Disease prognosis and therapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC): a 6-year epidemiological study between 2015-2021.

Background: Lung cancer is the top cause of mortality in males and the second largest cause of cancer-related fatalities in women worldwide. Non-small cell lung cancer (NSCLC) cases are discovered at an advanced stage, raising major challenges in disease management and survival outcomes. This study aimed to investigate the clinical findings and management of stage IIIB and IV NSCLC patients for better decision-making, disease management, and understanding of this fatal disease. Methods: In this cohort study of 340 patients, a total of 140 (41.2%) were diagnosed with advanced-stage NSCLC at a mean age of 64 years. The electronic data of patients from 2015 to 2021 who met the inclusion criteria were retrieved from two tertiary hospitals in Riyadh, Saudi Arabia, and an Excel sheet was used to record the variables. Patients' data including all categorical variables such as gender, stage, metastasis, ALK, EGFR, and ROS, etc., and continuous variables such as age and body mass index (BMI) were retrieved and analyzed. Results: The multivariate Cox-regression model indicated that smoking was the significant risk factor of death for two-thirds of male smokers (37.9%), with a median survival time of 123 days. Disease progression was higher with pleural and brain metastasis, and localized metastasis was the highest in 75% of patients. The intent of treatment was mainly palliative, however, a statistically significant association was found with the simultaneous use of chemotherapy and immunotherapy. Patients' response to first-line treatment revealed a significant improvement if chemotherapy treatment was maintained at the same dose without interruption of dosage. Conclusions: The overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required for better decision-making to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.

Evolutionary analysis of LMP-1 genetic diversity in EBV-associated nasopharyngeal carcinoma: Bioinformatic insights into oncogenic potential.

EBV latent membrane protein 1 (LMP-1) is an important oncogene involved in the induction and maintenance of EBV infection and the activation of several cell survival and proliferative pathways. The genetic diversity of LMP-1 has an important role in immunogenicity and tumorigenicity allowing escape from host cell immunity and more metastatic potential of LMP-1 variants. This study explored the evolutionary of LMP-1 in EBV-infected patients at an advanced stage of nasopharyngeal carcinoma (NPC). Detection of genetic variability in LMP-1 genes was carried out using Sanger sequencing. Bioinformatic analysis was conducted for translation and nucleotide alignment. Phylogenetic analysis was used to construct a Bayesian tree for a deeper understanding of the genetic relationships, evolutionary connections, and variations between sequences. Genetic characterization of LMP-1 in NPC patients revealed the detection of polymorphism in LMP-1 Sequences. Motifs were identified within three critical LMP-1 domains, such as PQQAT within CTAR1 and YYD within CTAR2. The presence of the JACK3 region at specific sites within CTAR3, as well as repeat regions at positions (122-132) and (133-143) within CTAR3, was also annotated. Additionally, several mutations were detected including 30 and 69 bp deletions, 33 bp repeats, and 15 bp insertion. Although LMP-1 strains appear to be genetically diverse, they are closely related to 3 reference strains: prototype B95.8, Med- 30 bp deletion, and Med + 30 bp deletion. In our study, one of the strains harboring the 30 bp deletion had both bone and bone marrow metastasis which could be attributed to the fact that LMP-1 is involved in tumor metastasis, evasion and migration of NPC cells. This study provided valuable insights into genetic variability in LMP-1 sequences of EBV in NPC patients. Further functional studies would provide a more comprehensive understanding of the molecular characteristics, epidemiology, and clinical implications of LMP-1 polymorphisms in EBV-related malignancies.

Mutations at the conserved N-Terminal of the human Rhinovirus capsid gene VP4, and their impact on the immune response.

Rhinoviruses (RV) are the major cause of chronic obstructive pulmonary disease and are associated with exacerbation development as well as community-acquired pneumonia in children, leading to substantial morbidity, mortality, and hospital admission. Here we have examined how changes at the amino terminal of the conserved VP4 epitope of different RV serotypes may affect pulmonary cytokine and chemokine responses and disease severity. Samples positive for rhinovirus were used for genetic characterization, followed by profiling gene expression of pulmonary Th1 and Th2 cytokines/chemokines by RT-PCR arrays. Genetic sequencing and homology 3D modeling revealed changes at the amino terminal of the conserved viral protein 4 (VP4) epitope in the RV-A101 serotype, especially serine at several positions that are important for interactive binding with the host immune cells. We found dysregulation of pulmonary gene expression of Th1- and Th2-related cytokines and chemokines in RV-A 101 and RV-C 8 pneumonia patients. These findings might contribute to a better understanding of RV immunity and the potential mechanisms underlying the pathogenesis of severe RV infections, but further functional studies are needed to confirm the causal relationship.

The correlation between soluble human leukocyte antigen (sHLA-G) levels and +3010 polymorphism.

Human leukocyte antigen-G (HLA-G) is classified as non-classical HLA, located in the short arm of chromosome 6 and composed of seven introns and eight exons. The HLA-G gene has a lower frequency polymorphism in the coding area and higher variability at the regulatory 5'- and 3'-untranslated regions linked to HLA-G microRNA regulation. HLA-G molecule is known to have an immunomodulatory and tolerogenic features role. In 199 Saudi individuals, we examined the association between plasma soluble HLA-G (sHLA-G) levels and eight polymorphic different sites, including 14 bp ins/del/+3003T-C/+3010C-G/+3027C-A/+3035C-T/+3142C-G/+3187A-G/+3196C-G single nucleotide polymorphisms (SNPs) in exon 8 in the HLA-G gene. Our results revealed higher frequency for rs17179101C (97%), rs1707T (92%) and rs9380142A (73%) alleles. Greater frequencies for the tested genotypes were observed in 3027C/C (rs17179101) (93%), 14 bp (rs1704) ins/del (92%), +3003T/T (rs1707) (85%) and +3035C/T (rs17179108) (79%) SNP genotypes. Moreover, we observed a significant association of sHLA-G with +3010G/C (rs1710) SNP. In conclusion, we showed a significant association between 3010G/C (rs1710) SNP and the sHLA-G level among our sample for Saudi populations. Our findings demonstrated that specific SNP within the HLA-G gene is linked to sHLA-G molecule secretion, suggesting sHLA-G levels may be regulated genetically.

Comprehensive Transcriptome Analysis Reveals the Distinct Gene Expression Patterns of Tumor Microenvironment in HPV-Associated and HPV-Non Associated Tonsillar Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the most prevalent and has a particularly aggressive clinical course with poor disease outcomes. The tumor microenvironment (TME) of HNSCC is complex and heterogeneous, playing a crucial role in effective cancer therapy. Understanding the interaction between cancer inflammation, immunity, oncogenes, and tumor suppressor genes is essential for developing effective cancer treatments. This study aimed to gain a comprehensive understanding of the transcriptomes of the TME in TSCC, both associated with human papillomavirus (HPV) and not associated with HPV. The gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immunity crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis were analyzed. We identified 40 differentially expressed genes related to the communication between tumor cells and the cellular mediators of inflammation and immunity crosstalk. In HPV-positive TSCC patients, 33 genes were over-expressed with a fold change greater than 1.5, and 26 of these genes were unique to this group. In contrast, HPV-negative TSCC patients had 11 up-regulated genes. The results further showed that 48 gene transcripts related to oncogenesis, tumor suppression, angiogenesis, and apoptosis were up-regulated in both HPV-positive and HPV-negative TSCC patients. Among the HPV-positive TSCC patients, 37 genes were over-expressed, while the HPV-negative TSCC patients had 11 up-regulated genes. The tumor microenvironment (TME) of HPV-associated and HPV-non-associated TSCC exhibited distinct characteristics, including the dysregulation of various genes involved in cellular mediators, inflammation, immunity crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Additionally, we detected six Hr-HPV genotypes in 81% of the TSCC patients, with HPV-16 and HPV-35 being the most common types, followed by HPV-45 and HPV-18. HPV-39 and 31 were also identified. The presence of Hr-HPV genotypes in TSCC patients varied from single to multiple infections. In conclusion, we observed distinct heterogeneity in the transcriptome of the microenvironment in HPV-associated and non-associated TSCC. Further in vitro and in vivo studies are needed to investigate the functional implications of the identified over-expressed genes. Also, deeper molecular pathways and immunological studies on the TME are required to determine the potential of targeting genes for cancer therapy.

Assessing disparities in medical students' knowledge and attitude about monkeypox: a cross-sectional study of 27 countries across three continents.

Background and aims: The recent monkeypox (Mpox) outbreak confirmed by the World Health Organization (WHO) underscores the importance of evaluating the knowledge and attitude of medical students toward emerging diseases, given their potential roles as healthcare professionals and sources of public information during outbreaks. This study aimed to assess medical students' knowledge and attitude about Mpox and to identify factors affecting their level of knowledge and attitude in low-income and high-income countries. Methods: A cross-sectional study was conducted on 11,919 medical students from 27 countries. A newly-developed validated questionnaire was used to collect data on knowledge (14 items), attitude (12 items), and baseline criteria. The relationship between a range of factors with knowledge and attitude was studied using univariate and multivariate analyses. Results: 46% of the study participants were males; 10.7% were in their sixth year; 54.6% knew about smallpox; 84% received the coronavirus disease 2019 (COVID-19) vaccine; and 12.5% had training on Mpox. 55.3% had good knowledge of Mpox and 51.7% had a positive attitude towards it. Medical students in their third, fifth, or sixth year high- income countries who obtained information on Mpox from friends, research articles, social media and scientific websites were positive predictors for good knowledge. Conversely, being male or coming from high-income countries showed a negative relation with good knowledge about Mpox. Additionally, a positive attitude was directly influenced by residing in urban areas, being in the fifth year of medical education, having knowledge about smallpox and a history of receiving the coronavirus disease 2019 (COVID-19) vaccine. Receiving information about Mpox from social media or scientific websites and possessing good knowledge about Mpox were also predictors of a positive attitude. On the other hand, being male, employed, or receiving a training program about Mpox were inversely predicting positive attitude about Mpox. Conclusion: There were differences in knowledge and attitude towards Mpox between medical students in low and high-income countries, emphasizing the need for incorporating epidemiology of re-emerging diseases like Mpox into the medical curriculum to improve disease prevention and control.

Corrigendum: Factors influencing participation in COVID-19 clinical trials: a multinational study.

[This corrects the article DOI: 10.3389/fmed.2021.608959.].

Moderately Low Effectiveness of the Influenza Quadrivalent Vaccine: Potential Mismatch between Circulating Strains and Vaccine Strains.

The annual seasonal influenza vaccination is the most effective way of preventing influenza illness and hospitalization. However, the effectiveness of influenza vaccines has always been controversial. Therefore, we investigated the ability of the quadrivalent influenza vaccine to induce effective protection. Here we report strain-specific influenza vaccine effectiveness (VE) against laboratory-confirmed influenza cases during the 2019/2020 season, characterized by the co-circulation of four different influenza strains. During 2019-2020, 778 influenza-like illness (ILI) samples were collected from 302 (39%) vaccinated ILI patients and 476 (61%) unvaccinated ILI patients in Riyadh, Saudi Arabia. VE was found to be 28% and 22% for influenza A and B, respectively. VE for preventing A(H3N2) and A(H1N1)pdm09 illness was 37.4% (95% CI: 43.7-54.3) and 39.2% (95% CI: 21.1-28.9), respectively. The VE for preventing influenza B Victoria lineage illness was 71.7% (95% CI: -0.9-3), while the VE for the Yamagata lineage could not be estimated due to the limited number of positive cases. The overall vaccine effectiveness was moderately low at 39.7%. Phylogenetic analysis revealed that most of the Flu A genotypes in our dataset clustered together, indicating their close genetic relatedness. In the post-COVID-19 pandemic, flu B-positive cases have reached three-quarters of the total number of influenza-positive cases, indicating a nationwide flu B surge. The reasons for this phenomenon, if related to the quadrivalent flu VE, need to be explored. Annual monitoring and genetic characterization of circulating influenza viruses are important to support Influenza surveillance systems and to improve influenza vaccine effectiveness.

Analysis of the nasopharyngeal microbiome and respiratory pathogens in COVID-19 patients from Saudi Arabia.

BACKGROUND: Infection with SARS-CoV-2 may perturb normal microbiota, leading to secondary infections that can complicate the viral disease. The aim of this study was to probe the alteration of nasopharyngeal (NP) microbiota in the context of SARS-CoV-2 infection and obesity and to identify other respiratory pathogens among COVID-19 cases that may affect patients' health. METHODS: A total of 107 NP swabs, including 22 from control subjects and 85 from COVID-19 patients, were processed for 6S amplicon sequencing. The respiratory pathogens causing secondary infections were identified by RT-PCR assay, using a kit that contained specific primers and probes combinations to amplify 33 known respiratory pathogens. RESULTS: No significant (p > 0.05) difference was observed in the alpha and beta diversity analysis, but specific taxa differed significantly between the control and COVID-19 patient groups. Genera of Sphingomonas, Kurthia, Microbacterium, Methylobacterium, Brevibacillus, Bacillus, Acinetobacter, Lactococcus, and Haemophilus was significantly abundant (p < 0.05) in COVID-19 patients compared with a healthy control group. Staphylococcus was found in relatively high abundance (35.7 %) in the COVID-19 patient groups, mainly those treated with antibiotics. A relatively high percentage of Streptococcus was detected in COVID-19 patient groups with obesity or other comorbidities. Respiratory pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Salmonella species, along with Pneumocystis jirovecii fungal species were detected by RT-PCR mainly in the COVID-19 patients. Klebsiella pneumoniae was commonly found in most of the samples from the control and COVID-19 patients. Four COVID-19 patients had viral coinfections with human adenovirus, human rhinovirus, enterovirus, and human parainfluenza virus 1. CONCLUSIONS: Overall, no substantial difference was observed in the predominant NP bacterial community, but specific taxa were significantly changed between the healthy control and COVID-19 patients. Comparatively, an increased number of respiratory pathogens were identified in COVID-19 patients, and NP colonization by K. pneumoniae was probably occurring in the local population.

Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study.

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.

Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity.

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-ß, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-ß, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy.

Association between inflammatory cytokines/chemokines, clinical laboratory parameters, disease severity and in-hospital mortality in critical and mild COVID-19 patients without comorbidities or immune-mediated diseases.

There are limited data on inflammatory cytokines and chemokines; the humoral immune response; and main clinical laboratory parameters as indicators for disease severity and mortality in patients with critical and mild COVID-19 without comorbidities or immune-mediated diseases in Saudi Arabia. We determined the expression levels of major proinflammatory cytokines and chemokines; C-reactive protein (CRP); procalcitonin; SARS-CoV-2 IgM antibody and twenty-two clinical laboratory parameters and assessed their usefulness as indicators of disease severity and in-hospital death. Our results showed a significant increase in the expression levels of SARS-CoV-2 IgM antibody; IL1-ß; IL-6; IL-8; TNF-α and CRP in critical COVID-19 patients; neutrophil count; urea; creatinine and troponin were also increased. The elevation of these biomarkers was significantly associated and positively correlated with in-hospital death in critical COVID-19 patients. Our results suggest that the levels of IL1-ß; IL-6; IL-8; TNF-α; and CRP; neutrophil count; urea; creatinine; and troponin could be used to predict disease severity in COVID-19 patients without comorbidities or immune-mediated diseases. These inflammatory mediators could be used as predictive early biomarkers of COVID-19 disease deterioration; shock and death among COVID-19 patients without comorbidities or immune-mediated diseases.

Analyzing the Difference in the Length of Stay (LOS) in Moderate to Severe COVID-19 Patients Receiving Hydroxychloroquine or Favipiravir.

Background: The coronavirus 2019 (COVID-19) disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus led to a global pandemic. HCQ and FPV were used early in the pandemic as a treatment modality for COVID-19. Various studies evaluated the HCQ and FPV effectiveness, based on the mortality endpoint and showed conflicting results. We hypothesize that analyzing the difference in the LOS as a significant endpoint would be of a major interest, especially for healthcare providers, to prevent a lengthy hospitalization and disease progression. Methods: This is a retrospective observational study, conducted via a medical chart review of COVD-19 patients who were admitted between April 2020 and March 2021 with a moderate to severe illness. The LOS endpoint was tested using the paired Wilcoxon signed-rank (WSR) model. Prior to using the WSR model, the balance between the HCQ and FPV groups, the propensity score matching, the LOS distribution, and the normality assumptions were tested. Two sensitivity statistical analyses were conducted to confirm the results (stratified log-rank test and U Welch test after transforming the LOS by the squared root values). Results: A total of 200 patients were included for the analysis: 83 patients in the HCQ group and 117 patients in the FPV group. Thirty-seven patients were matched in each group. The LOS data was positively skewed and violated the normality (Shapiro−Wilk p < 0.001) and had an unequal variance (Levene's test, p = 0.019). The WSR test showed no statistical significance in the LOS endpoint, with a median of −0.75 days (95% confidence interval: −4.0 to 2.5, p = 0.629), in favor of the HCQ group (four days), in comparison to seven days of the FPV group. The WSR findings were further confirmed with the stratified log rank test (p = 740) and the U Welch test (p = 391). Conclusions: The study concluded that the HCQ and FPV treatments have a comparable effectiveness in terms of the LOS in the moderate to severe COVID-19 patients. This study highlights the importance of analyzing the LOS as a relevant endpoint, in order to prevent the costs of a lengthy hospitalization and disease progression. The current study also emphasizes the importance of applying the appropriate statistical testing when dealing with two-sample paired data and analyzing non-parametric data such as the LOS.

Development and Validation of ScriptTaq COVID PCR: An In-House Multiplex rRT-PCR for Low-Cost Detection.

The COVID-19 pandemic necessitated an extensive testing for active SARS-CoV-2 infection. However, securing affordable diagnostic tests is a struggle for low-resource settings. We report herein the development and validation of an in-house multiplex real-time RT-PCR diagnostic test for the detection of active COVID-19 infection (ScriptTaq COVID PCR). Furthermore, we describe two methods for RNA extraction using either an in-house silica column or silica-coated magnetic beads to replace commercial RNA extraction kits. Different buffer formulations for silica column and silica-coated magnetic beads were tested and used for RNA isolation. Taq polymerase enzyme and thermostable reverse transcriptase enzyme were purified from bacterial clones. Primers/probes sequences published by the WHO and CDC were used for the qualitative detection of the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes, respectively. ScriptTaq COVID PCR assay was able to detect up to 100 copies per reaction of the viral RdRP and N genes. The test demonstrated an overall agreement of 95.4%, a positive percent agreement (PPA) of 90.2%, and a negative percent agreement (NPA) of 100.0% when compared with two commercially available kits. ScriptTaq COVID PCR diagnostic test is a specific, sensitive, and low-cost alternative for low-resource settings.

Prediction and Classification of COVID-19 Admissions to Intensive Care Units (ICU) Using Weighted Radial Kernel SVM Coupled with Recursive Feature Elimination (RFE).

Healthcare systems have been under immense pressure since the beginning of the COVID-19 pandemic; hence, studies on using machine learning (ML) methods for classifying ICU admissions and resource allocation are urgently needed. We investigated whether ML can propose a useful classification model for predicting the ICU admissions of COVID-19 patients. In this retrospective study, the clinical characteristics and laboratory findings of 100 patients with laboratory-confirmed COVID-19 tests were retrieved between May 2020 and January 2021. Based on patients' demographic and clinical data, we analyzed the capability of the proposed weighted radial kernel support vector machine (SVM), coupled with (RFE). The proposed method is compared with other reference methods such as linear discriminant analysis (LDA) and kernel-based SVM variants including the linear, polynomial, and radial kernels coupled with REF for predicting ICU admissions of COVID-19 patients. An initial performance assessment indicated that the SVM with weighted radial kernels coupled with REF outperformed the other classification methods in discriminating between ICU and non-ICU admissions in COVID-19 patients. Furthermore, applying the Recursive Feature Elimination (RFE) with weighted radial kernel SVM identified a significant set of variables that can predict and statistically distinguish ICU from non-ICU COVID-19 patients. The patients' weight, PCR Ct Value, CCL19, INF-ß, BLC, INR, PT, PTT, CKMB, HB, platelets, RBC, urea, creatinine and albumin results were found to be the significant predicting features. We believe that weighted radial kernel SVM can be used as an assisting ML approach to guide hospital decision makers in resource allocation and mobilization between intensive care and isolation units. We model the data retrospectively on a selected subset of patient-derived variables based on previous knowledge of ICU admission and this needs to be trained in order to forecast prospectively.

Recall of Prior Knowledge in Medical Microbiology Among Medical Interns: A Multicenter Cross-Sectional Assessment in Saudi Arabia.

Background: Retention of basic biomedical sciences knowledge is of great importance in medical practice. This study aimed to provide some insights into medical interns' ability to recall theoretical knowledge of medical microbiology and to explore factors that affect its retention. Methods: In this cross-sectional study conducted between January and March 2019, an anonymized questionnaire with 10 validated multiple-choice questions about medical microbiology was distributed as hard copies to test the ability to recall knowledge of Saudi medical interns in three tertiary training hospitals in Riyadh, Saudi Arabia. Results: A total of 300 medical interns [164 females (54.7%) and 136 males (45.3%)], in three major tertiary medical care centers in Riyadh, Saudi Arabia, voluntarily participated in the study. Almost a third of participants, 107 (36.4%), graduated from medical schools adopting a traditional curriculum, whereas 184 (63.6%) graduated from medical schools adopting problem-based learning (PBL) instructional approach. The overall mean score out of 10 marks was 3.9±1.8 with almost 82% failures scoring less than six marks. Both total and pass/fail grades were significantly associated with interns who graduated from private colleges. Scores were not significantly associated with any of the investigated parameters except type of college (governmental vs private) with a p-value of 0.049. Conclusion: The current study revealed an overall poor recall of knowledge in microbiology among interns. Our findings suggest a need for a careful revision of curriculum to correct deficiencies, particularly in teaching medical microbiology. Integration of basic sciences is required as well as aligning teaching of basic medical sciences with clinical skills.

Assessment of IL-1ß, IL-6, TNF-α, IL-8, and CCL 5 levels in newly diagnosed Saudi patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle-aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro-inflammatory cytokines and chemokines can contribute to the pathogenesis of RA. AIM: In the current study, we assessed the potential of serum concentrations of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-8, and C-C motif chemokine ligand (CCL)5 as early predictive markers for RA. METHODS: In addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme-linked immunosorbent assay was used to quantify the serum IL-1ß, IL-6, TNF-α, IL-8, and CCL5 levels in the samples. RESULTS: Our results indicated that RF, CRP, and ESR levels were higher in RA patients compared to controls. Furthermore, serum levels of IL-1ß, IL-6, IL-8, and CCL5, but not TNF-α, significantly increased in RA patients compared to controls. CONCLUSION: Overall, the findings suggested that IL-1ß, IL-6, IL-8, and CCL5 can be used as biomarkers in the early diagnosis of RA.

Cardiovascular complications and outcomes among athletes with COVID-19 disease: a systematic review.

BACKGROUND: Current evidence still emerging regarding the risk of cardiovascular (CV) sequel associated with coronavirus disease 2019 (COVID-19) infection, and considerable replicated studies are needed to ensure safe return-to-play. Therefore, we aimed in this systematic review to measure the prevalence of CV complications suffered by COVID-19 athletic patients, explore the outcomes, optimal approaches to diagnoses, and safe return-to-play considerations. METHODS: A systematic search on post COVID-19 infection quantitative studies among athletes was conducted following MeSH terms in Medline, Cochrane Library, Ovid, Embase and Scopus (through 15 January 2022). We included peer-reviewed studies reported athletes' CV complications and the outcomes post COVID-19 infection. Editorials, letters, commentaries, and clinical guidelines, as well as duplicate studies were excluded. Studies involving non-athletic patients were also excluded. Quality assessment was performed using Newcastle-Ottawa Scale. RESULTS: We included 15 eligible articles with a total of 6229 athletes, of whom 1023 were elite or professional athletes. The prevalence of myocarditis ranged between 0.4% and 15.4%, pericarditis 0.06% and 2.2%, and pericardial effusion between 0.27% and 58%. Five studies reported elevated troponin levels (0.9-6.9%). CONCLUSIONS: This study provides a low prevalence of CV complications secondary to COVID-19 infection in short-term follow-up. Early recognition and continuous assessment of cardiac abnormality in competitive athletes are imperative to prevent cardiac complications. Establishing a stepwise evaluation approach is critical with an emphasis on imaging techniques for proper diagnosis and risk assessment for a safe return to play.

SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis.

The human population is currently facing the third and possibly the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China, on 31 December 2019 and spread within a short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt to many point mutation and recombination events; particularly in the spike gene, which enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. Both animal reservoir and intermediate host for SARS-CoV-2 are still unresolved and necessitate further investigation. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed, including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that the SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from natural reservoirs is a priority.

Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality.

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1ß, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1ß, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19.