Recurrent and Metastatic Head and Neck Cancer: Mechanisms of Treatment Failure, Treatment Paradigms, and New Horizons.

Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms of metastasis.

The Effectiveness of the Gnana Laryngeal Mask Airway II (GLA-II) With Novel Suction Tubing in Gastrointestinal (GI) Cases.

Introduction: The Gnana laryngeal mask airway II (GLA-II) is a supraglottic airway device similar to the classic laryngeal mask airway, except it has an additional suction port. This suction port allows for the removal of secretions and saliva. A previous version of the Gnana laryngeal airway 4 was made of silicone, while this newer version is made of polyvinyl chloride (PVC), which is more affordable.

Laryngopharyngeal Reflux Pathophysiology, Clinical Presentation, and Management: A Narrative Review.

Laryngopharyngeal reflux (LPR) is a common and often misinterpreted clinical entity responsible for various symptoms affecting the upper aerodigestive tract. This narrative literature review aims to review the pathophysiology, symptoms, and management of LPR, emphasizing the emerging understanding of gastric content reflux in aerodigestive tissue irritation. Understanding the pathophysiology of LPR will allow general practitioners and specialists to accurately recognize and treat a condition that causes substantial morbidity in the affected patients.

Hyperkalemia: Pharmacotherapies and Clinical Considerations.

Hyperkalemia has been defined as a condition where a serum potassium level is >5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction.

The impact of supraventricular arrhythmias on the outcomes of guideline-compliant implantable cardioverter defibrillator programming.

Introduction: Several implantable cardioverter defibrillators (ICD) programming strategies are applied to minimize ICD therapy, especially unnecessary therapies from supraventricular arrhythmias (SVA). However, it remains unknown whether these optimal programming recommendations only benefit those with SVAs or have any detrimental effects from delayed therapy on those without SVAs. This study aims to assess the impact of SVA on the outcomes of ICD programming based on 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal ICD programming and testing guidelines.

Non-steroidal Anti-inflammatory Drug (NSAID)-, Potassium Supplement-, Bisphosphonate-, and Doxycycline-Mediated Peptic Ulcer Effects: A Narrative Review.

Peptic ulcers are a common condition that arises from an imbalance between acid production and gastroduodenal protective factors. Various drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), potassium supplements, bisphosphonates, and doxycycline, can increase the development of peptic ulcers. NSAIDs are one of the most common medications prescribed for pain relief, and they also inhibit the formation of cyclooxygenase-1 (COX-1).

Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8 T cells via ME1 up-regulation.

Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8 T cells. We have termed the rebound of cytotoxic CD8 T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience.

The Role of Alpha-2 Agonists for Attention Deficit Hyperactivity Disorder in Children: A Review.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases.

A Novel Humanized PD-1/PD-L1 Mouse Model Permits Direct Comparison of Antitumor Immunity Generated by Food and Drug Administration-Approved PD-1 and PD-L1 Inhibitors.

Seven different anti-PD-1 and PD-L1 mAbs are now widely used in the United States to treat a variety of cancer types, but no clinical trials have compared them directly. Furthermore, because many of these Abs do not cross-react between mouse and human proteins, no preclinical models exist in which to consider these types of questions. Thus, we produced humanized PD-1 and PD-L1 mice in which the extracellular domains of both mouse PD-1 and PD-L1 were replaced with the corresponding human sequences.

Programming of implantable cardioverter defibrillators for primary prevention: outcomes at centers with high vs. low concordance with guidelines.

Background: While ICD therapy reduction programming strategies are recommended in current multi-society guidelines, concerns remain about a possible trade-off between the benefits of ICD therapy reduction and failure to treat episodes of ventricular arrhythmias. The study is to evaluate the outcomes of primary prevention patients followed in centers with high and low concordance with the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal ICD programming and testing guidelines.

Methods: Consecutive patients with primary prevention ICD implantation from two centers between 2014 and 2016 were included.

Recurrent biventricular takotsubo cardiomyopathy with fatal outcome.

A woman in her 60s presented initially with nausea, vomiting and abdominal pain. She rapidly progressed to respiratory failure requiring intubation. ECG demonstrated no significant ST segment changes.

NKG7 Is a T-cell-Intrinsic Therapeutic Target for Improving Antitumor Cytotoxicity and Cancer Immunotherapy.

Cytotoxic CD8 T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. By evaluating human CD8 T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function.

Sleep health mediates the relationship between physical activity and depression symptoms.

Purpose: This study aimed to investigate cross-sectional associations between physical activity, sleep health, and depression symptoms using mediation models.

Methods: Participants (N = 1576, M = 39.3 years, 40% female) were recruited online from Amazon's Mechanical Turk crowd-sourcing service.

Non-invasive immunoPET imaging of PD-L1 using anti-PD-L1-B11 in breast cancer and melanoma tumor model.

Introduction: Immunotherapy targeting PD-1/PD-L1 immune checkpoint inhibition (ICI) is efficacious in various solid and hematologic malignancies. However, the response rate to PD-1/PD-L1 therapy is only 15-35%. To obtain optimal clinical response to ICI therapies, a reliable assessment of tumor PD-L1 expression is needed to select appropriate patients, and a non-invasive imaging-based assessment of PD-L1 expression is critically needed.

Case Report: Simultaneous Hyperprogression and Fulminant Myocarditis in a Patient With Advanced Melanoma Following Treatment With Immune Checkpoint Inhibitor Therapy.

We report here a patient with stage IV mucosal melanoma treated with dual immune checkpoint inhibitor (ICI) therapy (Nivolumab/Ipilimumab) who experienced rapid disease progression and metastatic spread within three weeks of first infusion. Surprisingly, this patient also developed fulminant myocarditis within the same time frame. Immunohistochemical staining of the primary tumor and a metastatic omental lesion revealed robust CD8 PD-1 T cell infiltration after ICI treatment, as would be expected following immune activation.

Costal Cartilage Lateral Crural Strut Graft for Correction of External Nasal Valve Dysfunction in Primary and Revision Rhinoplasty.

Objective: To evaluate and compare the costal cartilage lateral crural strut graft's (LCSG) ability to support a weak lateral crus in patients with external nasal valve dysfunction (EVD) undergoing primary versus revision functional rhinoplasty.

Methods: This is a prospective cohort study of 26 patients (mean [SD]: 40.23 [6.

Increased canonical NF-kappaB signaling specifically in macrophages is sufficient to limit tumor progression in syngeneic murine models of ovarian cancer.

Background: New treatment options for ovarian cancer are urgently required. Tumor-associated macrophages (TAMs) are an attractive target for therapy; repolarizing TAMs from M2 (pro-tumor) to M1 (anti-tumor) phenotypes represents an important therapeutic goal. We have previously shown that upregulated NF-kappaB (NF-κB) signaling in macrophages promotes M1 polarization, but effects in the context of ovarian cancer are unknown.

Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas.

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses.

Variability of the Anterior Ethmoid Artery in Endoscopic Sinus Surgery.

Introduction: The anterior ethmoidal artery (AEA) demonstrates anatomic variability relative to its descent from the anterior skull base. Our study's objective was to assess for correlation of AEA descent and laterality, in addition to correlation of AEA descent and the presence of supraorbital ethmoid cells (SOEC) and concha bullosae (CB).

Method: A retrospective study was performed at a tertiary rhinology center from January 2019 to January 2020.

Transient Left Atrial Appendage Inversion During Transcatheter Closure Device Placement.

A 72-year-old female patient underwent left atrial appendage closure. During recapture of the occlusion device, transient inversion of the appendageal wall occurred. We describe the mechanism with real-time imaging and share our experience of handling this situation.

Programming implantable cardioverter-defibrillator in primary prevention: Guideline concordance and outcomes.

Background: Inappropriate therapy is a common adverse effect in patients with an implantable cardioverter-defibrillator (ICD) that may be prevented by appropriate programming.

Objective: The purpose of this study was to assess the outcomes of device programming based on a 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and a 2019 focused update on optimal ICD programming and testing.

Methods: Consecutive patients who underwent ICD insertion for primary prevention from 2014-2016 at 3 centers were included in the retrospective analysis.

Paradox-driven adventures in the development of cancer immunology and immunotherapy.

After more than one hundred years of documented trials, immunotherapy has become a standard of care in the treatment of human cancer. Much of the knowledge that led to recent breakthroughs seems quite logical from today's point of view. However, what we now cite as facts were originally considered , meaning something contrary to expectations or perceived opinion at the time.

Immunity drives regulation in cancer through NF-κB.

Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breast cancer (BLBC), genome-wide 5hmC changes related to regulation. We further demonstrate that repression is associated with high expression of immune markers and high infiltration by immune cells.

Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?

Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting.