Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

The impact of postoperative aspirin in patients undergoing Woven EndoBridge: a multicenter, institutional, propensity score-matched analysis.

BACKGROUND: The Woven EndoBridge (WEB) device is frequently used for the treatment of intracranial aneurysms. Postoperative management, including the use of aspirin, varies among clinicians and institutions, but its impact on the outcomes of the WEB has not been thoroughly investigated. METHODS: This was a retrospective, multicenter study involving 30 academic institutions in North America, South America, and Europe. Data from 1492 patients treated with the WEB device were included. Patients were categorized into two groups based on their postoperative use of aspirin (aspirin group: n=1124, non-aspirin group: n=368). Data points included patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Propensity score matching (PSM) was applied to balance variables between the two groups. RESULTS: Prior to PSM, the aspirin group exhibited significantly higher rates of modified Rankin scale (mRS) mRS 0-1 and mRS 0-2 (89.8% vs 73.4% and 94.1% vs 79.8%, p<0.001), lower rates of mortality (1.6% vs 8.6%, p<0.001), and higher major compaction rates (13.4% vs 7%, p<0.001). Post-PSM, the aspirin group showed significantly higher rates of retreatment (p=0.026) and major compaction (p=0.037) while maintaining its higher rates of good functional outcomes and lower mortality rates. In the multivariable regression, aspirin was associated with higher rates of mRS 0-1 (OR 2.166; 95% CI 1.16 to 4, p=0.016) and mRS 0-2 (OR 2.817; 95% CI 1.36 to 5.88, p=0.005) and lower rates of mortality (OR 0.228; 95% CI 0.06 to 0.83, p=0.025). However, it was associated with higher rates of retreatment (OR 2.471; 95% CI 1.11 to 5.51, p=0.027). CONCLUSIONS: Aspirin use post-WEB treatment may lead to better functional outcomes and lower mortality but with higher retreatment rates. These insights are crucial for postoperative management after WEB procedures, but further studies are necessary for validation.

Quantitative image signature and machine learning-based prediction of outcomes in cerebral cavernous malformations.

PURPOSE: There is increasing interest in novel prognostic tools and predictive biomarkers to help identify, with more certainty, cerebral cavernous malformations (CCM) susceptible of bleeding if left untreated. We developed explainable quantitative-based machine learning models from magnetic resonance imaging (MRI) in a large CCM cohort to demonstrate the value of artificial intelligence and radiomics in complementing natural history studies for hemorrhage and functional outcome prediction. MATERIALS AND METHODS: One-hundred-eighty-one patients from a prospectively registered cohort of 366 adults with CCM were included. Fluid attenuated inversion recovery (FLAIR) T2-weighted brain images were preprocessed, and CCM and surrounding edema were segmented before radiomic feature computation. Minority class oversampling, dimensionality reduction and feature selection methods were applied. With prospective hemorrhage as primary outcome, machine learning models were built, cross-validated, and compared using clinico-radiologic, radiomic, and combined features. SHapley Additive exPlanations (SHAP) was used for interpretation to determine the radiomic features with most contribution to hemorrhage prediction. RESULTS: The highest performances in hemorrhage predictions on the test set were combining radiomic and clinico-radiological features with an area under the curve (AUC) of 83% using linear regression and selected features, and an F1 score of 61% and 85% sensitivity using K-nearest neighbors with principal component analysis (PCA). Multilayer perceptron had the best performance predicting modified Rankin Scale ≥ 2 with an AUC of 74% using PCA derived features. For interpretation of the selected radiomic signature XGBoost model, Shapley additive explanations highlighted 6 radiomic features contributing the most to hemorrhage prediction. CONCLUSION: Quantitative image-based modeling using machine learning has the potential to highlight novel imaging biomarkers that predict hemorrhagic and functional outcomes, ensuring more precise and personalized care for CCM patients.

First-line thrombectomy strategy for carotid terminus occlusions: A systematic review and meta-analysis.

Background: Little research has focused on the performance of mechanical thrombectomy (MT) in carotid terminus occlusions (CTOs). Therefore, the best first-line thrombectomy strategy for CTOs remains unclear. Purpose: To compare the safety and efficacy outcomes of three first-line thrombectomy techniques in CTOs. Methods: A systematic literature search was conducted in Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, and Cochrane Central Register of Clinical Trials databases. Studies providing safety and efficacy outcomes for endovascular treatment of CTOs were included. Data regarding successful recanalization, functional independence, symptomatic intracranial hemorrhage (sICH), and first pass efficacy (FPE) were extracted from the included studies. A random-effects model was used to calculate prevalence rates and their corresponding 95% confidence intervals (CI), and subgroup analyses were performed to assess the impact of the initial MT technique on safety and efficacy outcomes. Results: Six studies with 524 patients were included. The overall successful recanalization rate was 85.84% (95% CI = 77.96-94.52), and subgroup analysis did not show a significant difference among the three first-line MT techniques. Overall rates of functional independence and FPE were 39.73% (95% CI = 32.95-47.89) and 32.09% (95% CI = 22.93-44.92), respectively. The combined stent retriever (SR) and aspiration (ASP) technique achieved significantly higher first-pass efficacy rates compared to SR or ASP alone. The overall sICH rate was 9.89% (95% CI = 4.88-20.07), and subgroup analysis did not demonstrate a significant difference across groups. The sICH rates of SR, ASP, and SR + ASP were 8.49% (95% CI = 1.76-40.93), 6.8% (95% CI = 4.59-10.09), and 7.12% (95% CI = 0.27-100), respectively. Conclusions: Our results support that MT is highly effective for CTOs with functional independence rates of 39%. Additionally, in our meta-analysis, the SR + ASP technique was associated significantly greater rates of FPE compared to SR or ASP alone, without an increase in sICH rates. Prospective, large-scale studies are necessary to determine the optimal first-line MT technique in the endovascular treatment of CTOs.

Technical and clinical success after venous sinus stenting for treatment of idiopathic intracranial hypertension using a novel guide catheter for access: Case series and initial multi-center experience.

INTRODUCTION: Venous sinus stenting is a well established alternative to cerebrospinal fluid diversion for the treatment of idiopathic intracranial hypertension (IIH) with associated venous sinus stenosis. During this procedure, distal guide catheter placement within the venous sinuses may be desirable to facilitate stent delivery. We report our initial experience using the TracStar LDP™ (Imperative Care, Campbell, USA, 0.088-inch inner diameter) as the guide catheter for intracranial access during venous sinus stenting. METHODS: A multi-institutional retrospective chart review of a prospectively maintained IRB-approved database was performed. Consecutive patients who underwent venous sinus stenting from 1/1/2020-9/6/2021 for IIH were included. Patient characteristics, procedural details, TracStar distal reach, outcomes, and complications were collected and analyzed. RESULTS: Fifty-eight patients were included. The mean age was 33.8 years and 93.1% of patients were female. Visual changes prompted evaluation in 86.2% of patients. Stent placement was successful in all patients. The TracStar LDP catheter was advanced to the location of stent placement in 97.9% of cases in which it was attempted. The large 0.088-inch inner diameter lumen enabled compatibility with all desired stent sizes ranging from six to 10 millimeters. Gradient pressure across transverse sinus stenosis dropped from an average of 19.5 mmHg pre-procedure to 1.7 mmHg post-stent placement (p < 0.001). Clinical improvement was achieved in 87.9% (51/58) of patients. There were no catheter-related complications. CONCLUSION: The TracStar LDP is a safe and effective access platform for reaching treatment locations in patients who present with idiopathic intracranial hypertension and who are candidates for venous sinus stent placement.

Clinical and Prognostic Significance of Baseline Serum Vitamin D Levels in Hospitalized Egyptian Covid-19 Patients.

Background and Aim: Vitamin D is a hormone with essential roles in both cellular metabolism and immunity. It controls calcium homeostasis and modulates innate and adaptive immune system responses. Many studies suggested an association between vitamin D deficiency and clinical outcomes of covid-19 infection, while others failed to document such a relation. The present study aimed to evaluate the clinical and prognostic significance of baseline vitamin D levels in hospitalized Egyptian covid-19 patients. Patients and Methods: The present retrospective study included 300 hospitalized covid-19 patients. Patients were submitted to standard clinical, laboratory, and radiological assessment. According to vitamin D levels, patients were classified to have normal levels (≥30), insufficient levels (20-29) or deficient levels (<20). Results: According to their vitamin D levels, patients were classified into those with normal vitamin D (n=135), others with vitamin D insufficiency (n=114), and a third group with vitamin D deficiency (n=51). Patients with normal vitamin D levels and vitamin D insufficiency are significantly younger [median (IQR): 49.0 (39.0-57.0) versus 51.0 (40.0-61.0) and 55.0 (43.0-62.0) years, respectively, p=0.012] and had less frequency of severe disease (24.4% versus 40.4% and 51.0%, respectively) when compared with those with vitamin D deficiency. Moreover, they had significantly lower levels of D dimer [median (IQR): 1.5 (0.9-2.5) versus 1.8 (0.9-3.1) and 2.0 (1.0-3.2)], CRP [median (IQR): 58.0 (30.0-120.0) versus 76.0 (42.5-160.0) and 105.0 (74.0-208.0), respectively, p<0.001], ferritin [median (IQR): 458.0 (240.0-759.0) versus 606.0 (433.8-897.8) and 820.0 (552.0-1087.0), respectively, p<0.001], and procalcitonin [median (IQR): 290.0 (152.0-394.0) versus 372.5 (227.0-530.5) and 443.0 (272.0-575.0), respectively, p<0.001]. Only lower vitamin D levels were significant predictors of mortality in multivariate analysis [OR (95% CI): 0.88 (0.84-0.92), p<0.001]. Conclusion: Low vitamin D levels are related to exaggerated inflammatory response, disease severity, and poor clinical outcome in hospitalized covid-19 patients.

Stroke-Related Sarcopenia among Two Different Developing Countries with Diverse Ethnic Backgrounds (Cross-National Study in Egypt and China).

The prevalence of stroke-related sarcopenia differs according to the diagnostic criteria, the cut-off point for assessment, and ethnicity. Egypt and China are developing countries with different races where no research concerning stroke-related sarcopenia has been performed yet. We aimed to evaluate the prevalence of possible sarcopenia and confirmed sarcopenia among Egyptian and Chinese stroke survivors using the Asian Working Group of Sarcopenia (AWGS-2019) criteria and to assess the variables associated with the prevalence rate. A prospective cross-sectional study was carried out among 200 Egyptian and 195 Chinese stroke survivors from 2019 to 2021 using a structural health questionnaire. A hand-held dynamometer was used to measure grip strength. Anthropometric measures were used to estimate muscle mass. Data were analyzed using SPSS statistics version 20. p-values < 0.05 were considered statistically significant. The prevalence of possible sarcopenia ranged from 20.0% to 34.4% among Egyptian and Chinese groups, except for the Egyptian females where it was 52.0%. The prevalence of sarcopenia in both populations ranged from 13.6% to 18.6%. Pre-stroke independent variables that accelerated possible sarcopenia were age, history of dyslipidemia, diabetes mellitus, and ischemic heart disease, but stroke severity was a post-stroke risk factor. Age was the only pre-stroke variable for sarcopenia, while quitting smoking and having good nutritional status were variables for the reduction of possible sarcopenia. Quitting smoking, having a good nutritional status, and early rehabilitation reduced sarcopenia development. Controlling vascular risk factors, enhancing rehabilitation, and nutritional therapy are protective measures against sarcopenia. Longitudinal studies are required to identify further risk factors.

Evaluation of gene expression of PLEKHS1, AADAC, and CDKN3 as novel genomic markers in gastric carcinoma.

Gastric cancer (GC) is considered lethal aggressive cancer. In Egypt, GC has a low incidence but unfortunately, it is mostly diagnosed at an advanced stage with a poor prognosis. Assessment of novel markers that can be used in the early detection of GC is an urgent need. The present study was performed to assess the association of the Pleckstrin homology domain-containing S1 (PLEKHS1)، arylacetamide deacetylase (AADAC, and Cyclin-dependent kinase inhibitor 3 (CDKN3) genes with GC and to correlate their gene expression levels with tumor stage, grade, and other clinicopathological features. The current work was performed on forty gastric tissue samples; twenty in Group 1 with GC tissues at different stages, and grades and twenty in Group 2 (control group) with non-tumorous tissue. PLEKHS1, AADAC, and CDKN3 gene expression were assessed by RT-qPCR. AADAC, CDKN3 genes were significantly (p<0.001) upregulated, while PLEKHS1 gene was significantly (p<0.001) downregulated in the GC group than the control group. AADAC gene expression exhibited a high significant (p<0.001) positive correlation with the tumor grades and the tumor stages. A high significant negative correlation between AADAC, and CDKN3 gene expression (r = -.760, p<0.001) was found. The three studied parameters showed high significant sensitivity and specificity in the prediction of the presence of GC. PLEKHS1, AADAC, and CDKN3 gene expressions were suggested to be used as diagnostic and predictive biomarkers of GC, additionally, AADAC may be used as a prognostic marker in these patients for further future confirming studies.

Cerebral Amyloid Angiopathy and Atrial Fibrillation: An up to Date Case Report.

Concurrent Cerebral Amyloid Angiopathy (CAA) and Atrial Fibrillation are becoming an increasingly common dilemma in clinical practice due to the aging population and the comorbidities associated with it. In such patients, the physician must appreciate and strike the difficult balance between the risk of ischemic strokes from atrial fibrillation on one hand, and that of intracerebral hemorrhage from coexisting CAA on the other. Anticoagulation is necessary for the former but potentially deleterious for the latter. In this case report, we present the case of a 67-year-old woman with a long history of atrial fibrillation on rivaroxaban who recently began to experience recurrent transient neurological deficits that were later diagnosed as amyloid spells related to concomitant CAA. While there is no clear-cut consensus in published literature on how to best manage these patients regarding the use of anticoagulation, it is recommended to involve a multidisciplinary team for optimal management of these patients.

Endovascular Versus Surgical Arteriovenous Fistulas: A Systematic Review and Meta-analysis.

Rationale & Objective: To facilitate the process of dialysis for patients with kidney failure, an arteriovenous fistula (AVF) is created using either a surgical or percutaneous approach. We sought to compare the efficacy and procedural outcomes in creating an AVF percutaneously using Ellipsys (Avenu Medical) or WavelinQ (Becton Dickinson Medical) with surgery in all patients with kidney failure requiring a permanent AVF for dialysis. Study Design: Systematic review and meta-analysis. Setting & Study Populations: All patients requiring a permanent AVF for dialysis. Selection Criteria for Studies: We included studies that compared either the Ellipsys device or WavelinQ directly with surgery to create an AVF for long-term dialysis. Data Extraction: Two reviewers independently reviewed the studies and extracted the data. Conflicts were resolved with a discussion and approval from the senior author. Analytical Approach: Fixed-effects or random-effects models were used to pool the fixed sizes and 95% CIs based on the level of heterogeneity. Results: There was no statistically significant difference observed between surgical AVF and endovascular AVF when comparing the primary outcomes of procedural success (OR = 1.44; 95% CI, 0.35, 5.88; P = 0.61; I2 = 0%), complications (OR = 0.28; 95% CI, 0.06, 1.46; P = 0.13; I2 = 69%), and the secondary outcomes of interest that included follow-up time (mean difference [MD] = -17.71; 95% CI, -189.53, 154.12; P = 0.84; I2 = 94%), failure rate (OR = 1.03; 95% CI, 0.21, 5.13; P = 0.97; I2 = 85%), and time to 2-needle cannulation (MD = -5.40; 95% CI, -38.88, 28.08; P = 0.75; I2 = 0%). However, a statistically significant difference was seen among the 2 groups for procedural time (MD = -54.25; 95% CI, -59.78, -48.71; P < 0.001; I2 = 98%), number of interventions needed to maintain patency (OR = 1.73; 95% CI, 1.22, 2.45; P < 0.01; I2 = 94%), and primary patency rate (OR = 0.34; 95% CI, 0.23,0.52; P < 0.001; I2 = 0%). Limitations: The total number of studies included in this review was limited, with 3 of the 4 included studies being retrospective and only 1 being prospective. There was a lack of heterogeneity and randomization. Conclusions: Percutaneous fistula creation using Ellipsys or WavelinQ is a unique and safe alternative with outcomes comparable to surgery. Future studies are needed, including observational studies in current clinical practice, to evaluate the efficacy and outcomes of endovascular AVF creation in clinical populations.

Correlation of serum apelin level with carotid intima-media thickness and insulin resistance in a sample of Egyptian patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a growing health problem in Egypt, with a significant impact on morbidity and mortality. Measurement of the carotid Intima-media thickness (CIMT) allows early detection of atherosclerotic blood vessel diseases. Apelin is an adipose tissue-derived hormone that may be associated with insulin resistance (IR). This study aimed to assess the level of serum apelin in patients with T2DM and its relation to IR and CIMT. Materials and Methods: A case-control study was conducted on 60 patients with T2DM and 30 healthy controls. T2DM was diagnosed based on American Diabetes Association criteria. The study was carried out at Al-Zahraa University Hospital, Cairo, Egypt, through the period from June to December 2019. The laboratory investigations included serum apelin and blood glucose hemostasis markers. CIMT was assessed using B-mode ultrasonography. Results: Patients' group had a statistically significant higher apelin level than healthy controls (407.96 ± 291.07 versus 83.32 ± 10.55 ng/dL, P < 0.001). The correlation analysis showed that the serum apelin level correlated positively with glycemic indices, body weight, and waist circumference (P < 0.05). At cutoff value of >96 ng/dL, the serum apelin exhibited a sensitivity of 98.3% and specificity of 96.7%, positive predictive value of 98.1%, and negative predictive value of 96.5%, with a diagnostic accuracy of 95.1%. Serum apelin correlated positively with CIMT (r = 0.296, P = 0.022). Logistic regression analysis showed that systolic and diastolic blood pressures, Homeostasis Model Assessment of IR, and CIMT were independent predictors of serum apelin. Conclusion: Serum apelin may be correlated with the degree of carotid atherosclerosis and hence can be used as a prognostic biomarker.

Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report.

BACKGROUND: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19. PATIENTS & METHODS: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin. RESULTS: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 â€‹× â€‹109/l (SD â€‹= â€‹2.70) which constituted a significant drop from a baseline value of 5.2 â€‹× â€‹109/l (SD â€‹= â€‹2.24). The mean relative reduction in ANC was -0.2729 (SD â€‹= â€‹0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue â€‹= â€‹8.96 â€‹× â€‹10-8 and an adjusted R2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. CONCLUSIONS: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

Antibiotic misuse and compliance with infection control measures during COVID-19 pandemic in community pharmacies in Egypt.

BACKGROUND: Globally, antibiotics misuse by the public has been reported in the era of COVID-19, despite the discouraging instructions of the World Health Organization, especially for mild cases. OBJECTIVE: Is to describe this antibiotic misuse and its contributing factors. Also, to measure the pharmacists' application of infection preventive practices during the pandemic. METHODS: A cross-sectional study was conducted among randomly selected Egyptian community pharmacists (Center, East, Delta, and Upper Egypt) using a questionnaire and direct interviews from 1 to 30 August 2020. The questionnaire consisted of two parts, the first covered pharmacist's demographic data and their application of basic infection preventive practices (eg, wearing face masks, regular hand sanitization, etc), and the other part was related to antibiotic dispensing patterns. Data were descriptively analyzed and the impact of participant experience on the responses was evaluated using the χ2 test. RESULTS: From 480 randomly selected Egyptian community pharmacists, 413 (87%) consented to participate in the study. 86.7% of the participants were keen to wear face masks (n = 358) and 86.2% kept regular hand sanitization (n = 356); whereas, 46.9% (n = 194) maintained adequate antibiotic stock supply during the pandemic. Nearly 67% (n = 275) of the pharmacists reported that patients were more likely to be given antibiotics for showing any sign or symptom of COVID-19 infection, and 82% (n = 74 278) of the dispensed antibiotics were given upon physician recommendation. Azithromycin, Ceftriaxone, and Linezolid were the major antibiotics dispensed to COVID-19 presumptive patients Azithromycin was given to ~40% of presumptive patients showing only mild or moderate symptoms for 5-10 days. Additionally, antibiotic combinations were given to 74% (n = 62 479) of home-isolated patients for a maximum of 2 weeks. CONCLUSIONS: Pharmacists applied suitable sanitation and infection control protocols. Meanwhile, antibiotics were dispensed heavily during this pandemic without proper clinical indication and for long durations supporting the idea of antibiotic misuse.

Antioxidant and anti-inflammatory properties of alpha-lipoic acid protect against valproic acid-induced liver injury.

Valproic acid (VPA) is one of the most used antiepileptic drugs despite of its many adverse effects such as anemia, leucopenia, thrombocytopenia, and liver toxicity. The hepatoprotective effect of alpha-lipoic acid (ALA) was confirmed. The aim of this study was to detect the protective effect of ALA against the adverse effects of VPA. To study this, 30 white albino Wistar male rats were divided into four groups. Group I was the control group; Group II included rats that received ALA (100 mg·kg-1·day-1) orally for 14 days; Group III and Group IV included rats that received VPA (500 mg·kg-1·day-1) for 15 days intraperitoneally, but Group IV rats received ALA (100 mg·kg-1·day-1) orally for 14 days prior to VPA. Blood samples were collected and livers were excised from rats for colorimetric analysis and quantitative real-time PCR. The rats that received VPA showed leucopenia, thrombocytopenia, a significant decrease of superoxide dismutase, glutathione, nuclear factor erythroid 2-related factor 2, and sirtuin 1, besides a significant increase of malondialdehyde and tumor necrosis factor α. Prior treatment with ALA prevented all these results; ALA protected against VPA-induced liver damage and hematological disturbance via antioxidant and anti-inflammatory properties.

Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions.

The current study was prepared to assess the underlying mechanism of diclofenac (Diclo)-stimulated renal oxidative damage (50 mg/kg/day for two consecutive days I.P) and antioxidative, and antiapoptotic effects of Thymoquinone (20 mg/kg/day for 21 days P.O). Exposure of rats to Diclo significantly increased serum urea and creatinine, decreased GSH, catalase, and total antioxidant capacity with a concomitant increase of lipid peroxidation. Diclo significantly decreased renal mitochondrial viability %, increased DNA fragmentation %, caspase 3 activity, and cytochrome C (Cyt C) concentration. Molecular investigations revealed that Diclo administration caused a significant reduction of mitofusin-2 (Mfn2) and increase of microRNA-34a (miR-34a) mRNA expressions with a concomitant decrease of Nrf2 and HO-1 mRNA expressions/protein levels and increase of NF-κB mRNA expressions. Thymoquinone restored renal oxidative/antioxidant redox. Thymoquinone significantly increased the renal mitochondrial viability % and reduced renal DNA fragmentation %, caspase 3 activity, and Cyt C. Moreover, thymoquinone modulated renal Mfn2 and miR-34a as compared to Diclo group. Our findings were confirmed by immunohistochemical assays for detecting the iNOS and NOX4 in renal tissue as well as histopathological investigations. Obtained results demonstrated that thymoquinone possess a potential antioxidant, antiapoptotic defense and exhibited a strong nephroprotective activity against Diclo-induced toxicity.

Preparation and appraisal of self-assembled valsartan-loaded amalgamated Pluronic F127/Tween 80 polymeric micelles: Boosted cardioprotection via regulation of Mhrt/Nrf2 and Trx1 pathways in cisplatin-induced cardiotoxicity.

This study aimed to develop valsartan (VAL)-loaded mixed micelles and investigate their cardioprotective potential and molecular mechanisms through Mhrt/Nrf2 and Trx1 pathways. VAL-loaded mixed micelles have not been elaborated and their impact on Mhrt/Nrf2 and Trx1 pathways has not been yet inspected. VAL-loaded mixed micelles were prepared, incorporating Pluronic F127 and Tween 80, adopting thin-film hydration method. The micelles were evaluated for drug entrapment efficiency, loading characteristics, particle size, morphology, in vitro drug release and micelles storage stability. The pharmacokinetic studies were explored in rats. Also, VAL suspension and mixed micelles were tested in cisplatin-induced cardiotoxicity in rats either pre to or simultaneously with cisplatin. RNA expression of lnc Mhrt and protein expression of Nrf2, Trx1, Ask1, AMPK and caspase 3, oxidative stress and cardiac injury markers besides tailed DNA% by comet assay were assessed. Pharmacokinetic studies evoked a 3.75-fold increase in oral bioavailability as compared with VAL suspension. Overall, treatment with VAL-loaded mixed micelles was superior to VAL suspension in decreasing oxidative stress and cardiac injury markers and restoring the abnormalities occurred in Mhrt/Nrf2 and Trx1 pathways. Thus, mixed micelles would be promising nanocarrier for the engineering of VAL with reinforced pharmacokinetics and cardioprotection characteristics.

Antihepatocarcinogenic activity of whey protein concentrate and lactoferrin in diethylnitrosamine-treated male albino mice.

Hepatocellular carcinoma is considered one of the most prevalent and lethal malignancies worldwide. Chemotherapy with cytotoxic agents showed a low response rate with possible toxic effects. Recently, some emphases have been placed on the anticancer properties of bovine whey protein and its components, especially lactoferrin. The present study aimed to evaluate and compare the antihepatocarcinogenic activity of bovine whey protein concentrate (WPC, 300 and 600 mg/kg body weight) and lactoferrin (30 and 60 mg/kg body weight), orally and daily for 14 weeks, in the mice model of diethylnitrosamine (DEN)-induced hepatocarcinogenesis. The results showed that both WPC and lactoferrin (in a dose-dependent manner) alleviated significantly (P < .001) the elevation in serum markers of liver carcinoma and inflammation in the DEN-treated mice. Also, they exhibited a great amelioration in the livers' histological structure of the DEN-treated mice by 37.0% to 66.7%. In addition, they decreased significantly (P < .001) the hepatic DNA fragmentation in the DEN-treated mice by 23.1% to 32.7%. Only, the high doses of WPC and lactoferrin completely modulated the decrease in the activity of liver enzymic antioxidant defense system (catalase, glutathione peroxidase, and superoxide dismutase) and improved significantly (P < .01-.001) the concentration of hepatic reduced glutathione of the DEN-treated mice. Moreover, the high doses of WPC and lactoferrin reduced significantly (P < .05-.001) the elevation in the concentrations of hepatic active caspases 3, 8, and 9 of the DEN-treated mice. In conclusion, both WPC and lactoferrin were effective in inhibiting the hepatocarcinogenic activity of DEN in mice model through their ability to alleviate the hepatic inflammation and apoptosis.

Alpha lipoic acid protects against dexamethasone-induced metabolic abnormalities via APPL1 and PGC-1 α up regulation.

BACKGROUND: Glucocorticoids (GCs) have various uses in the medicine in different specialties. However, GCs administration is usually accompanying with multiple side effects such as hyperglycemia and hyperlipidemia. Alpha lipoic acid (ALA) has been documented to posse anti-diabetic properties. AIM OF THE STUDY: this study highlights the role of ALA in avoiding dexamethasone induced metabolic disturbance. MATERIALS & METHODS: 30 rats were randomly divided into 5 groups: Group (1): Control group; Groups 3, 4, and 5: rats received dexamethasone 1 mg/kg/day for 10 days; Groups 2, 4, and 5: Rats received ALA 100 mg/kg/day all the duration of the study, 2 weeks before dexamethasone, or concomitant with dexamethasone respectively. For each rat, we collected blood samples for measurement of glucose, lipid profiles, adiponectin, irisin, and Phosphoinositide 3-kinase (PI3K). We also isolated gastrocnemius muscles for measurement of insulin receptor substrate-1(IRS-1), peroxisome proliferator-activated receptor γ coactivator 1 α(PGC1-α), and adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1(APPL) gene expression. RESULTS: Dexamethasone administration caused hyperglycemia, hyperlipemia, decrease the level of adiponectin, irisin, and PI3K besides decreasing the gene expression of IRS-1, PGC-1 α, and APPL1. ALA administration pre or concomitant to dexamethasone avoided these results. CONCLUSION: ALA can prevent metabolic abnormalities induced by dexamethasone via PGC1α and APPL1 upregulation.