Analytical performance of OncoPrism-HNSCC, an RNA-based assay to inform immune checkpoint inhibitor treatment decisions for recurrent/metastatic head and neck squamous cell carcinoma.

Background: While immune checkpoint inhibitor (ICI) therapies can significantly improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC), only about 15-20% benefit from such treatments. Clinical tests that guide the use of ICIs are therefore critically needed. OncoPrism-HNSCC was developed to address this need.

Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study.

Background: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients.

Cellaca® PLX image cytometer as an alternative for immunophenotyping, GFP/RFP transfection efficiencies, and apoptosis analysis.

Cell and gene therapy is a fast-growing field for cancer therapeutics requiring reliable instrumentation and technologies. Key parameters essential for satisfying Chemistry Manufacturing and Controls criteria standards are routinely performed using flow cytometry. Recently, image cytometry was developed for cell characterization and cell-based assays but had not yet demonstrated sufficient sensitivity for surface marker detection.

Multidimensional biomarker predicts disease control in response to immunotherapy in recurrent or metastatic head and neck squamous-cell carcinoma.

Purpose: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

Mixed-Model Curriculum for Nerve Block Education in Emergency Medicine Residency.

Introduction With the rising opioid epidemic, there has been a push for multimodal pain management within the emergency department. Nerve blocks have been shown to be an effective pain management strategy for many conditions, with improved success when used with ultrasound. However, there is no generally accepted method for teaching residents how to perform nerve blocks.

Nurses and Efficacy of Ultrasound-Guided Versus Traditional Venous Access: A Systemic Review and Meta-Analysis.

Background: Ultrasound-guided venous cannulation is an increasingly popular tool for peripheral intravenous catheter placement among nursing providers as opposed to standard of care landmark-based placement methods. This systematic review and meta-analysis assessed the use of ultrasound-guided versus landmark-based catheter cannulation among nursing providers across existing literature.

Methods: PubMed, Scopus, and Embase were searched for eligible studies from their beginning to June 11, 2021.

Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.

Purpose: To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design.

Experimental Design: Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis.

Results: All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy.

T cell subtype profiling measures exhaustion and predicts anti-PD-1 response.

Anti-PD-1 therapy can provide long, durable benefit to a fraction of patients. The on-label PD-L1 test, however, does not accurately predict response. To build a better biomarker, we created a method called T Cell Subtype Profiling (TCSP) that characterizes the abundance of T cell subtypes (TCSs) in FFPE specimens using five RNA models.

73-year-old Female with Syncope and Motor Vehicle Collision.

Introduction: Patients with traumatic injuries can be difficult to assess, and their evaluation often evolves in the emergency department (ED). We describe how an ED attending physician member developed a differential diagnosis for this presentation, arrived at a suspected diagnosis, and what test he proposed to prove his hypothesis.

Case Presentation: This clinicopathological case presentation details the initial assessment and management of a 73-year-old female who presented to the ED following a motor vehicle collision precipitated by a syncopal episode.

Quantitative and Qualitative Analysis of Emergency Physician Performed Biparietal Diameter Estimate for Gestational Age.

Background: An accurate estimation of fetal gestational age is essential for the management of pregnant patients who present to the emergency department (ED). Point-of-care-ultrasound (POCUS) is an integral part of emergency medicine training and includes measurement of fetal gestational age by the biparietal diameter (BPD) method.

Objectives: In this study we performed a quantitative assessment of emergency physician (EP)-performed BPD estimate of gestational age to identify the percentage of studies performed in our department that had an estimated gestational age within 14 days of an adjusted radiological or obstetrical estimation.

CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes.

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common soft tissue sarcoma subtypes and is devastating in the advanced/metastatic stage. Despite the observation of clinical responses to inhibitors, little is known about the immune microenvironment in relation to patient prognosis.

Methods: We performed a retrospective study of 61 patients with DDLPS.

Predictive Immune Modeling of Solid Tumors.

Immunotherapies show promise in the treatment of oncology patients, but complex heterogeneity of the tumor microenvironment makes predicting treatment response challenging. The ability to resolve the relative populations of immune cells present in and around the tumor tissue has been shown to be clinically-relevant to understanding response, but is limited by traditional techniques such as flow cytometry and immunohistochemistry (IHC), due the large amount of tissue required, lack of accurate cell type markers, and many technical and logistical hurdles. One assay (e.

Analytical Performance of an Immunoprofiling Assay Based on RNA Models.

As immuno-oncology drugs grow more popular in the treatment of cancer, better methods are needed to quantify the tumor immune cell component to determine which patients are most likely to benefit from treatment. Methods such as flow cytometry can accurately assess the composition of infiltrating immune cells; however, they show limited use in formalin-fixed, paraffin-embedded (FFPE) specimens. This article describes a novel hybrid-capture RNA sequencing assay, ImmunoPrism, that estimates the relative percentage abundance of eight immune cell types in FFPE solid tumors.

Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss.

The role of the stromal compartment in tumor progression is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells, and its expression levels correlate with poor prognosis. This observation led us to investigate whether inhibition of p38MAPKα could reduce breast cancer metastases in a clinically relevant model.

c-Myb and C/EBPβ regulate OPN and other senescence-associated secretory phenotype factors.

Tumorigenesis results from the convergence of cell autonomous mutations and corresponding stromal changes that promote tumor cell growth. Senescent cells, which secrete a plethora of pro-tumorigenic factors termed the senescence-associated secretory phenotype (SASP), play an important role in tumor formation. Investigation into SASP regulation revealed that many but not all SASP factors are subject to NF-kB and p38MAPK regulation.

p38 MAPK inhibits nonsense-mediated RNA decay in response to persistent DNA damage in noncycling cells.

Persistent DNA damage induces profound alterations in gene expression that, in turn, influence tissue homeostasis, tumorigenesis, and cancer treatment outcome. However, the underlying mechanism for gene expression reprogramming induced by persistent DNA damage remains poorly understood. Here, using a highly effective bioluminescence-based reporter system and other tools, we report that persistent DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, in noncycling cells.

Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis.

Age is a significant risk factor for the development of cancer. However, the mechanisms that drive age-related increases in cancer remain poorly understood. To determine if senescent stromal cells influence tumorigenesis, we develop a mouse model that mimics the aged skin microenvironment.

p38MAPK plays a crucial role in stromal-mediated tumorigenesis.

Unlabelled: Neoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importance in tumorigenesis, the mechanisms that control TME-derived factor expression remain poorly understood.

The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.

Retinal photoreceptors entrain the circadian system to the solar day. This photic resetting involves cAMP response element binding protein (CREB)-mediated upregulation of Per genes within individual cells of the suprachiasmatic nuclei (SCN). Our detailed understanding of this pathway is poor, and it remains unclear why entrainment to a new time zone takes several days.

Automated quantification of budding Saccharomyces cerevisiae using a novel image cytometry method.

The measurements of concentration, viability, and budding percentages of Saccharomyces cerevisiae are performed on a routine basis in the brewing and biofuel industries. Generation of these parameters is of great importance in a manufacturing setting, where they can aid in the estimation of product quality, quantity, and fermentation time of the manufacturing process. Specifically, budding percentages can be used to estimate the reproduction rate of yeast populations, which directly correlates with metabolism of polysaccharides and bioethanol production, and can be monitored to maximize production of bioethanol during fermentation.

Tissue factor contributes to neutrophil CD11b expression in alpha-naphthylisothiocyanate-treated mice.

Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice.

Review of surgical management of cystic hydatid disease in a resource limited setting: Turkana, Kenya.

Objective: Cystic hydatid disease is a zoonotic infection of humans caused by infection with the larval stage of Echinococcus granulosus. The prevalence rate (5-10%) in Turkana, Northern Kenya is among the highest worldwide. With an increase in foreign travel and migration of peoples, practitioners need to be aware of diseases common in these countries and their rarer manifestations.