Generality of Enhancing the Dissolution Rates of Free Acid Amorphous Solid Dispersions by the Incorporation of Sodium Hydroxide.

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.

Treatment options and long-term outcomes in pediatric spinal cord vascular malformations: a case report and review of the literature.

A 16-month-old female was admitted for prolonged fever, gait ataxia, and neurogenic bowel and bladder. Neurological exam was significant for decreased sensory and motor functions in bilateral lower extremities. Initial MRI showed a thoracic spine hematoma and diagnostic angiogram revealed a large AVM and aneurysm. The patient underwent surgical resection of the hematoma and AVM, as well as clipping and later endovascular coiling of the aneurysm. Due to significant hemorrhage perioperatively, she developed spastic paraplegia improved by baclofen and onabotulinumtoxin A injections. The aims of this paper were to conduct a systematic review of the literature on pediatric spinal cord vascular malformations and analyze trends in treatment options and long-term neurological outcomes. PubMed searches were conducted using keywords "pediatric spinal vascular malformation" and "pediatric spinal AVM", yielding 34 results after abstract screening and cross-reference. Endovascular embolization was determined to have better long-term outcomes, with 10/19 (52.6%) patients with postoperative complications associated with open vascular surgeries. Open versus endovascular surgical decisions can be difficult with unique spinal AVM pathologies in pediatric patients. Important considerations such as size, location, neurological deficits, and risk of rupture are important factors to consider in treating these patients. We recommend endovascular treatment as a first-line approach due to lower risk of hemorrhage and postoperative deficits.

Sex-Based Differences in the Presentation of Myocardial Infarction.

The authors report a case of a middle-aged female presenting with a chief complaint of shoulder pain. Workup revealed a non-ST-segment elevation myocardial infarction. The typical symptoms of myocardial infarction and the evaluation of a non-ST-segment elevation myocardial infarction are discussed. The authors highlight the sex-based differences in the presentation of myocardial infarction and remind us to keep a broad differential and consider atypical presentations.

Total and partial posterior quadrant disconnection for medically refractory epilepsy: A systematic review.

PURPOSE: Posterior quadrant disconnection (PQD) is a surgical procedure for medically refractory epilepsy (MRE) involving diffuse regions of the temporo-parieto-occipital lobes. We sought to compare factors and efficacy according to PQD extent. METHODS: We performed a systematic review of the literature reporting the use of PQD since 2004. We analyzed various characteristics of pooled cases, including the role of preoperative studies in patient selection, intraoperative techniques, and outcomes. RESULTS: Our review of 137 patients from nine studies revealed 66% undergoing total PQD and 34% undergoing partial PQD. Interictal electroencephalography (EEG) findings were predominantly characterized as lateralized for total PQD (56%) and localized within the ipsilateral posterior quadrant in patients undergoing partial PQD (53%). Metabolic functional studies [positron emission tomography (PET) or ictal single-photon emission computed tomography (SPECT)] played a role in surgical decision-making in 42% of patients who underwent total PQD. Wada and/or functional magnetic resonance imaging (fMRI) was more often utilized for partial PQD (22%) than total PQD (3%) as was intracranial electroencephalography (icEEG) (30% versus 13%, respectively). Overall, 75% of total PQD patients achieved seizure freedom [defined as Engel I or International League Against Epilepsy (ILAE) Class 1 outcome] in comparison to 63% of partial PQD patients (p = .078). New visual field deficits were seen in 12% and new or worsened hemiparesis in 6%. For patients in either cohort, concordance of interictal and ictal EEG findings was found to be predictive of seizure freedom (p = .048). CONCLUSION: Both total and partial PQD represent effective alternatives for managing patients with MRE whose seizure onset zone (SOZ) involves a diffuse region within the posterior quadrant. While PET and/or SPECT frequently aided in the decision to proceed with total PQD, patients who underwent a tailored, partial multilobar resection were more likely to undergo Wada and/or fMRI testing as well as stage I icEEG studies.