Cause-Specific Mortality among HIV-Infected Persons in One Medical Center, Tehran, Iran

Background: Human immunodeficiency virus (HIV) is one of the major infectious agents, which has important role in the public health challenges, which have affected the world's economic and social situation recent decades. During the last decades, millions of people died due to HIV infection worldwide. However, data remain limited on the causes of death among HIV-infected in Iranian population. The aim of the present study was to assess the cause specific death among HIV positive inpatient persons in Iran.Materials and Methods: This surveillance was conducted on inpatient HIV positive admissions at Masih Daneshvari Hospital, Tehran, Iran during October 2016 and April 2017.All patient’s data were collected via abstraction form, which were ascertained, from medical records and from written logbooks that were kept by the nursing staff on the ward. The data of each admission was recorded from the medical reports at the time of admission and upon discharge. All laboratory data were collected and recorded separately.Results: Fifty persons were diagnosed as HIV-infected patients, of which 58% of them were classified as AIDS patients. Our findings indicated that the cause of hospitalization were pulmonary 54%, neurological 20%, gastrointestinal 16%, and dermal 10% complications. Overall, 21 patients (42%) were diagnosed with pulmonary tuberculosis, of which one patient died from tuberculosis complications. Four patients died during the study period.Conclusion: In conclusion, early treatment and/or early use of ART can be improved outcomes. Therefore, early HIV testing and early ART use play important role in mortality reduction among eligible persons

Olfactory and gustatory manifestations in hospitalized patients with COVID-19

Background: Pulmonary involvement is the main clinical and imaging feature of the novel corona virus disease (COVID-19). However, some patients present with upper airway symptoms. Aim: In this study, we report upper respiratory manifestations, specifically focusing on smell and taste disorders in COVID-19. Methods: We performed this cross-sectional prospective study in patients admitted to Masih Daneshvari Hospital, a tertiary referral center in Tehran, Iran, with severe COVID-19 as documented by the polymerase chain reaction assay. Results: We included 268 hospitalized patients, 183 (68.3%) men and 85 (31.7%) women. The average age was 52.8±16.4. The sinonasal symptoms included nasal obstruction (44 [16.4%]), rhinorrhea (31 [11.5%]), sneeze (33 [12.3%]), headache (77 [28.6%]), facial pain (12 [4.5%]), associated with hypogeusia (65 [24.2%]) and olfactory dysfunction (90 [33.5%]). In 35 (38.9%) patients with olfactory symptoms, change in the smell was the sole initial manifestation of COVID-19. On logistic regression, the relationship between the olfactory symptoms and headache (p=0.002), nasal obstruction (p=0.0001) and sneeze (p=0.018) were statistically significant. Conclusion: We report a considerable prevalence of olfactory and gustatory symptoms in hospitalized patients with COVID-19. Not infrequently, these symptoms were the sole initial presenting symptoms in the course COVID-19. During the current pandemic, we suggest that presence of these symptoms should mandate expedited screening for COVID-19, isolation and close monitoring of the patients for evolution of the clinical course

Real-time RT-PCR Detection of HCN4 and ADAM8 genes in ventilator-associated pneumonia patients Hospitalized in intensive care unit

IntroductionVentilator-associated pneumonia (VAP)  is One of the most serious and  prevalence of  complication  among patients in the intensive care unit nosocomial infections, which are often recognized after detecting symptoms. To date, there has been no proper clinical and diagnostic marker for early detection of this disease. In this study, two HCN4 and ADAM8 genes in patients with VAP were assessed to be used as a biomarker to recognize and distinguish the disease.   MethodologyThis study was done in Masih Daneshvari Hospital affiliated to Shahid Beheshti University of Medical Sciences,Tehran,Iran since 2015-2016 and was case /control study . current study was administered by using peripheral blood samples, including 30 patients with VAP and 30 Healthy person. First, the peripheral blood samples were taken and then RNA was extracted and then synthesis CDNA. Finally, the evaluation of genes was performed by Realtime PCR method.   FindingsIn peripheral blood samples, patients individuals , 10 out of 30 cases had positive HCN4 markers. Among the healthy individuals, 6 out of 30 cases had positive HCN4  biomarkers. Moreover, in ADAM8 marker patients individuals, 13 out of 30 cases had positive ADAM8 marker and 8 out of 30 healthy individuals had positive ADAM8 biomarkers.ConclusionGenes HCN4 and ADAM8  assessment with Real Time-PCR  in this study can be used as promising markers in early detection of VAP disease. More extensive studies on larger sample sizes may yield higher sensitivity for these molecular markers

Changes in glycosylated haemoglobin and treatment outcomes in patients with tuberculosis in Iran: a cohort study.

BACKGROUND: Diabetes mellitus (DM) affects tuberculosis (TB) treatment outcomes, mostly by increasing recurrence, mortality and treatment failure. The objectives were to determine the pattern of change in glycosylated haemoglobin (HbA1c) level in new TB patients admitted to hospital at the start and 3-months after TB treatment, and to relate the measurements at these two time intervals to whether patients successfully completed treatment. METHODS: A prospective cohort study was conducted on hospitalized new TB patients at Masih Daneshvari Hospital from 2012 to 2013. All patients were tested for HbA1c at the beginning and 3 months after initiation of TB treatment. Changes in HbA1c were compared to TB treatment outcome. RESULTS: There were 317 new TB cases admitted to hospital of which 158 had HbA1c at baseline and 3-months. Of these, 67 (42%) had normal values, 54 had an elevated HbA1c at either base-line or 3-months (uncertain diabetes status) and 37 (24%) had elevated HbA1c (≥6.5%) at both time points (DM). There were differences between the groups: those with DM were older, had a known history of DM and a higher prevalence of cavities on chest x-ray. There were 150 (95%) patients who successfully completed treatment with no significant differences between the groups. CONCLUSION: There were changes in HbA1c during the first three-months of anti-TB treatment, but these were not associated with differences in TB treatment outcomes. Transient hyperglycemia should be considered in TB patients and needs to be taken into account in planning care and management

The analysis of exosomal micro-RNAs in peripheral blood mononuclear cell-derived macrophages after infection with bacillus Calmette–Guérin by RNA sequencing

AbstractObjective/BackgroundTuberculosis (TB) is a major global threat to human health, especially in low-income countries. The diagnosis of TB is challenging because of the limitations of specificity and sensitivity with the current diagnostics. Novel, selective biomarkers for TB would be of great practical value. Exosomes are bioactive vesicles with 30–100nm in diameter, which are secreted from almost all cell types and are found in virtually every human body fluid. Exosomes transport micro-RNAs (miRNAs), which are post-transcriptional regulators of gene expression, around the body and allow miRNAs to modulate biological pathways in target cells. Our aim was to investigate the potential of exosomal miRNAs as biomarkers by examining their release from human monocyte-derived macrophages (MDMs) after infection with Mycobacterium using miRNA sequencing.MethodsHuman monocytes were obtained from blood and driven to an MDM phenotype using standard protocols. MDMs were infected with Mycobacterium bovis Bacillus Calmette–Guérin (BCG) or left uninfected as control. Exosomes were collected 72 h postinfection from the cell culture medium and subjected to RNA isolation. Small RNA libraries were constructed and RNA sequencing performed. The raw reads were filtered to eliminate adaptor and primer sequences, and the sequences in FASTQ format were run against the mature human miRNA sequences available in miRBase using BLAST software using a Linux operating system. Micro-RNAs were identified using E=0.01 or 1.ResultsInfection of MDMs with BCG lead to the release of a number of exosomal miRNAs. These mainly consisted with Let-7 family members, miR-155, miR-146a, miR-145, and miR-21 all of which were predicted to target important immune-related genes and pathways.ConclusionThis study provides evidence for the release of specific miRNAs from BCG-infected MDMs. These results need to be confirmed and the presence of this panel of miRNAs tested in the blood of patients to determine their selectivity and specificity as a diagnostic in patients with TB

HIV and tuberculosis trends and survival of coinfection in a referral center in Tehran: A 12-year study

AbstractObjective/backgroundThe risk of mortality and morbidity among tuberculosis (TB) and human immunodeficiency virus (HIV) coinfected patients is significantly higher than that of patients infected with TB alone. The aim of this study was to evaluate the survival of TB-HIV patients in a TB-referral center during a 10-year follow-up.MethodsAll TB-HIV patients in our referral center were enrolled in the study from 2003 to 2014, and patients were divided into two groups: HIV-TB patients without a history of TB treatment (new cases of TB) and HIV-TB patients with a history of TB treatment. Both groups were treated based on World Health Organization TB-treatment guidelines, and multivariate analysis was performed to evaluate risk factors of all-cause mortality.ResultsDuring the study, 22 HIV-TB patients with a history of TB treatment and 263 HIV-TB patients with newly diagnosed TB were included. Baseline demographic and clinical characteristics were similar, except that miliary TB (98% vs. 2%) and mortality (97% vs. 3%; p=0.06) were more likely in HIV patients with newly diagnosed TB. During TB treatment and subsequent follow-up, two patients did not respond to treatment and 92 (32.3%) patients died, whereas the cure rate was 60%. Pneumothorax [hazard ratio (HR): 3.17], coinfection (herpes zoster, toxoplasmosis, cytomegalovirus infection, Pneumocystis jiroveci, candidiasis, and other opportunistic infection; HR: 1.75), CD4<100cells/mL (HR: 1.96), thrombocytopenia (HR: 2.29), and lack of treatment with antiretroviral agents (ART; HR: 2.82) were significantly associated with all-cause mortality according to multivariate analysis.ConclusionOur retrospective review of coinfected TB-HIV patients hospitalized in Tehran showed that the management and monitoring of coinfection, pneumothorax and other adverse effects, as well as early initiation of ART, improved patient survival

Usefulness of pulmonary artery diameter in diagnosing pulmonary hypertension in patients admitted to tuberculosis intensive care unit

AbstractObjective/backgroundPulmonary hypertension (PH) can be a complication of patients with severe pulmonary tuberculosis (TB). We aimed to study the correlation between pulmonary artery (PA) diameter (PAD) as measured by computed tomography (CT) and mean PA pressure (mPAP) as measured by echocardiography. We also aimed to determine the accuracy of PAD in diagnosing PH in patients with pulmonary TB.MethodsWe retrospectively investigated the correlation between PAD measured using CT and mPAP measured using echocardiography in 132 patients with TB and PH, and 68 patients with TB but without PH, admitted to the TB intensive care unit at Masih Daneshvari Hospital in Tehran, Iran. We used logistic regression analysis to determine the relationships between PAD, PA diameter to ascending aorta (AA) ratio, and area of PA to area of AA ratio with mPAP. Using receiver operating characteristic analysis, we examined the utility of the PAD in predicting PH (mPAP ⩾25mmHg).ResultsPAD had a significant correlation with mPAP (p<0.005 and r=0.47). Also, PA:AA ratio and area of PA to area of AA ratio had significant correlation with mPAP (r=0.48 and r=0.47, respectively; p<0.001). The threshold of 29mm for PAD was determined using ROC. This index had a sensitivity of 0.55, specificity of 70.2 and area under curve of 0.66.ConclusionAlthough PAD and PA:AA ratio are useful in assessing of presence of PH, we conclude that these CT parameters are not sufficient for ruling in or ruling out PH in this group of patients

T cell cytokine responses in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis following stimulation with proteins purified from Mycobacterium tuberculosis MDR clinical isolates

AbstractObjectiveTuberculosis (TB) is a devastating disease that remains a major health threat worldwide. The appearance of Mycobacterium tuberculosis strains resistance to current antibiotics is a growing problem, both in the third world and in developed countries. Completion of genomic sequencing of M. tuberculosis provides a strong foundation for subsequent identification of proteins to aid the understanding of protein function and the discovery of new drug targets or a TB vaccine. This study employed a proteomics approach to identify proteins from antibiotic resistant M. tuberculosis isolates and compare them to drug-sensitive isolates to determine the role of T cells in multidrug-resistant (MDR)-TB patients against M. tuberculosis-purified proteins (Rv0147) as compared with healthy subjects.MethodsProteins were extracted by Triton X-114 detergent-phase separation and precipitated by adding saturated ammonium sulfate to the supernatant. Following isoelectric focusing, proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Mass spectrometry was performed, and protein sequences were determined. Peripheral bloom mononuclear cells (PBMCs) were cultured, and autologous T cells were isolated from PBMCs by negative selection. Cells were subsequently cultured at 37°C in 5% CO2, followed by stimulation with 10μg/mL of the protein candidate (Rv0147) for 72h. Culture supernatants were assayed for interleukin (IL)-10 and interferon (IFN)-γ by enzyme-linked immunosorbent assay.ResultsThe identified proteins included Rv3057c, Rv0009, Rv3161c, Rv3614c, Rv0685, Rv2986c, Rv0443, Rv2114, Rv3311, Rv0831, Rv3804, and Rv3614c, and our results showed that the majority of upregulated or overexpressed proteins belonged to pathways associated with cellular metabolism, cell wall integrity, respiration, or cell membrane construction. Additionally, Rv1876 from MDR-TB isolates was predicted to be involved in the expression of bacterioferritin exclusively in MDR-TB-related resistance to first-line TB drugs. Furthermore, Rv2031c (HspX) was induced under oxygen-deficient conditions, and hypothetical protein (Rv2744c) and two membrane- and cell-wall-fraction proteins (Rv0379 and Rv1886c) were also identified. Analysis revealed increased percentages of INF-γ and decreased IL-10 levels in MDR-TB patients as compared with those observed in normal subjects.ConclusionFour identified membrane or membrane-associated proteins, including bacterioferritin, GroEs, HspX, and Ef-Tu, may be potential targets for the development of novel prophylactic diagnostics and therapeutic strategies against TB. Our results suggested that T cells stimulated by the protein candidate Rv0147 may be shifted to T helper 1 status in MDR-TB patients

Evaluating the Effects of Umifenovir Compared to Lopinavir/Ritonavir in the Management of Patients with COVID-19: A Randomized Controlled Trial

Background. Due to the lack of specific safe medications for the treatment of COVID-19, medications used for other similar conditions are being tested to alleviate the condition of COVID-19 patients, resulting in acceptable outcomes in some cases. Umifenovir (Arbidol®) is used to treat influenza viruses by inhibiting the fusion of the virus with the host cell. According to previous findings, umifenovir may inhibit SARS-CoV-2 infection by interfering with the release of SARS-CoV-2 from inside the cell. This study aimed to determine the effects of umifenovir, a fusion inhibitor, versus lopinavir/ritonavir in treating patients with COVID-19. Methods. This study was a randomized controlled trial consisting of 90 confirmed COVID-19 patients divided into the lopinavir/ritonavir group and the umifenovir group. The lopinavir/ritonavir group received 100/25 mg twice, while the umifenovir group was given 200 mg thrice a day, in both groups, for seven days. Outcomes included mortality rate and the need for mechanical ventilation or intensive care unit admission. Length of stay in the hospital and ICU and the lab tests trend were also assessed. Results. The mortality rate and the need for admission to the ICU were significantly lower in the umifenovir group (8% vs. 27.5%; P-value = 0.02). Moreover, The levels of white blood cells were also lower in the umifenovir group than in the control group by day 10 (6.2 (5.3-7.4) vs. 10.8 (9.9-13); P-value &lt;0.001). Conclusions. Umifenovir may reduce the need for admission to the ICU and mortality rate in patients with COVID-19 compared with lopinavir/ritonavir. The lab test trends were also in favor of umifenovir use.

Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study

Background: Anti-tuberculosis drug-induced hepatotoxicity can result from genetic polymorphism of the isoniazid (INH) metabolizing enzyme. This study aimed to determine the effect of genetic polymorphism of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genes on serum isoniazid level and drug-induced hepatotoxicity. Methods: A cross-sectional study was conducted on 120 patients (with and without hepatotoxicity) with pulmonary tuberculosis from June 2019 to April 2022 in Tehran (Iran). High-performance liquid chromatography was used to measure the serum concentration of INH and acetylisoniazid (AcINH). NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Data were analyzed using SPSS software (version 22.0) with independent two-sample t test, Chi square test, or Fisher’s exact test. P<0.05 was considered statistically significant.Results: A total of 40 patients showed hepatotoxicity. The risk of anti-tuberculosis drug-induced hepatotoxicity was significantly higher in patients who are slow acetylator (SA) phenotype than in rapid or intermediate acetylator (P<0.001). NAT2*4/*4 genotypes were not found in patients with hepatotoxicity. The frequency of NAT2*5 and NAT2*6 haplotypes and serum INH concentration was significantly higher in patients with hepatotoxicity than in those without (P=0.003, P<0.001, and P<0.001, respectively). NAT2*4 haplotype was correlated with protection against hepatotoxicity. A combination of SA and CYP2E1 C1/C1 genotype was significantly associated with hepatotoxicity (P<0.001). Conclusion: Hepatotoxicity in Iranian patients with tuberculosis was confirmed due to the presence of NAT2 SA polymorphism. Determining NAT2 and CYP2E1 genotypes and/or INH concentration can be a valuable tool to identify patients susceptible to hepatotoxicity