Comparative Analysis of Biopsy Techniques for Cervical Lymphoma: A Retrospective Cohort Review.

Introduction: Lymphoma is the most common neck mass malignancy in adults but can present diagnostic challenges due to controversy surrounding the best initial biopsy approach. In this study, the authors characterize the diagnostic pathway in adults with lymphoma (or leukemia) presenting initially as a neck mass and examine the biopsy procedures required for diagnosis in a large community-based practice setting.

Methods: Using data from a retrospective cohort of 4103 adults referred to otolaryngology with a neck mass (5% found to be malignant), the authors identified the subset with lymphoma (or leukemia) and examined the time to diagnosis and the number and type of biopsies required for diagnosis.

A Comparison of In-Person and Telemedicine Triage in Otolaryngology.

Introduction: The integration of virtual visits has been met with skepticism by many surgical specialties, including otolaryngology, due to the lack of a complete physical exam. Analysis of differences in the workup between patients triaged virtually or in-person is warranted.

Methods: A chart review was performed for a cohort of adults undergoing septoplasty (January 2021-May 2022).

Differences in Patient Secure Message Volume Among Otolaryngologists: A Retrospective Cohort Study.

Objective: To identify differences in inbox and secure message burden among otolaryngologists based on demographics and subspecialty over 4 years.

Methods: Inbox data were queried from January 2019 until December 2022. Otolaryngologists were categorized into cohorts by area of practice and gender.

Microdebrider complications in sinus surgery: Analysis of the openFDA database.

Objective: Functional endoscopic sinus surgery is a commonly performed otolaryngologic procedure that often uses the microdebrider device for tissue removal. Given the ubiquitous nature of the instrument, we sought to better define the patterns of device failure using the postmarket surveillance openFDA database.

Methods: The openFDA database was queried for all microdebrider-related adverse events from January 1, 2000 to November 1, 2020.

Subunit Reconstruction With Local and Regional Flaps of a Total Cervicofacial Defect From Necrotizing Fasciitis.

A 60-year-old woman with a ∼450 cm 2 right cervicofacial defect following successful treatment of necrotizing fasciitis was consulted for reconstruction. She had complete orbital, malar, buccal, labial, submental, and anterolateral neck skin and soft tissue defects and near complete defects of the forehead and nasal sidewall. She underwent reconstruction with a large 24 cm×11 cm supraclavicular, deltopectoral, forehead rotational, and labial advancement flaps with skin grafting of the orbit.

The diagnosis of nontuberculous cervicofacial lymphadenitis: A systematic review.

Background: Nontuberculous mycobacterial cervicofacial lymphadenitis (NTMCL) is an uncommon condition detected in young immunocompetent children who typically present with a nontender neck mass. Various tests have been proposed to assist in the work-up of suspected NTMCL, with varying diagnostic utility. This systematic review investigates the sensitivity of the various diagnostic methods used in the work-up of pediatric NTMCL.

Steroid Efficacy on Audiologic Recovery in Patients With Sudden Sensorineural Hearing Loss and Vestibular Schwannoma: A Retrospective Review.

Objectives: The objectives of this study are to (i) estimate the incidence of vestibular schwannoma (VS) among patients in an integrated healthcare system who present for evaluation of sudden sensorineural hearing loss (SSNHL) and (ii) evaluate the efficacy of empiric steroid therapy on audiologic recovery among SSNHL patients ultimately diagnosed with VS.

Methods: A retrospective chart review was performed on patients presenting with SSNHL in 2021 at a multicenter integrated healthcare system serving over 4 million members. Patient demographics, audiometric data, VS diagnosis, therapeutic steroid intervention, and data regarding treatment response were recorded.

Nasal Septal Mucocele Causing Saddle Nose Deformity.

Nasal septal mucoceles are a rare occurance, and reports in the current literature are limited. We describe the case of a 73-year-old woman who developed a nasal septal mucocele several days after an episode of angioedema. The lesion was treated with 2 rounds of needle aspiration with antibiotics and the application of silastic splints.

Sport and Recreational Causes of Nasal Bone Fractures.

Objective: Nasal bone fractures are the most common facial bone fractures. However, there is limited literature on the etiology of these fractures, particularly distribution across sports and other recreational activities.

Methods: The Nationwide Electronic Injury Surveillance System (NEISS) national injury database was queried for emergency department visits involving the diagnosis of nasal or nose fractures associated with sports and recreation activities over the most recent 10 year span available.

Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells.

Epidemiological evidence indicates that cadmium and arsenic exposure increase lung cancer risk. Cadmium and arsenic are environmental contaminants that act as endocrine disruptors (EDs) by activating estrogen receptors (ERs) in breast and other cancer cell lines but their activity as EDs in lung cancer is untested. Here, we examined the effect of cadmium chloride (CdCl2) and sodium arsenite (NaAsO2) on the proliferation of human lung adenocarcinoma cell lines.

Inhibition of the Inositol Kinase Itpkb Augments Calcium Signaling in Lymphocytes and Reveals a Novel Strategy to Treat Autoimmune Disease.

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes.

Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor.

The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck.

Themis sets the signal threshold for positive and negative selection in T-cell development.

Development of a self-tolerant T-cell receptor (TCR) repertoire with the potential to recognize the universe of infectious agents depends on proper regulation of TCR signalling. The repertoire is whittled down during T-cell development in the thymus by the ability of quasi-randomly generated TCRs to interact with self-peptides presented by major histocompatibility complex (MHC) proteins. Low-affinity TCR interactions with self-MHC proteins generate weak signals that initiate 'positive selection', causing maturation of CD4- or CD8αβ-expressing 'single-positive' thymocytes from CD4(+)CD8αβ(+) 'double-positive' precursors.

Coreceptor affinity for MHC defines peptide specificity requirements for TCR interaction with coagonist peptide-MHC.

Recent work has demonstrated that nonstimulatory endogenous peptides can enhance T cell recognition of antigen, but MHCI- and MHCII-restricted systems have generated very different results. MHCII-restricted TCRs need to interact with the nonstimulatory peptide-MHC (pMHC), showing peptide specificity for activation enhancers or coagonists. In contrast, the MHCI-restricted cells studied to date show no such peptide specificity for coagonists, suggesting that CD8 binding to noncognate MHCI is more important.

GRB2-mediated recruitment of THEMIS to LAT is essential for thymocyte development.

Thymocyte-expressed molecule involved in selection (THEMIS) is a recently identified regulator of thymocyte positive selection. THEMIS's mechanism of action is unknown, and whether it has a role in TCR-proximal signaling is controversial. In this article, we show that THEMIS and the adapter molecule growth factor receptor-bound protein 2 (GRB2) associate constitutively through binding of a conserved PxRPxK motif within the proline-rich region 1 of THEMIS to the C-terminal SH3-domain of GRB2.

Does melanoma begin in a melanocyte stem cell?

What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC) and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebrafish model. Zebrafish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs.

Extrafollicular dermal melanocyte stem cells and melanoma.

Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs) persist after birth in the superficial nerve sheath of peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed on the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of melanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and a very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self-renewal, expansion and differentiation are reviewed.

Protein kinase C η is required for T cell activation and homeostatic proliferation.

Protein kinase C η (PKCη) is abundant in T cells and is recruited to the immunological synapse that is formed between a T cell and an antigen-presenting cell; however, its function in T cells is unknown. We showed that PKCη was required for the activation of mature CD8+ T cells through the T cell receptor. Compared with wild-type T cells, PKCη-/- T cells showed poor proliferation in response to antigen stimulation, a trait shared with T cells deficient in PKCθ, which is the most abundant PKC isoform in T cells and was thought to be the only PKC isoform with a specific role in T cell activation.

siRNA-like double-stranded RNAs are specifically protected against degradation in human cell extract.

RNA interference (RNAi) is a set of intracellular pathways in eukaryotes that controls both exogenous and endogenous gene expression. The power of RNAi to knock down (silence) any gene of interest by the introduction of synthetic small-interfering (si)RNAs has afforded powerful insight into biological function through reverse genetic approaches and has borne a new field of gene therapeutics. A number of questions are outstanding concerning the potency of siRNAs, necessitating an understanding of how short double-stranded RNAs are processed by the cell.