Potential metabolic sequelae to the terrorist attack of October 7th, 2023.

Objective/hypothesis: Evaluate cardiometabolic risk as a potential sequel to a mass terrorist attack using October 7th, 2023 as a focus.

Methods: Narrative review surveying PubMed, PsycNet, UN and Council on Foreign Relations websites on. 1.

Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer.

Importance: The National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer suggest that RNA next-generation sequencing (NGS) may improve the detection of fusions and splicing variants compared with DNA-NGS alone. However, there is limited adoption of RNA-NGS in routine oncology clinical care today.

Objective: To analyze clinical evidence from a diverse cohort of patients with advanced lung adenocarcinoma and compare the detection of NCCN-recommended actionable structural variants (aSVs; fusions and splicing variants) via concurrent DNA and RNA-NGS vs DNA-NGS alone.

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.

An Era of Advances in Systemic Therapies for Advanced Thyroid Cancer.

Thyroid carcinomas comprise distinct pathologic subtypes. However, advancements in characterizing the molecular tumorigenesis of thyroid cancers have changed the treatment paradigm in the past decade. Genetic profiling has become an integral component of personalizing cancer care.

A functional identification platform reveals frequent, spontaneous neoantigen-specific T cell responses in patients with cancer.

The clinical impact of tumor-specific neoantigens as both immunotherapeutic targets and biomarkers has been impeded by the lack of efficient methods for their identification and validation from routine samples. We have developed a platform that combines bioinformatic analysis of tumor exomes and transcriptional data with functional testing of autologous peripheral blood mononuclear cells (PBMCs) to simultaneously identify and validate neoantigens recognized by naturally primed CD4 and CD8 T cell responses across a range of tumor types and mutational burdens. The method features a human leukocyte antigen (HLA)-agnostic bioinformatic algorithm that prioritizes mutations recognized by patient PBMCs at a greater than 40% positive predictive value followed by a short-term in vitro functional assay, which allows interrogation of 50 to 75 expressed mutations from a single 50-ml blood sample.

Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells.

Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.

Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients.

Background: Pembrolizumab has a manageable safety profile as described in its label, which was primarily based on 2799 patients who participated in clinical trials for melanoma or non-small cell lung cancer. Here, we evaluated the safety of pembrolizumab in a broader population of patients from 31 advanced cancer clinical trials across 19 cancer types.

Methods: Safety was analyzed in patients who received at least one dose of pembrolizumab (200 mg every 3 weeks [Q3W], 10 mg/kg Q2W or Q3W, or 2 mg/kg Q3W).

Facts and Hopes in Neoadjuvant Immunotherapy: Current Approvals and Emerging Evidence.

In 2021 and 2022, two immune checkpoint inhibitors received FDA approval in the neoadjuvant setting for the treatment of early-stage triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). Several more studies have since indicated the benefits, and challenges, of administering neoadjuvant immunotherapy prior to definitive surgery in the gastrointestinal, head and neck, and cutaneous realms. In addition, numerous ongoing phase II and phase III trials are investigating outcomes of neoadjuvant immune treatment in early-stage disease.

Pan-Cancer Analysis of Patient Tumor Single-Cell Transcriptomes Identifies Promising Selective and Safe Chimeric Antigen Receptor Targets in Head and Neck Cancer.

Chimeric antigen receptor (CAR) T cell therapies have yielded transformative clinical successes for patients with blood tumors, but their full potential remains to be unleashed against solid tumors. One challenge is finding targets, which we define intuitively to be cell surface proteins that are expressed widely by cancer cells but minimally by healthy cells in the tumor microenvironment and other normal tissues. Analyzing patient tumor single-cell transcriptomics data, we first defined and quantified selectivity and safety scores of existing CAR targets for indications in which they are in clinical trials or approved.

Linked CD4+/CD8+ T cell neoantigen vaccination overcomes immune checkpoint blockade resistance and enables tumor regression.

Therapeutic benefit to immune checkpoint blockade (ICB) is currently limited to the subset of cancers thought to possess a sufficient tumor mutational burden (TMB) to allow for the spontaneous recognition of neoantigens (NeoAg) by autologous T cells. We explored whether the response to ICB of an aggressive low-TMB squamous cell tumor could be improved through combination immunotherapy using functionally defined NeoAg as targets for endogenous CD4+ and CD8+ T cells. We found that, whereas vaccination with CD4+ or CD8+ NeoAg alone did not offer prophylactic or therapeutic immunity, vaccines containing NeoAg recognized by both subsets overcame ICB resistance and led to the eradication of large established tumors that contained a subset of PD-L1+ tumor-initiating cancer stem cells (tCSC), provided the relevant epitopes were physically linked.

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.

Neoantigen-specific stem cell memory-like CD4 T cells mediate CD8 T cell-dependent immunotherapy of MHC class II-negative solid tumors.

CD4 T cells play key roles in a range of immune responses, either as direct effectors or through accessory cells, including CD8 T lymphocytes. In cancer, neoantigen (NeoAg)-specific CD8 T cells capable of direct tumor recognition have been extensively studied, whereas the role of NeoAg-specific CD4 T cells is less well understood. We have characterized the murine CD4 T cell response against a validated NeoAg (CLTC) expressed by the MHC-II-deficient squamous cell carcinoma tumor model (SCC VII) at the level of single T cell receptor (TCR) clonotypes and in the setting of adoptive immunotherapy.

Method for estimation of apoptotic cell fraction of cytotherapy using in vivo fluorine-19 magnetic resonance: pilot study in a patient with head and neck carcinoma receiving tumor-infiltrating lymphocytes labeled with perfluorocarbon nanoemulsion.

Background: Adoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC).

Transoral Surgery in HPV-Positive Oropharyngeal Carcinoma: Oncologic Outcomes in the Veterans Affairs System.

Objectives: Most transoral robotic surgery (TORS) literature for HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPC) derives from high-volume tertiary-care centers. This study aims to describe long-term recurrence and survival outcomes among Veterans Health Administration patients.

Materials And Methods: Using the US Veterans Affairs database, we identified patients with HPV-OPC treated with TORS between January 2010 and December 2016.

Linked CD4 /CD8 T cell neoantigen vaccination overcomes immune checkpoint blockade resistance and enables tumor regression.

Therapeutic benefit to immune checkpoint blockade (ICB) is currently limited to the subset of cancers thought to possess a sufficient tumor mutational burden (TMB) to allow for the spontaneous recognition of neoantigens (NeoAg) by autologous T cells. We explored whether the response of an aggressive low TMB squamous cell tumor to ICB could be improved through combination immunotherapy using functionally defined NeoAg as targets for endogenous CD4 and CD8 T cells. We found that, whereas vaccination with CD4 or CD8 NeoAg alone did not offer prophylactic or therapeutic immunity, vaccines containing NeoAg recognized by both subsets overcame ICB resistance and led to the eradication of large established tumors that contained a subset of PD-L1 tumor-initiating cancer stem cells (tCSC), provided the relevant epitopes were physically linked.

Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway.

The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy in cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly understood relative to E6 and E7. Here, we demonstrate that HPV E5 is a negative regulator of anti-viral interferon (IFN) response pathways, antigen processing, and antigen presentation.

Combining transcutaneous interferential-current for nerve inhibition with a robotic assistant device for increasing ankle dorsiflexion in walking.

Background: A kilohertz-frequency alternating current transcutaneously applied was introduced as a novel neuromodulation technology for nerve inhibition innervating antagonist muscles. Combining this electrical nerve inhibition with a robotic assistance device has been proposed but not investigated.

Research Question: This study aimed to demonstrate the effect of combining electrical nerve inhibition with a wearable robotic device on increasing ankle dorsiflexion during walking.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

Objective: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA.

Methods: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate).

Eganelisib, a First-in-Class PI3Kγ Inhibitor, in Patients with Advanced Solid Tumors: Results of the Phase 1/1b MARIO-1 Trial.

Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors.

Patients And Methods: Dose-escalation cohorts received eganelisib 10-60 mg as monotherapy (n = 39) and 20-40 mg when combined with nivolumab (n = 180).

Expert Consensus Statement: Management of Dysphagia in Head and Neck Cancer Patients.

Objective: To develop an expert consensus statement (ECS) on the management of dysphagia in head and neck cancer (HNC) patients to address controversies and offer opportunities for quality improvement. Dysphagia in HNC was defined as swallowing impairment in patients with cancers of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, or hypopharynx.

Methods: Development group members with expertise in dysphagia followed established guidelines for developing ECS.