Intralesional epileptiform activity in a fourth ventricular hamartoma associated with epileptic hemifacial spasm in a toddler: illustrative case.

Background: Focal epilepsy caused by a posterior fossa lesion is a rare phenomenon. In these cases, seizure onset typically occurs during the first few months of life, with episodes of epileptic hemifacial spasms and abnormal eye movements. Patients often present with drug-resistant epilepsy and often require resection for the best chance of seizure freedom.

Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies.

Purpose: The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied.

Patients And Methods: Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy.

Results: Patients received monotherapy (n = 67) or combination therapy (n = 171) elraglusib doses 1 to 15 mg/kg twice weekly.

GSK-3 Inhibitor Elraglusib Enhances Tumor-Infiltrating Immune Cell Activation in Tumor Biopsies and Synergizes with Anti-PD-L1 in a Murine Model of Colorectal Cancer.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that has been implicated in numerous oncogenic processes. GSK-3 inhibitor elraglusib (9-ING-41) has shown promising preclinical and clinical antitumor activity across multiple tumor types. Despite promising early-phase clinical trial results, there have been limited efforts to characterize the potential immunomodulatory properties of elraglusib.

GSK-3 inhibitor elraglusib enhances tumor-infiltrating immune cell activation in tumor biopsies and synergizes with anti-PD-L1 in a murine model of colorectal cancer.

Unlabelled: Inhibition of GSK-3 using small-molecule elraglusib has shown promising preclinical antitumor activity. Using in vitro systems, we found that elraglusib promotes immune cell-mediated tumor cell killing, enhances tumor cell pyroptosis, decreases tumor cell NF-κB-regulated survival protein expression, and increases immune cell effector molecule secretion. Using in vivo systems, we observed synergy between elraglusib and anti-PD-L1 in an immunocompetent murine model of colorectal cancer.

Underrepresented patient views and perceptions of personalized medication treatment through pharmacogenomics.

Within an institutional pharmacogenomics implementation program, we surveyed 463 outpatients completing preemptive pharmacogenomic testing whose genetic results were available to providers for guiding medication treatment. We compared views and experiences from self-reported White and Black patients, including education level as a covariate across analyses. Black patients were less confident about whether their providers made personalized treatment decisions, and overwhelmingly wanted a greater role for their genetic information in clinical care.

Anesthesia providers as stakeholders to adoption of pharmacogenomic information in perioperative care.

Objectives: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care.

Methods: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program.

Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application.

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II.

Procedural frequency: Results from 18 academic, community and freestanding emergency departments.

Background: Emergency physicians must maintain procedural skills, but clinical opportunities may be insufficient. We sought to determine how often practicing emergency physicians in academic, community and freestanding emergency departments (EDs) perform 4 procedures: central venous catheterization (CVC), tube thoracostomy, tracheal intubation, and lumbar puncture (LP).

Methods: This was a retrospective study evaluating emergency physician procedural performance over a 12-month period.

The impact of hospital boarding on the emergency department waiting room.

Background: Patient boarding in the emergency department (ED) is a significant issue leading to increased morbidity/mortality, longer lengths of stay, and higher hospital costs. We examined the impact of boarding patients on the ED waiting room. Additionally, we determined whether facility type, patient acuity, time of day, or hospital occupancy impacted waiting rooms in 18 EDs across a large healthcare system.

The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer.

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase, has been implicated in the pathogenesis of many cancers, with involvement in cell-cycle regulation, apoptosis, and immune response. Small-molecule GSK-3β inhibitors are currently undergoing clinical investigation. Tumor sequencing has revealed genomic alterations in , yet an assessment of the genomic landscape in malignancies is lacking.

A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers.

Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices).

Pharmacogenomic-Based Decision Support to Predict Adherence to Medications.

Poor adherence is associated with worse disease outcomes. Pharmacogenomics provides a possible intervention to address adherence. We hypothesized that pharmacogenomic-informed care could increase adherence.

Electronic medical record-based interventions to encourage opioid prescribing best practices in the emergency department.

Objective: Overdose from opioids has reached epidemic proportions. Large healthcare systems can utilize existing technology to encourage responsible opioid prescribing practices. Our study measured the effects of using the electronic medical record (EMR) with direct clinician feedback to standardize opioid prescribing practices within a large healthcare system.

Conversion of Laparoscopic Roux en Y Gastric Bypass (RYGB) to Single Anastomosis Duodenal Switch (SADS).

Background: The surgical management of weight regain following RYGB remains controversial. Simpler modifications such as endoscopic suturing and banding the bypass have had variable efficacy. Distalization of the bypass has resulted in a high risk of malabsorption-related complications as reported by Amor et al.

Patient-provider communications about pharmacogenomic results increase patient recall of medication changes.

Effective doctor-patient communication is critical for disease management, especially when considering genetic information. We studied patient-provider communications after implementing a point-of-care pharmacogenomic results delivery system to understand whether pharmacogenomic results are discussed and whether medication recall is impacted. Outpatients undergoing preemptive pharmacogenomic testing (cases), non-genotyped controls, and study providers were surveyed from October 2012-May 2017.

Assessment of provider-perceived barriers to clinical use of pharmacogenomics during participation in an institutional implementation study.

Objective: The objective of this study was to study provider attitudes of and perceived barriers to the clinical use of pharmacogenomics before and during participation in an implementation program.

Participants And Methods: From 2012 to 2017, providers were recruited. After completing semistructured interviews (SSIs) about pharmacogenomics, providers received training on and access to a clinical decision support tool housing patient-specific pharmacogenomic results.

Analyzing the clinical actionability of germline pharmacogenomic findings in oncology.

Background: Germline and tumor pharmacogenomics impact drug responses, but germline markers less commonly guide oncology prescribing. The authors hypothesized that a critical number of clinically actionable germline pharmacogenomic associations exist, representing clinical implementation opportunities.

Methods: In total, 125 oncology drugs were analyzed for positive germline pharmacogenomic associations in journals with impact factors ≥5.

Simplifying the use of pharmacogenomics in clinical practice: Building the genomic prescribing system.

Background: A barrier to the use of genomic information during prescribing is the limited number of software solutions that combine a user-friendly interface with complex medical data. We built and designed an online, secure, electronic custom interface termed the Genomic Prescribing System (GPS).

Methods: Actionable pharmacogenomic (PGx) information was reviewed, collected, and stored in the back-end of GPS to enable creation of customized drug- and variant-specific clinical decision support (CDS) summaries.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk.

Assessment of patient perceptions of genomic testing to inform pharmacogenomic implementation.

Objective: Pharmacogenomics seeks to improve prescribing by reducing drug inefficacy/toxicity. However, views of patients during pharmacogenomic-guided care are largely unknown. We sought to understand the attitudes and perceptions of patients in an institutional implementation project and hypothesized that views would differ on the basis of experience with pharmacogenomic-guided care.