Anterior Spinal Artery Syndrome in a Patient With Multilevel Cervical Disc Disease: A Case Report.

Anterior spinal artery syndrome (ASAS) is a rare form of spinal cord infarction, making its incidence and prevalence difficult to determine. We present the case of a 60-year-old woman with multiple vascular risk factors who experienced a sudden onset of severe lower limb weakness, raising immediate concerns about spinal cord ischemia. Diagnostic evaluations confirmed ASAS, although the exact cause and mechanism of her spinal cord infarction remained undetermined. The potential presence of significant cervical disc disease suggests fibrocartilaginous embolism (FCE) as a possible underlying mechanism, despite the lack of direct evidence. This case underscores the importance of clinical awareness and timely intervention in patients with similar symptoms and vascular risk factors. Early recognition, cause identification, and appropriate management are crucial for improving outcomes in spinal cord ischemia, guiding specific treatment strategies, and potentially preventing recurrence.

Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes.

This study aimed to provide an understanding of the influence of eugenol on CYP1A2, 2C9, 2D6, and 3A4 in human liver microsomes (HLM). Specific substrate for CYP1A2, 2C9, 2D6, and 3A4 were incubated in HLM with or without eugenol. The formation of their respective metabolites was assessed with HPLC analytical methods. Eugenol at 1, 10 and 100 µM levels inhibited the activity of CYP1A2 and CYP2C9 by 23.38 %, 23.57 %, 39.80 % and 62.82 %, 63.27 %, 67.70 % respectively. While, CYP2D6 and CYP3A4 activity was decreased by 40.70 %, 45.88 %, 62.68 % and 37.41 %, 42.58 % and 67.86 % at 1, 10 and 100 µM eugenol level respectively. The IC50 value of eugenol for CYP2D6 and CYP3A4 was calculated as 11.09 ± 3.49 µM and 13.48 ± 3.86 µM respectively. Potential herb-drug interactions was noted when eugenol is administered simultaneously with medications metabolized by these enzymes, most notably CYP2C9, CYP2D6 and CYP3A4.

The Trend of Antibiotic Consumption After the COVID-19 Pandemic: Approach to Future Outbreaks.

Background: Earlier reports suggested high rates of antibiotic utilization among COVID-19 patients despite the lack of direct evidence of their activity against viral pathogens. Different trends in antibiotic consumption during 2020 compared to 2019 have been reported. Purpose: The objective of this study is to assess the impact of COVID-19 pandemic on antibiotic consumption in the presence of active Antibiotic Stewardship Program. Methods: This study represented a five years assessment of the consumption of the commonly prescribed antibiotics measured as DDDs/100-Bed Days. We analyzed the data by using nonparametric Friedman and Friedman tests to compare the antibiotic consumption before and during the three subsequent waves of COVID-19. Results: Antibiotic consumption through the DDDs/100-BD has shown reduction in the median of antibiotics consumption of most antibiotics during the period of COVID-19 as compared to the pre-COVID-19 period, which was significant for meropenem and ciprofloxacin, except colomycin that slightly increased. Significant reduction in the consumption of imipenem and meropenem during the second and third waves as compared to the pre-COVID period. Throughout the years, significant reductions were observed between 2018 and 2019 (p=<.001), 2018 and 2020 (p=0.008), and 2018 and 2022 (p=0.002). Conclusion: The reduction in antibiotic consumption is attributed to the strong influence if the ASP and the reluctance of people to visit hospitals during the COVID-19 pandemic. Other related COVID-19 precautions such as physical distance, good hand hygiene, facemasks, that resulted in the prevention of secondary bacterial infections have contributed to the reduction in antibiotic utilization during the pandemic.

A Rare Case of Contralateral Ischemic Stroke Recurrence Post-Reperfusion: Successful Management Through Timely Thrombectomy.

Stroke is a predominant contributor to global mortality and disability and represents a complex and heterogeneous disease characterized by diverse risk factors and clinical presentations. The likelihood of stroke patients being at risk of a second stroke within the first five years is higher, especially within the initial two weeks. The distressing prospect of experiencing recurrent stroke shortly after reperfusion therapy adds an additional layer of complexity, potentially reversing prior progress. In the present case, we describe a patient who experienced a recurrent stroke within 24 hours, affecting the contralateral middle cerebral artery (MCA). This recurrence occurred after the individual underwent thrombolysis therapy for the initial stroke, emphasizing the intricate challenges associated with managing such cases and the imperative for targeted interventions to mitigate further risks and enhance patient outcomes.

Assessing the influence of COVID-19 on influenza prevalence: A multicenter time series study.

BACKGROUND: During the COVID-19 pandemic, countries around the world implemented various interventions to manage the spread of respiratory illnesses, including influenza. However, there is a lack of studies that have assessed the influence of COVID-19 on influenza prevalence in Saudi Arabia. In this study, we aimed to evaluate the prevalence of positive influenza cases before and during the COVID-19 pandemic in relation to the mitigation measures and policy initiatives in Saudi Arabia. METHODS: A multicenter, time-series cross-sectional study was conducted to evaluate influenza prevalence before and during the COVID-19 pandemic between 01/01/2017 and 31/12/2021. This study included all patients who were screened for influenza infection at healthcare facilities across Saudi Arabia using polymerase chain reaction (PCR). The primary outcome was to determine the prevalence of influenza infections before and during the COVID-19 pandemic, while the secondary outcome was to describe the demographic data and comorbidities of the included patients in both periods. RESULTS: During the study period, 5238 cases were identified based on a positive PCR result for influenza virus. The yearly number of influenza cases in the pre-COVID-19 period was 1123 (2.03 %), 1075 (1.63 %), and 1883 (2.20 %) cases in 2017, 2018, and 2019, respectively. On the other hand, the number of cases during the COVID-19 pandemic was 417 (0.63 %) and 740 (1.27 %) in 2020 and 2021, respectively, with a comparable number of performed tests. Patients infected with the influenza virus between 2020 and 2021 were older than patients who were infected before the COVID-19 pandemic. CONCLUSION: The study found a lower number of influenza cases during the COVID-19 pandemic, with no clear peak during November and December 2020 and 2021.

Incidence and risk factors of contrast-induced nephropathy in acute stroke patients undergoing computed tomography angiography: A single-center study.

OBJECTIVES: To investigate the prevalence and risk factors linked to contrast-induced nephropathy in this specific patient population, aiming to ensure the highest quality of clinical care. METHODS: In a retrospective analysis, all patients who presented with an acute stroke to King Fahad Hospital, Jeddah, Emergency Department from March until November 2022 and underwent Computed Tomography Angiography (CTA) brain, Inclusion criteria were as follows: a baseline creatinine results and CTA examination performed within 24 hours of symptom onset and an available early (<5 days after CTA) follow-up creatinine result. RESULTS: Among 246 stroke patients in the emergency, 182 underwent brain CTA and 8.24% had Contrast-Induced Nephropathy (CIN). intracerebral hemorrhage (ICH) increased CIN risk 7-fold (OR=6.7; 95% CI: 1.23-33.3). Abnormal baseline raised CIN risk 8-fold (OR=7.8; 95% CI: 1.74-35.1). hypertension doubled the risk for CIN (OR=2.1; 95% CI: 1.26-6.98) CONCLUSION: The incidence of CIN was 8.2%, particularly elevated in patients with ICH, hypertension, tissue plasminogen administration, and abnormal baseline, necessitating vigilance in managing acute stroke cases.

Hand Knob Syndrome Secondary to Ipsilateral Concomitant Carotid Fibromuscular Dysplasia and Proximal Atherosclerotic Disease.

One of the uncommon stroke presentations is the isolated wrist drop syndrome, caused by a stroke affecting the hand knob area, with the embolic mechanism being the most commonly identified mechanism. Here, we present the case of a 62-year-old female patient who presented with acute-onset isolated wrist drop secondary to right internal carotid artery fibromuscular dysplasia with a string of beads appearance and coexisting proximal atherosclerotic severe stenosis. The patient underwent successful carotid artery stenting. Patients with hand knob stroke may present a diagnostic dilemma and can be misdiagnosed as having peripheral neuropathy due to the absence of pyramidal signs and other symptoms of cortical involvement, leading to delayed or inappropriate treatment.

The landscape of biomedical research progress, challenges and prospects in Saudi Arabia-A systematic review.

Introduction: The main objective of this review was to synthesize the progress, challenges and prospects of biomedical research in Saudi Arabia in order to provide a holistic view to all stakeholders, such as policy makers, decision makers, and local researchers along with external collaborators interested in the field of biomedical research in this region. Methods: A systematic review was conducted using the scientific literature for bibliometric studies in the field of biomedical research in Saudi Arabia that comprehensively covered past few decades using PubMed. The search was performed by combining verified Medical Subject Heading (MeSH) terms: "biomedical research", "bibliometrics", "Saudi Arabia" using boolean operator "AND". The data collection was done from January to June 2022 by both authors. Results: Out of 202 articles yielded from initial search, 13 articles met all of the inclusion criteria and were examined in details. The outcome of analysis showed that with the augmentation of Research and Development (R&D) globalization in Saudi Arabia, researchers are publishing internationally and collaborating globally, academic and research centers are enriching research environment and policies, and government is taking many initiatives to bolster biomedical research; but still more improvements needs to be achieved by Saudi Arabia to be in the list of strong competitive leading nations in the global biomedical research field. Conclusions: There were various key challenges related to biomedical publications and bibliometric aspects for Saudi Arabia that included: publishing preferences, quality of publications, indexing services, international scientific community, and importantly barriers related to planning, funding, training, resources and support at institutional and national levels. This review provided some insights and recommendations to enhance biomedical research in Saudi Arabia that included: effective policies, health priorities, building infrastructures, greater investments, high incentives, skilled recruitment, competitive training and engagement of community that can play a vital role in this context.

Neuromyelitis Optica Spectrum Disorder: A Rare Case of Transverse Myelitis and Autonomic Dysfunction.

Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating central nervous system disease commonly presenting with optic neuritis and transverse myelitis. Its pathology is mediated by serum aquaporin 4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG) antibodies. It can present in a relapsing and monophasic pattern and is diagnosed using the diagnostic criteria published in 2015 by the international panel on neuromyelitis optica (NMO) diagnosis. We describe the case of a 25-year-old man who had a history of painful eye movement and complete loss of vision affecting his left eye for which he was diagnosed with optic neuritis two months prior to presentation. The patient presented with transverse myelitis followed by a picture of autonomic dysfunction in the form of labile blood pressure and heart rate readings associated with profuse sweating as well as significant MRI findings. Neuromyelitis optica was diagnosed with positive AQP4-IgG and longitudinally extensive transverse myelitis. Treatment was initiated with pulse steroid and plasmapheresis followed by oral prednisolone and azathioprine following which the patient's condition stabilized.

MICaFVi: A Novel Magnetic Immuno-Capture Flow Virometry Nano-Based Diagnostic Tool for Detection of Coronaviruses.

COVID-19 has resulted in a pandemic that aggravated the world's healthcare systems, economies, and education, and caused millions of global deaths. Until now, there has been no specific, reliable, and effective treatment to combat the virus and its variants. The current standard tedious PCR-based tests have limitations in terms of sensitivity, specificity, turnaround time, and false negative results. Thus, an alternative, rapid, accurate, and sensitive diagnostic tool that can detect viral particles, without the need for amplification or viral replication, is central to infectious disease surveillance. Here, we report MICaFVi (Magnetic Immuno-Capture Flow Virometry), a novel precise nano-biosensor diagnostic assay for coronavirus detection which combines the MNP-based immuno-capture of viruses for enrichment followed by flow-virometry analysis, enabling the sensitive detection of viral particles and pseudoviruses. As proof of concept, virus-mimicking spike-protein-coated silica particles (VM-SPs) were captured using anti-spike-antibody-conjugated MNPs (AS-MNPs) followed by detection using flow cytometry. Our results showed that MICaFVi can successfully detect viral MERS-CoV/SARS-CoV-2-mimicking particles as well as MERS-CoV pseudoviral particles (MERSpp) with high specificity and sensitivity, where a limit of detection (LOD) of 3.9 µg/mL (20 pmol/mL) was achieved. The proposed method has great potential for designing practical, specific, and point-of-care testing for rapid and sensitive diagnoses of coronavirus and other infectious diseases.

Reversible CT Scan Hypodensity in Acute Ischemic Stroke Patient With Low Initial Alberta Stroke Program Early CT Score (ASPECTS) Following Endovascular Thrombectomy: A Case Report.

According to current American and European guidelines, mechanical thrombectomy is recommended only for patients with an Alberta Stroke Program Early CT Score (ASPECTS) of 6 or higher. However, recent literature suggests that the potential benefits of reperfusion therapy should not be solely determined by baseline ASPECTS. In this case report, we present a young female patient with a low initial ASPECTS (4-5), who underwent mechanical thrombectomy and showed marked improvement in both CT imaging and clinical symptoms. Our findings potentially show that mechanical thrombectomy may be beneficial even for patients with an initial ASPECTS ≤ 5. These results may contribute to the growing evidence supporting the use of mechanical thrombectomy as a viable treatment option for acute ischemic stroke patients with low baseline ASPECTS.

Salivary Antibody Responses to Two COVID-19 Vaccines following Different Vaccination Regimens.

Background: To date, little is known about the salivary mucosal immune response following different COVID-19 vaccine types or after a booster (3rd) dose of the BNT162b2 (BNT) vaccine. Methods: A total of 301 saliva samples were collected from vaccinated individuals and arranged into two cohorts: cohort 1 (n = 145), samples from individuals who had received two doses against SARS-CoV-2; cohort 2 (n = 156), samples from individuals who had received a booster of BNT vaccine. Cohorts 1 and 2 were sub-stratified into three groups based on the types of first and second doses (homologous BNT/BNT, homologous ChAdOx1/ChAdOx1, or heterologous BNT/ChAdOx1vaccinations). Salivary immunoglobulin G (IgG) response to SARS-CoV-2 spike glycoprotein was measured by ELISA, and clinical demographic data were collected from hospital records or questionnaires. Results: Salivary IgG antibody responses against different vaccines, whether homologous or heterogeneous vaccination regimens, showed similar levels in cohorts 1 and 2. Compiling all groups in cohort 1 and 2 showed significant, albeit weak, negative correlations between salivary IgG levels and time (r = -0.2, p = 0.03; r = -0.27, p = 0.003, respectively). In cohort 2, the durability of salivary IgG after a booster dose of BNT162b2 significantly dropped after 3 months compared to the <1 month and 1-3 months groups. Conclusions: Different COVID-19 vaccine types and regimens elicit similar salivary anti-SARS-CoV-2 IgG with modest waning over time. Boosting with BNT162b2 vaccine did not produce an evident increase in mucosal IgG response whereby COVID-19 recovered subjects show higher salivary IgG than naive, post-vaccination subjects. The ChAdOx1/ChAdOx1 regimen showed better correlation between salivary IgG levels and durability. These findings highlight the importance of developing oral or intra-nasal vaccines to induce stronger mucosal immunity.

Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-ß1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-ß1b and lopinavir-ritonavir did not significantly differ between the two groups. Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

Heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels.

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir-Ritonavir and Interferon ß-1b), we evaluated the heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-ß1b and lopinavir-ritonavir and 38 received placebo. Interferon-ß1b and lopinavir-ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-ß1b and lopinavir-ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).

Persistence of Anti-SARS-CoV-2 Spike IgG Antibodies Following COVID-19 Vaccines.

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.

Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells.

Lipid rafts in cell plasma membranes play a critical role in the life cycle of many viruses. However, the involvement of membrane cholesterol-rich lipid rafts in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether the presence of cholesterol-rich microdomains is required for the entry of SARS-CoV-2 into host cells. Our results show that depletion of cholesterol in the rafts by methyl-beta-cyclodextrin (MßCD) treatment impaired the expression of the cell surface receptor angiotensin-converting enzyme 2 (ACE2), resulting in a significant increase in SARS-CoV-2 entry into cells. The effects exerted by MßCD could be substantially reversed by exogenous cholesterol replenishment. In contrast, disturbance of intracellular cholesterol homeostasis by statins or siRNA knockdown of key genes involved in the cholesterol biosynthesis and transport pathways reduced SARS-CoV-2 entry into cells. Our study also reveals that SREBP2-mediated cholesterol biosynthesis is involved in the process of SARS-CoV-2 entry in target cells. These results suggest that the host membrane cholesterol-enriched lipid rafts and cellular cholesterol homeostasis are essential for SARS-CoV-2 entry into cells. Pharmacological manipulation of intracellular cholesterol might provide new therapeutic strategies to alleviate SARS-CoV-2 entry into cells.

Immunogenicity of High-Dose MVA-Based MERS Vaccine Candidate in Mice and Camels.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime-boost vaccinations in mice and camels. METHODS: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. RESULTS: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). CONCLUSIONS: MVA-MERS vaccine, administered in a homologous prime-boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans.

Analysis of potential risk factors associated with COVID-19 and hospitalization.

Coronavirus disease 2019 (COVID-19) was found to cause complications in certain groups of people, leading to hospitalization. Several factors have been linked to this, such as gender, age, comorbidity, and race. Understanding the precise reasons for the COVID-19-induced complications might help in designing strategies to minimize hospitalization. A retrospective, cross-sectional observational study was conducted for patients in a COVID-19-designated specialty hospital after obtaining ethical clearance. Patients' demographic and clinical characteristics, such as age, gender, race, vaccinated status, complications, comorbidities, and medications, were retrieved from the hospital medical database. The data were statistically analyzed to determine the association between the predictors and the outcomes of COVID-19. An odds ratio (both unadjusted and adjusted) analysis was carried out to determine the risk factors for hospitalization [non-intensive care (non-ICU) and intensive care (ICU)] due to COVID-19. The data from the study indicated that the majority of patients hospitalized due to COVID-19 were male (>55%), aged > 60 years (>40%), married (>80%), and unvaccinated (>71%). The common symptoms, complications, comorbidities, and medications were fever, pneumonia, hypertension, and prednisolone, respectively. Male gender, patients older than 60 years, unemployed, unvaccinated, complicated, and comorbid patients had an odds ratio of more than 2 and were found to be significantly (p < 0.05) higher in ICU admission. In addition, administration of prednisolone and remdesivir was found to significantly reduce (p < 0.05) the odds ratio in ICU patients. The analysis of the data suggested that male gender, age above 60 years, and unvaccinated with comorbidities increased the complications and resulted in hospitalization, including ICU admission. Hypertension and type 2 diabetes associated with obesity as metabolic syndrome could be considered one of the major risk factors. Preventive strategies need to be directed toward these risk factors to reduce the complications, as well as hospitalization to defeat the COVID-19 pandemic.