Trametinib: a novel signal transduction inhibitor for the treatment of metastatic cutaneous melanoma.

Purpose: The pharmacology, pharmacokinetics, clinical efficacy, safety, administration, cost, and place in therapy of trametinib for the treatment of metastatic melanoma are reviewed.

Summary: Approximately 40-60% of malignant melanomas have gene mutations at codon 600 of the BRAF gene that result in the activation of the mitogen-activated protein kinase (MAPK) pathway. Trametinib is the first-in-class mitogen-activated, extracellular signal-regulated kinase (MEK) inhibitor that targets a kinase in the MAPK pathway that plays a key role in oncogenic cell proliferation, survival, invasion, tumor angiogenesis, and escape from apoptosis.

Oral anticoagulation in atrial fibrillation.

Atrial fibrillation affects approximately 5 million patients in the United States. The rate of stroke in adults with atrial fibrillation depending on their risk factors varies between 1-20% annually. Anticoagulation with vitamin K antagonists such as warfarin has been the mainstay therapy but it is cumbersome and requires close follow-up.

Evaluation of the impact of a pertussis cocooning program on infant pertussis infection.

Background: Tetanus, diphtheria and acellular pertussis immunization of infant contacts (cocooning) is recommended by the Centers for Disease Control and Prevention to prevent infant pertussis. We determined whether implementing a cocooning program at Ben Taub General Hospital, Houston, reduced severe pertussis in young infants.

Methods: Infants ≤6 months of age, diagnosed with pertussis (determined by International Classification of Diseases, Ninth Revision codes and microbiology records) at 4 hospitals, and born at times when only postpartum women (January 2008 through May 2009) and all infant contacts (June 2009 through August 2011) were offered tetanus, diphtheria and acellular pertussis vaccine at Ben Taub General Hospital were compared with infants born preintervention (May 2004 through December 2007).

Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury.

Transactivation response DNA-binding protein 43 (TDP-43) proteinopathy has recently been reported in chronic traumatic encephalopathy, a neurodegenerative condition linked to prior history of traumatic brain injury (TBI). While TDP-43 appears to be vulnerable to proteolytic modifications under neurodegenerative conditions, the mechanism underlying the contribution of TDP-43 to the pathogenesis of TBI remains unknown. In this study, we first mapped out the calpain or caspase-3 TDP-43 fragmentation patterns by in vitro protease digestion.

Rapid progression of pulmonary blastomycosis in an untreated patient of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is associated with a state of immunosuppression characterized by hypogammaglobulinemia as well as B and T lymphocyte dysfunction. Though opportunistic infections are common in CLL patients, particularly after treatment, reports of infections by endemic dimorphic fungi are very few. Here we report a case of pulmonary blastomycosis in a CLL patient who initially presented with an indolent pulmonary mass lesion.

Measurement of ulnar variance from the lateral radiograph: a comparison of techniques.

Purpose: To determine the reliability of measuring ulnar variance on lateral wrist radiographs and to compare this technique with previously described methods.

Methods: Ulnar variance was measured in 100 normal wrist radiographs using the methods of perpendiculars, central reference point, and the lateral radiograph by 3 surgeons on 2 occasions. Intraobserver repeatability and agreement between raters and methods were assessed and compared.

Challenges in providing critical care for patients with anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is characterized by a constellation of psychiatric, neurologic, autonomic, and cardiopulmonary manifestations. Although patients typically recover with appropriate treatment, they commonly require weeks to months of inpatient care, including prolonged stays in critical care units. This case series not only advocates for consideration of the disease in the appropriate context but also specifically highlights the distinct challenges intensivists encounter caring for patients with NMDARE.

The clinical manifestations, diagnosis, and treatment of adrenal emergencies.

Emergency medicine physicians should be able to identify and treat patients whose clinical presentations, including key historical, physical examination, and laboratory findings are consistent with diagnoses of primary, secondary, and tertiary adrenal insufficiency, adrenal crisis, and pheochromocytoma. Failure to make a timely diagnosis leads to increased morbidity and mortality. As great mimickers, adrenal emergencies often present with a constellation of nonspecific signs and symptoms that can lead even the most diligent emergency physician astray.

Disorders of sodium and water balance.

Dysnatremias occur simultaneously with disorders in water balance. The first priority is to correct dehydration; once the patient is euvolemic, the sodium level can be reassessed. In unstable patients with hyponatremia, the clinician should rapidly administer hypertonic saline.

Derangements of potassium.

Changes in potassium elimination, primarily due to the renal and GI systems, and shifting potassium between the intracellular and extracellular spaces cause potassium derangement. Symptoms are vague, but can be cardiac, musculoskeletal, or gastrointestinal. There are no absolute guidelines for when to treat, but it is generally recommended when the patient is symptomatic or has ECG changes.

Acceptability of immunization in adult contacts of infants: possibility of expanding platforms to increase adult vaccine uptake.

Objective: Adult vaccination coverage is low and current strategies are unlikely to achieve Healthy People 2020 targets. We determined the attitude of adult infant contacts toward recommended adult vaccines and their willingness to receive vaccines should they be available during hospital visits or prenatal or infant clinic appointments.

Methods: Survey of predominantly Hispanic, underinsured and medically underserved infant contacts at a county hospital in Houston, Texas where a pertussis cocooning program is offered.

Common femoral vein reconstruction using internal jugular vein after blast injury.

Common femoral vein traumatic injuries are rare. Surgical management is controversial and by nature case specific. In this report, we present an unusual case of an isolated common femoral vein injury from a gunshot blast repaired with an interposition internal jugular vein bypass.

Preparing for effective communications during disasters: lessons from a World Health Organization quality improvement project.

Background: One hundred ninety-four member nations turn to the World Health Organization (WHO) for guidance and assistance during disasters. Purposes of disaster communication include preventing panic, promoting appropriate health behaviors, coordinating response among stakeholders, advocating for affected populations, and mobilizing resources.

Methods: A quality improvement project was undertaken to gather expert consensus on best practices that could be used to improve WHO protocols for disaster communication.

Masked and overt autoantibodies specific to the DPD epitope of 65-kDa glutamate decarboxylase (GAD65-DPD) are associated with preserved β-cell functional reserve in ketosis-prone diabetes.

Context: Ketosis-prone diabetes (KPD), defined by presentation with diabetic ketoacidosis (DKA), comprises 4 subgroups based on the presence or absence of islet cell autoantibodies (A(-) or A(+)) and β-cell functional reserve (β(-) or β(+)). Among A(+) KPD, autoantibody epitope reactivity to 65-kDa glutamate decarboxylase (GAD65), defined by monoclonal GAD65Ab(DPD), was associated with greater β-cell functional reserve. In a majority of healthy individuals, GAD65Ab are present in the sera but are masked by anti-idiotypic antibodies; in contrast, overtly GAD65Ab-positive patients with autoimmune type 1 diabetes patients lack these anti-idiotypic antibodies.

Rapidly evolving large extracranial vertebral artery pseudoaneurysm in Behçet's disease: Case report and review of the literature.

Behçet's disease is a multisystem chronic autoimmune disease of unknown etiology with a wide spectrum of symptoms and organ system involvement. Arterial manifestations, particularly of the extracranial vertebral arteries, are rare. We report an unusual case of an African American patient with Behçet's disease, who presented with bilateral spontaneous vertebral artery pseudoaneurysms.

Crash test rating and likelihood of major thoracoabdominal injury in motor vehicle crashes: the new car assessment program side-impact crash test, 1998-2010.

Background: The National Highway Traffic Safety Administration's New Car Assessment Program (NCAP) implemented side-impact crash testing on all new vehicles since 1998 to assess the likelihood of major thoracoabdominal injuries during a side-impact crash. Higher crash test rating is intended to indicate a safer car, but the real-world applicability of these ratings is unknown. Our objective was to determine the relationship between a vehicle's NCAP side-impact crash test rating and the risk of major thoracoabdominal injury among the vehicle's occupants in real-world side-impact motor vehicle crashes.

Posterior urethral complications of radical prostatectomy.

The incidence of vesicourethral anastomotic stenosis following radical prostatectomy has fallen over the past two decades, but it remains a relatively common complication of this procedure. Options for management include endoscopic and surgical approaches. These options are briefly discussed in this review and a management algorithm is proposed.

Prospective nutritional analysis of a diverse trauma population demonstrates substantial hypovitaminosis D.

Objectives: There are several metabolic factors known to be important for the maintenance of bone and muscle function. Causes of deficiency are multifactorial and can include such things as geographic region, latitude, and socioeconomic factors. The purpose of this study was to determine the prevalence of metabolic deficiencies.

Neutrophil gelatinase associated lipocalin in acute kidney injury.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family of proteins. Usually, NGAL is produced and secreted by kidney tubule cells at low levels, but the amount produced and secreted into the urine and serum increases dramatically after ischemic, septic, or nephrotoxic injury of the kidneys. The purpose of our review article is to summarize the role of NGAL in acute kidney injury (AKI), emergent, and intensive care.