Publications by authors named "Ali Akbar Velayati"

145 Publications

Characterization of Clinical Isolates of Mycobacterium simiae Using Drug Susceptibility Tests and Molecular Analyses.

Curr Microbiol 2021 Apr 13. Epub 2021 Apr 13.

Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), World Health Organization Collaborating Centre, Shahid Beheshti University of Medical Sciences (Medical Campus), Darabad, PO 19575/154, Tehran, 19556, Iran.

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.
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http://dx.doi.org/10.1007/s00284-021-02486-wDOI Listing
April 2021

Combination therapy of IFNβ1 with lopinavir-ritonavir, increases oxygenation, survival and discharging of sever COVID-19 infected inpatients.

Int Immunopharmacol 2021 Mar 26;92:107329. Epub 2020 Dec 26.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Interferon Beta-1a (IFN-β1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-β1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-β1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-β1-a on outcome and all-cause mortality. 152 cases in IFN-β1-a group and 304 cases as control group were included. IFN-β1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-β1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-β1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-β1-a in COVID-19 treatment.
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http://dx.doi.org/10.1016/j.intimp.2020.107329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762801PMC
March 2021

A review on favipiravir: the properties, function, and usefulness to treat COVID-19.

Expert Rev Anti Infect Ther 2020 Dec 29:1-9. Epub 2020 Dec 29.

Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences , Tehran, Iran.

Introduction: At this time, there is no specific therapeutic or vaccine for treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, available drugs for treatment of other viral infections may be useful to treat COVID-19.

Areas Covered: The focus of the current review was studying the main characteristics of favipiravir and its usefulness to treat COVID-19. An electronic search was done by using Pubmed and Google scholar.

Expert Opinion: Based on the mechanism of action and safety of favipiravir, the drug may be a promising candidate for compassionate use against the SARS-CoV-2 infection. Favipiravir has a wide range of activity against many single-stranded RNA viruses, is well tolerated in humans and has a high barrier to resistance. However, high doses of the agent are necessary to obtain an efficient antiviral activity. Favipiravir is teratogen in pregnant women and associated with the hyperuricemia. Therefore, the administration of the drug should be well controlled. Investigating the antiviral prophylactic potency of favipiravir and search for its pro-drugs and/or analogs showing improved activity and/or safety are critical.
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http://dx.doi.org/10.1080/14787210.2021.1866545DOI Listing
December 2020

SARS-CoV‑2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms.

Wien Med Wochenschr 2021 Feb 14;171(1-2):3-6. Epub 2020 Dec 14.

Clinical Research Department, Pasteur Institute of Iran, No:69, Pasteur Ave, 1316943551, Tehran, Iran.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the ongoing pandemic, has spread into more than 200 countries to date. The disease which is caused by the virus is termed COVID-19. In most cases, it presents at first like common flu with cough and other respiratory symptoms. Nevertheless, other symptoms have been reported, such as a feeling of extreme fatigue, gastrointestinal symptoms, or acute onset of olfactory and gustatory dysfunction. Here we report a series of 10 cases (1 male, 9 females) observed between February and April 2020, with an undulating appearance and disappearance of symptoms. Weeks passed before the diagnosis was established. Symptoms resolved rapidly after treatment with hydroxychloroquine. It seems that the course of COVID-19 can be mild or moderate but with a long persistence of symptoms, and may therefore remain obscure. This may cause a public health issue because of the long infectivity of these patients.
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http://dx.doi.org/10.1007/s10354-020-00793-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734614PMC
February 2021

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

Tanaffos 2020 Nov;19(2):122-128

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127).

Materials And Methods: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU).

Results: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%).

Conclusion: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680520PMC
November 2020

Real Clinical Practice and Therapeutic Management Following COVID-19 Crisis in two Hospitals in Iran: A Statistical and Conceptual View.

Tanaffos 2020 Nov;19(2):112-121

Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680514PMC
November 2020

An Overview of Genetic Information of Latent Mycobacterium tuberculosis.

Tuberc Respir Dis (Seoul) 2021 Jan 30;84(1):1-12. Epub 2020 Oct 30.

Mycobacteriology Research (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mycobacterium tuberculosis has infected more than two billion individuals worldwide, of whom 5%-10% have clinically active disease and 90%-95% remain in the latent stage with a reservoir of viable bacteria in the macrophages for extended periods of time. The tubercle bacilli at this stage are usually called dormant, non-viable, and/or non-culturable microorganisms. The patients with latent bacilli will not have clinical pictures and are not infectious. The infections in about 2%-23% of the patients with latent status become reactivated for various reasons such as cancer, human immunodeficiency virus infection, diabetes, and/or aging. Many studies have examined the mechanisms involved in the latent state of Mycobacterium and showed that latency modified the expression of many genes. Therefore, several mechanisms will change in this bacterium. Hence, this study aimed to briefly examine the genes involved in the latent state as well as the changes that are caused by Mycobacterium tuberculosis. The study also evaluated the relationship between the functions of these genes.
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http://dx.doi.org/10.4046/trd.2020.0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801807PMC
January 2021

Human genetic background in susceptibility to tuberculosis.

Int J Mycobacteriol 2020 Jul-Sep;9(3):239-247

Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Tuberculosis (TB), especially in developing countries, is a major threat to human health. The pathogenesis of TB remains poorly understood, and <5%-10% of individuals infected with Mycobacterium tuberculosis (MTB) will develop clinical disease. The human genetic factors contributing to susceptibility or resistance to TB pathogenesis have been investigated by high-throughput and low-throughput association studies. Genetic polymorphisms of several genes including TLR, IGRM, VDR, ASAP1, AGMO, FOXP1, and UBLCP1 effect on the disease phenotype and also the outcome of TB treatment. Recently, microRNAs (miRNAs), which negatively regulated gene expression at the posttranscriptionally level, have gained increasing attention due to their altered expression in various human diseases, including some infections. They are crucial posttranscriptional regulators of immune response in both innate and adaptive immunity. It has been established in recent studies that the host immune response against MTB is regulated by many miRNAs, most of which are induced by MTB infection. Moreover, differential expression of miRNAs in TB patients may help distinguish between TB patients and healthy individuals or latent TB. In this review, we summarize and discuss the literature and highlight the role of selected single nucleotide polymorphisms and miRNAs that have been associated with TB infection.
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http://dx.doi.org/10.4103/ijmy.ijmy_118_20DOI Listing
August 2020

A Review on Remdesivir: A Possible Promising Agent for the Treatment of COVID-19.

Drug Des Devel Ther 2020 6;14:3215-3222. Epub 2020 Aug 6.

Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The novel coronavirus 2019 (2019-nCoV), formally named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel human infectious coronavirus. The disease caused by SARS-CoV-2 is named COVID-19. Development and manufacturing of specific therapeutics and vaccines to treat COVID-19 are time-consuming processes. At this time, using available conventional therapeutics along with other treatment options may be useful to fight COVID-19. In different clinical trials, efficacy of remdesivir (GS-5734) against Ebola virus has been demonstrated. Moreover, remdesivir may be an effective therapy in vitro and in animal models infected by SARS and MERS coronaviruses. Hence, the drug may be theoretically effective against SARS-CoV-2. Remdesivir is a phosphoramidate prodrug of an adenosine C-nucleoside. By entrance into respiratory epithelial cells in human, the prodrug is metabolized to a nucleoside triphosphate as the active form. The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP). The nucleoside analog is incorporated into the generating RNA strand and causes a delayed stop in the viral replication process. Knowledge about the potential efficacy of remdesivir against coronaviruses has been restricted to in vitro studies and animal models. However, information related to COVID-19 is rapidly growing. Several clinical trials are ongoing for the management of COVID-19 using remdesivir. In this study, characteristics of remdesivir and its usage for treatment of COVID-19 are reviewed based on an electronic search using PubMed and Google Scholar.
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http://dx.doi.org/10.2147/DDDT.S261154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425093PMC
August 2020

Caspofungin: a review of its characteristics, activity, and use in intensive care units.

Expert Rev Anti Infect Ther 2020 12 23;18(12):1213-1220. Epub 2020 Jul 23.

Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences , Tehran, Iran.

Introduction: Candidemia is the fourth frequent reason of healthcare-related bloodstream infections in critically ill patients. For initial management of (suspected) invasive candidiasis in critically ill patients, usage of an echinocandin, e.g. caspofungin, has been recommended.

Areas Covered: In this study, characteristics of caspofungin and its use in intensive care unit (ICU) patients are reviewed based on an electronic search using PubMed and Google scholar.

Expert Opinion: Caspofungin is a semisynthetic derivative from pneumocandin B and the first member of the echinocandins that was approved by the U.S. Food and Drug Administration (FDA) to fight fungal infection. Caspofungin inhibits the enzyme β(1,3)-D-glucan synthase of the fungal cell wall resulted in inhibition of the synthesis of β(1,3)-D-glucan. For critically ill patients, inter- and intraindividual variations affect the caspofungin concentration. The incidence rates and densities of candidemia in surgical ICUs may be higher than medical ICUs resulting in a higher burden of candidemia in surgical ICUs. However, the mortality rate in surgical ICU patients with candidemia is higher than that medical ICU patients due to differences in their underlying conditions.
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http://dx.doi.org/10.1080/14787210.2020.1794817DOI Listing
December 2020

Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients.

J Clin Immunol 2020 08 30;40(6):872-882. Epub 2020 Jun 30.

Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital condition characterized by a selective predisposition to infections caused by weakly virulent mycobacteria and other types of intra-macrophagic pathogens. The 16 genes associated with MSMD display a considerable level of allelic heterogeneity, accounting for 31 distinct disorders with variable clinical presentations and prognosis. Most of MSMD deficiencies are isolated, referred to as selective susceptibility to mycobacterial diseases. However, other deficiencies are syndromic MSMD, defined by the combination of the mycobacterial infection with another, equally common, infectious, specific phenotypes. Herein, we described a series of 32 Iranian MSMD cases identified with seven distinct types of molecular defects, all of which are involved in the interferon gamma (IFNγ) immunity, including interleukin IL-12 receptor-β1 (IL-12Rβ1) deficiency (fifteen cases), IL-12p40 deficiency (ten cases), and IL-23R deficiency (three cases), as well as IFNγ receptor 1 (IFNγR1) deficiency, IFNγ receptor 2 (IFNγR2) deficiency, interferon-stimulated gene 15 (ISG15) deficiency, and tyrosine kinase 2 (TYK2) deficiency each in one case. Since the first report of two MSMD patients in our center, we identified 30 other affected patients with similar clinical manifestations. As the number of reported Iranian cases with MSMD diagnosis has increased in recent years and according to the national vaccination protocol, all Iranian newborns receive BCG vaccination at birth, early diagnosis, and therapeutic intervention which are required for a better outcome and also prevention of similar birth defects. Therefore, we investigated the clinical and molecular features of these 32 patients. The current report also defined novel classes of pathological mutations, further expanding our knowledge of the MSMD molecular basis and associated clinical manifestations.
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http://dx.doi.org/10.1007/s10875-020-00813-7DOI Listing
August 2020

Non-coding RNAs and Exosomes: Their Role in the Pathogenesis of Sepsis.

Mol Ther Nucleic Acids 2020 Sep 15;21:51-74. Epub 2020 May 15.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA 02114, USA; Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa. Electronic address:

Sepsis is characterized as an uncontrolled host response to infection, and it represents a serious health challenge, causing excess mortality and morbidity worldwide. The discovery of sepsis-related epigenetic and molecular mechanisms could result in improved diagnostic and therapeutic approaches, leading to a reduced overall risk for affected patients. Accumulating data show that microRNAs, non-coding RNAs, and exosomes could all be considered as novel diagnostic markers for sepsis patients. These biomarkers have been demonstrated to be involved in regulation of sepsis pathophysiology. However, epigenetic modifications have not yet been widely reported in actual clinical settings, and further investigation is required to determine their importance in intensive care patients. Further studies should be carried out to explore tissue-specific or organ-specific epigenetic RNA-based biomarkers and their therapeutic potential in sepsis patients.
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http://dx.doi.org/10.1016/j.omtn.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272511PMC
September 2020

Association of specific viral infections with childhood asthma exacerbations.

Interv Med Appl Sci 2019 Mar;11(1):17-20

Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Asthma exacerbations may occur due to a variety of triggers including respiratory viruses. The aim of this study was to determine the role of particular viral infections in asthma exacerbations in children.

Materials And Methods: The study was performed at Dr. Daneshvari Hospital Pediatric Emergency Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2014 and 2015. A nasopharyngeal aspirate or swab was obtained from each patient during admission. All samples were maintained at 4 °C until submission to the virology laboratory and were tested for respiratory viruses by nucleic acid testing.

Results: A total of 60 patients with asthma exacerbations were recruited for this study. Of the 60 samples collected from the patients with acute asthma exacerbations, rhinovirus was detected in 12 patients (20%), respiratory syncytial virus in 5 (8%), adenovirus in 5 (8%), and influenza virus in 1 (1.6%). Respiratory pathogens were not detected in 37 (61%) samples. All the samples investigated showed single viral infection.

Conclusions: To conclude, the most common viruses detected were rhinovirus followed by respiratory syncytial virus (RSV) and adenovirus. RSV was more commonly associated with more severe attacks. Both the study design (e.g., time of sampling, age of the patients, etc.) and also the method used for viral detection influence the frequency of detection of the respiratory viruses.
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http://dx.doi.org/10.1556/1646.10.2018.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044566PMC
March 2019

Pulmonary complications of predominantly antibody immunodeficiencies in a tertiary lung center.

Interv Med Appl Sci 2019 Mar;11(1):1-7

Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: Respiratory infections are expressed very soon in the life in humoral immunodeficiencies and often lead to chronic irreversible complications such as bronchiectasis and chronic airflow limitation. This study was conducted to evaluate the pulmonary complications of predominantly antibody immunodeficiencies to show the benefits of timely diagnosis and appropriate therapy.

Patients And Methods: The information of 48 patients involved with a type of predominantly antibody immunodeficiencies, including sex, type of primary immunodeficiency, age at the onset of symptoms, age at diagnosis, recurrent infections, respiratory symptoms, and pulmonary radiological and functional abnormalities were recorded and analyzed.

Results: In 48 patients evaluated, the mean age at diagnosis was 25.63 years. The mean diagnostic delay was estimated to be 13.62 years. The most recurring clinical manifestations, sinusitis (69.6%), otitis (43.5%), and recurrent pneumonia were the cause of frequent admissions in 68.8% of these patients. Bronchiectasis was frequently found (58.3%) in these patients mostly involving the middle and lower lobes (48.8% and 41.5%, respectively).

Conclusions: Respiratory complications, infectious or non-infectious, determine the prognosis of the disease in patients with predominantly antibody immunodeficiencies. Timely diagnosis and appropriate management may improve life expectancy and the quality of life in these patients.
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http://dx.doi.org/10.1556/1646.10.2018.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044568PMC
March 2019

Prevalence of Mycobacterium abscessus among the Patients with Nontuberculous Mycobacteria.

Arch Iran Med 2020 03 1;23(3):163-168. Epub 2020 Mar 1.

Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 Ι 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.
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March 2020

A novel evaluation of genetic polymorphism in BCG adenitis.

Turk J Pediatr 2019 ;61(3):466-470

Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran.

Hassanzad M, Farnia P, Darougar S, Velayati AA. A novel evaluation of genetic polymorphism in BCG adenitis. Turk J Pediatr 2019; 61: 466-470. Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine which has been used to prevent tuberculosis, according to the World Health Organization (WHO) recommendation in parts of the world with an incidence of tuberculosis infection more than 1%. The incidence of BCG adverse reactions differs between regions with regional lymphadenitis as the most common presentation. The aim of this study was to detect the impact of polymorphisms causing BCG lymphadenitis in children receiving BCG vaccination at birth. Eight healthy infants with BCG adenitis from 4 to 12 months old were enrolled. All these patients underwent a thorough physical examination, abdominopelvic ultrasound evaluation to detect distant lymphadenopathies and immunodeficiency screening tests for any possible underlying immunodeficiency disorders. Then genotyping for known mutations was performed using restriction fragments length polymorphism (PCR-RFLP) assays. Sequencing was performed for IL-12 Rβ1, IFN-ϒ receptor 1, IL-10, TNF-α and P2X7. The mean age of onset of the adenitis was 6.5 months. TNF-857, IL-12Rβ1 705, IL-10 1082, and IFN-ϒ- 56 single nucleotide polymorphisms (SNPs) were common in the children studied. The most frequent polymorphism found in the patients with BCG adenitis except one, was the P2X7 -762 polymorphism. To conclude, these polymorphisms are more common in some ethnic populations but not others and make the genetic basis of immunity to BCG strains and the occurrence of post-BCG lymphadenitis in otherwise healthy children.
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http://dx.doi.org/10.24953/turkjped.2019.03.026DOI Listing
July 2020

Disseminated Bacille Calmette-Guérin infection at a glance: a mini review of the literature.

Adv Respir Med 2019 ;87(4):239-242

Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis in children with specific primary immunodeficiencies.

Material And Methods: We conducted a systematic review of clinical practice articles by searching Medline, PubMed, Embase, Scopus, Web of Science and Google Scholar from their inception to date.

Results: Thirty-seven articles were included regarding BCG vaccination and its dissemination in children with primary immunodeficiencies. Articles on dissemination after intravesicular BCG were excluded from the study.

Conclusions: Since disseminated BCG vaccination may be the first manifestation of a primary immunodeficiency disease, a comprehensive search for immunological defects in children developing these problems after BCG vaccination seems rational.
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http://dx.doi.org/10.5603/ARM.2019.0040DOI Listing
February 2020

Evaluation of Quality of Life in Terms of Sinonasal Symptoms in Children with Cystic Fibrosis.

Biomol Concepts 2019 Jun 17;10(1):91-98. Epub 2019 Jun 17.

Mycobacteriology Research Center, National, Tehran, Iran.

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.
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http://dx.doi.org/10.1515/bmc-2019-0011DOI Listing
June 2019

Evaluation of Silymarin for management of anti-tuberculosis drug induced liver injury: a randomized clinical trial.

Gastroenterol Hepatol Bed Bench 2019 ;12(2):138-142

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 anti-tuberculosis 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536020PMC
January 2019

Study Protocol on Antimicrobial Stewardship in a Tertiary Respiratory Referral Hospital.

Tanaffos 2018 Mar;17(3):183-187

Clinical Tuberculosis and Epidemiology Research Center, NIRTLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 drug-resistance 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428375PMC
March 2018

Fungal epidemiology in cystic fibrosis patients with a special focus on Scedosporium species complex.

Microb Pathog 2019 Apr 8;129:168-175. Epub 2019 Feb 8.

Center of Expertise in Microbiology, Infection Biology and Antimicrobial Pharmacology, Tehran, Iran.

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.
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http://dx.doi.org/10.1016/j.micpath.2019.02.009DOI Listing
April 2019

Etiology of Respiratory Complications among Iranian HIV Infected Patients.

Tanaffos 2019 Feb;18(2):96-103

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 CD cell count was 90±131 ×10 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 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. 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230122PMC
February 2019

CT-measured pulmonary artery diameter as an independent predictor of pulmonary hypertension in cystic fibrosis.

Pol J Radiol 2018 23;83:e401-e406. Epub 2018 Aug 23.

Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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, HCo, PCo, 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], = 0.005, paediatric patients: 22.63 mm [±4.4] vs. 17.10 mm [±4.64], = 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], = 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.
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http://dx.doi.org/10.5114/pjr.2018.79204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334125PMC
August 2018

Reappraisal of Frequency of Common Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Iranian Cystic Fibrosis Patients.

Tanaffos 2018 Feb;17(2):73-81

Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Disease, (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 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 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320558PMC
February 2018

TNFα -857 C/T and TNFR2 +587 T/G polymorphisms are associated with cystic fibrosis in Iranian patients.

Eur J Med Genet 2019 Nov 22;62(11):103584. Epub 2018 Nov 22.

Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Identification of modifier genes influencing phenotype of cystic fibrosis (CF) patients has become a challenge in CF pathophysiology, prognostic estimations and development of new therapeutic strategies. The aim of this study was to explore the association between four genetic polymorphisms of three modifier genes with CF, by comparing their alleles, genotypes and haplotype frequencies in patients and controls. In this favor, two regulatory polymorphic loci in TNFα promoter (-857C/T, rs1799724 and -238A/G, rs361525) and two functional polymorphic loci in TNFR1 (+36A/G, rs767455) and TNFR2 (+587T/G, rs1061622) were genotyped in 70 patients and 79 controls, using PCR-RFLP. Clinical pulmonary data were also recorded from all studied patients. Results indicated that an association was observed between both T allele and CT/TT genotypes of TNFα (P = 0.0005, OR = 7.06, 95% CI = 3.71-13.45) with CF under dominant model of inheritance. GG genotype of TNFR2 +587 (P = 0.0005, OR = 4.92, 95%CI = 2.34-10.34) was significantly associated with CF using recessive model. Consistently, more severe pulmonary disorder was found for patients carrying either T dominant allele of TNFα -857 or GG genotype of TNFR2 +587 polymorphic sites. Despite an association of A-T and G-T haplotypes with CF, no significant association was found between these haplotypes and clinical parameters of CF. Overall, TNFα -857 T allele and GG genotype of TNFR2 +587 were more frequent in CF patients compared to healthy controls and hence, they showed an association with CF and severe pulmonary phenotype in Iranian patients.
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http://dx.doi.org/10.1016/j.ejmg.2018.11.018DOI Listing
November 2019

Pulmonary Function and Hospital Admission in Patients with Cystic Fibrosis Based on Household Second-Hand Smoking.

Tanaffos 2018 Jan;17(1):37-41

Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 FE 25-75 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087526PMC
January 2018

Good's Syndrome-Association of the Late Onset Combined Immunodeficiency with Thymoma: Review of Literature and Case Report.

Iran J Allergy Asthma Immunol 2018 Feb;17(1):85-93

Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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February 2018

Drug-resistant Mycobacterium tuberculosis: Epidemiology and role of morphological alterations.

J Glob Antimicrob Resist 2018 03 16;12:192-196. Epub 2017 Oct 16.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden. Electronic address:

In this brief review, various forms of drug-resistant tuberculosis (DR-TB) are discussed. The focus of the study is to highlight morphological alterations of DR-TB bacilli at the cellular level.
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http://dx.doi.org/10.1016/j.jgar.2017.10.006DOI Listing
March 2018