Cytomegalovirus Infection in Adult Patients with Inflammatory Bowel Disease: A Literature Review.

Human cytomegalovirus (HCMV) is classified within the Herpesvirales order and is prevalent in 50%‒80% of the general population. Most carriers experience this infection without noticeable clinical symptoms. HCMV causes a lifelong latent infection that can be reactivated due to immune disorders and inflammation. The reactivation of HCMV becomes particularly significant when it coincides with inflammatory bowel disease (IBD). While cytomegalovirus (CMV) colitis in IBD patients was identified years ago, the role of CMV in triggering flare-ups, acute severe colitis, treatment resistance, and other outcomes in IBD patients experiencing CMV reactivation remains a subject of ongoing debate. In this review, we aim to address an updated insight into aspects related to the CMV colitis in IBD patients including epidemiology, risk factors, clinical features, diagnostic tests, histology, place of immunosuppressants and indications for antiviral treatment. We suggest for personalized and thorough assessment based on the disease phase and colitis severity when prescribing drugs to these patients. Furthermore, we emphasize the importance of regular patient follow-up to monitor drug side effects, ensuring treatment success, and minimizing the risk of colectomy.

Tocilizumab in ICU-admitted COVID-19 Patients: A Retrospective Study.

Background: Severe and critically-ill COVID-19 patients are characterized by a severe inflammatory response. Pharmacologic inhibition of acute-phase inflammatory pathways such as IL-6 receptor inhibitor, Tocilizumab (TCZ) may improve patient outcomes in these cases. Consequently, the therapeutic benefit of TCZ was evaluated in this study. Methods: We evaluated intravenous tocilizumab in severe and critically ill adult COVID-19 patients who met pre-defined stringent CRS criteria. A single-center, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between March 20, 2020 and March 20, 2021. In total, 354 patients were included in our study. Mortality and time to hospital discharge were compared between patients who received tocilizumab treatment (n = 177) and those who did not (n = 177). Results: A total of 354 patients were analyzed whereas 177 patients were included in each group. In those receiving TCZ, all-cause mortality was significantly reduced, corresponding to an adjusted hazard ratio (HR) of 0.57, (95% confidence interval (CI): 0.43-0.76; P < 0.001). Furthermore, time to discharge was significantly improved in the TCZ group (HR: 1.66; 95%CI: 1.17-2.36, P = 0.004). Invasive mechanical ventilation was not statistically different among the study groups after adjusting for confounding variables (HR: 1.38; 95%CI: 0.89-2.14; P = 0.139). Dosing frequency was independent of survival status (P = 0.676). Conclusion: The use of TCZ in ICU-hospitalized patients resulted in improved patient survival and reduced duration of hospitalization. Further studies are needed to confirm the efficacy of TCZ in severe and critical COVID-19 cases.

Decoding dysregulated angiogenesis in HTLV-1 asymptomatic carriers compared to healthy individuals.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the first identified human retrovirus responsible for two significant diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although the majority of infected individuals remain asymptomatic carriers, a small percentage may develop ATLL or HAM/TSP. In tumorigenesis, a crucial process is angiogenesis, which involves the formation of new blood vessels. However, the precise mechanism of HTLV-1 associated angiogenesis remains unclear. This study aims to investigate the gene regulation involved in the angiogenesis signaling pathway associated with HTLV-1 infection. The research enrolled 20 male participants, including asymptomatic carriers and healthy individuals. Blood samples were collected and screened using ELISA for HTLV-1 confirmation, and PCR was performed for both Tax and HBZ for validation. RNA extraction and cDNA synthesis were carried out, followed by RT-qPCR analysis targeting cellular genes involved in angiogenesis. Our findings indicate that gene expression related to angiogenesis was elevated in HTLV-1 ACs patients. However, the differences in gene expression of the analyzed genes, including HSP27, Paxillin, PDK1, PTEN, RAF1, SOS1, and VEGFR2 between ACs and healthy individuals were not statistically significant. This suggests that although angiogenesis-related genes may show increased expression in HTLV-1 infection, they might not be robust indicators of ATLL progression in asymptomatic carriers. The results of our study demonstrate that angiogenesis gene expression is altered in ACs of HTLV-1, indicating potential involvement of angiogenesis in the early stages before ATLL development. While we observed elevated angiogenesis gene expression in ACs, the lack of statistical significance between ACs and healthy individuals suggests that these gene markers may not be sufficient on their own to predict the development of ATLL in asymptomatic carriers.

Illuminating (HTLV-1)-induced adult T-cell leukemia/lymphoma transcriptomic signature: A systems virology approach.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a poor prognosis malignancy of peripheral T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The low survival rates observed in the patients are the result of the lack of sufficient knowledge about the disease pathogenesis. METHODS: In the present study, we first identified differentially expressed genes in ATLL patients and the cellular signaling pathways affected by them. Then, genes of these pathways were subjected to more comprehensive evaluations, including WGCNA and module validation studies on five external datasets. Finally, potential biomarkers were selected for qRT-PCR validation. RESULTS: Thirteen signaling pathways, including Apoptosis, Human T-cell leukemia virus 1 infection, IL-17 signaling pathway, pathways in cancer, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, and seven others were selected for deeper investigations. Results of our in-depth bioinformatics evaluations, highlighted pathways related to regulation of immune responses, T-cell receptor and activation, regulation of cell signaling receptors and messengers, Wnt signaling pathway, and apoptosis as key players in ATLL pathogenesis. MAPK3, PIK3CD, KRAS, NFKB1, TNF, PLCB3, PLCB2, PLCB1, MAPK11, JUN, ITPR1, ADCY1, GNAQ, ADCY3, ADCY4, CHEK1, CCND1, SOS2, BAX, FOS and GNA12 were identified as possible biomarkers. Upregulation of ADCY1 and ADCY3 genes was confirmed via qRT-PCR. CONCLUSIONS: In this study, we performed a deep bioinformatic examination on a limited set of genes with high probabilities of involvement in the pathogenesis of ATLL. Our results highlighted signaling pathways and genes with potential key roles in disease formation and resistance against current treatment strategies. Further studies are required to test the possible benefits of highlighted genes as biomarkers and targets of treatment.

A Review of Antibiotic Efficacy in COVID-19 Control.

Severe acute respiratory disease is associated with chronic secondary infections that exacerbate symptoms and mortality. So far, many drugs have been introduced to treat this disease, none of which effectively control the coronavirus. Numerous studies have shown that mitochondria, as the center of cell biogenesis, are vulnerable to drugs, especially antibiotics. Antibiotics were widely prescribed during the early phase of the pandemic. We performed a literature review to assess the reasons, evidence, and practices on the use of antibiotics in coronavirus disease 2019 (COVID-19) in- and outpatients. The current research found widespread usage of antibiotics, mostly in an empirical context, among COVID-19 hospitalized patients. The effectiveness of this approach has not been established. Given the high death rate linked with secondary infections in COVID-19 patients and the developing antimicrobial resistance, further study is urgently needed to identify the most appropriate rationale for antibiotic therapy in these patients.

Investigation of microbial coinfection in 453 septic COVID-19 patients admitted to hospital; a retrospective study.

Aim: We evaluated the rate of COVID-19 microbial coinfection in an Iranian population. Methods: In this single-center, retrospective observational study, we evaluated 453 septic COVID-19 patients for possible coinfection in an Iranian hospital. Results: Overall, 211 (46.57%) cases died due to COVID-19 complications. Positive respiratory secretion and blood cultures were reported in 99 (21.9%) and 19 (4.2%) cases. Klebsiella species were the most commonly isolated microorganisms in respiratory (n = 50, 50.5%) and blood (n = 10, 52.6%) specimens. After adjustment for underlying disorders, positive respiratory microbial cultures significantly increase the odds of developing death, intubation, and ICU admission and negatively impact healthy discharge (P < 0.05). Conclusion: Coinfections with bacteria and fungi independently contribute to poor outcomes in septic COVID-19 patients.

COVID-19 bacterial/fungal coinfection is associated with severe mortality rates as it complicates the primary viral infection. This study evaluated 453 patients admitted to an Iranian hospital with COVID-19 and concomitant sepsis for microbial coinfection. A total of 99 (21.9%) cases had positive respiratory secretion cultures, and 19 (4.2%) had positive blood cultures. Klebsiella species were the most commonly yielded microorganism in both respiratory (n = 50, 50.5%) and blood (n = 10, 52.6%) specimens. Bacterial and fungal microbial coinfection are independent determinants of poor outcomes in septic COVID-19 cases.

Severity of SARS-CoV-2 reinfection in vaccinated healthcare workers.

Background and Objectives: The most appropriate approach to control the SARS-CoV-2 epidemic is the widespread adoption of vaccination. Several vaccines against SARS-CoV-2 have been developed and authorized for use in various geographical regions. The aim of this study is to evaluate the efficacy of the vaccination agents presently utilized by healthcare workers (HCWs), and to investigate whether different COVID-19 vaccines would result in the alleviation of symptoms and the severity of clinical presentation. Materials and Methods: This multi-center survey was conducted on 329 vaccinated HCWs who were reinfected with COVID-19 between January 8, 2021 and April 8, 2021, in Tehran, Iran. Results: Overall, 92.1% and 70.8% of the participants had received 2 and 3 cumulative doses of COVID-19 vaccines, respectively. There were no differences between first/second and third-dose vaccines with the severity of SARS-CoV-2 infection. Expectedly, vaccination resulted in a less severe clinical presentation of SARS-CoV-2 infection, as reported by the participants. Conclusion: The results suggest that the efficacy of the vaccination agents presently utilized by HCWs was acceptable with no significant difference in vaccine type. Participants receiving at least two doses of vaccines in this survey exceeded 90%, which is comparably higher than studies conducted in other countries.

Identification of novel miRNAs potentially involved in the pathogenesis of adult T-cell leukemia/lymphoma using WGCNA followed by RT-qPCR test of hub genes.

BACKGROUND: Adult T-cell Lymphoma/Leukemia (ATLL) is characterized by the malignant proliferation of T-cells in Human T-Lymphotropic Virus Type 1 and a high mortality rate. Considering the emerging roles of microRNAs (miRNAs) in various malignancies, the analysis of high-throughput miRNA data employing computational algorithms helps to identify potential biomarkers. METHODS: Weighted gene co-expression network analysis was utilized to analyze miRNA microarray data from ATLL and healthy uninfected samples. To identify miRNAs involved in the progression of ATLL, module preservation analysis was used. Subsequently, based on the target genes of the identified miRNAs, the STRING database was employed to construct protein-protein interaction networks (PPIN). Real-time quantitative PCR was also performed to validate the expression of identified hub genes in the PPIN network. RESULTS: After constructing co-expression modules and then performing module preservation analysis, four out of 15 modules were determined as ATLL-specific modules. Next, the hub miRNA including hsa-miR-18a-3p, has-miR-187-5p, hsa-miR-196a-3p, and hsa-miR-346 were found as hub miRNAs. The protein-protein interaction networks were constructed for the target genes of each hub miRNA and hub genes were identified. Among them, UBB, RPS15A, and KMT2D were validated by Reverse-transcriptase PCR in ATLL patients. CONCLUSION: The results of the network analysis of miRNAs and their target genes revealed the major players in the pathogenesis of ATLL. Further studies are required to confirm the role of these molecular factors and to discover their potential benefits as treatment targets and diagnostic biomarkers.

A case report of prolonged COVID-19-positive RT-PCR for five months.

The COVID-19 gold standard assessment tool remained the RT-PCR of upper respiratory tract specimen extracted by the nasopharyngeal swab. A positive result would decrease through a three-week course and eventually be undetectable. The maximum duration of viral shedding is 83 days. Besides, COVID-19 RT-PCR remained positive for 74 days in a patient suffering from lymphoma. In this study, we have presented a 56-year-old male patient, a known case of lymphoma since 2015, who experienced many episodes of chemotherapy with a five-month positive RT-PCR COVID-19 laboratory test and finally was intubated and then died of opportunistic pulmonary infections. COVID-19 patients with concurrent lymphoma failed to remove the virus thoroughly, despite providing appropriate treatment regimens.

Comparative study of CNR1 and CNR2 cannabinoid receptors expression levels in COVID-19 patients with and without diabetes mellitus: Recommendations for future research targets.

BACKGROUND AND AIMS: The COVID-19 pandemic has prompted researchers to look for effective therapeutic targets. The effect of endocannabinoid system against infectious diseases is investigated for several years. In this study, we evaluated the expression level of CNR1 and CNR2 genes in patients with COVID-19 with and without diabetes to provide new insights regarding these receptors and their potential effect in COVID-19 disease. METHODS: In this study, peripheral blood monocytes cells (PBMCs) were isolated from eight different groups including COVID-19 patients, diabetic patients, and healthy individuals. RNA were extracted to evaluate the expression level of CNR1 and CNR2 genes using real-time PCR. The correlation between the expression levels of these genes in different groups were assessed. RESULTS: A total of 80 samples were divided into 8 groups, with each group consisting of ten samples. When comparing severe and moderate COVID-19 groups to healthy control group, the expression levels of the CNR1 and CNR2 genes were significantly higher in the severe and moderate COVID-19 groups. There were no significant differences between the mild COVID-19 group and the healthy control group. It was found that the expression levels of these genes in patients with diabetes who were infected with SARS-COV-2 did not differ across COVID-19 groups with varying severity, but they were significantly higher when compared to healthy controls. CONCLUSION: Our study suggests the possible role of endocannabinoid system during SARS-COV-2 pathogenicity as the expression of CNR1 and CNR2 were elevated during the disease.

Effect of Ammonium Chloride in addition to standard of care in outpatients and hospitalized COVID-19 patients: A randomized clinical trial.

OBJECTIVE: The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections. DESIGN: In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients. RESULTS: A total of 120 patients were included in the trial, 60 of which were assigned to the Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57-16.06; p = 0.195)). Recovery time and viral burden were significantly lower in the Ammonium Chloride group, corresponding to an odds ratios of 1.8 (95% CI, 1.15-2.83; p = 0.01) and 7.90 (95% CI, 1.62-14.17; p = 0.014), respectively. CONCLUSION: The findings of this study advocate the careful addition of Ammonium Chloride to standard of care for COVID-19 patients.

Is vancomycine still a choice for chronic osteomyelitis empirical therapy in iran?

BACKGROUND: Pyogenic bacteria and especially Staphylococcus aurous (S. aurous) are the most common cause of chronic osteomyelitis. Not only treatment protocol of chronic osteomyelitis occasionally is amiss but also this malady responds to treatment difficultly. OBJECTIVES: This study investigates antibiotic resistance pattern of S. aurous isolated from Iranian patients who suffer from chronic osteomyelitis by two methods: disk diffusion (Kirby bauyer) and E-test (Epsilometer test) to find Vancomycin susceptibility and MIC (Minimum inhibitory concentration). PATIENTS AND METHODS: One hundred and thirty one patients who suffer from chronic osteomyelitis which have been referred to both governmental and private hospitals at 2010 were tried out for culturing of osteomyelitis site (sites). Antibiotic susceptibility and MIC of isolated bacteria were investigated by Kirby bauyer and E-test respectively. RESULTS: Samples were collected from bone (73.4%), surrounding tissue (14.6%) and wound discharge (12%). S. aureus was isolated from 49.6% of the samples. According to disc diffusion, methicillin resistance S. aureus (MRSA) was 75% and Vancomycin resistance S. aurous (VRSA) was 0% and based on MIC, MRSA was 68.5% and VRSA was 0%. According to MIC experiments, maximum sensitivity was against to Vancomycin (90.2%) and ciprofloxacin (54.4%) respectively but based on disc diffusion, maximum sensitivity was against to Vancomycin (97.7%) and ciprofloxacin (43.2%), respectively (P = 0.001). E-test (9.8%) in comparison with Disc diffusion (2.3%) showed higher percent of intermediate susceptibility to Vancomycin (P = 0.017). CONCLUSIONS: Comparison of antibiograms and MICs showed that Kirby bauyer technique especially for detection of VISA strains is not reliable comparison with E-test. Already VRSA strains have not detected in Iranian chronic osteomyelitis, Thus Vancomycin is the first choice for chronic osteomyelitis empirical therapy in Iran yet.