Mepolizumab-Induced Posterior Reversible Encephalopathy Syndrome (PRES), a new patient report.

BACKGROUND: Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic state characterized by seizures, headache, vision change, paresis, and altered mental status. PRES has an important place in medicine due to the wide variety of causative diseases, infections, and medications that precipitate its mysterious onset. Although exposure to medications, particularly immunosuppressants, cancer chemotherapy, and biologic drugs, is a common occurrence in patients who develop PRES, Mepolizumab has never before been associated. CASE PRESENTATION: This report of a 67-year-old male patient outlines the first reported case of Mepolizumab-induced PRES in the literature. CONCLUSIONS: Treatment of severe asthma, asthma-exacerbations, and diseases such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) with Mepolizumab is rapidly gaining popularity ever since the drug's recent FDA-approval. This report aims to raise awareness of this potentially life-threatening and previously unreported side effect of Mepolizumab since early identification of the causative agent is the key to preventing the severe neurologic disability and possible death that may occur from the delayed treatment of PRES.

An Orientation to Aviation Psychiatry: With 30 Case Examples and a 10-Year Follow-up.

ABSTRACT: This report orients general psychiatrists to assessment and care for "safety sensitive" aviation workers. Our case study of 30 sequential aviation patients consists of demographic, clinical, and aviation characteristics plus a 10-year follow-up. Relatively few pilots and other aviation workers self-identified their psychiatric condition. Aviation outcomes associated with psychiatric disorder included personnel injury and/or aircraft damage (three cases), imminent risk without injury or damage (nine cases), impaired aviation functioning without imminent risk (15 cases), and neither risk nor psychiatric disorder or impairment (three cases). Mood, anxiety, and substance use disorders comprised the most common diagnoses. Ten years later, 23 patients were employed (21 in aviation); seven were disabled or deceased. General psychiatrists will find aviation cases clinically familiar but requiring added evaluation for aviation safety and potential interaction with the Federal Aviation Agency and airline supervisors.

Genetics of Malignant Hyperthermia: A Brief Update.

Malignant hyperthermia susceptibility (MHS) and the associated condition malignant hyperthermia (MH) are rare but well-known disorders in the field of anesthesiology. MHS is usually determined by a history of a family member developing a positive episode during general anesthesia and then confirmed by an invasive caffeine halothane contracture test (CHCT). More recently, within the context of MH as a pharmacogenetic disorder, the question of whether or not MHS can be principally genetically determined is of high importance as knowledge of detailed pathogenesis may prevent against its largely invariable lethality if untreated. Thus, in this brief report, genetic terms, as well as updates in the genetics of MHS, will be reviewed in order to better understand both the condition and the current research.

Status Epilepticus in Post-Transplantation Hyperammonemia Involves Careful Metabolic Management.

Hyperammonemia is a condition that may result after solid organ transplantation, particularly lung transplantation. However, it is very uncommon for this presentation to occur more than 30 days post-transplantation. Hyperammonemia and the resulting encephalopathy typically manifest with altered sensorium, a clinical situation which is not often included in the differential diagnosis of presumed nonconvulsive status epilepticus (NCSE). Seizures are common among this subset of patients with hyperammonemia and may be refractory to traditional treatments. Evidence of elevated intracranial pressure by invasive monitoring and neuroimaging findings of diffuse cerebral edema are commonly reported. Here we examine the therapeutic importance of identifying the specific cause of hyperammonemic encephalopathy, a condition which may result in status epilepticus and ultimately cerebral edema or even brain death.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids May Extend above and below Pons and Is Associated with Other Autoimmune Diseases.

Many autoimmune diseases can affect the central nervous system, and their varying clinical presentations often confound a straightforward diagnosis. In this report, we describe a unique presentation of CLIPPERS syndrome. To our knowledge, this is the first case to demonstrate significant supratentorial involvement with symmetric and non-confluent lesions in the medial orbitofrontal cortex; additionally, this is the second case to describe an association between diagnoses of hypothyroidism and CLIPPERS.

Intrawound vancomycin application after spinal surgery: a propensity score-matched cohort analysis.

OBJECTIVE: Surgical site infection (SSI) following spine surgery is associated with increased morbidity and healthcare costs. In an effort to reduce SSI rates, the application of intrawound vancomycin powder has gained popularity. However, there is limited high-quality evidence to support the safety and efficacy of this practice. The authors sought to determine if intrawound application of vancomycin powder improves 90-day overall SSI rates. METHODS: The authors performed a retrospective, vancomycin exposure-matched cohort study at a single tertiary care hospital over 21 months. They included all patients undergoing elective spinal surgery and stratified the patients into two groups: those who received intrawound vancomycin powder application and those who received no application of vancomycin powder. The primary outcome of interest was the 90-day overall SSI rate. Secondary outcomes included rates of superficial SSI, deep SSI, wound disruption, and a post hoc analysis of the microbiology and minimum inhibitory concentrations. Baseline patient demographics, clinical presentation, comorbidities, perioperative factors, and 90-day postoperative outcomes were manually abstracted from patient charts. To mitigate bias, we performed 1:1 matching after calculating propensity scores and identified 1 patient from the no-vancomycin cohort for each patient in the vancomycin cohort. RESULTS: A total of 997 patients met our inclusion criteria (473 patients receiving vancomycin and 524 patients not receiving vancomycin). Propensity score matching produced 221 matched pairs. Risk-adjusted analysis demonstrated similar overall SSI rates between the groups (OR 1.9, p = 0.329). On unadjusted analysis, the overall 90-day SSI rate was greater in the vancomycin group (n = 10 [4.5%]) than in the no-vancomycin group (n = 5 [2.3%]) (p < 0.001), as were the superficial SSI rate (7 [3.2%] vs 4 [1.8%], p < 0.001), deep SSI rate (3 [1.4%] vs 1 [0.5%], p < 0.001), and wound disruption rate (5 [2.3%] vs 1 [0.5%], p < 0.001). No cultured isolate demonstrated vancomycin resistance. CONCLUSIONS: The authors observed no difference in SSI rates after the intrawound application of vancomycin powder during spine surgery. Vancomycin use did not contribute to antimicrobial resistance; however, it may select out gram-negative bacteria and increase rates of wound disruption.

Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments.

Defining the principles of T cell migration in structurally and mechanically complex tumor microenvironments is critical to understanding escape from antitumor immunity and optimizing T cell-related therapeutic strategies. Here, we engineered nanotextured elastic platforms to study and enhance T cell migration through complex microenvironments and define how the balance between contractility localization-dependent T cell phenotypes influences migration in response to tumor-mimetic structural and mechanical cues. Using these platforms, we characterize a mechanical optimum for migration that can be perturbed by manipulating an axis between microtubule stability and force generation. In 3D environments and live tumors, we demonstrate that microtubule instability, leading to increased Rho pathway-dependent cortical contractility, promotes migration whereas clinically used microtubule-stabilizing chemotherapies profoundly decrease effective migration. We show that rational manipulation of the microtubule-contractility axis, either pharmacologically or through genome engineering, results in engineered T cells that more effectively move through and interrogate 3D matrix and tumor volumes. Thus, engineering cells to better navigate through 3D microenvironments could be part of an effective strategy to enhance efficacy of immune therapeutics.

Engineering Elastic Nano- and Micro-Patterns and Textures for Directed Cell Motility.

We present a reproducible protocol for fabrication of polyacrylamide (PAA) hydrogel-based nano-patterns and nano-textures with a wide range of elastic rigidities to study fundamental cell behaviors, such as mechanosensitivity and motility. We explore the benefits of this protocol by successfully testing the compatibility of the PAA platforms with super-resolution microscopy, which is largely unavailable with platforms of nano-scale textures made from different polymers. We also utilized soft and rigid nano-textures to study the mechanosensing basis of T cell behavior and phenotype. For complete information on the generation and use of this protocol, please refer to Tabdanov et al. (2018b).

A Unique Case Report on Hypersensitivity Vasculitis as an Allergic Reaction to the Herpes Zoster Vaccine.

Hypersensitivity vasculitis (HV) or leukocytoclastic vasculitis is a rare small-vessel vasculitis that may occur as a manifestation of the body's extreme allergic reaction to a drug, infection, or other foreign substance. Characterized by the presence of inflammatory neutrophils in vessel walls, HV results in inflammation and damage to blood vessels, primarily in the skin. Histologically, when neutrophils undergo leukocytoclasia and release nuclear debris into the vasculature, vascular damage manifests as palpable purpura. The incidence of HV is unknown and its relationship and interaction with certain vaccinations is rare and poorly understood. Affected patients with HV generally have a good prognosis; however, fatality may occur if organs such as the central nervous system, heart, lungs, or kidneys are involved. We report a unique case of a 60-year-old man who presented with a serious case of HV after receiving the herpes zoster vaccine. A thorough literature review yielded only one similar case of vascular reaction to the varicella vaccine that was reported in the Annals of Internal Medicine in 1997; however, no other reported cases with regard to the herpes zoster vaccine have been found. Our case presents a rare glimpse into HV that may result from varicella vaccine administration.

Microtubule-Actomyosin Mechanical Cooperation during Contact Guidance Sensing.

Cancer cell migration through and away from tumors is driven in part by migration along aligned extracellular matrix, a process known as contact guidance (CG). To concurrently study the influence of architectural and mechanical regulators of CG sensing, we developed a set of CG platforms. Using flat and nanotextured substrates with variable architectures and stiffness, we show that CG sensing is regulated by substrate stiffness and define a mechanical role for microtubules and actomyosin-microtubule interactions during CG sensing. Furthermore, we show that Arp2/3-dependent lamellipodia dynamics can compete with aligned protrusions to diminish the CG response and define Arp2/3- and Formins-dependent actin architectures that regulate microtubule-dependent protrusions, which promote the CG response. Thus, our work represents a comprehensive examination of the physical mechanisms influencing CG sensing.

Bimodal sensing of guidance cues in mechanically distinct microenvironments.

Contact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.