Musculoskeletal Tumor Society Member Survey: Intra-Operative Peripheral Margins in Soft Tissue Sarcoma.

Background And Objectives: Routine intraoperative peripheral margin sampling is often employed by musculoskeletal surgical oncologists. Several recommendations exist regarding this practice pattern. It is unknown what the practice patterns of Musculoskeletal Tumor Society (MSTS) members are.

Intraoperative Peripheral Frozen Margin Assessment in Soft Tissue Sarcoma.

Background/objectives: Intraoperative peripheral margin sampling in soft tissue sarcoma (STS) is a routine practice among musculoskeletal oncologists. Practice patterns are variable, and evidence to support it is lacking. Rates of peripheral margin sampling at our institution were analyzed in addition to its clinical utility and cost-effectiveness.

Visceral fat area and subcutaneous fat area as measures of body composition in soft tissue sarcoma.

Background And Objectives: Soft tissue sarcomas (STS) are a heterogenous group of malignancies of mesenchymal origin. Given recent data linking obesity as well as the pattern of fat distribution with cancer outcomes, we sought to investigate the association of visceral fat area (VFA) and subcutaneous fat area (SFA) with oncologic outcomes in patients with STS undergoing surgery.

Methods: We analyzed data from 88 patients with STS diagnosed from 2008 to 2022.

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus.

Genetic Screen in a Preclinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities.

Purpose: High-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging.

Experimental Design: To address this, we utilized a pooled genetic screening approach, informed by The Cancer Genome Atlas (TCGA) data, to identify key drivers and modifiers of sarcoma development that were validated in vivo.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation.

Background: Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g.

Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

Background: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product.

Improved characterization and translation of NK cells for canine immunotherapy.

The field of cancer immunology has seen a meteoric rise in interest and application due to the discovery of immunotherapies that target immune cells, often leading to dramatic anti-tumor effects. However, successful cellular immunotherapy for solid tumors remains a challenge, and the application of immunotherapy to dogs with naturally occurring cancers has emerged as a high yield large animal model to bridge the bench-to-bedside challenges of immunotherapies, including those based on natural killer (NK) cells. Here, we review recent developments in the characterization and understanding of canine NK cells, a critical springboard for future translational NK immunotherapy research.

Characterization of natural killer and cytotoxic T-cell immune infiltrates in pancreatic ductal adenocarcinoma.

Background And Objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor response to systemic therapies, including immunotherapy. Given the immunotherapeutic potential of natural killer (NK) cells, we evaluated intratumoral NK cell infiltrates along with cytotoxic T cells in PDAC to determine their association with patient outcomes.

Methods: We analyzed tumors from 93 PDAC patients treated from 2012 to 2020.

Regionalization of pancreatic surgery in California: Benefits for preventing postoperative deaths and reducing healthcare costs.

Introduction: Pancreatic cancer (PC) surgery has been associated with improved outcomes and value when performed at high-volume centers (HVC; ≥20 surgeries annually) compared to low-volume centers (LVC). Some have used these differences to suggest that regionalization of PC surgery would optimize patient outcomes and expenditures.

Methods: A Markov model was created to evaluate 30-day mortality, 30-day complications, and 30-day costs.

Scrutinizing the use of contrasted chest CTs in extremity sarcoma staging and surveillance.

Background: Since 2015, the American College of Radiology (ACR) has recommended staging for lung metastasis via chest computed tomography (CT) without contrast for extremity sarcoma staging and surveillance. The purpose of this study was to determine our institutional compliance with this recommendation.

Methods: This was a retrospective chart review of patients diagnosed with sarcoma in the extremities who received CT imaging of the chest for pulmonary staging and surveillance at our institution from 2005 to 2023.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques.

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis.

Regulation of human and mouse bystander T cell activation responses by PD-1.

Bystander activation of memory T cells occurs via cytokine signaling alone in the absence of T cell receptor (TCR) signaling and provides a means of amplifying T cell effector responses in an antigen-nonspecific manner. While the role of Programmed Cell Death Protein 1 (PD-1) on antigen-specific T cell responses is extensively characterized, its role in bystander T cell responses is less clear. We examined the role of the PD-1 pathway during human and mouse non-antigen-specific memory T cell bystander activation and observed that PD-1+ T cells demonstrated less activation and proliferation than activated PD-1- populations in vitro.

Accelerometry measures of physical activity and sedentary behavior: Associations with cognitive functioning in MS.

Background: Cognitive dysfunction is a pervasive symptom of multiple sclerosis (MS). Correlational evidence on the relationships between physical activity, sedentary behavior, and cognition has been mixed and limited to a few activity measures. The collinearity of accelerometry-based metrics has precluded an assessment of the full activity spectrum.

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial.

Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes.

Intratumoral NKp46 natural killer cells are spatially distanced from T and MHC-I cells with prognostic implications in soft tissue sarcoma.

Introduction: Soft tissue sarcomas (STS) are rare, heterogenous malignancies with an unmet need for novel immunotherapies. Tumor infiltrating lymphocytes (TILs) have been linked with favorable outcomes in STS patients, though the contribution of natural killer (NK) cells and spatial relationships of TILs with MHC-I expressing cells lacks detailed characterization.

Experimental Design: Using archived and prospectively collected specimens, we evaluated intratumoral NK cells by immunohistochemistry (IHC), flow cytometry, and immunofluorescence (IF).

Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study.

Background: In a parallel-group, international, phase 3 study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and Beta (B.1.

Multifaceted effects of obesity on cancer immunotherapies: Bridging preclinical models and clinical data.

Obesity, defined by excessive body fat, is a highly complex condition affecting numerous physiological processes, such as metabolism, proliferation, and cellular homeostasis. These multifaceted effects impact cells and tissues throughout the host, including immune cells as well as cancer biology. Because of the multifaceted nature of obesity, common parameters used to define it (such as body mass index in humans) can be problematic, and more nuanced methods are needed to characterize the pleiotropic metabolic effects of obesity.

Changing estimates of leadership ability before a programme: retrospective self-assessments and response-shift bias.

Background: Most evaluations of clinical leadership development programmes rely on self-assessments. Self-assessments are vulnerable to response-shift bias. Using retrospective then-tests may help to avoid this bias.

Buruli-RifDACC: Evaluation of the efficacy and cost-effectiveness of high-dose versus standard-dose rifampicin on outcomes in disease, a protocol for a randomised controlled trial in Ghana.

Background: Buruli ulcer (BU) can lead to disfiguring ulcers and permanent disability. The 2030 World Health Organization (WHO) road map for Neglected Tropical Diseases (NTDs) calls for major scaling up in diagnosis and management to eliminate disability due to the disease. Current treatment for BU is with daily oral rifampicin (10mg/kg dose) and clarithromycin (15mg/kg dose) for eight weeks, combined with standard gauze wound dressings.