Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma.

Background: The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.

Methods: We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs.

Glibenclamide for Brain Contusions: Contextualizing a Promising Clinical Trial Design that Leverages an Imaging-Based TBI Endotype.

TBI heterogeneity is recognized as a major impediment to successful translation of therapies that could improve morbidity and mortality after injury. This heterogeneity exists on multiple levels including primary injury, secondary injury/host-response, and recovery. One widely accepted type of primary-injury related heterogeneity is pathoanatomic-the intracranial compartment that is predominantly affected, which can include any combination of subdural, subarachnoid, intraparenchymal, diffuse axonal, intraventricular and epidural hemorrhages.

Hypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide.

Brain edema after a large stroke causes significant morbidity and mortality. Here, we seek to identify pharmacodynamic markers of edema that are modified by intravenous (i.v.

Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review.

Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012.

(Sulfonylurea Receptor-1) Impact on Brain Atrophy after Traumatic Brain Injury Varies by Sex.

Females have been understudied in pre-clinical and clinical traumatic brain injury (TBI), despite distinct biology and worse clinical outcomes versus males. Sulfonylurea receptor 1 (SUR1) inhibition has shown promising results in predominantly male TBI. A phase II trial is ongoing.

Association of Refractory Pain in the Acute Phase After Subarachnoid Hemorrhage With Continued Outpatient Opioid Use.

Objective: Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use.

Methods: We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence.

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI.

Pipeline Diameter Significantly Impacts the Long-Term Fate of Jailed Side Branches during Treatment of Intracranial Aneurysms.

Background And Purpose: Although covered side branches typically remain patent acutely following Pipeline Embolization Device embolization of intracranial aneurysms, the long-term fate of these vessels remains uncertain. We therefore elected to investigate factors that may influence the long-term patency of these covered side branches.

Materials And Methods: We retrospectively evaluated the long-term patency of side branches covered by the Pipeline Embolization Device at our institution during treatment of intracranial aneurysms with at least 6 months of conventional angiography follow-up.

Performance of International Classification of Diseases-based injury severity measures used to predict in-hospital mortality and intensive care admission among traumatic brain-injured patients.

Background: The International Classification of Diseases (ICD) is the main classification system used for population-based traumatic brain injury (TBI) surveillance activities but does not contain direct information on injury severity. International Classification of Diseases-based injury severity measures can be empirically derived or mapped to the Abbreviated Injury Scale, but no single approach has been formally recommended for TBI.

Objective: The aim of this study was to compare the accuracy of different ICD-based injury severity measures for predicting in-hospital mortality and intensive care unit (ICU) admission in TBI patients.