The Diagnostic Utility of PRAME in Primary Cutaneous Dedifferentiated and Transdifferentiated Melanomas.

Melanomas show a wide spectrum of clinical, morphological, immunohistochemical, and molecular features, which can impact treatment and prognosis. Dedifferentiated and transdifferentiated melanomas (DTM) are defined as melanomas which have lost conventional melanocytic morphologic and immunohistochemical features, showing sarcomatous morphology and/or immunohistochemical staining of other cell lineages, and as such, can be mistaken for other entities such as collision tumors and undifferentiated spindle cell tumors. In this series, we highlight the utility of preferentially expressed antigen in melanomas (PRAME) in diagnosing undifferentiated/dedifferentiated melanomas.

Use and outcomes of antihypertensive medication treatment in the US hypertensive population: A gender comparison.

Background: Although effective antihypertensive medications have existed for decades, only about half of the hypertensive individuals are considered to have controlled blood pressure. Limited research studies have investigated gender disparity in the utilization and effectiveness of antihypertensive medications treatment. To examine the gender difference in antihypertensive medications' use and the effect of using antihypertensive medication treatment on blood pressure control among the U.

More Drug Monitoring and Less CT Scans of the Brain: Gabapentin Overdose in Two Peritoneal Dialysis Patients.

In parallel with the decline of renal excretory function, drug dosing of many drugs becomes more challenging. Finding the right dose is even more difficult if kidney replacement therapy is instituted. This is further aggravated by the fact that even for substances with a narrow therapeutic range, drug monitoring is only rarely offered, let alone advocated.

Virtual Behavioral Health Treatment Satisfaction and Outcomes Across Time.

Purpose: The COVID-19 pandemic continues to have major and long-lasting impacts on health care delivery and mental health. As health care shifted to telehealth, legislation was adjusted to expand telehealth allowances, creating a unique opportunity to elucidate outcomes. The aim of this study was to assess long-term patient and clinician satisfaction and outcomes with virtual behavioral health.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

Background: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient.

Comparative lung distribution of radiolabeled tobramycin between nebulized and intravenous administration in a mechanically-ventilated ovine model, an observational study.

Background: Ventilator-associated pneumonia is common and is treated using nebulized antibiotics. Although adequate pulmonary biodistribution is important for antibiotic effect, there is a lack of data for both intravenous (IV) and nebulized antibiotic administration during mechanical ventilation.

Objective: To describe the comparative pulmonary regional distribution of IV and nebulized technetium-99m-labeled tobramycin (Tc-tobramycin) 400 mg in a mechanically-ventilated ovine model.

Racial and ethnic differences in patients involved in alcohol-impaired motor vehicle crashes and its related clinical outcomes among various age groups in the U.S.

1) to determine whether the proportion of alcohol-impaired patients involved in motor vehicle crashes (MVCs) varies by race/ethnicity within different age groups; 2) to explore the relationship between alcohol impairment, race/ethnicity and clinical outcomes among patients involved in MVCs across age groups. The 2012 National Trauma Data Bank (NTDB) queried for patients aged 16-55 involved in MVCs who received a blood ethanol test on admission. Of the 44,216 patients involved in MVC, 68% were White, 14% Black, and 13% were Hispanic.

Pre-clinical study protocol: Blood transfusion in endotoxaemic shock.

The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort.

Lung Pharmacokinetics of Tobramycin by Intravenous and Nebulized Dosing in a Mechanically Ventilated Healthy Ovine Model.

Background: Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs.

Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock.

Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.

Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock.

Background: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.

The effects of normovolemic anemia and blood transfusion on cerebral microcirculation after severe head injury.

Background: Cerebral regional microcirculation is altered following severe head injury. In addition to tissue disruption, partial pressure of tissue oxygenation is impaired due to an increase in the oxygen tissue gradient. The heterogenic distribution of cerebral microcirculation is multifactorial, and acute anemia challenges further the delivery of oxygen to tissues.

In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study.

Development of pediatric ventricular assist devices (VADs) has significantly lagged behind that of adult devices. This frustrating reality is reflected by the fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric-specific device in the USA. An alternative option is an off-label use of adult continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes patient-device size mismatch in small children.

A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models.

Background: Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic.

Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.

Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.

Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.

Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.

Cerebral Microcirculation and Histological Mapping After Severe Head Injury: A Contusion and Acceleration Experimental Model.

Background: Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow.

Objective: This study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury.

Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation.

Background: Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO.

Objective: To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient.

Design, Participants And Intervention: An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours.

An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.

Background: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock.

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients.

Aim: Prostate cancer (PCa) is the second most common cancers in men worldwide. Its incidence can be influenced by several risk factors including genetic susceptibility. Therefore the search for the expression of a certain gene (ERG) and its rearrangement could give us clues for proper identification of PCa.

Cerebral microcirculation during mild head injury after a contusion and acceleration experimental model in sheep.

Background: Cerebral microcirculation after head injury is heterogeneous and temporally variable. Regions at risk of infarction such as peri-contusional areas are vulnerable to anaemia. However, direct quantification of the cerebral microcirculation is clinically not feasible.

Activation of the protein C pathway and endothelial glycocalyx shedding is associated with coagulopathy in an ovine model of trauma and hemorrhage.

Introduction: Acute traumatic coagulopathy (ATC) is an endogenous coagulopathy that develops following tissue injury and shock. The pathogenesis of ATC remains poorly understood, with platelet dysfunction, activation of the protein C pathway, and endothelial glycocalyx shedding all hypothesized to contribute to onset. The primary aim of this study was to develop an ovine model of traumatic coagulopathy, with a secondary aim of assessing proposed pathophysiological mechanisms within this model.

Quantification of perflutren microsphere contrast destruction during transit through an ex vivo extracorporeal membrane oxygenation circuit.

Background: Echocardiography is a key investigation in the management of patients on extracorporeal membrane oxygenation (ECMO). However, echocardiographic images are often non-diagnostic in this patient population. Contrast-enhanced echocardiography may overcome many of these limitations but contrast microspheres are hydrodynamically labile structures prone to destruction from shear forces and turbulent flow, which may exist within an ECMO circuit.

Cerebral Microcirculation during Experimental Normovolaemic Anemia.

Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia.