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A fourteen-day experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS): An Iranian treatment protocol

Abstract: Abstract View references (9) COVID-19 is currently causing concern in the medical community as the virus is spreading around the world. It has a heavy global burden, particularly in low-income countries. The clinical spectrum of COVID-19 pneumonia ranges from mild to critically ill cases and Acute Respiratory Distress Syndrome. An expert panel was held and an internal protocol was developed to manage the COVID-19 induced ARDS according to WHO recommendations and NIH guidelines. Different therapeutic regimens were employed on this protocol based on the ARDS severity and the patients’ special characteristics. The mortality rate, the rate of survivors, and non-survivors were reported. Of the 231 suspected cases of COVID-19 admitted to the hospital during two weeks, 72 patients were admitted to ICU with diagnosis confirmed by RT-PCR. In total, mortality in the ICU was 25% (n = 18) among ARDS patients over two weeks. COVID-19 induced ARDS is a major concern. The rapid progression of ARDS needs specific protocol based on patients’ characteristics and rapid action. © 2020, Iranian Journal of Pharmaceutical Research. All rights reserved.

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Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial

Abstract: Abstract View references (68) Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). The study endpoints were all-cause mortality rate, changes in oxygen-support level, oxygen saturation, body temperature, respiratory rate, and laboratory variables during the study, and drug safety. Of 126 patients enrolled, 86 had severe and 40 had critical disease. Most patients were male (63.49%) and aged below 65 (78.57%). By day 14 of the study, 4.65% (4/86) of severe patients and 50.00% (20/40) of critical patients died. By the end, 6.98% (6/86) of severe patients and 60.00% (24/40) of critical patients died. Outcomes concerning three additional endpoints (oral temperature, oxygen saturation, and respiratory rate) were significantly improved as early as three days after tocilizumab administration in both groups of subjects, more considerably in severe patients. Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure. © 2020

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Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial

Abstract:Abstract Background: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. Methods: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. Results: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. Conclusions: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage. © 2020 Elsevier B.V.

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Demographics, laboratory parameters and outcomes of 1061 patients with coronavirus disease 2019: a report from Tehran, Iran

Abstract:We aimed to determine the characteristics of coronavirus disease 2019 (COVID-2019) among the Iranian population. In this study, we collected and analysed the demographics, laboratory findings and outcomes of patients with COVID-19 who were admitted to Masih Daneshvari Hospital in Tehran, Iran between 20 February 2020 and 2 April 2020. Among 1061 patients, 692 (65.2%) were male and the median age was 55 years (interquartile range (IQR), 44–66 years). Totally, 129 (12.2%) patients died during hospitalization in the ward or intensive care unit. From the remaining 932 individuals, 46 (5.0%) were admitted to the intensive care unit and 886 (95.0%) were hospitalized in the ward. Those patients who died were significantly older than those hospitalized in the ward (p < 0.001). The median absolute number of lymphocytes was 1.2 × 103/μL (IQR 0.9 × 103 to 1.6 × 103/μL) and 708 (66.7%) patients had lymphopenia (absolute lymphocyte count <1500/μL). Among the laboratory tests, D-dimer, serum ferritin and albumin had the strongest correlations with mortality (r = 0.455, r = 0.412, r = –0.406, respectively; p < 0.001 for each one). In conclusion, laboratory findings could provide useful information with regard to the management of individuals with COVID-19. © 2020 The Authors

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

Abstract:Introduction: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapeutic strategy for the coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). There are inconclusive data in this regard and causes of VV-ECMO failure are not yet understood well. Case Series: Here, seven patients with COVID-19-induced ARDS who underwent VV-ECMO introduced and causes of VV-ECMO failure discussed. Medical records of seven COVID-19 patients treated with VV-ECMO were retrospectively evaluated to determine the clinical outcomes of VV-ECMO. Oxygenator failure occurred in four patients whom needed to oxygenator replacement. Successful VV-ECMO decannulation was done in three patients, however finally one patient survived. Conclusions: Hypercoagulability state and oxygenator failure were the most main etiologies for VV-ECMO failure in our study. All patients with COVID-19 undergoing VV-ECMO should be monitored for such problems and highly specialized healthcare team should monitor the patients during VV-ECMO. © 2020 Wiley Periodicals LLC

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Prevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID-19 patients

Abstract:Background: Considerable evidence suggests that smell dysfunction is common in coronavirus disease-2019 (COVID-19). Unfortunately, extant data on prevalence and reversibility over time are highly variable, coming mainly from self-report surveys prone to multiple biases. Thus, validated psychophysical olfactory testing is sorely needed to establish such parameters. Methods: One hundred severe acute respiratory syndrome?coronavirus-2 (SARS-CoV-2)-positive patients were administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT) in the hospital near the end of the acute phase of the disease. Eighty-two were retested 1 or 4 weeks later at home. The data were analyzed using analysis of variance and mixed-effect regression models. Results: Initial UPSIT scores were indicative of severe microsmia, with 96% exhibiting measurable dysfunction; 18% were anosmic. The scores improved upon retest (initial test: mean, 21.97; 95% confidence interval [CI], 20.84-23.09; retest: mean, 31.13; 95% CI, 30.16-32.10; p 0.0001); no patient remained anosmic. After 5 weeks from COVID-19 symptom onset, the test scores of 63% of the retested patients were normal. However, the mean UPSIT score at that time continued to remain below that of age- and sex-matched healthy controls (p 0.001). Such scores were related to time since symptom onset, sex, and age. Conclusion: Smell loss was extremely common in the acute phase of a cohort of 100 COVID-19 patients when objectively measured. About one third of cases continued to exhibit dysfunction 6 to 8 weeks after symptom onset. These findings have direct implications for the use of olfactory testing in identifying SARS-CoV-2 carriers and for counseling such individuals with regard to their smell dysfunction and its reversibility. © 2020 ARS-AAOA, LLC

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Molecular identification, phylogenetic analysis and antifungal susceptibility patterns of Aspergillus nidulans complex and Aspergillus terreus complex isolated from clinical specimens

Abstract:Objective: Aspergillus sections Terrei and Nidulantes are the less common causes of invasive aspergillosis and pulmonary aspergillosis (PA) in immunocompromised patients when compared to A. fumigatus and A. flavus. Identifying these fungi as the infectious agent is crucial because of the resistance to amphotericin B (AMB) and increased lethality. The aim of this study was to identify the molecular status, evaluate the genetic diversity and examine the antifungal susceptibility profile of the uncommon Aspergillus species. Forty-five uncommon Aspergillus species were identified based on the microscopic and macroscopic criteria. Then, the molecular identification was performed using the sequencing beta tubulin (benA) gene. In vitro antifungal susceptibility to amphotericin B (AMB), itraconazole (ITC), ravuconazole (RAV), voriconazole (VRC), caspofungin (CFG) isavuconazole (ISA) and posaconazole (POS) test was performed according to the CLSI M38-A2 guidelines. Results: A. terreus was the most species detected, followed by A. nidulans, A. latus, A. ochraceus, and A. citrinoterreus, respectively. The analysis of the benA gene showed the presence of 12 distinct genotypes among the A. terreus isolates. The other species did not show any intraspecies variation. CFG exhibited the lowest MEC50/MIC50 (0.007 μg/mL), followed by POS (0.125 μg/mL), VRC, ITC, ISA (0.25 μg/mL), RAV (0.5 μg/mL), and AMB (8 μg/mL). Among all the isolates, only 15.5% (7/45) were susceptible to AMB. Conclusion: Antifungal susceptibility pattern of the uncommon Aspergillus species is useful to improve patient management and increase knowledge concerning the local epidemiology. Moreover, this information is necessary when an outbreak dealing with drug-resistant infections occurs. © 2020 Elsevier Masson SAS

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The efficiency of the polymerase chain reaction methods for the detection of common pathogens in patients with chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term breathing problems and poor airflow. It tends to worsen or progress over time. Some COPD cases may also develop bacterial infections, such as Haemophilus influenzae (Hi), Streptococcus pneumoniae (Sp), Mycoplasma pneumoniae (Mp), and Chlamydia pneumoniae (Cp). The present study aimed at employ the molecular methods conventional polymerase chain reaction (PCR) and real-time PCR as two complementary and more sensitive methods for detecting such infections. METHODS: This is a descriptive cross-sectional study, for which a total of 109 samples of respiratory secretion were collected from the COPD patients suspected of having bacterial infection under the supervision of a pulmonologist. Then, the samples were subject to DNA extraction. The next step included some molecular experiments using available kits and specially designed primers. Finally, they were analyzed through statistical tests. RESULTS: There was no significant difference in terms of gender (P value >0.05). The patients aged 62.4±12.2 on average. In the case of Mp, 3 out of 109 subjects were found to be positive using the kits, while two ones proved to be positive using the primers (the second method). In the case of Hi, 12 and 9 subjects were positive by using standard kits and employing second method, respectively. The obtained relative frequencies for Mp and Hi were respectively 3% and 11%. CONCLUSIONS: Overall, the methods under study proved efficient in terms of sensitivity and accuracy as compared to both traditional/conventional methods and similar research findings. In addition, PCR with the designed primers exhibited acceptable results in terms of sensitivity and specificity as compared to PCR with commercial kits. © 2020 EDIZIONI MINERVA MEDICA.

We evaluated the potential role of IL-2 in whole blood stimulated with Mycobacterium tuberculosis-specific antigens in the QuantiFERON-TB Gold In Tube (QFT-G-IT) for the discrimination of active and latent tuberculosis. In this study, patients were recruited from the infectious diseases ward at the Masih Daneshvari Hospital, National Research Institute of Tuberculosis and Lung Diseases (NRITD), affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran. Individuals were classified as having active TB when the diagnosis was confirmed by positive M. tuberculosis culture from sputum specimens and positive response to QFT-G-IT test. LTBI was defined as a positive response to QFT-G-IT in the absence of symptomatic, microbiological, or radiological evidence of active tuberculosis. Healthy controls were BCG vaccinated individuals with no known exposure to M. tuberculosis and a negative response to the QFT-G-IT. We do not include in the study individuals who had positive human immunodeficiency virus screening result. The study received approval from the Ethical Committee of Tehran University of medical sciences.

In this study, thirty patients with active TB and 30 cases with LTBI had positive QFT-G-IT test and all of the controls (N = 30) had negative QFT-G-IT result. After 72-h of stimulation by antigens from the QFT-G-IT assay, IL-2 secretion was quantitated in supernatants by using ELISA (Mabtech AB, Sweden). All the plasma specimens were tested in duplicate and expressed in pg/ml. The differences in levels of IL-2 among groups were analyzed using non-parametric analysis of variance with the Kruskall–Wallis test. As shown in Fig. 1, LTBI group induced significantly greater production of IL-2 than patients with active TB infection (P value = 0.019, Kruskal–Wallis test). The discrimination performance (assessed by the area under ROC curve) between LTBI and patients with active TB was 0.816 (95%CI: 0.72–0.97) (Fig. 2). Cut-offs were estimated at various sensitivities and specificities and at the maximum Youdens index (YI), i.e. sensitivity specificity–1. Maximum discrimination was reached at a cut-off of 13.9 pg/mL for IL-2 following stimulation with 82% sensitivity, 86% specificity, 85% PPV and 83% NPV.

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The Immune Response and Immunopathology of COVID-19

Abstract:Coronaviruses were first discovered in the 1960s and are named due to their crown-like shape. Sometimes, but not often, a coronavirus can infect both animals and humans. An acute respiratory disease, caused by a novel coronavirus (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 previously known as 2019-nCoV) was identified as the cause of coronavirus disease 2019 (COVID-19) as it spread throughout China and subsequently across the globe. As of 14th July 2020, a total of 13.1 million confirmed cases globally and 572,426 deaths had been reported by the World Health Organization (WHO). SARS-CoV-2 belongs to the β-coronavirus family and shares extensive genomic identity with bat coronavirus suggesting that bats are the natural host. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003. It mainly spreads through the respiratory tract with lymphopenia and cytokine storms occuring in the blood of subjects with severe disease. This suggests the existence of immunological dysregulation as an accompanying event during severe illness caused by this virus. The early recognition of this immunological phenotype could assist prompt recognition of patients who will progress to severe disease. Here we review the data of the immune response during COVID-19 infection. The current review summarizes our understanding of how immune dysregulation and altered cytokine networks contribute to the pathophysiology of COVID-19 patients. © Copyright © 2020 Mortaz, Tabarsi, Varahram, Folkerts and Adcock.

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Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis

Abstract:Background: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. Methods: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. Findings: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0–2·9) for all patients with HIV-infection, 1·8 (1·5–2·2) for HIV-positive patients on ART, and 4·2 (3·0–5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. Interpretation: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. Funding: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America. © 2020 Elsevier Ltd

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COVID-19-Related severe heterogeneous acute respiratory distress syndrome: A therapeutic challenge

Abstract:Background: A heterogeneous pattern was detected in COVID-19 severe acute respiratory distress syndrome (ARDS) patients. The aim of this study was to define special features and individualized treatment modalities for this fatal infectious disease. Methods: Thirty-six patients diagnosed as COVID-19 severe ARDS were chosen. Lung mechanics (compliance), the extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI), and serum concentrations of immunology markers (interleukin [IL]-1β, IL-6, IL-8, ferritin, and C-reactive protein) were measured. Accordingly, individualized treatment consisting of Actemra, hemoperfusion (HP), continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO) was implemented for each patient. Results: Patients were categorized according to the lung compliance: 18 in L type with compliance >40 cc/cmH2O and 18 in H type with compliance ≤40 cc/cmH2O. In 16 patients, standard mechanical ventilation management and antiviral therapy were unsuccessful; therefore, hemodynamic and immunity responses were evaluated. Results of transpulmonary thermodilution in L-type patients surprisingly showed EVLWI = 8.8 ± 1.3 (6.9-9.7) and PVPI = 2.4 ± 0.1 (2.2-2.6). In the H-type patients, five cases showed EVLWI = 8.7 ± 0.8 (7.5-9.8) and PVPI = 2.6 ± 0.3 (2.1-2.8) which were subclassified as Ha type and five cases with EVLWI = 17.5 ± 1.9 (15.7-20.6) and PVPI = 3.9 ± 0.4 (3.5-4.5) were named Hb type. By measuring immunologic markers, these two groups were subdivided into high and low marker groups. Individualized treatment resulted in 2 survivals with Actemra, 1 with HP, 2 with HP + CRRT, and 1 with ECMO. Conclusion: According to the heterogeneity of COVID-19 severe ARDS presentation, which is due to various immunologic and hemodynamic responses, a systematic approach is an important and relatively successful strategy in choosing the appropriate treatment modality. © 2020 Medknow.

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Proteomic and genomic biomarkers for Non-Small Cell Lung Cancer: Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin

Abstract:Background: The development of lung cancer is a multifactorial process that involves the environmental and genetic factors. The mortality rate of this cancer is higher than breast, colorectal, and prostate cancers. In this study, we try to analyze the proteome of patients with Non-Small Cell Lung Cancer (NSCLC) and compare it with the healthy samples. Methods: This study has compared 30 lung tissue samples from patients with NSCLC and 30 healthy samples using proteomics and RT-PCR. Hence, tissue samples were obtained from the surgical ward in sterile conditions, and then, protein extraction applied to them. At the next stage, two-dimensional electrophoresis and mass spectrometry LCMS/MS were performed for protein isolation and sequencing, respectively. Results: The proteome analysis identified more than 40 differences in proteomic pattern of normal lung tissues compared to lung tissues with NSCLC. Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin proteins were identified. Molecularly, it has also been shown that the two main proteins of Peroxiredoxin-2 and Alpha-1 antitrypsin were upregulated, and the expression of Haptoglobin protein was downregulated in cancer tissue. Conclusion: The results of this study showed that there are some differences in term of protein content between the normal and cancerous lung tissues. Further studies are needed to evaluate these proteins that investigate whether these proteins can candidate as biomarkers to use in the early diagnosis of patients with NSCLC. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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COVID-19 and substance use disorders: Recommendations to a comprehensive healthcare response. an international society of addiction medicine practice and policy interest group position paper

Abstract:Coronavirus Disease 2019 (COVID-19) is escalating all over the world and has higher morbidities and mortalities in certain vulnerable populations. People Who Use Drugs (PWUD) are a marginalized and stigmatized group with weaker immunity responses, vulnerability to stress, poor health conditions, high-risk behaviors, and lower access to health care services. These conditions put them at a higher risk of COVID-19 infection and its complications. In this paper, an international group of experts on addiction medicine, infectious diseases, and disaster psychiatry explore the possible raised concerns in this issue and provide recommendations to manage the comorbidity of COVID-19 and Substance Use Disorder (SUD). © 2020 Iran University of Medical Sciences. All rights reserved.

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Prevalence and Mechanisms of Carbapenem Resistance in Acinetobacter baumannii: A Comprehensive Systematic Review of Cross-Sectional Studies from Iran

Abstract:Introduction: Carbapenem-resistant Acinetobacter baumannii (CRAB) is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. An understanding of the epidemiology of CRAB and the mechanisms of resistance to carbapenems is necessary to develop strategies to curtail their spread. Methods: Electronic databases were searched from January 1995 to December 2017 for all studies, which: (1) provide data on the frequency and antibiotic resistance profile of the isolated A. baumannii and (2) describe the mechanisms of carbapenem resistance in detail. Results: Sixty-eight studies were found referring to mechanisms of carbapenem resistance in clinical isolates of A. baumannii, and 56 studies were found referring to the frequency of CRAB. The pooled frequency of carbapenem resistance was 85.1% (95% confidence interval [CI]: 82.2-88.1) in 8,067 clinical isolates of A. baumannii. Resistances due to blaOXA23 (55.3%), blaOXA24 (41.4%), and blaOXA58 (5.2%) genes were the most prevalent reported mechanisms of resistance to carbapenem, respectively. Conclusions: Our data warn that CRAB will rise if the current situation remains uncontrolled. Better control infection strategies and antibiotic managements, particularly in the health care systems, are needed to limit the spread of this pathogen. © Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.

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Successful Treatment of Covid-19 Associated Cytokine Release Syndrome with Colchicine. A Case Report and Review of Literature

Abstract:We describe the case of a 42 year old, healthy patient with Covid-19 who despite improvement in his respiratory symptoms developed a mild to moderate cytokine release syndrome (CRS) and an associated monoarticular gout flare. Since the patient refused admission to the hospital and had stable vital signs, we chose to treat him with a safe anti-inflammatory and non-immunosuppressive therapy. To hit two birds with one stone, we considered colchicine, as it has systemic anti-inflammatory effects and is also effective in gout flare. Unexpectedly, 48 hours after treatment, not only did his ongoing fever and toe pain disappear, he also had significant improvements in his general state of health and all his inflammatory markers including fibrinogen, ferritin, D-dimer, and IL-6 levels normalized. To our knowledge, the use of colchicine in Covid-19 and CRS has not been reported. This observation merits the consideration of colchicine as a safe, inexpensive and oral medication for the treatment of mild to moderate CRS in Covid-19 patients. More importantly, in Covid-19 patients with early lung involvement colchicine may be an appropriate candidate to prevent CRS in adjunction with routine antiviral agents. Indeed, multicenter, randomized controlled studies are required to evaluate the benefits of this therapy. © 2020, © 2020 Taylor & Francis Group, LLC.

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Proteomic and genomic biomarkers for Non-Small Cell Lung Cancer: Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin

Abstract:Background: The development of lung cancer is a multifactorial process that involves the environmental and genetic factors. The mortality rate of this cancer is higher than breast, colorectal, and prostate cancers. In this study, we try to analyze the proteome of patients with Non-Small Cell Lung Cancer (NSCLC) and compare it with the healthy samples. Methods: This study has compared 30 lung tissue samples from patients with NSCLC and 30 healthy samples using proteomics and RT-PCR. Hence, tissue samples were obtained from the surgical ward in sterile conditions, and then, protein extraction applied to them. At the next stage, two-dimensional electrophoresis and mass spectrometry LCMS/MS were performed for protein isolation and sequencing, respectively. Results: The proteome analysis identified more than 40 differences in proteomic pattern of normal lung tissues compared to lung tissues with NSCLC. Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin proteins were identified. Molecularly, it has also been shown that the two main proteins of Peroxiredoxin-2 and Alpha-1 antitrypsin were upregulated, and the expression of Haptoglobin protein was downregulated in cancer tissue. Conclusion: The results of this study showed that there are some differences in term of protein content between the normal and cancerous lung tissues. Further studies are needed to evaluate these proteins that investigate whether these proteins can candidate as biomarkers to use in the early diagnosis of patients with NSCLC. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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EPA and DHA have selective toxicity for PBMCs from multiple myeloma patients in a partly caspase-dependent manner

Abstract: Poly-unsaturated fatty acids (PUFAs) have been shown to have cytotoxic effects in both solid and non-solid tumors. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among the most studied PUFAs. The aim of the present study was to evaluate the cytotoxic effects of these two fatty acids (FAs) in the peripheral blood mononuclear cells (PBMCs) obtained from untreated patients (new cases) with confirmed symptomatic multiple myeloma (MM). Our results showed that EPA at the concentration of 100 μM and DHA at 50 and 100 μM induce potent apoptotic effects in the PBMCs of MM patients (P < 0.05) as evidenced by Annexin V and propidium iodide (PI) staining, while they have little or no effects on the PBMCs isolated from healthy donors (P > 0.05). The observed effects were concentration- and time-dependent and 72 h treatment with DHA at a concentration of 100 μM had the strongest effect (P < 0.01). CD138 + cells isolated from MM patients showed great sensitivity to EPA/DHA. EPA- and DHA-induced apoptosis was significantly inhibited by the pan-caspase inhibitor (Z-VAD-FMK), indicating that cell death was at least partly dependent on caspase activation. The results of the present study showed that EPA and DHA have selective toxicities for malignant human plasma cells from MM patients, but not for mononuclear cells of healthy donors. These results warrant further studies with larger study populations to investigate the usefulness of PUFAs as a promising adjunctive therapy in the treatment of MM. © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

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