Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.

Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known.

Accuracy of Entrustment-Based Assessment: Implications for Programs and Patients.

Although entrustment-supervision ratings are more intuitive compared to other rating scales, it is not known whether their use accurately assesses the appropriateness of care provided by a resident. To determine the frequency of incorrect entrustment ratings assigned by faculty and whether accuracy of an entrustment-supervision scale differed by resident performance when the scripted resident performance level is known. Faculty participants rated standardized residents in 10 videos using a 4-point entrustment-supervision scale.

Gender Differences in Work-Based Assessment Scores and Narrative Comments After Direct Observation.

Background: While some prior studies of work-based assessment (WBA) numeric ratings have not shown gender differences, they have been unable to account for the true performance of the resident or explore narrative differences by gender.

Objective: To explore gender differences in WBA ratings as well as narrative comments (when scripted performance was known).

Design: Secondary analysis of WBAs obtained from a randomized controlled trial of a longitudinal rater training intervention in 2018-2019.

Immune and ionic mechanisms mediating the effect of dexamethasone in severe COVID-19.

Introduction: Severe COVID-19 is characterized by cytokine storm, an excessive production of proinflammatory cytokines that contributes to acute lung damage and death. Dexamethasone is routinely used to treat severe COVID-19 and has been shown to reduce patient mortality. However, the mechanisms underlying the beneficial effects of dexamethasone are poorly understood.

Faculty Perceptions of Frame of Reference Training to Improve Workplace-Based Assessment.

Background: Workplace-based assessment (WBA) is a key assessment strategy in competency-based medical education. However, its full potential has not been actualized secondary to concerns with reliability, validity, and accuracy. Frame of reference training (FORT), a rater training technique that helps assessors distinguish between learner performance levels, can improve the accuracy and reliability of WBA, but the effect size is variable.

Comparison of Anterior and Lateral Approach in Hip Hemiarthroplasty for Femur Neck Fractures in the Elderly: Clinical and Radiographic Outcomes.

Introduction: Many surgical approaches have been described for hip hemiarthroplasty (HHA) treating femur neck fractures (FNFs). Direct lateral approach (DLA) is one of the most used. Today, the direct anterior approach (DAA) has become very attractive, but it seems to involve more intra-operative fractures.

Effectiveness of SB4 Transition from Originator Etanercept in Rheumatoid Arthritis and Axial Spondyloarthritis: A Subgroup Analysis from the BENEFIT Study.

Objectives: The pan-European BENEFIT study of patients with stable rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who transitioned from reference etanercept to SB4 found no clinically meaningful changes in disease control after transition. The analysis aims to illustrate the peculiarities of the Italian cohort of patients compared with the whole population to provide a more real-life approach to the data for the Italian rheumatologists, ruling out possible local confounding factors.

Methods: A prospective study for up to 6 months following transition was conducted.

Management of Femur Fractures during COVID-19 Pandemic Period: The Influence of Vaccination and Nosocomial COVID-19 Infection.

The COVID-19 pandemic management has led to a significant change in orthopedic surgical activity. During the pandemic, femur fractures in patients over 65 years of age have maintained a constant incidence. Our study will focus on this fragile population, analyzing the incidence of SARS-CoV-2 infection during hospital stays and the clinical and radiographic orthopedic outcomes.

How the Potassium Channel Response of T Lymphocytes to the Tumor Microenvironment Shapes Antitumor Immunity.

Competent antitumor immune cells are fundamental for tumor surveillance and combating active cancers. Once established, tumors generate a tumor microenvironment (TME) consisting of complex cellular and metabolic elements that serve to suppress the function of antitumor immune cells. T lymphocytes are key cellular elements of the TME.

Can Rater Training Improve the Quality and Accuracy of Workplace-Based Assessment Narrative Comments and Entrustment Ratings? A Randomized Controlled Trial.

Purpose: Prior research evaluating workplace-based assessment (WBA) rater training effectiveness has not measured improvement in narrative comment quality and accuracy, nor accuracy of prospective entrustment-supervision ratings. The purpose of this study was to determine whether rater training, using performance dimension and frame of reference training, could improve WBA narrative comment quality and accuracy. A secondary aim was to assess impact on entrustment rating accuracy.

Qualitative Study of Orthopedic Surgery Milestones 1.0: Burdens and Benefits.

Objective: The purpose of this study was to explore the context and mechanisms by which the first set of Milestones impacted the processes of the Clinical Competency Committee, how programs have incorporated the Milestones into their program, and to understand more about the resident perspective in order to improve Orthopedic Surgery Milestones.

Design, Setting, And Participants: In 2020 all 201 accredited orthopedic surgery residency programs were invited to participate in qualitative telephone interviews to assess their experience with the Milestones and complete a supplemental online survey about their Clinical Competency Committee. Participants were comprised of a self-selected sample and complemented by a purposeful sample to ensure a breadth of perspectives.

Immune Checkpoint Inhibitors Regulate K Channel Activity in Cytotoxic T Lymphocytes of Head and Neck Cancer Patients.

Programmed death receptor-1 (PD-1) and its ligand (PD-L1) interaction negatively regulates T cell function in head and neck squamous cell carcinoma (HNSCC). Overexpression of PD-1 reduces intracellular Ca fluxes, and thereby T cell effector functions. In HNSCC patients, PD-1 blockade increases KCa3.

Intravenous treatment with biphosphates in Complex Regional Pain Syndrome.

Complex Regional Pain Syndrome (CRPS) is a pathological persistence of spontaneous or evoked disproportionate pain. Several drugs are employed, but only bisphosphonates seem to have good outcomes. The purpose of our research is to analyze the characteristics of the cases victims of CRPS and study the beneficial effect of the intravenous nerindronic acid sodium salt (Nerixia®), in an attempt to improve the results in this disabling disease.

Targeted knockdown of the adenosine A receptor by lipid NPs rescues the chemotaxis of head and neck cancer memory T cells.

In solid malignancies, including head and neck squamous cell carcinoma (HNSCC), the immunosuppressive molecule adenosine, which accumulates in the tumor, suppresses cytotoxic CD8 T cell functions including chemotaxis and tumor infiltration. Adenosine functions through binding to the adenosine A receptor (AR) present on T cells. In order to increase T cell migration into the tumor, the negative effect of adenosine must be abrogated.

Trauma workload during COVID19 lockdown: an analysis of incidence in 4 million people.

Background: Aim of this study is to report the trauma workload during COVID19 lockdown in a region of four million people and to compare it with the same period in 2019.

Methods: The regional register for A&E admissions and hospitalizations has been reviewed in order to compare the number of A&D admission, the triage colour codes rates, aetiology of trauma, number of patients hospitalized for trauma, number of fractures that required surgery, type of fractures and injuries and mean patients' age.

Results: During lockdown 7314 patients were admitted in A&E, while 22,508 patients were admitted in 2019.

Targeted knockdown of Kv1.3 channels in T lymphocytes corrects the disease manifestations associated with systemic lupus erythematosus.

Lupus nephritis (LN) is an autoimmune disease with substantial morbidity/mortality and limited efficacy of available therapies. Memory T (Tm) lymphocytes infiltrate LN kidneys, contributing to organ damage. Analysis of LN, diabetic nephropathy, and healthy donor kidney biopsies revealed high infiltration of active CD8 Tm cells expressing high voltage-dependent Kv1.

PD1 blockade enhances K channel activity, Ca signaling, and migratory ability in cytotoxic T lymphocytes of patients with head and neck cancer.

Background: Immunotherapy has emerged as a promising treatment modality for head and neck squamous cell carcinoma (HNSCC). Pembrolizumab, an anti-programmed death 1 antibody, is an immunotherapy agent currently approved for metastatic HNSCC and curative intent clinical trials. Although clinical responses to pembrolizumab are promising, many patients fail to respond.

Activation and degranulation of CAR-T cells using engineered antigen-presenting cell surfaces.

Adoptive cell transfer of Chimeric Antigen Receptor (CAR)-T cells showed promising results in patients with B cell malignancies. However, the detailed mechanism of CAR-T cell interaction with the target tumor cells is still not well understood. This work provides a systematic method for analyzing the activation and degranulation of second-generation CAR-T cells utilizing antigen-presenting cell surfaces.

CD244 represents a new therapeutic target in head and neck squamous cell carcinoma.

Background: Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8 T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs).

Methods: Using de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244 mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses.

A Compartmentalized Reduction in Membrane-Proximal Calmodulin Reduces the Immune Surveillance Capabilities of CD8 T Cells in Head and Neck Cancer.

The limited ability of cytotoxic CD8 T cells to infiltrate solid tumors and function within the tumor microenvironment presents a major roadblock to effective immunotherapy. Ion channels and Ca-dependent signaling events control the activity of T cells and are implicated in the failure of immune surveillance in cancer. Reduced KCa3.

Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration.

Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson's disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders.

Combining nerve and tendon transfers in tetraplegia: a proposal of a new surgical strategy based on literature review.

Spinal cord injury (SCI) is very common, most frequently resulting from motor vehicle accidents and falling from a height. Often, SCI occurs at the cervical level, resulting in tetraplegia, which consists of loss of effective arm and/or hand function. For these patients, hand function is considered the most desired function, above bowel, bladder and sexual function.