National Research Institute of Tuberculosis and Lung Diseases
Recent publications
Objective: The aim was to investigate the risk factors for relapse and death in patients with EGPA recruited at pneumonological center and mainly ANCA-negative. Methods: We retrospectively recruited 86 patients. Relapse was defined as the recurrence or appearance of new organ symptoms. The study endpoint included the final examination. Results: Relapses occurred in 34.9% of the patients, while 9.3% died. Immunosuppressive therapy (p = 0.042), prolonged low-dose corticosteroid treatments (mainly for asthma) (p = 0.006), and longer follow-up duration (p = 0.004) were associated with a higher relapse risk, while advanced EGPA severity (p = 0.0015) and activity (p = 0.044), older age of onset (p = 0.030), symptomatic cardiac involvement (p = 0.007), and post-inflammatory cardiac fibrosis (p = 0.038) were associated with a higher risk of death. Sinusitis (p = 0.028) and prolonged low-dose corticosteroid treatments (p = 0.025) correlated with a better prognosis. Relapses did not have an impact on the mortality (p = 0.693). Conclusion: Relapses in EGPA remain frequent, although they do not impact mortality. Cardiac involvement is common, but clinically symptomatic cardiomyopathy is associated with a higher risk of death. Asthma requiring chronic corticosteroid treatments is associated with a lower risk of death, although the risk of EGPA recurrence is significantly higher.
Background: Remdesivir is effective against SARS-Cov-2 with little evidence of its adverse effect on the cardiac system. The aim of the present study is investigating the incidence of bradycardia in COVID-19 patients treated with Remdesivir. Methods: This prospective longitudinal study was conducted in a tertiary center on COVID-19 patients for Remdesivir therapy. The objectives were to investigate the incidence of sinus bradycardia, and also the association between their demographics, underlying diseases, and the disease severity with developing bradycardia in COVID-19 patients treated with Remdesivir. Results: Of 177 patients, 44% were male. The mean (±standard deviation) age of patients was 49.79 ± 15.16 years old. Also, 33% were hospitalized due to more severe symptoms. Oxygen support was required for all hospitalized subjects. A total of 40% of the patients had comorbidities, with the most common comorbidity being hypertension. The overall incidence of bradycardia (heart rate<60 bpm) in patients receiving Remdesivir was 27%, of whom 70% had extreme bradycardia (heart rate <50 bpm). There was also a statistically significant reduction in heart rate after five doses of Remdesivir compared to the baseline heart rates. In the multivariable model, none of the covariates including age above 60 years, female sex, CRP>50 mg/L, O2 saturation<90%, underlying cardiovascular disease, hypertension and diabetes mellitus, and beta-blockers were associated with Remdesivir-induced bradycardia. No association was found between the COVID-19 severity indicators and bradycardia. Conclusion: As sinus bradycardia is a prevalent adverse cardiac effect of Remdesivir, it is recommended that all COVID-19 patients receiving Remdesivir, be evaluated for heart rate based on examination; and in the case of bradyarrhythmia, cardiac monitoring should be performed during administration to prevent adverse drug reactions.
Rodent models of lipopolysaccharide (LPS)–induced pulmonary inflammation are used for anti-inflammatory drug testing. We aimed to characterize mice responses to aerosolized LPS alone or with intraperitoneal (i.p.) delivery of alpha1-antitrypsin (AAT). Balb/c mice were exposed to clean air or aerosolized LPS (0.21 mg/mL) for 10 min per day, for 3 d. One hour after each challenge, animals were treated i.p. with saline or with (4 mg/kg body weight) one of the AAT preparations: native (AAT), oxidized (oxAAT), recombinant (recAAT), or peptide of AAT (C-36). Experiments were terminated 6 h after the last dose of AATs. Transcriptome data of mice lungs exposed to clean air versus LPS revealed 656 differentially expressed genes and 155 significant gene ontology terms, including neutrophil migration and toll-like receptor signaling pathways. Concordantly, mice inhaling LPS showed higher bronchoalveolar lavage fluid neutrophil counts and levels of myeloperoxidase, inducible nitric oxide synthase, IL-1β, TNFα, KC, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Plasma inflammatory markers did not increase. After i.p. application of AATs, about 1% to 2% of proteins reached the lungs but, except for GM-CSF, none of the proteins significantly influenced inflammatory markers. All AATs and C-36 significantly inhibited LPS-induced GM-CSF release. Surprisingly, only oxAAT decreased the expression of several LPS-induced inflammatory genes, such as Cxcl3, Cd14, Il1b, Nfkb1, and Nfkb2, in lung tissues. According to lung transcriptome data, oxAAT mostly affected genes related to transcriptional regulation while native AAT or recAAT affected genes of inflammatory pathways. Hence, we present a feasible mice model of local lung inflammation induced via aerosolized LPS that can be useful for systemic drug testing.
Purulent pericarditis (PP) is rare disease, and if left untreated, it is associated with very high mortality, nearly 100%. A considerable clinical problem due to PP is a very high probability of developing constrictive pericarditis (CP). Pericardial drainage is essential in the treatment of PP and should be performed urgently. The use of broad-spectrum antibiotic therapy is equally important. Unfortunately, fibrin deposits often create occulated spaces and reservoirs that reduce the penetration of antibiotics and their effectiveness. The rationale for the intrapericardial use of fibrinolytic drugs in PP is based on their ability to dissolve fibrin strands and collagen fibres, thus improving the penetration of antibiotics to the pericardial sac and lowering the risk of CP. The choice of the drug, as well as its dosage and the method of administration is still under debate. The authors of the article share their experiences and review current literature on this rare topic.
Background and aims: Due of its low cost, rapid speed, data record, and vast communication coverage, information and communication technology might be useful for health-related fields in times of crisis. By providing medical or hygienic services to a patient who lives elsewhere using communication methods like email, fax, cellphones, applications, and wireless gadgets, telemedicine can aid in the better management of diseases. Reviewing the potential role of telemedicine in the pandemic of infectious diseases with a focus on the Coronavirus disease 2019 (COVID-19) epidemic was the main goal of this study. Methods: "Google Scholar," "PubMed," "Science Direct," and "Scopus" databases were searched to collect the papers that identify the advantages and disadvantages of telemedicine in the disease pandemic. Searched keywords include: telepharmacy, telemedicine, remote communication, pandemic(s), epidemic, distant care, distant communication, phone consulation, video conference communication and patient education. Results: Information and communication technology are crucial, especially when dealing with pandemics of infectious diseases like COVID-19. Less "in-person" patient visits to hospitals as a result of telemedicine eventually means less labor for the medical staff, less viral exposure for patients, and ultimately less disease spread. By establishing a bidirectional reciprocal relationship between patients and healthcare providers although they are in separate geographical areas, it can improve patient health status. Conclusion: Governments are currently facing a significant budgetary burden because to the COVID-19 pandemic. Since patients are not sent to medical facilities in person, which could be a source of infection, telemedicine reduces disease spread while saving money.
Introduction: This study aimed to study the trend, histologic pattern, geographical distribution, and characteristics of nasopharyngeal carcinoma (NPC) and nasopharyngeal neoplasms (NPN) from 2003 to 2017 in Iran. Materials and methods: The Ministry of Health and Medical Education collected NPN cases from the corresponding university in each province and stored them in Iran National Cancer Registry (INCR) database. The Joinpoint program calculated the average annual percent change (AAPC) and its 95% confidence interval (CI). The jump model minimized the interfering effect of INCR transformation. Results: 3653 NPN cases were reported between 2003-2010 and 2014-2017, with a mean age of 49.04 ± 18.31 years and a male-to-female ratio of 2.15. The age-standardized incidence rate (ASIR) per 100,000 person-years was 0.30 for females and 0.68 for males in 2017. Although the ASIR/100,000 of NPN raised from 0.35 to 0.49 during 2003-2017, the trend was constant with an AAPC of -2% (95% CI: -4.8% to 0.9%). The age-specific incidence rate was highest in the older than 70 population (1.56/100,000). NPC formed 77.1% of NPNs and showed a constant pattern (AAPC CI: -5.7% to 0.2%), in contrast to the significant increase of non-keratinizing squamous cell carcinoma (AAPC CI: 2.3%to 24.5%). Conclusions: Nasopharynx cancer is rare in Iran, and NPC incidence remained constant from 2003 to 2017, unlike previously reported rising trend. However, non-keratinizing squamous cell carcinoma exhibited a significant increase, and future studies are needed to examine the role of the Epstein-Barr virus on this growth rate.
Background: Little is known about the association between Human Immunodeficiency Virus (HIV) infection and risk of death among hospitalized COVID-19 patients. We aimed to investigate this association using a multicenter study. Material and methods: This multicenter study was conducted using the registry database of Coronavirus Control Operations Headquarter from March 21, 2021 to January 18, 2020 in the province of Tehran, Iran. The interest outcome was COVID-19 death among hospitalized patients living with and without HIV. The Cox regression models with robust standard error were used to estimate the association between HIV infection and risk of COVID-19 death. The subgroup and interaction analysis were also performed in this study. Results: 326052 patients with COVID-19 were included in the study, of whom 127 (0.04%) were living with HIV. COVID-19 patients with HIV were more likely to be female, older, and to have symptoms such as fever, muscular pain, dyspnea and cough. The death proportion due to COVID-19 was 18 (14.17%) and 21595 (6.63%) among HIV and non-HIV patients, respectively. Patients living with HIV had lower mean survival time compared to those without HIV (26.49 vs. 15.31 days, P-value = 0.047). Crude risk of COVID-19 death was higher among HIV patients than in non-HIV group (hazard ratio[HR]: 1.60, 1.08-2.37). Compared to those without HIV, higher risk of COVID-19 death was observed among patients with HIV after adjusting for sex (1.60, 1.08-2.36), comorbidities (1.49, 1.01-2.19), cancer (1.59, 1.08-2.33), and PO2 (1.68, 1.12-2.50). However, the risk of COVID-19 death was similar in patients with and without HIV after adjusting for age (1.46, 0.98-2.16) and ward (1.30, 0.89-1.89). Conclusion: We found no strong evidence of association between HIV infection and higher risk of COVID-19 death among hospitalized patients. To determine the true impact of HIV on the risk of COVID-19 death, factors such as age, comorbidities, hospital ward, viral load, CD4 count, and antiretroviral treatment should be considered.
Background: Since the emergence of coronavirus disease 2019 (COVID-19), the treatment protocols are continuously updated, based on the evidence gathered all around the world and reported to the World Health Organization. Like many other emerging infectious diseases, using convalescent plasma from those recovered from the disease was a preliminary treatment approach that showed partial effectiveness for severe COVID-19 patients. Besides, blood filtration strategies, such as hemoperfusion and plasmapheresis, are employed to lessen the load of inflammatory molecules. However, few studies compared their effects to conclude which treatment might be more efficacious for COVID-19 patients. We compared the effects of plasmapheresis or plasma exchange, convalescent plasma therapy, and hemoperfusion on O2 saturation and inflammatory factors in COVID-19 patients. Methods: In this retrospective study, 50 COVID-19 patients received standard treatments based the international guidelines. Patients were divided into 4 groups: hemoperfusion, plasmapheresis, plasma therapy, and control. The control group received only the standard treatments. The mortality rate, O2 saturation, and laboratory factors were compared between the 4 groups. Results: We found a significant decrease in the C-reactive protein level following hemoperfusion (32.75 ± 23.76 vs 13 ± 7.54 mg/dL; p = 0.032) but not plasmapheresis and plasma therapy. Besides, serum levels of lactate dehydrogenase (p = 0.327, 0.136, 0.550, for hemoperfusion, plasmapheresis, and plasma therapy, respectively) and other inflammatory molecules did not significantly change following treatments. There is also no significant difference in the mortality rate between the treatment groups (p = 0.353). Conclusion: It seems that hemoperfusion, plasmapheresis, and plasma therapy did not have considerable effects on decreasing the inflammation and mortality rate compared with standard treatment.
The global COVID-19 vaccination had an undeniable influence on the pandemic management, despite of having reported rare but life-threatening side-effects of vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare autoimmune complication determined by thrombocytopenia and thrombosis propensity in the circulatory system. The activation of antibodies against platelet factor-4 (PF-4) which mimics the heparin-induced thrombocytopenia (HIT) characteristic is the main known pathogenicity of the disease. Herein, we reported a case of VITT in a middle-aged woman with no previous history of thrombophilia or other medical conditions who presented with thrombosis of the left superficial femoral artery 3-days after receiving the second dose of inactivated BBIBP-CorV (Sinopharm) vaccine. The patient underwent bypass vascular surgery and received none-heparin anticoagulation consistent with high-dose intravenous immunoglobin. Eight days after the discharge, she was subsequently referred to our center with the presentation of sub-massive pulmonary thromboembolism in spite of receiving the prophylactic anticoagulants during follow-up period. Details on side-effects of COVID-19 vaccines, specifically the inactivated ones are yet to be fully ascertained. Clinicians should consider the history of COVID-19 vaccines in thromboembolism patients who do not have well-acknowledged risk factors. Further studies about the necessity of prophylactic anticoagulants and clinical judgment for receiving other vaccines in such patients are required.
Background SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect this wide spectrum of disease presentations. Methods Our pilot cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls. We determined plasma levels of nine acute phase proteins (APPs) by nephelometry, and full-length (M65), caspase-cleaved (M30) cytokeratin 18, and ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif 13) by ELISA. In addition, we examined whole plasma N-glycosylation by capillary gel electrophoresis coupled to laser-induced fluorescence detection (CGE-LIF). Results When compared to controls, COVID-19 patients had significantly lower concentrations of ADAMTS13 and albumin (ALB) but higher M30, M65, α1-acid glycoprotein (AGP), α1-antitrypsin (AAT), ceruloplasmin (CP), haptoglobin (HP), and high-sensitivity C-reactive protein (hs-CRP). The concentrations of α1-antichymotrypsin (ACT), α2-macroglobulin (A2MG) and serum amyloid A (SAA) proteins did not differ. We found significantly higher levels of AAT and M65 but lower ALB in severe compared to moderate COVID-19 patients. N-glycan analysis of the serum proteome revealed increased levels of oligomannose- and sialylated di-antennary glycans and decreased non-sialylated di-antennary glycan A2G2 in COVID-19 patients compared to controls. Conclusions COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight complexity of inflammatory process and grant further investigations.
Objective The actual impact of the pandemic on COVID-19 specific mortality is still unclear due to the variability in access to diagnostic tools. This study aimed to estimate the excess all-cause mortality in Iran until September 2021 based on the national death statistics. Results The autoregressive integrated moving average was used to predict seasonal all-cause death in Iran (R-squared = 0.45). We observed a 38.8% (95% confidence interval (CI) 29.7%–40.1%) rise in the all-cause mortality from 22 June 2020 to 21 June 2021. The excess all-cause mortality per 100,000 population were 178.86 (95% CI 137.2–220.5, M:F ratio = 1.3) with 49.1% of these excess deaths due to COVID-19. Comparison of spring 2019 and spring 2021 revealed that the highest percent increase in mortality was among men aged 65–69 years old (77%) and women aged 60–64 years old (86.8%). Moreover, the excess mortality among 31 provinces of Iran ranged from 109.7 (Hormozgan) to 273.2 (East-Azerbaijan) per 100,000 population. In conclusion, there was a significant rise in all-cause mortality during the pandemic. Since COVID-19 fatality explains about half of this rise, the increase in other causes of death and underestimation in reported data should be concerned by further studies.
Background: Thymomas are characterized by a low tumor mutation burden and a paucity of actionable mutations. Clinical behavior can vary from relatively indolent to very aggressive and impact survival. Platinum-based chemotherapy is the primary treatment modality for inoperable disease and is palliative in intent. Patients with advanced thymoma frequently experience disease recurrence after frontline therapy. Treatment options for relapsed thymoma are relatively limited. A case of recurrent thymoma harboring a breast cancer gene 2 (BRCA2) mutation was presented for multidisciplinary discussion at the International Thymic Malignancy Interest Group (ITMIG) Tumor Board meeting. Case description: A 63-year-old female presented with Tumor Node Metastasis (TNM) stage I, World Health Organization (WHO) subtype B1 thymoma at diagnosis and underwent surgical resection. First recurrence occurred in the left costophrenic recess and was treated with preoperative external beam radiotherapy (EBRT), surgical excision, and post-operative chemotherapy. Histology was consistent with WHO subtype B2 thymoma and genomic analysis of the resected tumor detected a BRCA2 mutation. Second recurrence occurred in the mediastinum and bilateral pleurae. Mediastinal disease was treated with EBRT, and the pleural deposits were observed initially. However, upon further progression, the case was discussed at the ITMIG tumor board meeting to determine optimal second line therapy for this patient. Conclusions: A potential role of poly (ADP-ribose) polymerase (PARP) inhibitors versus cytotoxic chemotherapy for treatment of BRCA2-mutated recurrent thymoma merits discussion. However, due to the absence of data to support the functional and therapeutic significance of BRCA2 mutations in patients with thymoma, the potential for severe toxicity associated with PARP inhibitors, and availability of other safe and effective alternatives, other treatment options should be considered. PARP inhibitors can be considered for treatment of BRCA2-mutated thymomas as part of a clinical trial or when other treatment options have been exhausted.
Background Bioimpedance vector analysis (BIVA) has been suggested as a valuable tool in assessing volume status in critically ill patients. However, its effectiveness in guiding fluid removal by continuous renal replacement therapy (CRRT) has not been evaluated. Methods In this randomized controlled trial, 65 critically ill patients receiving CRRT were allocated on a 1:1 ratio to have UF prescribed and adjusted using BIVA fluid assessment in the intervention group (32 patients) or conventional clinical parameters (33 patients). The primary outcome was the lean body mass (LBM) water content at CRRT discontinuation, and the secondary outcomes included the mortality rate, urinary output, the duration of ventilation support, and ICU stay. Results The study group was associated with a lower water content of LBM (80.7 ± 9.4 vs. 85.9 ± 10.4%; p < 0.05), and a higher mean UF-rate and urinary output (1.5 ± 0.8 vs. 1.2 ± 0.5 ml/kg/h and 0.9 ± 0.9 vs 0.5 ± 0.6 ml/kg/h, both: p < 0.05). The mortality rate, the length of ICU stay, and ventilation support duration were similar. Conclusion BIVA guided UF prescription may be associated with a lower rate of fluid overload. Larger studies are required to evaluate its impact on patients' outcomes.
Objective Since evidence linking carbohydrate consumption to diabetic nephropathy (DN) is scarce, and the association between a low carbohydrate diet and DN has not been investigated, we sought to investigate whether a higher low carbohydrate diet score (LCD) is associated with DN among women. Methods In a case control study, 105 women with T2D and DN, and 105 controls with T2D and without DN, who attended at Kowsar diabetes clinic in Semnan, Iran, were matched for age and diabetes duration. The data related to anthropometric and biochemical measures were collected and a food frequency questionnaire (FFQ) with 147-item, was used to assess dietary intake. Based on the FFQ we calculated an LCD score for each study participant. Multivariate logistic regression was performed to examine the association between LCD score and the odds of developing DN. Results The results of the study demonstrated that the LCD score was not significantly associated with DN in the crude model (OR = 0.39; 95%CI: 0.14-1.07, P=0.06). However, after adjusting for several confounders, subjects in the top quartile of LCD score were associated with 71% lower risk of DN (OR = 0.29; 95%CI: 0.10-0.86, P=0.02). A significant trend toward decreased urinary albumin excretion (UAE) was found with an increase in the LCD score (P=0.005). Conclusion A diet low in carbohydrates was inversely associated with risk of DN. Further observational studies and preferably randomized-controlled trials are needed to confirm the present results.
Background Combined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions. Methods We analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM , STAT3 (AD-LOF) , DNMT3B/ZBTB24 , and WAS mutations. Results A total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity ( p=0.004 ). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM , STAT3 (AD-LOF) , DNMT3B/ZBTB24 , and WAS mutations, however ATM- mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity. Conclusion About 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.
In 2022, the National Program for Influenza Prevention coalition will have its 10th anniversary; it is one of Poland’s oldest educational initiatives. The National Program for Influenza Prevention was initiated to prevent a further decline and promote influenza prevention in the A(H1N1) post-pandemic years. In this review, we summarize the structure and operational model of the coalition and identify core functional elements that make it a key non-governmental organization involved in the prophylactics of communicable diseases. The coalition-based organization can operate in a complex environment, such as vaccinations requiring scientific, economic, social, and psychological involvement, and communications with different groups. Anchored to the history of the National Program for Influenza Prevention, we review Poland’s vaccination landscape changes from the last ten years.
Background Cognitive impairments are linked to poor treatment response and disease control in allergic asthma. However, there are no studies exploring attention-related functional brain alterations in allergic asthma. Here, we explore attention deficit and its association with clinical characteristics and common neuropsychiatric disorders in patients with allergic asthma. Methods We recruited 38 participants, equally distributed into healthy and asthma groups. Behavioral, neurophysiological, and lung function assessment tools were used in this study. Results Our behavioral data show that allergic asthma induces attention impairment. Additionally, the event-related potentials (ERP) analysis reveals that this attention deficit is associated with a disruption in cognitive processing capability in frontal brain areas. These behavioral and neurophysiological abnormalities were strongly correlated with disease severity and neuropsychiatric comorbidities of asthmatic patients. Conclusion Together, here we propose that disrupted neurophysiological responses in frontal brain areas might lead to attention impairments in patients with allergic asthma. These findings could help characterizing the neuro-pathophysiology of cognitive disorders in allergic asthma, possibly opening the way for development of novel treatment strategies.
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49 members
Masoud Shamaei
  • Department of Pathology
Mohammad Seyedmehdi
  • Chronic Respiratory Diseases Research Center
Majid Marjani
  • Clinical Tuberculosis and Epidemiology Research Center
Parvaneh Baghaei Shiva
  • Clinical Tuberculosis and Epidemiology Research Center
Mehran Marashian
  • CRDRC, RDRN
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Tehran, Iran