Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

Intraoperative Seizure Under General Anesthesia Not Detected by EEG: A Case Report.

Intraoperative seizures under general anesthesia are infrequent. However, seizure activity under general anesthesia confirmed by contemporaneous EEG has been reported. We describe the case of a 39-year-old female undergoing right frontal brain tumor resection who experienced an intraoperative seizure.

Differences in Perioperative Management of Patients Undergoing Complex Spine Surgery: A Global Perspective.

Background: The aim of this survey was to understand institutional spine surgery practices and their concordance with published best practices/recommendations.

Methods: Using a global internet-based survey examining perioperative spine surgery practice, reported institutional spine pathway elements (n=139) were compared with the level of evidence published in guideline recommendations. The concordance of clinical practice with guidelines was categorized as poor (≤20%), fair (21%-40%), moderate (41%-60%), good (61%-80%), or very good (81%-100%).

CAR-T cells derived from multiple myeloma patients at diagnosis have improved cytotoxic functions compared to those produced at relapse or following daratumumab treatment.

Chimeric antigen receptor T cells (CAR-T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR-T directed against CS1 or B Cell Maturation antigen.

Fosaprepitant Does Not Interfere With Commonly Used Intraoperative Neuromonitoring Modalities Under General Anesthesia: A Preliminary Study.

Background: Fosaprepitant [Emend®], a neurokinin type-1 [NK-1] receptor antagonist, is a highly effective for the prophylaxis of postoperative nausea and vomiting [PONV] after general anesthesia; it is particularly effective in patients undergoing neurosurgical procedures. Based on the widespread distribution of NK-1 receptors in the central and peripheral nervous systems, we sought to determine whether fosaprepitant administration would interfere with commonly used intraoperative neurophysiologic monitoring modalities during general anesthesia.

Methods: Eleven patients having propofol-based general anesthesia for interventional neuroradiology procedures were administered 150 mg fosaprepitant intravenously after baseline electroencephalogram [EEG], transcranial motor evoked potential [TcMEP], and somatosensory evoked potential [SSEP] recordings were obtained.

First-in-man, first-in-class phase I study with the monopolar spindle 1 kinase inhibitor S81694 administered intravenously in adult patients with advanced, metastatic solid tumours.

Background: S81694 is an inhibitor of monopolar spindle 1 kinase, a target expressed in proliferating cells. CL1-81694-001 was the first-in-human study aiming at identifying a safe dosing schedule in solid tumour patients.

Patients And Methods: This trial was based on inter-individual dose-escalation of single agent S81694 in cohorts of ≥3 patients to assess the safety and tolerability and determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended phase II dose (RP2D), with S81694 given on days 1,8,15 of a 28-day cycle as 1-h infusion.

Modeling restoration of gefitinib efficacy by co-administration of MET inhibitors in an EGFR inhibitor-resistant NSCLC xenograft model: A tumor-in-host DEB-based approach.

MET receptor tyrosine kinase inhibitors (TKIs) can restore sensitivity to gefitinib, a TKI targeting epidermal growth factor receptor (EGFR), and promote apoptosis in non-small cell lung cancer (NSCLC) models resistant to gefitinib treatment in vitro and in vivo. Several novel MET inhibitors are currently under study in different phases of development. In this work, a novel tumor-in-host modeling approach, based on the Dynamic Energy Budget (DEB) theory, was proposed and successfully applied to the context of poly-targeted combination therapies.

Targeting DYRK1A/B kinases to modulate p21-cyclin D1-p27 signalling and induce anti-tumour activity in a model of human glioblastoma.

The dual-specificity tyrosine-regulated kinases DYRK1A and DYRK1B play a key role in controlling the quiescence-proliferation switch in cancer cells. Serum reduction of U87MG 2D cultures or multi-cellular tumour spheroids induced a quiescent like state characterized by increased DYRK1B and p27, and decreased pRb and cyclin D1. VER-239353 is a potent, selective inhibitor of the DYRK1A and DYRK1B kinases identified through fragment and structure-guided drug discovery.

Perioperative Care of Patients Undergoing Major Complex Spinal Instrumentation Surgery: Clinical Practice Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care.

Evidence-based standardization of the perioperative management of patients undergoing complex spine surgery can improve outcomes such as enhanced patient satisfaction, reduced intensive care and hospital length of stay, and reduced costs. The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) tasked an expert group to review existing evidence and generate recommendations for the perioperative management of patients undergoing complex spine surgery, defined as surgery on 2 or more thoracic and/or lumbar spine levels. Institutional clinical management protocols can be constructed based on the elements included in these clinical practice guidelines, and the evidence presented.

Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B.

The serine/threonine kinase DYRK1A has been implicated in regulation of a variety of cellular processes associated with cancer progression, including cell cycle control, DNA damage repair, protection from apoptosis, cell differentiation, and metastasis. In addition, elevated-level DYRK1A activity has been associated with increased severity of symptoms in Down's syndrome. A selective inhibitor of DYRK1A could therefore be of therapeutic benefit.

Structure-Guided Discovery of Potent and Selective DYRK1A Inhibitors.

The kinase DYRK1A is an attractive target for drug discovery programs due to its implication in multiple diseases. Through a fragment screen, we identified a simple biaryl compound that is bound to the DYRK1A ATP site with very high efficiency, although with limited selectivity. Structure-guided optimization cycles enabled us to convert this fragment hit into potent and selective DYRK1A inhibitors.

Rapid Blood Transfusion: The Importance of Hemodilution and Needleless Connectors.

Introduction:  Large-bore cannulas are critical to administering IV fluids and blood products during resuscitation and treatment of hemorrhage. Although catheter flow rates for crystalloid solutions are well defined, rapid administration of blood products is poorly characterized. In this in vitro study, we examined the effects of hemodilution and needleless connectors on red blood cell (RBC) flow rates.

Incidence of Anaphylaxis to Sugammadex in a Single-Center Cohort of 19,821 Patients.

Background: Sugammadex is a modified cyclodextrin that is being increasingly used in anesthetic practice worldwide for the reversal of the aminosteroid neuromuscular blockers rocuronium and vecuronium. Its safety profile, however, is incompletely understood. One such aspect is the incidence of anaphylactic reactions that occur after its administration.

Intraoperative Transcranial Motor-evoked Potential Stimulation Does Not Seem to Cause Seizures.

Background: Intraoperative neurophysiological monitoring is of critical importance in evaluating the functional integrity of the central nervous system during surgery of the central or peripheral nervous system. In a large recent study, transcranial motor-evoked potentials (TcMEPs) were found to be associated with a 0.7% risk of inducing a seizure as diagnosed by clinical observation and electromyography in patients having general anesthesia with intravenous anesthetics.

Intraoperative Kirschner Wire Migration during Robotic Minimally Invasive Spine Surgery.

We present the case of a 58-year-old woman who underwent a minimally invasive robotic-assisted L4-S1 instrumentation and fusion which was complicated by a Kirschner wire (K-wire) fracture and migration into the abdominal cavity necessitating emergent exploratory laparotomy. Retrieval of the K-wire proceeded without incident, and the patient had an otherwise uneventful surgery and recovery. This is the first such case description reported in the literature.

Paradoxical Critical Hyperkalemia After Acetazolamide for Cerebrovascular Reactivity Study: A Case Report.

We present the case of a 42-year-old man with moyamoya disease presenting for cerebral revascularization surgery who developed critical hyperkalemia following a single intravenous (iv) dose of 1000 mg of acetazolamide 1 day preoperatively for a cerebrovascular reactivity study. His potassium increased from 5.1 to 6.