Body Mass Index as a Predictor of COVID-19 Severity in ICU Patients in Saudi Arabia: A Retrospective Analysis.

Introduction The global coronavirus disease 2019 (COVID-19) pandemic has prompted research into various risk factors, including the role of body mass index (BMI) in disease severity. This study specifically examines the correlation between BMI and the severity of COVID-19 among intensive care unit (ICU) patients in Saudi Arabia, addressing a gap in region-specific data. The study aims to assess the impact of BMI on the severity of COVID-19 in a Saudi Arabian ICU patient cohort, providing insights into how this relationship varies in different demographic contexts. Materials and methods Employing a retrospective cohort design, the study analyzed data from adult ICU patients in Saudi Arabia diagnosed with COVID-19. It focused on variables like BMI at admission, demographic information, and COVID-19 outcomes including severity, recovery, and mortality. Statistical analysis involved regression models, adjusting for age, gender, and comorbidities. Results Unlike global observations, the study found no significant correlation between BMI and COVID-19 severity in the Saudi Arabian context. This suggests that in this specific demographic, other factors may be more critical in determining the severity of the disease. Conclusion Our findings challenge the global consensus on BMI as a key factor in COVID-19 severity, highlighting the importance of regional differences in disease dynamics. They underscore the need for localized healthcare strategies and further research into diverse demographic factors affecting COVID-19. This study contributes to a broader understanding of the pandemic and encourages region-specific approaches in both clinical and public health spheres.

Impact of Using Antiviral Therapy on COVID-19 Progression in ICU Patients: A Saudi Arabian Retrospective Analysis.

Background The COVID-19 pandemic has posed an unprecedented challenge to the global healthcare system, necessitating effective therapeutic strategies to mitigate its impact. This study investigates the significance of early antiviral therapy in the context of intensive care units (ICUs) and its potential to influence the progression and outcomes of severe COVID-19 cases. Methodology This retrospective cohort study leveraged a diverse patient population with confirmed severe COVID-19 admitted to ICUs. A total of 1,250 patients were included in the analysis, and their medical records were comprehensively reviewed. The study aimed to assess the impact of early antiviral therapy on patient outcomes, focusing on the administration of remdesivir within the first 48 hours of ICU admission. Results In a study of 1,250 COVID-19 patients, early antiviral therapy with remdesivir significantly reduced ICU admissions by 30% (N = 225) compared to standard care (N = 525). The early therapy group also exhibited a 20% lower mortality rate (N = 120) than the control group (N = 150). Demographic associations with antiviral usage were observed. Kaletra was favored by females, non-Saudi individuals, and healthcare workers, while favipiravir was associated with gender. Remdesivir and ribavirin use were linked to gender and Saudi nationality, while oseltamivir was related to gender, Saudi nationality, and body mass index. Microbiological cure rates were 15.4%, with 84.6% not achieving it. ICU outcomes included 37.7% deaths, 55.7% home discharges, and 6.6% transfers, while hospital outcomes featured 38.5% deaths, 54.4% home discharges, and 7.1% transfers. Conclusions This study presents a comprehensive analysis of COVID-19 patient demographics, antiviral medication associations, and clinical outcomes. The findings highlight the significance of tailoring treatment strategies based on patient characteristics and viral history. These insights contribute to a deeper understanding of COVID-19 management and can inform clinical decision-making and further research in this field.

The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion.

Lymphovascular invasion (LVI) is a common phenomenon in breast cancer (BC), and it is correlated to poor outcome. However, the biomarkers that influence the development of LVI remain to be defined. Through rigorous bioinformatics analyses, high mobility group protein 3 (HMGB3) was revealed as a driver gene that is associated with the presence of LVI. The purpose of this study was to further investigate the role of HMGB3 in the pathogenesis of LVI in BC. In vitro functional assays were performed to investigate the effect of HMGB3 silencing on cell proliferation, migration, adherence and transmigration of BC cell lines with dermal lymphatic endothelial cells (DLECs) and human vascular endothelial cells (HUVECs). The correlation of HMGB3 expression with clinicopathological parameters was also assessed at the transcriptomic and the proteomic levels using large BC cohorts with well-characterised LVI status. Silencing HMGB3 reduced cell proliferation, migration, adherence and transmigration across endothelial cell lines. At the mRNA and protein levels, high HMGB3 expression was significantly correlated with LVI-positivity, higher tumour grade, lymph nodal stage, hormone receptor negativity, HER2 positivity and poor outcome. Moreover, high HMGB3 expression was an independent predictor of shorter breast cancer-specific survival. HMGB3 plays an oncogenic function and contributes to the development of LVI in BC. Results warrant further investigation as a potential target to inhibit LVI in BC.

Prevalence of functional gastrointestinal disorders in Saudi infants and toddlers: A cross-sectional multicenter study.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are common pediatric problems, but their prevalence in Saudi Arabia is unknown. We aimed to assess the prevalence of FGIDs and risk factors among children in six regions of Saudi Arabia. METHODS: This was a cross-sectional multicenter study enrolling children aged 0-48 months, attending pediatric clinics. Questionnaires evaluated the clinical history, symptoms, and sociodemographic information. FGIDs were defined according to Rome IV criteria. RESULTS: The study involved 1011 infants and toddlers (mean [standard deviation (SD)] aged, 21.7 [19.4] months; FGIDs and mean [SD] age 17.4 [16.4] months; controls). FGIDs were diagnosed in 483 (47.7%) of all infants and toddlers. The prevalence of FGIDs was significantly higher in children aged 0-12 months than in those aged 13-48 months ( P < 0.001). The most common disorders were functional regurgitation (13.8%) in infants and functional constipation (9.6%) in toddlers. Univariate regression analysis confirmed that the rate of FGIDs was higher in term gestational age infants (odds ratio (OR) 2.7; 95% confidence interval (CI), 1.76-4.17, P < 0.001), in partial breastfeeding (OR 0.58; 95% CI, 0.40-0.84, P = 0.003), in formula feeding (OR 2.25; 95% CI, 1.51-3.35, P < 0.001), and in subjects with no history of food allergy (OR 2.40; 95% CI, 1.58-3.64, P < 0.001). CONCLUSION: FGIDs are common in Saudi infants and toddlers (47.7%). Regurgitation is most prevalent in infants, and functional constipation is most common in toddlers. Term gestational age infant, partial breastfeeding, formula feeding, and subjects with no history of food allergy are associated with the prevalence of FGIDs.

Secondary Metabolites, Biological Activities, and Industrial and Biotechnological Importance of Aspergillus sydowii.

Marine-derived fungi are renowned as a source of astonishingly significant and synthetically appealing metabolites that are proven as new lead chemicals for chemical, pharmaceutical, and agricultural fields. Aspergillus sydowii is a saprotrophic, ubiquitous, and halophilic fungus that is commonly found in different marine ecosystems. This fungus can cause aspergillosis in sea fan corals leading to sea fan mortality with subsequent changes in coral community structure. Interestingly, A. sydowi is a prolific source of distinct and structurally varied metabolites such as alkaloids, xanthones, terpenes, anthraquinones, sterols, diphenyl ethers, pyrones, cyclopentenones, and polyketides with a range of bioactivities. A. sydowii has capacity to produce various enzymes with marked industrial and biotechnological potential, including α-amylases, lipases, xylanases, cellulases, keratinases, and tannases. Also, this fungus has the capacity for bioremediation as well as the biocatalysis of various chemical reactions. The current work aimed at focusing on the bright side of this fungus. In this review, published studies on isolated metabolites from A. sydowii, including their structures, biological functions, and biosynthesis, as well as the biotechnological and industrial significance of this fungus, were highlighted. More than 245 compounds were described in the current review with 134 references published within the period from 1975 to June 2023.

The clinical significance of cyclin B1 (CCNB1) in invasive breast cancer with emphasis on its contribution to lymphovascular invasion development.

BACKGROUND: Lymphovascular invasion (LVI) is regulated through complex molecular mechanisms. Cyclin B1 (CCNB1) was previously determined as being associated with LVI using large cohorts of breast cancer (BC) and artificial neural network (ANN) technique. In this study, we aimed to assess the association between CCNB1 and LVI, other clinicopathological and other LVI-related biomarkers at the molecular (RNA transcriptomic) and proteomic levels in BC. METHODS: Two transcriptomic BC cohorts (n = 2834) were used to assess the association between the expression of CCNB1 at the mRNA level and clinicopathological characteristics and patient outcome. Tissue microarrays (TMAs) from a well-characterised BC cohort (n = 2480) with long-term outcome were also used to assess the clinical significance of CCNB1 protein expression using immunohistochemistry. RESULTS: High CCNB1 mRNA expression was associated with aggressive tumour behaviour, including LVI, larger size, higher tumour grade, high lymph nodal stage, hormonal receptor negativity, HER2 positivity and poor clinical outcome (all p < 0.0001). Similarly, high CCNB1 protein expression was associated with higher tumour grade, hormonal receptor negativity and HER2 positivity (all p < 0.0001). Additionally, there was a significant association between CCNB1- and LVI-related biomarkers including N-cadherin, P-cadherin and TWIST2 at the transcriptomic and proteomic level. Multivariate analysis revealed that CCNB1 was an independent predictor of shorter BC-specific survival (HR = 1.3; 95% CI 1.2-1.5; p = 0.010). CONCLUSION: CCNB1 is a key gene associated with LVI in BC and has prognostic value. More functional studies are warranted to unravel the mechanistic role of CCNB1 in the development of LVI.

Upregulation of Cyclin B2 (CCNB2) in breast cancer contributes to the development of lymphovascular invasion.

Lymphovascular invasion (LVI) is a key step in breast cancer (BC) metastasis. Targeting the molecular drivers of LVI can improve BC patients' management. However, the underlying molecular mechanisms of LVI are complex and interconnected with various carcinogenesis pathways. This study aimed to identify the key regulatory gene associated with LVI and to investigate its mechanisms of action and prognostic significance. Artificial neural network (ANN) was applied to two large transcriptomic datasets of BC with well-characterised LVI status. Cyclin B2 (CCNB2) was identified in the top genes associated with LVI positivity. In vitro functional assays were carried out to assess the role of CCNB2 in tumour cell behaviour and their interactions with endothelial cells using a panel of BC cell lines. Large annotated BC cohorts were used to assess the clinical and prognostic role of CCNB2 at the transcriptomic and protein levels. Knockdown (KD) of CCNB2 mRNA reduced BC cell migration, inhibited proliferation, blocked the G2/M transition during the cell cycle and increased the number of apoptotic cells. Importantly, KD of CCNB2 reduced BC cell lines adherence and transmigration across endothelial cell lines. High CCNB2 protein expression was independently associated with LVI positivity in addition to other features of aggressive behaviour, including larger tumour size, higher histological grade, hormonal receptor-negativity, and HER2-positivity, and with shorter survival. We conclude that CCNB2 plays a crucial role in LVI development in BC, implying that CCNB2 could confer a promising therapeutic target to inhibit LVI and reduce metastatic events.

The prognostic significance of interferon-stimulated gene 15 (ISG15) in invasive breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15) LVI status. Thus, we explored the prognostic significance of ISG15 in BC. METHODS: The prognostic significance of ISG15 mRNA was assessed in METABRIC (n = 1980), TCGA (n = 854) and Kaplan-Meier Plotter (n = 3951). ISG15 protein was evaluated using immunohistochemistry (n = 859) in early-stage invasive BC patients with long-term follow-up. The associations between ISG15 expression and clinicopathological features, expression of immune cell markers and patient outcome data were evaluated. RESULTS: High mRNA and protein ISG15 expression were associated with LVI, higher histological grade, larger tumour size, hormonal receptor negativity, HER2 positivity, p53 and Ki67. High ISG15 protein expression was associated with HER2-enriched BC subtypes and immune markers (CD8, FOXP3 and CD68). High ISG15 mRNA and ISG15 expressions were associated with poor patient outcome. Cox proportional multivariate analysis revealed that the elevated ISG15 expression was an independent prognostic factor of shorter BC-specific survival. CONCLUSION: This study provides evidence for the role of ISG15 in LVI development and BC prognosis. Further functional studies in BC are warranted to evaluate the therapeutic potential of ISG15.

Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer.

PURPOSE: Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC). METHODS: NOP10 expression was assessed at mRNA level employing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1980) and Cancer Genome Atlas (TCGA) BC cohorts (n = 854). Protein expression was evaluated on tissue microarray of a large BC cohort (n = 1081) using immunohistochemistry. The correlation between NOP10 expression, clinicopathological parameters and patient outcome was assessed. RESULTS: NOP10 expression was detected in the nucleus and nucleolus of the tumour cells. At the transcriptomic and proteomic levels, NOP10 was significantly associated with aggressive BC features including high tumour grade, high nucleolar score and poor Nottingham Prognostic Index. High NOP10 protein expression was an independent predictor of poor outcome in the whole cohort and in triple-negative BC (TNBC) class (p = 0.002 & p = 0.014, respectively). In chemotherapy- treated patients, high NOP10 protein expression was significantly associated with shorter survival (p = 0.03) and was predictive of higher risk of death (p = 0.028) and development of distant metastasis (p = 0.02) independent of tumour size, nodal stage and tumour grade. CONCLUSION: High NOP10 expression is a poor prognostic biomarker in BC and its expression can help in predicting chemotherapy resistance. Functional assessments are necessary to decipher the underlying mechanisms and to reveal its potential therapeutic values in various BC subtypes especially in the aggressive TNBC class.

Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer.

BACKGROUND: Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC. METHODS: MX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated. RESULTS: High MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0-2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival. CONCLUSION: This study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target.

The ITIM-Containing Receptor: Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) Modulates Immune Response and Confers Poor Prognosis in Invasive Breast Carcinoma.

BACKGROUND: The leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) plays a role in immune response homeostasis, extracellular matrix remodelling and it is overexpressed in many high-grade cancers. This study aimed to elucidate the biological and prognostic role of LAIR-1 in invasive breast cancer (BC). METHODS: The biological and prognostic effect of LAIR-1 was evaluated at the mRNA and protein levels using well-characterised multiple BC cohorts. Related signalling pathways were evaluated using in silico differential gene expression and siRNA knockdown were used for functional analyses. RESULTS: High LAIR-1 expression either in mRNA or protein levels were associated with high tumour grade, poor Nottingham Prognostic Index, hormone receptor negativity, immune cell infiltrates and extracellular matrix remodelling elements. High LAIR-1 protein expression was an independent predictor of shorter BC-specific survival and distant metastasis-free survival in the entire BC cohort and human epidermal growth factor receptor 2 (HER2)+ subtype. Pathway analysis highlights LAIR-1 association with extracellular matrix remodelling-receptor interaction, and cellular proliferation. Depletion of LAIR-1 using siRNA significantly reduced cell proliferation and invasion capability in HER2+ BC cell lines. CONCLUSION: High expression of LAIR-1 is associated with poor clinical outcome in BC. Association with immune cells and immune checkpoint markers warrant further studies to assess the underlying mechanistic roles.

The prognostic significance of wild-type isocitrate dehydrogenase 2 (IDH2) in breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is a prerequisite step in breast cancer (BC) metastasis. We have previously identified wild-type isocitrate dehydrogenase 2 (IDH2) as a key putative driver of LVI. Thus, we explored the prognostic significance of IDH2 at transcriptome and protein expression levels in pre-invasive and invasive disease. METHODS: Utlising tissue microarrays from a large well annotated BC cohort including ductal carcinoma in situ and invasive breast cancer (IBC), IDH2 was assessed at the transcriptomic and proteomic level. The associations between clinicopathological factors including LVI status, prognosis and the expression of IDH2 were evaluated. RESULTS: In pure DCIS and IBC, high IDH2 protein expression was associated with features of aggressiveness including high nuclear grade, larger size, comedo necrosis and hormonal receptor negativity and LVI, higher grade, larger tumour size, high NPI, HER2 positivity, and hormonal receptor negativity, respectively. High expression of IDH2 either in mRNA or in protein levels was associated with poor patient's outcome in both DCIS and IBC. Multivariate analysis revealed that IDH2 protein expression was an independent risk factor for shorter BC specific-survival. CONCLUSION: Further functional studies to decipher the role of IDH2 and its mechanism of action as a driver of BC progression and LVI are warranted.

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer.

PURPOSE: The epithelial-mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance of LCN2 expression in breast cancer. METHODS: The expression of LCN2 protein was immunohistochemically assessed in two well-characterised annotated cohorts of breast cancer (discovery cohort, n = 612; validation cohort, n = 1363). The relationship of LCN2 expression and subcellular location with the clinicopathological factors and outcomes of patients was analysed. RESULTS: Absent or reduced nuclear LCN2 expression was associated with features of aggressive behaviour, including high histological grade, high Nottingham Prognostic Index, high Ki67 labelling index, hormone receptor negativity and human epidermal growth factor receptor 2 positivity. The high cytoplasmic expression of LCN2 was correlated with lymph node positivity. The nuclear downregulation of LCN2 was correlated with the overexpression of EMT associated proteins (N-cadherin and Twist-related protein 2) and basal biomarkers (cytokeratin 5/6 and epidermal growth factor receptor). Unlike the cytoplasmic expression of LCN2, the loss of nuclear expression was a significant predictor of poor outcome. The combinatorial expression tumours with high cytoplasmic and low nuclear expression were associated with the worst prognosis. CONCLUSIONS: Tumour cell expression of LCN2 plays a role in breast cancer progression with loss of its nuclear expression which is associated with aggressive features and poor outcome. Further functional analysis is warranted to confirm the relationship between the subcellular localisation LCN2 and behaviour of breast cancer.

A key genomic subtype associated with lymphovascular invasion in invasive breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is associated with the development of metastasis in invasive breast cancer (BC). However, the complex molecular mechanisms of LVI, which overlap with other oncogenic pathways, remain unclear. This study, using available large transcriptomic datasets, aims to identify genes associated with LVI in early-stage BC patients. METHODS: Gene expression data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1565) was used as a discovery dataset, and The Cancer Genome Atlas (TCGA; n = 854) cohort was used as a validation dataset. Key genes were identified on the basis of differential mRNA expression with respect to LVI status as characterised by histological review. The relationships among LVI-associated genomic subtype, clinicopathological features and patient outcomes were explored. RESULTS: A 99-gene set was identified that demonstrated significantly different expression between LVI-positive and LVI-negative cases. Clustering analysis with this gene set further divided cases into two molecular subtypes (subtypes 1 and 2), which were significantly associated with pathology-determined LVI status in both cohorts. The 10-year overall survival of subtype 2 was significantly worse than that of subtype 1. CONCLUSION: This study demonstrates that LVI in BC is associated with a specific transcriptomic profile with potential prognostic value.