiae isolates were classified in four distinct M. simiae clusters and two single types. The minimum spanning analysis revealed that the isolates were grouped in three complexes. The data suggested that MIRI-VNTR typing is useful for typing of M. simiae isolates, however, MIRU-16 locus was absolutely absent in M. simiae. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are few studies to compare antibody response against anti-spike (S) and anti- nucleoprotein (N) SARS-CoV-2. OBJECTIVE: The aim of this study was to evaluate the IgG antibody production against S and N antigens of the virus and their correlation with the time and severity of the disease. METHODS: The IgG antibodies against S and N antigens of SARS-CoV-2 in serum specimens of 72 symptomatic patients who tested real-time reverse transcription polymerase chain reaction positive for SARS-CoV-2 were detected using the ELISA technique. Different antibody response was compared and the correlation with the time from disease onset and the severity was evaluated. RESULTS: Forty-eight of 72 (67%) patients tested positive for anti-SARS-CoV-2 antibodies, while 24 (33%) did not have detectable antibodies. Comparison of antibody levels for N and S antibodies showed that they correlate with each other well (r = 0.81; P < 0.001). However, sensitivity of anti-S SARS-CoV-2 IgG and anti-N SARS-CoV-2 IgG was 30% and 60%, during the first 7 days after symptom onset (r = 0.53; P = 0.111), but increased to 73% and 68% at more than 1-week post symptom onset (r = 0.89, P = 0.111), respectively. Cases with positive IgG response showed a decreased CD8 + T cells percentage compared to the negative IgG groups (26 ± 14 vs. 58 ± 32, p = 0.066 in anti-N IgG group and 28 ± 15 vs. 60 ± 45, p = 0.004 in anti-S IgG group, respectively). CONCLUSION: Nearly one-third of the confirmed COVID-19 patients had negative serology results. Lower percent positivity at early time points after symptom onset (less than 1 week) was seen using anti-S SARS-COV-2 IgG kit compare to the anti-N SARS-CoV-2 IgG; therefore, clinicians should interpret negative serology results of especially anti-S SARS-CoV-2 IgG with caution. [ABSTRACT FROM AUTHOR]

COVID-19 leads to mild symptoms within the majority of infected patients, but can cause severe multiple organ failure and death. There is only limited information regarding the consequences of this new emerging infection with congenital disorders. According to the previous studies, many people with Down syndrome are considered high risk for complications related to respiratory diseases. We report two trisomy 21 patients who suffered from COVID-19 and summarize the early experience with COVID-19 and Down syndrome. The course of the disease was severe in these two cases, and our concern is close monitoring of the patients with Down syndrome for early signs of COVID-19. [ABSTRACT FROM AUTHOR]

Background: The clinical characteristics of the novel coronavirus disease (COVID-19) were diverse and unspecific. Here, we identified the associated factors with surviving of COVID-19 ICU patients based on the clinical characteristics of patients admitted to one of the Corona Centre Hospitals of Iran. Materials and Methods: This cohort study was performed retrospectively from February to June 2020 on 133 COVID-19 patients admitted to 4 intensive care units of Masih Daneshvari Hospital in Tehran, Iran. Demographic, medical, clinical manifestation at admission, laboratory parameters and outcome data were obtained from medical records. Also the SOFA and APACHE II scores were calculated. All data were analyzed using SPSS (version 23, IBM Corp.) software. Results: The median (IQR) age of the patients was 62.0 (54.0-72.0) years in total. RT-PCR of throat swab SARS-CoV-2 in 80 patients (60.2%) was positive. Total mortality rate was 57.9 percent (77 patients). Dyspnea, hypertension and chronic pulmonary diseases were significantly common in non-survivors than survivors (p<0.05). Both SOFA and APACHE II scores were significantly higher in the non-survivors (p<0.05). Also other significant differences were observed in other parameters of the study. Conclusion: The mortality rate of COVID-19 patients admitted to ICU is generally high. Dyspnea as initial presentation and comorbidity, especially hypertension and pulmonary diseases, may be associated with higher risk of severe disease and consequent mortality rate. Also, higher SOFA and APACHE II scores could indicate higher mortality in patients admitted to ICU. [ABSTRACT FROM AUTHOR]

Background: The Coronavirus disease 2019 (COVID-19) outbreak quickly has spread and became a pandemic. However, no approved therapeutics or effective treatment is available for the treatment of these patients. The present study was done to retrospectively assess the treatment strategies (e.g., pharmaceutical care services) for COVID-19 patients in selected hospitals and highlight the importance of such services in the management of a pandemic. Materials and Methods: Data from a series of COVID-19 patients (978 patients; 658 males [66.9%] and 324 females [33.1%]) admitted to the selected hospitals in Tehran from 20 February to 19 March 2020 were retrieved retrospectively from the Health Information System (HIS) of the hospitals. The statistical tests were used for analyzing the effect and correlation of the variables (drugs) with the average length of stay (ALOS) in the hospital. Results: Diverse medication classes and old drugs with or without strong evidence of therapeutic effects against the novel coronavirus, some previously tried as a treatment for SARS-CoV and MERS-CoV, were mostly used for the treatment of patients in the hospitals. Many medications (broad-spectrum antibiotics and antivirals) or combination therapies are used without evidence of their therapeutic effects during pandemics. Conclusion: Therefore, guidelines should be provided for the off-label use of these drugs by policymakers and stakeholders during a pandemic emergency due to high demands. Also, monitoring of the HIS data can play an important role in improving public health response to emerging diseases. [ABSTRACT FROM AUTHOR]

Background: Considering the importance of the increasing incidence of non-tuberculous mycobacteria, especially Mycobacterium abscessus worldwide, we conducted a study to evaluate the incidence of these diseases in our area. The aim of this study was to evaluate the prevalence of M. abscessus in patients with non-tuberculous mycobacteria. Methods: This descriptive study was performed on 18,083 samples isolated from patients with non-tuberculous mycobacteria during 2011-2017 at the Mycobacteriology Research Center (MRC), Tehran, Iran. To identify the Mycobacterium species, a 439 bp fragment of the IS6110 gene was first amplified using primers TB1 and TB2. Samples with a negative polymerase chain reaction (PCR) result were analyzed to investigate non-tuberculosis mycobacteria (NTM), especially M. abscessus using the RFLP method. Results: Of the 18,083 samples, 5513 (30.49%, 95% CI, 12.95) strains of Complex Tuberculosis and 236 (1.31%, 95% CI, 1.84) strains of NTM were identified. The mean age of the patients with NTM was 18 years, and most of them were male. The most commonly identified species in this study were M. abscessus type I 32 (13.56%, 95% CI, 18.36) and M. abscessus type II 13 (5.51%, 95%CI, 20.04). Conclusion: In this study, we observed a high prevalence of Mycobacterium abscessus type 1 in patients. As the treatment protocol for non-TB mycobacteria is different from M. abscessus complex, the diagnosis of these species as soon as possible will be significant for physicians. [ABSTRACT FROM AUTHOR]

Abstract In this present study, for the first time, we evaluated the cystic fibrosis (CF) patients for the Scedosporium species and their antifungal susceptibility against eight antifungal agents. During one-year period, 90 Sputum samples were collected from Iranian CF patients. All samples were evaluated by direct microscopic examination, culture onto four different media including Malt extract agar, Inhibitory mold agar, Brain Heart Infusion and Scedo-Select III. The mold isolated fungi were identified by PCR-Sequencing of ITS and β-tubulin genes. In-vitro antifungal susceptibility was performed according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 guidelines. Out of 90 CF patients, 47 (52.2%) were male. The age of the patients ranged from 1 to 34 years (median of 15.84 ± 7.41 years). Overall, 3 (3.3%) cases were positive for Scedosporium spp. of which two isolates were characterized as Scedosporium boydii and one isolate as S. ellipsoideum. Among Aspergillus genus, A. flavus (29.4%) was the most prevalent species followed by A. tubingensis (24.7%), A. niger (17.0%) and A. fumigatus (14.5%). The minimum effective concentration ranges of micafungin, anidulafungin, and caspofungin were 0.008–0.031 μg/mL, 0.0625–0.25 μg/mL, and 0.0625–0.25 μg/mL, respectively. All isolates of Scedosporium species showed high minimum inhibitory concentration to the triazoles tested, except voriconazole. Our results showed that A. flavus and Scedosporium species are the most prevalent molds isolated from CF patient populations in Iran. Our findings have also showed that Scedo-Select III can be used as a reliable culture media for isolation of Scedosporium spp. in clinical samples. Highlights • The prevalence of Scedosporium species In Iranian patients with cystic fibrosis was 3.3%. • A. flavus was the most common species within the Aspergillus genus. • Scedo-Select III can optimize the growth of Scedosporium species within a mixed samples. • Scedosporium species showed an increased MIC against the main antifungal agents. [ABSTRACT FROM AUTHOR]

Aim: This study was performed to evaluate the potential efficacy of silymarin in the management of anti-tuberculosis medication's induced liver injury. Background: Hepatic toxicity is the most serious complication in treatment of tuberculosis. Methods: In a randomized double blind clinical trial (ACTRN12610000643077), 55 cases with hepatotoxicity caused by antituberculosis drugs were divided into two groups. Informed consents were obtained. The intervention group received silymarin and the control group received placebo. Severity of liver injury, the duration necessary for normalization of liver function and hospital stay were compared between the two groups. Results: There was not any statistically significant difference in the rate of adverse effects between silymarin and placebo groups. Conclusion: Although silymarin is considered a safe herbal medication, it was not effective to treat hepatic toxicity of anti-tuberculosis drugs. [ABSTRACT FROM AUTHOR]

Background: Infection with Human Immune deficiency Virus (HIV) is a growing problem in developing countries. Among HIV infected cases, respiratory complications are common, dissimilar in different setting and their diagnosis is challenging. The aim of this study was to determine the spectrum of infectious and non-infectious pulmonary complications among HIV infected patients. Materials and Methods: The retrospective study was done among 710 HIV infected patients admitted in Masih Daneshvari Hospital, National Research Institute of Tuberculosis and Lung Diseases, Tehran, Iran from January 2003 to March 2017. Demographic, clinical, radiologic and laboratory data of 836 episodes of pulmonary complications were reviewed and final diagnosis were extracted. Results: Mean of CD4 cell count was 90±131 x106 cells/L. Definite etiology was found for 653 episodes (78.1%) of pulmonary complications. Infectious respiratory diseases were clearly more common than non-infectious etiologies, 86.1 and 7.6%, respectively. Pulmonary tuberculosis, as the leading cause, involved 542 cases (64.8%) and Pneumocystis jiroveci (P. jiroveci) was the second infectious agent that was found in 111 cases (13.2%). Among non- infectious causes, bronchiectasis and Chronic Obstructive Pulmonary Disease (COPD) exacerbation were on the top of the list, 21 of 64 (32.8%) and 18 0f 64 (28.1%), respectively. Many patients had more than one etiology. P. jiroveci had the highest tendency for dual infections (43 episodes). Conclusion: Pulmonary complications, especially infections are common among HIV cases in Iran, among them tuberculosis is the most common. Respiratory problems may be the first presentation of HIV infection. Clinicians should be aware about the risk of dual infections. Screening for HIV among all tuberculosis cases and vice versa is recommend. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Sinusitis is a common complaint in children with cystic fibrosis. However, the actual prevalence of chronic rhinosinusitis and its effect on the quality of life of children have not been well considered. Therefore, the objective of this study was to determine the effect of sinonasal quality of life in children with cystic fibrosis. Materials and methods: This study was a diagnostic study performed on 80 children with cystic fibrosis ranging from 2 to 20 years old, who were referred to the cystic fibrosis clinic of Masih Daneshvari Hospital from 2017–2018. The questionnaires used in this study were chronic rhinosinusitis screening questionnaire based on the European task force and the evaluation of the sinonasal quality of life was based on the SN-5 survey. Results: Of the 80 patients with fibrosis from 2 to 20 years old who were recruited in the study, 41 patients were female (51.3%) and 39 were male (48.8%). In 61 cases (76.3%), there was no chronic rhinosinusitis and 19 cases (23.8%) had chronic rhinosinusitis. The mean SN-5 score in 19 patients with chronic rhinosinusitis was 3.4105 and the mean score of patients without rhinosinusitis was 1.8426, with a P-value of 0.000. The mean SN-5 score was significant between the two groups. In patients with nasal congestion, there was a significant difference in quality of life factors such as sinus infection, nasal obstruction, and allergy symptoms (P<0.001). In patients with facial pain, there was a significant difference in quality of life factors such as sinus infection, nasal obstruction, allergic symptoms, and physical activity limitation (P <0.001). There was also a significant difference in the quality of life factors such as sinus infection, nasal obstruction, and allergy symptoms in patients with postnasal drip (P <0.001). Conclusion: In children with cystic fibrosis, the quality of life of sinonasal has a significant relationship with absence of chronic rhinosinusitis. This study showed that children with chronic renosinusitis have significantly lower quality of sinonasal life than children with chronic rhinosinusitis. The results demonstrated that quality of life scores in sinus infections, nasal obstruction, and allergy symptoms were significantly higher in patients with chronic rhinosinusitis than in those without chronic rhinosinusitis. The findings of this study are important for improving children’s health related quality of life, as it leads to promoting communication between the patient and the health care provider, identifying overlooked problems, monitoring the progress of the disease and the burden of treatment, and promoting interventions in the daily life of patients. [ABSTRACT FROM AUTHOR]

Purpose: The role of computed tomography (CT) scan, as a promising prognostic imaging modality in cystic fibrosis (CF), has been widely investigated, focusing on parenchymal abnormalities. The aim of the present study was to evaluate the diagnostic performance of thoracic vascular parameters on CT to detect pulmonary hypertension (PH). Material and methods: CF patients who contemporaneously underwent CT and echocardiography were retrospectively enrolled. Baseline characteristics in addition to pulmonary artery diameter (PAD) and pulmonary to aortic (PA/A) ratio were compared between cohorts with and without PH, based on the results of echocardiography separately in paediatric patients (< 18) and adults (≥ 18). Results: Of a total 119 CF patients, 39 (32.8%) had PH (paediatric: 23/78, 29.5%, adult: 16/41, 39%). In paediatric CF patients, mean age, HCo3, PCo2, and pulmonary artery diameter (PAD) were significantly higher in the PH group compared to the non-PH group. Mean pulmo however, only PAD remained as the independent predictor of PH based on multivariate analysis (overall: 22.86 mm [±3.86] vs. 18.43 mm [±4.72], p = 0.005, paediatric patients: 22.63 mm [±4.4] vs. 17.10 mm [±4.64], p = 0.03). Using a cut off of 19.25 mm, the diagnostic performance of PAD to detect PH was found to be as follows: sensitivity = 82%, specificity = 70%, and accuracy = 73.1%. No significant difference was demonstrated in PAD between PH and non-PH groups in adults with CF (23.19 [±3.60] vs. 21.34 [±3.49], p = 0.7). Conclusions: In CF patients, PAD revealed an age-dependent performance to detect PH. PAD can be applied to predict pulmonary hypertension in paediatric CF patients and may be recommended to be routinely measured on follow-up chest CT scan in childhood CF. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship program is a comprehensive, longitudinal program designed to improve and measure the appropriateness of antimicrobial use while increasing patients' safety, decreasing cost of patients' care, and combating emerging antimicrobial resistance. Antimicrobial resistance, specially emerging multidrug-resistance and extremely drugresistance gram negative bacteria, is an important concern in the modern world. This is particularly problematic since antimicrobials in production pipelines are not meeting the demand for the emerging resistance micro-organisms; in another word "we are running out of options". Indiscriminate use of antimicrobial may increase the risk for resistance, and drug toxicity. The aim of this study is to implement an evidence-based antimicrobial stewardship program in a tertiary referral hospital. This study will assure consistency of the stewardship program and measure outcomes to further assess the effectiveness of this program. Materials and Methods: After establishment of antimicrobial stewardship committee and endorsement of policies the program will be conducted in all hospital medical wards. In an observational study, all patients receiving antimicrobials included in the program will be closely monitored for primary and secondary outcomes. Hospital's antimicrobial resistance patterns are monitored periodically to assess improvement. The quality indicators will be assessed to ensure proper execution of the program over time. Results: As a study protocol, there are no results available to be reported at this time. Conclusion: We are expecting to observe significant reduction in cost of antibiotic use shortly after program execution. By more appropriate utilization of antibiotics patients' safety will be increased. Furthermore, we are expecting to detect improvement in antimicrobial resistance patterns. [ABSTRACT FROM AUTHOR]

Background: Cystic Fibrosis (CF) is a life-threatening recessive genetic disorder resulting from mutations in the gene encoding the fibrosis transmembrane conductance regulator protein (CFTR). The CF clinical phenotype shows wide variation ranging from severe disease in early childhood in those homozygous for the p.Phe508del mutation to absence of the vas deferens in otherwise healthy men homozygous for the p.Arg117His mutation. Materials and Methods: DNA was extracted from whole blood from 62 patients with CF. The CFTR mutation was determined by Allele-Specific PCR assay. The spearman and linear regression analysis were used to obtain the correlation between phenotype and genotype relationship. Results: Out of total 62 patients, 35 (56.4%) were male. The mean age of the patients was 15.56 ± 6.65 years. Mutations in CFTR were detected in 64.5% of the patients. The commonest mutations were p.Phe508del (33.9%), p.Arg117His; [5T] (5.64%), p.Arg117His; [7T] (4.03%) and p.Trp1282X (5.64%). Mutations p.Ile507del (4%), p.Gly542X (4%), p.Asn1303Lys (2.42%), c.489+1G>T (1.6%), p.Gly551Asp (1.6%) and c.1585-1G>A (1.6%) were also detected. Most mutations were detected in west and south of Iran, while p.Phe508del mutation was dominant mutation (75%) in east and southeast of Iran. The study showed either an association between this mutation with severity of disease and sex or an association between p.Arg117His mutations and age at diagnosis. Conclusion: The geographic distribution of gene mutation in Iranian cystic fibrosis patients was very heterogenic. In spite of the study that showed a correlation between p.Phe508del and severity of disease, to find any correlation between genotype and phenotype a broad and multi-centered study is recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Smoking is a known predisposing factor to exacerbations in CF patients. But the effects of second-hand tobacco smoking are not yet clear. Hence, this study determined the clinical and spirometric presentations and urinary cotinine levels among cystic fibrosis patients over seven years of age in relation to their parent's smoking history. Materials and Methods: In this cross-sectional comparative study, 58 consecutive cystic fibrosis patients older than seven years of age were enrolled. These patients were divided into two equal groups: those with second-hand tobacco smoking and those without. Pulmonary function tests and hospital admission rates were compared across the groups. Results: The mean hospital admission times were 5.1±2.4 in the group with passive smoking, and 2.6±1.3 times in the group without (P<0.001). The cotinine level was reversely correlated to time interval passed from previous admissions (P=0.001, r=-0.432) in passive smokers and (P=0.021, r=0.314) in non-passive smokers. In the analysis of FEV1 with urine, there was a significant but negative relation between FEV1 and cotinine (P= 0.002). Besides, in the analysis of FE25- 75 and urine cotinine, there was also a significant and negative relationship (P=0.001). Conclusion: From our findings, we conclude that pulmonary function tests and hospital admission rate in patients with cystic fibrosis are associated with urinary cotinine level and household second-hand tobacco smoking. [ABSTRACT FROM AUTHOR]

Background: Respiratory failure secondary to recurrent respiratory infections is the most common cause of death in Cystic fibrosis (CF). Objectives: To assess the efficacy of noninvasive positive pressure ventilation (NIPPV) on respiratory function, use of accessory respiratory muscles, ease of physiotherapy for respiratory clearance, quality of sleep and nutritional status in CF patients with respiratory failure. Methods: All CF patients admitted to the pediatric department of Masih Daneshvari hospital, Tehran from March 2015 to January 2016 were studied. The inclusion criteria were clinical evidence of respiratory distress and signs of respiratory acidosis. The exclusion criteria were nausea and vomiting, not tolerating NIPPV, need for intubation, pneumothorax, presence of giant bullous emphysema or decreased level of consciousness. Baseline spirometry and venous blood gas (VBG) was obtained before and after NIPPV. A simple questionnaire was filled out for the nutritional status, sleep quality, ease of physiotherapy for airway clearance and the volume of secretions after NIPPV compared to baseline. Paired samples t-test and Wilcoxon Signed Rank test in SPSS version 16 were used for the before and after comparison of numerical and ordinal variables, respectively. Results: Out of a total of 53 CF hospitalized patients 17 met the inclusion criteria. There were 10 (58.8%) males and 7 (41.1%) females with a mean age of 11 ± 4.57 (10 - 25) years, mean weight of 31.85 ± 10.11 (13 - 48) kg and mean BMI of 14.16 ± 2.71 (5.9 - 18). The mean Saturation of peripheral oxygen (SPO2), respiratory rate (RR) and mean partial pressure of CO2 (PCO2) of patients before the intervention were 75 ± 13.25% (52 - 90%), 32 ± 11.17 (22 - 55) mmHg and 55.20 ± 17.62 (30.3 - 108), mmHg respectively. A significant difference was noted after the intervention in SPO2, venous PCO2 and RR compared to baseline (P < 0.05). The change in sleep quality (P = 0.001), nutritional status (P = 0.001) and ease of physiotherapy for respiratory clearance (P = 0.008) after NIPPV was statistically significant while the change in use of accessory respiratory muscles (P = 0.785) and the volume of secretions (P = 0.1) was not significant. Conclusions: NIPPV in CF patients with respiratory failure can improve the respiratory function, sleep quality and nutritional status of patients. Also, NIPPV enhances airway clearance during respiratory physiotherapy. [ABSTRACT FROM AUTHOR]

Dyspnea is one of the most complaints in the pulmonary diseases. Shortness of breath as a subjective symptom can decrease the quality of life of patients. Although symptomatic treatment of the patients with chemical drugs is efficient in sign reduction, drugs side effect and allowing the disease to become chronic are risky for patients. Nowadays, traditional medicine is considered as an effective strategy in patients' treatment by World Health Organization. This study discusses the causes of shortness of breath from the view of Iranian traditional medicine and describes some suggestion for treatment of causes of this problem. Persian medicine prioritizes prevention of diseases by offering some strategies. In case of disease occurrence, life style modifications and herbal pharmaceutical therapy are recommended. [ABSTRACT FROM AUTHOR]

Respiratory failure is a serious complication of H1N1 influenza that, if not properly managed, can cause death. When mechanical ventilation is not effective, the only way to save the patient's life is extracorporeal membrane oxygenation (ECMO). A prolonged type of cardiopulmonary bypass, ECMO is a high-cost management modality compared to other conventional types and its maintenance requires skilled personnel. Such staff usually comprises the members of open-heart surgical teams. Herein, we describe a patient with H 1N1 influenza and severe respiratory failure not improved by mechanical ventilation who was admitted to Masih Daneshvari Medical Center in March 2015. She was placed on ECMO, from which she was successfully weaned 9 days later. The patient was discharged from the hospital after 52 days. Follow-up till 11 months after discharge revealed completely active life with no problem. There should be a close collaboration among infectious disease specialists, cardiac anesthetists, cardiac surgeons, and intensivists for the correct timing of ECMO placement, subsequent weaning, and care of the patient. This team work was the key to our success story. This is the first patient to survive H1N1 with the use of ECMO in Iran. [ABSTRACT FROM AUTHOR]

Hepatic toxicity is the most serious adverse effect of anti tuberculosis drugs. This study was performed to evaluate the efficacy of silymarin as a hepatoprotective herbal agent. In a randomized double blind clinical trial, 70 new cases of pulmonary tuberculosis were divided into two groups. The intervention group was assigned to receive silymarin and the control group received placebo. Tuberculosis was treated by classic regimen consisting isoniazid, rifampin, pyrazinamide and ethambutol. No statistically significant difference was found between the two groups concerning the frequency of drug induced liver injury or mild elevation of liver enzymes. Silymarin was safe without any major side effect. Our results showed no significant hepatoprotective effect of silymarin among patients on tuberculosis treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development of ‘allergic asthma’ in animals but their effects in COPD are unknown. Objective: To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation. Design: We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation. Results: Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05). Conclusions: This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD. [ABSTRACT FROM AUTHOR]