Dissolution enhancement of Gefitinib by solid dispersion and complexation with ß-cyclodextrins: In vitro testing, cytotoxic activity, and tablet formulation.

Cancer is the leading cause of mortality worldwide. In patients with metastatic non-small cell lung cancer, epidermal growth factor receptor (EGFR) is often overexpressed. Gefitinib (GEF), an inhibitor of EGFR, is approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the low solubility and dissolution of GEF limits its bioavailability. Numerous methods, including solid dispersion (SD) and complexation, have been reported to enhance the dissolution of poorly soluble drugs. In this study, GEF complexes were prepared using methyl-ß-cyclodextrin (MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) in two molar ratios (1:1 and 1:2), furthermore, GEF SDs were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188(PXM) in three different ratios (1:2, 1:4 and 1:6 w/w). Dissolution studies were conducted on the prepared formulations. Dissolution results showed a 1.22-2.17-fold enhancement in drug dissolution after one hour compared to untreated GEF. Two formulations that showed higher dissolution enhancement were subsequently evaluated for in-vitro cytotoxicity and were formulated into tablets. The selected PVP-GEF (1:4 w/w) and MßCD-GEF (1:1M) formulas displayed improved cytotoxicity compared to untreated GEF. The IC50 values of the PVP-GEF and MßCD-GEF were 4.33 ± 0.66 and 4.84 ± 0.38 µM, respectively which are significantly lower (p < 0.05) than free GEF. In addition, the formulated tablets exhibited enhanced dissolution compared to pure GEF tablets. PVP-GEF SD tablets released (35.1 %±0.4) of GEF after one hour, while GEF-MßCD tablets released (42.2 % ± 0.7) after one hour. In the meantime, tablets containing pure GEF showed only 15 % ± 0.5 release at the same time. The findings of this study offer valuable insights for optimizing the dissolution and hence therapeutic capabilities of GEF while mitigating its limitations.

Pontine Infarction and Vertebral Artery Dissecting Aneurysm as the First Presentation of Behçet's Disease: A Case Report.

Behçet's disease (BD) is a systemic disease of inflammatory origin that appears most often in the third or fourth decade of life. Behçet's disease is hallmarked predominantly by mucocutaneous lesions and ocular involvement. Vertebral artery dissection and neurological manifestations are rare complications in Behçet's disease. We examine the case of a medically free 33-year-old male who was admitted to the emergency department complaining of sudden-onset dizziness, vomiting, and tinnitus. Neurological examination revealed fluctuating consciousness, multiple gaze nystagmus, motor deficit in the upper and lower limbs, bilateral Babinski sign, and truncal ataxia. Magnetic resonance imaging (MRI) showed a right pontine hyperintense lesion on T2-weighted images (T2WI). A right vertebral angiogram four months after the incident showed a dissection in the mid-cervical third of an anomalous duplicated origin arm of the right vertebral artery. This case describes an uncommon form of initial presentation of Behçet's disease via a pontine infarction triggered by a dissecting aneurysm in an anatomically rare variant of the vertebral artery.

Preference of Dental Practitioners toward the Use of Local and Topical Anesthetics for Pediatric Patients in Saudi Arabia: A Cross-Sectional Survey.

BACKGROUND: Local anesthesia administration techniques are slightly challenging to perform and master on the basis of experience. It is always delicate to adjust to the first patient injection, especially in children. This study investigated dental practitioners' preferences toward topical and local anesthetics for children in Saudi Arabia. MATERIALS AND METHODS: A questionnaire was sent through google forms to the participants, including sociodemographic characteristics, as well as perceptions of local anesthesia and topical anesthesia. The details for each demographic variable were based the gender, occupation, and experience years. Descriptive statistics were carried out using SPSS (version 24.0), where a p-value of 0.05 at a 95% confidence interval was considered significant. RESULT: A total of 274 responses were received from Saudi Arabian dental practitioners, whereby 92.3% preferred lidocaine, and, while choosing local anesthesia, most participants (57.7%) considered precise bodyweight. The majority of the participants selected 27 gauge needles for infiltrations (46.3%) and blocks (63.9%). Short needles were preferred by the majority (93.4%) of the dental practitioners for infiltration, while long needles (83.9%) were chosen for nerve blocks. Benzocaine (68.2%) was preferred by the majority of the dental practitioners for topical anesthesia, and 55.8% of them were not aware of the brand of the topical anesthesia. The majority of dental practitioners felt that topical anesthesia was effective prior to administration of local anesthesia, and 83.6% of the Arabian dental practitioners expressed that patients complained regarding the taste of topical anesthesia. There were mixed opinions observed among the genders and occupations of dental practitioners regarding anesthetics used. CONCLUSION: The dental practitioners' perceptions and preferences demonstrate that the most commonly preferred type of local anesthetic was lidocaine, whereas the most preferred type of topical anesthetic was benzocaine in gel form. Moreover, the most widely used factor in deciding the dosage of local anesthesia was precise body weight among Saudi dentists. The majority of participants preferred short needles for infiltrations and long needles for nerve blocks. The 27 gauge needle was chosen by the majority of the participants for both infiltration and nerve blocks.

Prevalence of cerebral venous thrombosis with the use of oral contraceptive pills during the Holy month of Ramadan.

OBJECTIVES: To identify the epidemiologic profile of cerebral vein thrombosis (CVT) among fasting women using oral contraceptive pills  (OCPs) during the holy month of Ramadan. Methods: This retrospective study was conducted on all patients diagnosed with CVT and using OCPs from records at a tertiary care hospital in Riyadh, Saudi Arabia during 2016-2017. The study participants were categorized into 2 groups (an intermittently fasting group during the holy month of Ramadan and a non-fasting group).  Results: Out of 108 female patients with CVT, 36.1% were secondary to OCP, of whom 41% participants were fasting. The most affected site was the transverse sinus. Holocephalic headache was more common amongst fasting group (68.8%) compared to non-fasting group (30.4%) (p=0.025). Dehydration (p=0.003) amongst the fasting group and protein S deficiency (p=0.027) in the non-fasting group were identified as the 2 prominent risk factors. Unfractionated heparin was the most common anticoagulant therapies used during the initiation phase for non-fasting (36.4%) and fasting groups (50%). Conclusion: All women who are using OCP should undergo formal written risk assessments for factors of CVT. Our study suggests that the negative effects of OCPs use might outweigh its benefits; thus, it should be prescribed with caution, more so in fasting patients.

The Prevalence of Fabry Disease Among Young Cryptogenic Stroke Patients.

Introduction Fabry disease is a metabolic storage disorder that causes disorders in multiple organs including the brain. Data regarding the prevalence of the disease among the Saudi stroke population is scarce. Hence, tests for the same are not conducted on a regular basis when investigating stroke of uncertain cause. Our study aimed to provide insight into whether testing for Fabry disease is justifiable in cryptogenic stroke patients who have no other features of the disease. Method This was a prospective study conducted at a single stroke center. We included young patients between the ages of 18 and 55 years who had confirmed and unexplained ischemic or hemorrhagic insults. Alpha-galactosidase enzyme testing was conducted in all suspected cases. Further genetic testing was performed in patients with abnormal enzyme results. Result A total of 51 patients met the inclusion criteria. The mean age was 42 years. All the included patients completed a workup of ischemia or hemorrhage. All cases had no clear etiology of their vascular events. All included patients lacked classic systemic manifestations of Fabry disease. We identified one case of borderline low α-galactosidase A (GLA) enzyme level. However, GLA genetic testing did not reveal any Fabry disease-related mutation. The study did not identify any subject with confirmed Fabry disease. Conclusion In this single-center study, we found that Fabry disease had a low prevalence among Saudi cryptogenic stroke patients who lack other systemic manifestations. Hence, Fabry testing is not generally considered in routine workup related to cryptogenic stroke.

Acute stroke patients treated with stent retrievers in carotid "T" occlusions have improved recanalization and outcome.

BACKGROUND: Recanalization rates and patient outcomes in acute occlusion of the carotid terminus have previously been poor. The use of stent-retrievers has resulted in better recanalization and patient outcomes. We sought to compare outcomes in patients treated with stent-retrievers to outcomes in older techniques. METHODS: We retrospectively compared a stent-retriever cohort to a historical cohort. We evaluated recanalization rates and good outcomes (defined as mRS < 2 at 30 days or 10 point drop in NIHSS). RESULTS: There were twenty patients treated with stent-retrievers versus nine without. The recanalization rate in patients treated with stent retrievers was significantly higher than that of other modalities (90% vs 33%, p=0.004). Good outcomes were significantly higher in the stent retriever cohort (70% vs 22%, p=0.041). CONCLUSION: The use of stent-retrievers in patients with carotid "T" occlusions shows promise in comparison to older techniques. A randomized trial comparing stent-retriever therapy to IV thrombolysis is warranted to determine the efficacy of this new generation of devices.

Dynamic characterization of the CT angiographic 'spot sign'.

BACKGROUND AND PURPOSE: Standard (static) CT angiography is used to identify the intracerebral hemorrhage (ICH) spot sign. We used dynamic CT-angiography to describe spot sign characteristics and measurement parameters over 60-seconds of image acquisition. METHODS: We prospectively identified consecutive patients presenting with acute ICH within 4.5 hours of symptom onset, and collected whole brain dynamic CT-angiography (dCTA). Spot parameters (earliest appearance, duration, maximum Hounsfield unit (HU), time to maximum HU, time to spot diagnostic definition, spot volume and hematoma volumes) were measured using volumetric analysis software. RESULT: We enrolled 34 patients: three were excluded due to secondary causes of ICH. Of the remaining 31 patients there were 18 females (58%) with median age 70 (range 47-86) and baseline hematoma volume 33 ml (range 0.7-103 ml). Positive dCTA spot sign was present in 13 patients (42%) visualized as an expanding 3-dimensional structure temporally evolving its morphology over the scan period. Median time to spot appearance was 21 s (range 15-35 seconds). This method allowed tracking of spots evolution until the end of venous phase (active extravasation) with median duration of 39 s (range 25-45 seconds). The average density and time to maximum density was 204HU and 30.8 s (range 23-31 s) respectively. Median time to spot diagnosis was 20.8 s using either 100 or 120HU definitions. CONCLUSION: Dynamic CTA allows a 3-dimensional assessment of spot sign formation during acute ICH, and captured higher spot sign prevalence than previously reported. This is the first study to describe and quantify spot sign characteristics using dCTA; these can be used in ongoing and upcoming ICH studies.

Thrombolysis despite recent stroke: a case series.

BACKGROUND AND PURPOSE: Thrombolysis in ischemic stroke is contraindicated in patients who have had a stroke within 3 months. However, it is unclear whether thrombolytic therapy is associated with adverse outcomes in this population. We report the characteristics and outcomes of patients treated with systemic recombinant tissue-type plasminogen activator in the context of known or unknown recent stroke. METHODS: We identified patients who received recombinant tissue-type plasminogen activator despite recent stroke (within 3 months of acute thrombolysis). Clinical and radiological findings were collected, including early neurological worsening and hemorrhagic transformation on unenhanced computed tomography at 24 hours. Clinical outcome measured by modified Rankin Scale was determined at 3 months from onset. RESULTS: Six patients presenting with acute stroke within 3 months of previous stroke were identified (median age, 76 years; median National Institutes of Health Stroke Scale, 8.5). Hemorrhagic transformation was seen in the follow-up computed tomography scan in 3 of 6 cases: all were hemorrhagic transformation 1 (petechial hemorrhage), asymptomatic, and mostly located within the area of subacute infarction. There was no early neurological deterioration, and 3 patients had modified Rankin Scale ≤ 2 after 3 months. CONCLUSIONS: In our center, we thrombolysed 6 patients despite recent stroke. Three patients had asymptomatic petechial hemorrhagic transformation within the area of subacute infarct, without apparent neurological worsening. Prospective studies are needed to explore the possible safety of tissue-type plasminogen activator in the context of previous subacute stroke in otherwise eligible patients.

Angioplasty as an adjuvant therapy for the treatment of acute ischemic stroke.

BACKGROUND: Different endovascular techniques can be employed to achieve vessel recanalization in acute stroke. We assessed whether an endovascular strategy that included angioplasty was safe and effectively recanalized acutely occluded intracranial vessels. METHODS: We retrospectively reviewed 70 patients that received intra-arterial therapy for acute stroke. Patients were divided into two groups depending on whether they had received angioplasty as part of their endovascular treatment. RESULTS: Angioplasty was used in the treatment of 35/70 patients (50%). Median baseline NIHSS was 15. The site of occlusion was at the M1 in 11 patients, M1/M2 in 3, ICA/M1 in 13 and vertebrobasilar in 8 patients. Intravenous thrombolysis was administered to 16/35 patients (46%). Angioplasty was used alone in 4 patients, in combination with intra-arterial thrombolysis in 27 and with a mechanical retrieval device or stent in 13 patients. Recanalization (TICI 2-3) was achieved in 23/35 patients (66%). Median time from symptom onset to recanalization was six hours. In patients where angioplasty was employed, symptomatic intracranial hemorrhage occurred in 2/35 (6%), which was similar to patients that were not treated with angioplasty. A favorable functional outcome (mRS=2) was achieved in 20% (7/35) at 24 hour and 34% (12/35) at one month. All patients that had a favorable outcome had recanalized. CONCLUSION: In this small cohort, an endovascular treatment strategy that employed angioplasty was safe and effectively recanalized acutely occluded intracranial vessels. Angioplasty should be considered as a potential treatment option in interventional acute stroke trials.