P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids.

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations' potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils.

BACKGROUND: Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils. OBJECTIVE: This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy. METHODS: The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated. RESULTS: The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0. CONCLUSION: The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.

Correction: Jamal et al. Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells. Nanomaterials 2022, 12, 4029.

In the original publication [...].

Novel sulfonamide-indolinone hybrids targeting mitochondrial respiration of breast cancer cells.

Breast cancer (BC) still poses a threat worldwide which demands continuous efforts to present safer and efficacious treatment options via targeted therapy. Beside kinases' aberrations as Aurora B kinase which controls cell division, BC adopts distinct metabolic profiles to meet its high energy demands. Accordingly, targeting both aurora B kinase and/or metabolic vulnerability presents a promising approach to tackle BC. Based on a previously reported indolinone-based Aurora B kinase inhibitor (III), and guided by structural modification and SAR investigation, we initially synthesized 11 sulfonamide-indolinone hybrids (5a-k), which showed differential antiproliferative activities against the NCI-60 cell line panel with BC cells displaying preferential sensitivity. Nonetheless, modest activity against Aurora B kinase (18-49% inhibition) was noted at 100 nM. Screening of a representative derivative (5d) against 17 kinases, which are overexpressed in BC, failed to show significant activity at 1 µM concentration, suggesting that kinase inhibitory activity only played a partial role in targeting BC. Bioinformatic analyses of genome-wide transcriptomics (RNA-sequencing), metabolomics, and CRISPR loss-of-function screens datasets suggested that indolinone-completely responsive BC cell lines (MCF7, MDA-MB-468, and T-47D) were more dependent on mitochondrial oxidative phosphorylation (OXPHOS) compared to partially responsive BC cell lines (MDA-MB-231, BT-549, and HS 578 T). An optimized derivative, TC11, obtained by molecular hybridization of 5d with sunitinib polar tail, manifested superior antiproliferative activity and was used for further investigations. Indeed, TC11 significantly reduced/impaired the mitochondrial respiration, as well as mitochondria-dependent ROS production of MCF7 cells. Furthermore, TC11 induced G0/G1 cell cycle arrest and apoptosis of MCF7 BC cells. Notably, anticancer doses of TC11 did not elicit cytotoxic effects on normal cardiomyoblasts and hepatocytes. Altogether, these findings emphasize the therapeutic potential of targeting the metabolic vulnerability of OXPHOS-dependent BC cells using TC11 and its related sulfonamide-indolinone hybrids. Further investigation is warranted to identify their precise/exact molecular target.

Impact of residual coronary lesions on outcomes of myocardial infarction patients with multi-vessel disease.

BACKGROUND: The residual burden of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) drew a growing interest. The residual SYNTAX Score (rSS) was a strong prognostic factor of adverse events and all-cause mortality in patients who underwent PCI. In addition, the SYNTAX Revascularization Index (SRI), a derivative of rSS, was used to figure out the treated proportion of CAD and could be used as a prognostic utility in PCI for patients with multi-vessel disease (MVD). PURPOSE: We aimed at the assessment of the use of rSS and the SRI as predictors of in-hospital outcomes and up to two-year cumulative follow-up outcomes in patients with MVD who had PCI for the treatment of ST-Elevation Myocardial Infarction (STEMI) or Non-STEMI (NSTEMI). METHODS: We recruited 149 patients who had either STEMI or NSTEMI while having MVD and received treatment with PCI. We divided them into tertiles based on their rSS and SRI values. We calculated baseline SYNTAX Score (bSS) and rSS using the latest version of the calculator on the internet, and we used both scores to calculate SRI. The study end-points were In-hospital composite Major Adverse Cardiovascular Events (MACE) and its components, in-hospital death, and follow-up cumulative MACE up to 2 years. RESULTS: Neither rSS nor SRI were significant predictors of in-hospital adverse events, while female sex, hypertension, and left ventricular ejection fraction were independent predictors of in-hospital MACE. At the two-year follow-up, Kaplan-Meyer analysis showed a significantly increased incidence of MACE within the third rSS tertile (rSS > 12) compared to other tertiles (log rank p = 0.03). At the same time, there was no significant difference between the three SRI tertiles. Unlike SRI, rSS was a significant predictor of cumulative MACE on univariate Cox regression (HR = 1.037, p < 0.001). On multivariate Cox regression, rSS was a significant independent predictor of two-year cumulative MACE (HR = 1.038, p = 0.0025) along with female sex, hypertension, and left ventricular ejection fraction. We also noted that all patients with complete revascularization survived well throughout the entire follow-up period. CONCLUSIONS: Neither rSS nor SRI could be good predictors of in-hospital MACE, while the rSS was a good predictor of MACE at two-year follow-up. Patients with rSS values > 12 had a significantly higher incidence of cumulative MACE after 2 years. The best prognosis was achieved with complete revascularization.

In patients with chronic heart failure which polypharmacy pheno-groups are associated with adverse health outcomes? (Polypharmacy pheno-groups and heart failure outcomes).

BACKGROUND: Patients with heart failure are living longer with the inevitable morbidity of rising medication counts. It remains uncertain what fraction of this ensuing polypharmacy exactly predicts adverse clinical outcomes. METHODS: This prospective study examined records of patients admitted to a Weill Cornell-affiliated tertiary medical institution with a confirmed diagnosis of heart failure between January 2018 to January 2022. Each patient's medications for the past four months were tallied, and a definitional threshold of ≤4, ≥5, ≥10 medications was established. The primary outcome was all-cause mortality within the study period. RESULTS: Out of a total of 7354 patients included in the study, 70 % were males with a median age of 59 years IQR (48-71). The median (IQR) age-adjusted Charlson Comorbidity Index (CCI) was 21-5. A total of 1475 (20 %) participants died within the study period. Patient cohorts with excessive polypharmacy (≥9 medications) had the highest probability of survival up to 1.6 years compared to those with lower medication thresholds (≤4); the mortality rate decreased by 18 % for patients with excessive polypharmacy [HR = 0.82, 95 % CI: 0.71-0.94]). Conversely, patients with non-heart failure-related polypharmacy had increased risks of ICU admissions (aOR = 1.78, 95 % CI: 1.13-2.70). CONCLUSION: In an examination of a database of patients with chronic heart failure, major non-heart failure-related polypharmacy was associated with increased risks in intensive care admissions. Excessive polypharmacy was associated with increased rates of survival.

Biological evaluation of indirect restorations in endodontically treated posterior teeth with deeply located proximal margins following deep margin elevation versus surgical crown lengthening: a randomized controlled trial.

OBJECTIVE: The current clinical trial was conducted to evaluate the effect of proximal indirect restorations in endodontically treated posterior teeth with deeply located margins following deep margin elevation compared to surgical crown lengthening. MATERIAL AND METHODS: Deep proximal cavities in endodontically treated posterior teeth were randomly assigned into two groups; deep margin elevation (DME) or crown lengthening (CL). The clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), crestal bone level (CBL), and secondary caries were evaluated at the baseline, 1, 3, 6, 9, and 12 months. RESULTS: A total of 20 proximal cavities were included in the study; there was no significant difference between the two groups regarding mean CAL values at the baseline and 1 month, while there was a significant difference between the two groups in all other periods. Regarding the PD, there was no statistical significance between the two groups except at 9 and 12 months, where CL showed higher mean PD values than DME. There was no statistically significant difference in BOP or CBL between the two groups. CONCLUSIONS: DME and CL are considered clinically successful with favorable biologic responses. CLINICAL RELEVANCE: The deep margin elevation approach could provide a more conservative solution when relocating deeply seated cervical margins in a more coronal position. DME reduced the number of visits and time needed for the restoration of endodontically treated teeth. Surgical crown lengthening remains a gold standard procedure in the re-establishment of the supracrestal tissue attachment, especially in cases where cervical margins are beyond the elevation capacity.

Design, Synthesis, and Antisickling Investigation of a Thiazolidine Prodrug of TD-7 That Prolongs the Duration of Action of Antisickling Aromatic Aldehyde.

The synthetic allosteric effector of hemoglobin, TD-7 has been investigated as a potential therapeutic agent for the treatment of sickle cell disease. The pharmacologic activity of TD-7 is due to formation of a Schiff-base interaction between its aldehyde group and the two N-terminal αVal1 amines of hemoglobin, effectively inhibiting sickling of red blood cells. However, TD-7 faces a challenge in terms of poor oral bioavailability due to rapid in-vivo oxidative metabolism of its aldehyde functional group. To address this shortcoming, researches have explored the use of a L-cysteine ethyl ester group to cap the aldehyde group to form a thiazolidine aromatic aldehyde prodrug complex, resulting in the improvement of the metabolic stability of this class of compounds. This report details the synthesis of a thiazolidine prodrug of TD-7, referred to as Pro-7, along with a comprehensive investigation of Pro-7 functional and biological properties. In an in-vitro Hb modification and Hb oxygen affinity studies using normal whole blood, as well as erythrocyte sickling inhibition using sickle whole blood, Pro-7 exhibited a gradual onset but progressive increase in all activities. Additionally, in-vivo pharmacokinetic studies conducted with Sprague Dawley rats demonstrated that Pro-7 can undergo hydrolysis to release TD-7. However, the blood concentration of TD-7 did not reach the desired therapeutic level. These findings suggest that the incorporation of the L-cysteine ethyl ester group to TD-7 represents a promising strategy to enhance the metabolic stability of aromatic aldehydes that could lead to the development of a more effective drug for the treatment of sickle cell disease.

Enhancing Ezetimibe Anticancer Activity Through Development of Drug Nano-Micelles Formulations: A Promising Strategy Supported by Molecular Docking.

Background: Ezetimibe, initially recognized as a cholesterol-lowering agent, has recently attracted attention due to its potential anticancer properties. We aimed to explore an innovative approach of enhancing the drug anticancer activity through the development of drug nano-formulations. Materials and Methods: Fifteen different nano-micelles formulations were prepared utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127. The prepared formulations were characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulations were morphologically characterized using light and transmission electron microscopies and the drug-binding mode with the active site was investigated using the molecular docking. Cell viability against MCF-7 and T47D was studied. Apoptosis and cell cycle were assessed. Results: The prepared formulations were in the nano-size range (34.01 ± 2.00-278.34 ± 9.11 nm), zeta potential values were very close to zero, and the TPGS-based micelles formulations showed the highest ezetimibe EE (94.03 ± 1.71%). Morphological study illustrated a well-defined, spherical nanoparticles with a uniform size distribution. Molecular docking demonstrated good interaction of ezetimibe with Interleukin-1 Beta Convertase through multiple hydrogen bonding, covalent bond, and hydrophobic interaction. TPGS-based nano-micelle formulation (F5) demonstrated the lowest IC50 against MCF-7 (4.51 µg/mL) and T47D (8.22 µg/mL) cancer cells. When T47D cells were treated with IC50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC50 dose of ezetimibe. Cell cycle analysis revealed that both ezetimibe and F5-treated T47D cells exhibited an increase in the subG1 phase, indicating reduced DNA content and cell death. Conclusion: These findings suggest that F5 could serve as a proficient drug delivery system in augmenting the cytotoxic activity of ezetimibe against breast cancer.

Incorporation of Perillyl Alcohol into Lipid-Based Nanocarriers Enhances the Antiproliferative Activity in Malignant Glioma Cells.

Perillyl alcohol (PA), a naturally existing monocyclic terpene related to limonene, is characterized by its poor aqueous solubility and very limited bioavailability. Its potential anti-cancer activity against malignant glioma has been reported. The aim was to develop PA-loaded lipid-based nanocarriers (LNCs), and to investigate their anti-cancer activity against two different brain cell lines. Non-medicated and PA-loaded LNCs were prepared and characterized. The mechanism of cytotoxic activity of PA was conducted using a molecular docking technique. The cell viabilities against A172 and ANGM-CSS cells were evaluated. The results revealed that the average particle size of the prepared LNCs ranged from 248.67 ± 12.42 to 1124.21 ± 12.77 nm, the polydispersity index was 0.418 ± 0.043-0.509 ± 0.064, while the zeta potential ranged from -36.91 ± 1.31 to -15.20 ± 0.96 mV. The molecular docking studies demonstrated that the drug had binding activity to human farnesyltransferase. Following exposure of the two glioblastoma cell lines to the PA-loaded nanoformulations, MTS assays were carried out, and the data showed a far lower half-maximal inhibitory concentration in both cell lines when compared to pure drug and non-medicated nanocarriers. These results indicate the potential in vitro antiproliferative activity of PA-loaded LNCs. Therefore, the prepared PA-loaded nanocarriers could be used to enhance drug delivery across the blood-brain barrier (BBB) in order to treat brain cancer, especially when formulated in a suitable dosage form. The size, surface charge, and lipid composition of the LNCs make them promising for drug delivery across the BBB. Detailed pharmacokinetic and pharmacodynamic assessments, including the evaluation of BBB penetration, are necessary to better understand the compound's distribution and effects within the brain.

Complications with the use of Angio-Seal vascular closure device and their management.

Vascular closure devices (VCDs) are being increasingly used for achieving hemostasis after diagnostic and therapeutic endovascular procedures. Although uncommon, complications may be encountered which are associated with the use of these VCDs. We report four cases where the use of Angio-Seal (Terumo, Somerset, New Jersey, USA) was followed by complications. Three cases presented with acute limb ischemia, among them, two patients had arterial occlusion at the vascular access site and one patient had embolization of the footplate anchor of the closure device. One case presented with pseudoaneurysm at the common femoral artery access site along with occlusion at origin of the superficial femoral artery. We have described the mechanism in which these complications occur and the successful management of these cases preventing potential amputation and limb loss. The risk factors which increase the risk of complications with the use of Angio-Seal VCD were reviewed and the strategy to avoid these complications with particular emphasis on the utility of ultrasound when using Angio-Seal VCD is discussed. A strategy to manage these complications has been discussed while deciding on endovascular management or surgical management, especially in patients with challenging presentation and those with multiple comorbidities making them at very high risk for surgery.

Exploring the Enhanced Antiproliferative Activity of Turmeric Oil and 6-Mercaptopurine in a Combined Nano-Particulate System Formulation.

6-Mercaptopurine (6-MP) is a chemotherapeutic agent with inadequate efficacy due to its poor aqueous solubility and limited bioavailability. Turmeric oil is a naturally occurring bioactive substance obtained from the rhizomes of Curcuma longa Linn that has well-known antiproliferative activities. The aim of this study was to develop a 6-MP-loaded turmeric oil-based self-nanoemulsifying drug delivery system (SNEDDS) to improve the anticancer activity of 6-MP. Turmeric oil was extracted and used in a range of 15-25% to develop SNEDDS formulations utilizing tween 80 and dimethyl sulfoxide as the surfactant and cosurfactant, respectively. The size, charge, and effect of the formulations on the viability against HepG2 and MCF-7 cell models, as well as the apoptosis and cell cycle, were analyzed. The prepared SNEDDS formulations were in the size range of 425.7 ± 7.4-303.6 ± 19.3 nm, using a polydispersity index of 0.429-0.692 and electronegative surface charges. Moreover, 6-MP-loaded SNEDDS with 15% turmeric oil content (F1) showed smaller particle sizes and a noticeable antiproliferative activity against both cell line models. Also, F1 showed a higher rate of late apoptosis than the pure drug and the corresponding non-medicated formulation. A morphological study revealed significant changes in the HepG2 cells compared to untreated cells. More cells halted in the S phase, and a marked decrease in the proportions of cells in the G1/G0 phase was observed when using SNEDDS formulation compared to pure drug. Thus, SNEDDS formulation is a promising drug delivery system for improving the antiproliferative activity of 6-MP, especially when turmeric oil is incorporated.

Epidemiology and outcome of an acute kidney injuries in the polytrauma victims admitted at the apex trauma center in Dubai.

BACKGROUND: Polytrauma from road accidents is a common cause of hospital admissions and deaths, frequently leading to acute kidney injury (AKI) and impacting patient outcomes. METHODS: This retrospective, single-center study included polytrauma victims with an Injury Severity Score (ISS) >25 at a tertiary healthcare center in Dubai. RESULTS: The incidence of AKI in polytrauma victims is 30.5%, associated with higher Carlson comorbidity index (P=0.021) and ISS (P=0.001). Logistic regression shows a significant relationship between ISS and AKI (odds ratio [OR], 1.191; 95% confidence interval [CI], 1.150-1.233; P<0.05). The main causes of trauma-induced AKI are hemorrhagic shock (P=0.001), need for massive transfusion (P<0.001), rhabdomyolysis (P=0.001), and abdominal compartment syndrome (ACS; P<0.001). On multivariate logistic regression AKI can be predicated by higher ISS (OR, 1.08; 95% CI, 1.00-1.17; P=0.05) and low mixed venous oxygen saturation (OR, 1.13; 95% CI, 1.05-1.22; P<0.001). The development of AKI after polytrauma increases length of stay (LOS)-hospital (P=0.006), LOS-intensive care unit (ICU; P=0.003), need for mechanical ventilation (MV) (P<0.001), ventilator days (P=0.001), and mortality (P<0.001). CONCLUSIONS: After polytrauma, the occurrence of AKI leads to prolonged hospital and ICU stays, increased need for mechanical ventilation, more ventilator days, and a higher mortality rate. AKI could significantly impact their prognosis.

Endovascular intervention in treatment of refractory epistaxis.

Objective: Angiographic embolization is an established method of treating intractable cases of posterior epistaxis. This study aimed to test the effectiveness and safety of this method in treating cases refractory to conservative methods. Methods: A descriptive retrospective analysis of consecutive cases referred to the department of interventional radiology with refractory epistaxis from January 2001 to December 2018 and received a selective angiographic embolization of the sphenopalatine artery was done. Only epistaxis of idiopathic origin was included in the study. Results: During this period, 98 embolizations were performed. The success rate reached 81.6%. Minor complications were registered in 5%, with no single major complication. The length of stay was 10.5 ± 5.6. Conclusion: Selective angiographic embolization is an effective, safe, and minimally invasive method in treating refractory epistaxis.

Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability.

Valsartan (VST) is a poorly soluble antihypertensive drug characterized by its limited dissolution rate and low bioavailability. This study aims to improve VST solubility and dissolution rate via developing liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS), which is expected to enhance VST bioavailability. This aim was achieved via two designs of experiment. The first was the simplex-lattice design to optimize VST-loaded-SNEDDS using sesame oil, Tween 80, and polyethylene glycol 400. The second was the 32-3-level factorial design to optimize the liquisolid system using the SNEDDS-loaded VST and Neusilin®US2 as a carrier and fumed silica as a coating material. Different excipient ratios (X1) and varioussuper-disintegrants (X2) were also used in developing the optimized VST-LSTs. Thein vitrodissolution of VST from LSTs was compared with the marketed product (Diovan®). Non-compartmental analysis of plasma data after extravascular input with the linear trapezoidal method was used to calculate thepharmacokinetic parameters of the optimized VST-LSTs compared with the marketed tablet in male Wistar rats. The optimized SNEDDS compromised 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9 mg/ml loading capacity. Also, the SNEDDS-loaded VST tablet revealed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min. On the other hand, the marketed product took 1 h for the entire drug to be released.Moreover, the maximum plasma concentration (Cmax) of the optimizedVST-LSTwas6585.33 ng/ml within 1 h (Tmax), compared to 2884.67 ng/ml within 2 h of the marketed tablet.The relative bioavailability of the SNEDDS-loaded VST tablet was 213.7% compared to that of the marketed tablet, indicating that this formulation approach could be applied for increasing solubility, dissolution behavior in GIT, and bioavailability of poorly water-soluble drugs.

Developing a mortality risk prediction model using data of 3663 hospitalized COVID-19 patients: a retrospective cohort study in an Egyptian University Hospital.

PURPOSE: Since the declaration of COVID-19 as a pandemic, a wide between-country variation was observed regarding in-hospital mortality and its predictors. Given the scarcity of local research and the need to prioritize the provision of care, this study was conducted aiming to measure the incidence of in-hospital COVID-19 mortality and to develop a simple and clinically applicable model for its prediction. METHODS: COVID-19-confirmed patients admitted to the designated isolation areas of Ain-Shams University Hospitals (April 2020-February 2021) were included in this retrospective cohort study (n = 3663). Data were retrieved from patients' records. Kaplan-Meier survival and Cox proportional hazard regression were used. Binary logistic regression was used for creating mortality prediction models. RESULTS: Patients were 53.6% males, 4.6% current smokers, and their median age was 58 (IQR 41-68) years. Admission to intensive care units was 41.1% and mortality was 26.5% (972/3663, 95% CI 25.1-28.0%). Independent mortality predictors-with rapid mortality onset-were age ≥ 75 years, patients' admission in critical condition, and being symptomatic. Current smoking and presence of comorbidities particularly, obesity, malignancy, and chronic haematological disorders predicted mortality too. Some biomarkers were also recognized. Two prediction models exhibited the best performance: a basic model including age, presence/absence of comorbidities, and the severity level of the condition on admission (Area Under Receiver Operating Characteristic Curve (AUC) = 0.832, 95% CI 0.816-0.847) and another model with added International Normalized Ratio (INR) value (AUC = 0.842, 95% CI 0.812-0.873). CONCLUSION: Patients with the identified mortality risk factors are to be prioritized for preventive and rapid treatment measures. With the provided prediction models, clinicians can calculate mortality probability for their patients. Presenting multiple and very generic models can enable clinicians to choose the one containing the parameters available in their specific clinical setting, and also to test the applicability of such models in a non-COVID-19 respiratory infection.

Incorporating sodium deoxycholate endorsed the buccal administration of avanafil to heighten the bioavailability and duration of action.

The highly effective phosphodiesterase type 5 inhibitor (avanafil; AVA) is routinely prescribed to treat erectile dysfunction. The drug has poor oral bioavailability and undergoes a significant first-pass metabolism. Therefore, altering AVA's solubility and choosing a different delivery method may boost its effectiveness. Nine different solid dispersion formulations utilizing polyvinylpyrrolidone (PVP) at three different ratios were prepared and characterized. The Box-Behnken design was employed to optimize AVA-buccal tablets. The pre-compression and post-compression characteristics of the tablets were assessed. The mucoadhesion strength of the optimized tablet was investigated using cow buccal mucosal tissue. In vivo performance of the optimized tablets was examined on human volunteers compared to the commercial tablets. PVP K90 at 2:1 drug to polymer ratio showed the highest solubilization capacity. The mucoadhesive polymer type and percentage and the mucopenetration enhancer percentage were significantly affect the mucoadhesion strength, tablet hardness, and the initial and cumulative AVA released from the prepared tablets. The optimized AVA-buccal tablet showed 4.96 folds increase in the mean residence time, higher plasma exposure, and an improvement in the relative bioavailability of AVA by 1076.27% compared with the commercial tablet. Therefore, a successful approach to deal with AVA first-pass metabolism and low bioavailability could be to employ buccal tablets containing a solubility-enhanced form of AVA.