Is lobectomy sufficient for multifocal papillary thyroid microcarcinoma?

IMPORTANCE: Multifocal papillary thyroid microcarcinoma (PTMC) has been associated with a higher incidence of lymph node involvement, bilateral involvement, and extrathyroidal extension compared to unifocal papillary thyroid cancer (PTC). OBJECTIVE: To describe the incidence and determinants of survival for patients with multifocal PTMC using the Surveillance, Epidemiology, and End Result (SEER) database. DESIGN, SETTING, PARTICIPANTS: The SEER registry was utilized to calculate survival trends for patients with PTMC between 2010 and 2015. Patient data was then analyzed with respect to age, sex, race, multifocality, and types of surgery rendered. MAIN OUTCOMES AND MEASURES: Overall Survival (OS) and Disease Specific Survival (DSS). RESULTS: 22,283 cases of papillary thyroid microcarcinoma (T1a N0 M0) were identified. The cohort was composed of 82.6 % females, and about 82 % of patients were of white race. The mean age at diagnosis was 51.9 years. Multifocal PTMC was present in 32.2 % of the tumors (n = 7186). 73.9 % of patients underwent total thyroidectomy and 23.0 % received lobectomy. OS at 2 and 5 years was 98 % and 95 %, respectively. Multivariate analysis revealed that age, sex, and multifocality were determinants of OS. Only age was a determinant of DSS. Kaplan-Meier survival analysis revealed that multifocal PTMC had similar mean OS between lobectomy and total thyroidectomy patients (69.59 months versus 69.82 months). CONCLUSIONS AND RELEVANCE: PTMC has a good prognosis. Our analysis revealed that age was a determinant of OS and DSS; sex and multifocality were also prognosticators for OS. The type of surgery, whether lobectomy or total thyroidectomy, was not a determinant of survival in multifocal PTMC.

Integrative Approach to Rhinosinusitis: An Update.

Rhinosinusitis is characterized by inflammation of the mucosa involving the paranasal sinuses and the nasal cavity and is one of the most common and significant health care problems, with significant impairment of quality of life. Current standard conventional management of rhinosinusitis commonly uses multiple therapeutic modalities to break the cycle of chronic disease. However, to date, there is no consensus as to the optimal treatment algorithm for patients with chronic rhinosinusitis. There is a growing interest in the use of complementary and integrative medicine for the treatment of rhinosinusitis. This article update focuses on an integrative approach to rhinosinusitis.

Acupuncture and the Otolaryngology-Head & Neck Surgery Patient.

The use of acupuncture among US adults was estimated at nearly 40% in 2012. A study from the United Kingdom in 2010 found 60% of otolaryngologic patients had used a form of complementary or integrative medicine, with greater than a third in the last year alone. Acupuncture, a therapeutic modality of traditional Chinese medicine, has been used for millennia in Asian countries. Within otolaryngology, acupuncture has been used for a variety of conditions encompassing otology, laryngology, rhinology, and pediatrics. Herein, we review the current literature on the applications of acupuncture for a range of ENT disorders.

Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.

The activation of T cells and the initiation of an immune response is tightly controlled through the crosstalk of both positive and negative regulators. Two adaptors that function as negative regulators of T cell activation are adaptor in lymphocytes of unknown function X (ALX) and linker for activation of X cell (LAX). Previously, we showed that T cells from mice deficient in ALX and LAX display similar hyperresponsiveness, with increased IL-2 production and proliferation upon TCR/CD28 stimulation, and that these adaptors physically associate. In this study, we analyze the nature of the association between ALX and LAX. We demonstrate that this association occurs in the absence of TCR/CD28 signaling via a mechanism independent of both tyrosine phosphorylation of LAX and the SH2 domain of ALX. Cotransfection of ALX with LAX resulted in LAX tyrosine phosphorylation in the absence of TCR/CD28 stimulation. ALX-mediated LAX phosphorylation depends upon the ALX SH2 domain, which functions to recruit Lck to LAX. We also show that LAX, like ALX, can inhibit RE/AP reporter activation. However, in contrast to its inhibition of NFAT, the inhibition of RE/AP by LAX is independent of its tyrosine phosphorylation. Therefore, it can be concluded that inhibition of signaling events involved in T cell activation by LAX occurs through mechanisms both dependent on and independent of its tyrosine phosphorylation.

Efficient and Stable Solar Hydrogen Generation of Hydrophilic Rhenium-Disulfide-Based Photocatalysts via Chemically Controlled Charge Transfer Paths.

Effective charge separation and rapid transport of photogenerated charge carriers without self-oxidation in transition metal dichalcogenide photocatalysts are required for highly efficient and stable hydrogen generation. Here, we report that a molecular junction as an electron transfer path toward two-dimensional rhenium disulfide (2D ReS2) nanosheets from zero-dimensional titanium dioxide (0D TiO2) nanoparticles induces high efficiency and stability of solar hydrogen generation by balanced charge transport of photogenerated charge carriers. The molecular junctions are created through the chemical bonds between the functionalized ReS2 nanosheets (e.g., -COOH groups) and -OH groups of two-phase TiO2 (i.e., ReS2-C6H5C(═O)-O-TiO2 denoted by ReS2-BzO-TiO2). This enhances the chemical energy at the conduction band minimum of ReS2 in ReS2-BzO-TiO2, leading to efficiently improved hydrogen reduction. Through the molecular junction (a Z-scheme charge transfer path) in ReS2-BzO-TiO2, recombination of photogenerated charges and self-oxidation of the photocatalyst are restrained, resulting in a high photocatalytic activity (9.5 mmol h-1 per gram of ReS2 nanosheets, a 4750-fold enhancement compared to bulk ReS2) toward solar hydrogen generation with high cycling stability of more than 20 h. Our results provide an effective charge transfer path of photocatalytic TMDs by preventing self-oxidation, leading to increases in photocatalytic durability and a transport rate of the photogenerated charge carriers.

Negative regulation of interleukin-2 and p38 mitogen-activated protein kinase during T-cell activation by the adaptor ALX.

Activation of naïve T cells requires synergistic signals produced by the T-cell receptor (TCR) and by CD28. We previously identified the novel adaptor ALX, which, upon overexpression in Jurkat T cells, inhibited activation of the interleukin-2 (IL-2) promoter by TCR/CD28, suggesting that it is a negative regulator of T-cell activation. To further understand the physiological role of ALX, ALX-deficient mice were generated. Purified T cells from ALX-deficient mice demonstrated increased IL-2 production, CD25 expression, and proliferation in response to TCR/CD28 stimulation. Enhanced IL-2 production and proliferation were also observed when ALX-deficient mice were primed in vivo with ovalbumin-complete Freund's adjuvant and then restimulated ex vivo. Consistent with our initial overexpression studies, these data demonstrate that ALX is a negative regulator of T-cell activation. While TCR/CD28-mediated activations of phosphotyrosine induction, extracellular signal-regulated kinase 1/2, Jun N-terminal protein kinase, IkappaB kinase alpha/beta, and Akt were unaltered, constitutive activation of p38 mitogen-activated protein kinase and its upstream regulators MKK3/6 were observed for ALX-deficient splenocytes. The phenotype of ALX-deficient mice resembled the phenotype of those deficient in the transmembrane adaptor LAX, and an association between ALX and LAX proteins was demonstrated. These results suggest that ALX, in association with LAX, negatively regulates T-cell activation through inhibition of p38.

Integrative Medicine as a Bridge to Physician Wellness.

Burnout is increasingly recognized as an issue of major importance affecting physicians of all ages and disciplines and thereby patients, systems, and health care in general. At the 2017 American Academy of Otolaryngology-Head and Neck Surgery Foundation Annual Meeting, the scope of burnout in medicine was addressed, along with systematic issues that remain. While changing the culture of medicine and health systems to address this is needed, what strategies can health care providers use in their everyday lives to lessen the impact of burnout? Integrative medicine with its focus on wholeness of patient care, including the emotional, mental, social, and spiritual domains of health, is uniquely positioned in arming physicians with sets of tools to help them navigate patients to better health and healing. These very same methods are invaluable for personal self-care, as we are all potential patients. Integrative medicine is a pathway to improving one's own self-care and, thereby, improving patient care.

Integrative care of the patient with head and neck cancer.

OBJECTIVE: To review the literature on integrative care of the patient with head and neck cancer. METHODS: A review of the English language literature for articles relating to integrative care of patients with head and neck cancer, focusing on treatment of sequelae of surgery and chemoradiation. RESULTS: Many studies show a significant utilization of nontraditional (complementary/integrative) treatments by patients in dealing with head and neck cancer. Treatment of head and neck cancer entails potentially debilitating consequences of surgery and/or chemoradiation on cosmesis, speech, swallowing, breathing, and quality of life. While complementary/integrative treatments for head and neck cancer are not established as effective therapies, their use for relieving sequelae of treatment, improving quality of life, and providing potential chemoprevention is well documented. CONCLUSION: Given the landscape of increasing use of nontraditional methodologies by patients with head and neck cancer and the complexity of care, the head and neck cancer surgeon should be aware of the uses and abuses of complementary/integrative medicine by patients as they navigate their care. LEVEL OF EVIDENCE: 5.

Structure-Activity Relationships of GAG Mimetic-Functionalized Mesoporous Silica Nanoparticles and Evaluation of Acyclovir-Loaded Antiviral Nanoparticles with Dual Mechanisms of Action.

Mesoporous silica nanoparticles (MSNs) are drug delivery agents that are able to incorporate drugs within their pores. Furthermore, MSNs can be functionalized by attachment of bioactive ligands on their surface to enhance their activity, and nanoparticles modified with glycosaminoglycan (GAG) mimetics inhibit the entry of herpes simplex virus (HSV) into cells. In this study, structure-activity relationships of GAGs attached to MSNs were investigated in relation to HSV-1 and HSV-2, and acyclovir was loaded into the pores of MSNs. The sulfonate group was demonstrated to be essential for antiviral activity, which was enhanced by incorporating a benzene group within the ligand. Loading acyclovir into GAG mimetic-functionalized MSNs reduced the viral infection, resulting in nanoparticles that simultaneously target two distinct viral pathways, namely, inhibition of viral entry and inhibition of DNA replication.

Mass psychogenic illness presenting as acute stridor in an adolescent female cohort.

OBJECTIVES: We describe a cohort of patients with an unusual presentation of stridor, their evaluation and management, and their outcome. We review the pertinent English-language literature. METHODS: We performed a retrospective review of the records of 12 adolescent patients treated for acute-onset inspiratory stridor at the Departments of Otolaryngology-Head and Neck Surgery and Allergy and Immunology at the University of South Florida and the Department of Speech Pathology at the H. Lee Moffitt Cancer Center and Research Institute. Two additional patients received treatment elsewhere. Demographic, historical, and laboratory data, physical examination findings, and follow-up information were extracted. A review of both the Hillsborough County Department of Health epidemiological report and the English-language literature was performed. RESULTS: Fourteen female patients who attended a local high school developed audible inspiratory noise. Twelve of the 14 were seen at the University of South Florida Ear, Nose and Throat Center. The remaining 2 patients were evaluated by outside otolaryngologists but were included in all reports from the Department of Health. Environmental studies did not find noxious chemical or biological agents in the students' environments to explain the development of the symptoms. Physical and videostroboscopic examination identified two distinct laryngeal findings causing the audible stridor. One involved paradoxical vocal fold movement, and the other, supraglottic mucosal collapse into the airway. All patients underwent rigorous speech pathology intervention and structured treatment with either complete resolution or significant improvement, seen both clinically and on videostroboscopic evaluation. CONCLUSIONS: Audible stridor can arise from numerous disease processes. In the vast majority of presentations it occurs sporadically and on an individual basis. Our cohort is especially unusual because of the sheer number of patients. Our presentation of a case of mass psychogenic illness as the cause of vocal cord dysfunction with additional findings of laryngomalacia within a group of adolescent girls is the first in the English-language literature. The key to the diagnosis is recognition of the disorder and susceptible individuals by using a thorough physical examination with emphasis on the laryngoscopic and videostroboscopic findings. The systematic approach, undertaken by a team including an otolaryngologist, an allergist, a speech pathologist, and an epidemiologist, proved to be effective in the management of this complex disorder and highly unusual situation.

VcBBX, VcMYB21, and VcR2R3MYB Transcription Factors Are Involved in UV-B-Induced Anthocyanin Biosynthesis in the Peel of Harvested Blueberry Fruit.

This study was carried out to better understand the mechanism responsible for increasing the anthocyanins in blueberries after UV-B radiation at 6.0 kJ m-2 for 20 min. UV-B induced upregulation of genes involved in anthocyanin biosynthesis in blueberry fruit compared to a nontreated control. Phenylalanine ammonia lyase, chalcone synthase, and flavanone 3'-hydroxylase, which are enzymes that function upstream of anthocyanin biosynthesis, were significantly expressed by UV-B. Expression levels of VcBBX, VcMYB21, and VcR2R3MYB transcription factors (TFs) were upregulated by UV-B in the same manner as the anthocyanin biosynthesis genes. The significant increase in the expression of TFs occurred immediately after UV-B treatment and was then maximized within 3 h. In accordance with these changes, individual anthocyanin contents in the fruits treated with UV-B significantly increased within 6 h and were 2-3-fold higher than the control. Our results indicated that UV-B radiation stimulates an increase in anthocyanin biosynthesis, which could be upregulated by the TFs studied.

Bifunctional Succinylated ε-Polylysine-Coated Mesoporous Silica Nanoparticles for pH-Responsive and Intracellular Drug Delivery Targeting the Colon.

Conventional oral drug formulations for colonic diseases require the administration of high doses of drug to achieve effective drug concentrations at the target site. However, this exposes patients to serious systemic toxicity in order to achieve efficacy. To overcome this problem, an oral drug delivery system was developed by loading a large amount (ca. 34% w/w) of prednisolone into 3-aminopropyl-functionalized mesoporous silica nanoparticles (MCM-NH2) and targeting prednisolone release to the colon by coating the nanoparticle with succinylated ε-polylysine (SPL). We demonstrate for the first time the pH-responsive ability of SPL as a "nanogate" to selectively release prednisolone in the pH conditions of the colon (pH 5.5-7.4) but not in the more acidic conditions of the stomach (pH 1.9) or small intestine (pH 5.0). In addition to targeting drug delivery to the colon, we explored whether the nanoparticles could deliver cargo intracellularly to immune cells (RAW 264.7 macrophages) and intestinal epithelial cells (LS 174T and Caco-2 adenocarcinoma cell lines). To trace uptake, MCM-NH2 were loaded with a cell membrane-impermeable dye, sulforhodamine B. The SPL-coated nanoparticles were able to deliver the dye intracellularly to RAW 264.7 macrophages and the intestinal epithelial cancer cells, which offers a highly promising and novel drug delivery system for diseases of the colon such as inflammatory bowel disease and colorectal cancer.

GAG mimetic functionalised solid and mesoporous silica nanoparticles as viral entry inhibitors of herpes simplex type 1 and type 2 viruses.

A glycosaminoglycan mimetic was attached to the surface of solid and mesoporous silica nanoparticles to create novel antiviral agents against herpes simplex type 1 and type 2 viruses. The nanoparticles act as viral entry inhibitors that appear to block viral attachment and penetration into susceptible cells.

HPV-Positive Oropharyngeal Carcinoma: A Systematic Review of Treatment and Prognosis.

OBJECTIVE: Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma is increasing in incidence and appears to exhibit improved response to treatment and better survival than that of HPV- head and neck squamous cell carcinoma. The purpose of this systematic review was to examine the current literature regarding treatment and prognosis of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) and identify whether type of treatment (primarily surgery vs primarily radiation) significantly affects survival rates. DATA SOURCES: PubMed and Cochrane Library databases. REVIEW METHODS: A computerized search of the PubMed and Cochrane Library databases was performed to identify English-language articles published between January 1, 2000, and October 21, 2014. Studies were included only if they were prospective or retrospective observational series of OPSCC patients that reported HPV status, treatment regimen, and survival outcomes. Outcomes were determined for HPV+ and HPV- OPSCC patients, with subanalyses according to the type of treatment received. RESULTS: Fifty-six articles were eligible for this review. In the HPV+ analysis, the unadjusted hazard rate ratio (HR) for surgery vs radiation treatment was 1.33 (P = .114). Nine confounders were considered, and HRs were adjusted for each covariate. While HRs were almost all >1 for all covariates, none of the HRs was statistically significant at P < .05. The HR for HPV- OPSCC was higher for radiation than surgery. CONCLUSIONS: HPV+ OPSCC has an improved prognosis and lower rates of adverse events when compared with HPV- OPSCC. HPV- OPSCC had significantly worse outcomes when treated with primary radiation as compared with primary surgery. There was no statistically significant difference in HRs for HPV+ OPSCC with primary radiation vs primary surgery treatment.

Effect of prestorage UV-A, -B, and -C radiation on fruit quality and anthocyanin of 'Duke' blueberries during cold storage.

Ultraviolet (UV)-A, -B, and -C were radiated to full-ripe blueberries (cv. 'Duke'), and their effects on fruit qualities and phytonutrients during subsequent cold storage were investigated. The blueberries were exposed to each UV light at 6 kJ/m(2) and then stored at 0 °C for 28 days. Weight loss and decay of the fruits after UV treatment were significantly decreased during the cold storage. The total phenolics and antioxidant activities of blueberries after UV-B and -C treatments were always higher than those of the control and UV-A treatment. Individual anthocyanins were markedly increased during the 3 h after the UV-B and -C treatments. The correlation matrix between total phenolics, anthocyanins, and antioxidant activity measured by the 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) assay indicated a significantly close correlation with the individual anthocyanin contents. It was confirmed that the prestorage treatments of UV-B and -C increased the storability and phytochemical accumulation of the full-ripe 'Duke' blueberries during cold storage.

Betalain and betaine composition of greenhouse- or field-produced beetroot ( Beta vulgaris L.) and inhibition of HepG2 cell proliferation.

The composition of betalain, red or yellow pigments, and betaine (trimethylglycine or glycinebetaine) of nine beetroot ( Beta vulgaris L.) cultivars produced in the greenhouse or field was studied. Inhibition of HepG2 cell proliferation by betanin and betaine was also tested. Four predominant betalains, two betacyanins (betanin and isobetanin) and two betaxanthins (vulgaxanthin I and miraxanthin V), were isolated and quantified. Betanin and vulgaxanthin I were the major compounds in red and yellow beetroot extracts, respectively, and they comprised >90% of the betalain content in the tested cultivars. The total betalain content of beetroots produced from the field was between 650 and 800 µg/g fresh weight, approximately 25% higher than those from the greenhouse. The betaine content of the beetroot grown in the field was between 3.0 and 4.8 mg/g fresh weight, approximately 20% higher than in plants from the greenhouse. There was great variation among the cultivars with respect to their contents of betalains and betaine. In vitro cancer cell cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on HepG2 cells after exposure to betanin and betaine at concentrations ranging from 0 to 400 µg/mL and from 0 to 800 µg/mL for 48 h, respectively. Betanin resulted in a 49% inhibition of HepG2 cell proliferation at 200 µg/mL, and betaine yielded a 25% inhibition at 800 µg/mL, implying a higher cytotoxicity of betanin compared with betaine. The results indicated that the contents of health-beneficial compounds in beetroots, betalains and betaine, could be increased by modifying the growing conditions and that betanin and betaine extracted from beetroots had some anticancer effects against HepG2 cells.

Complementary and integrative treatments: atypical facial pain.

This article presents an overview of atypical facial pain for the practicing otolaryngologist. Discussion includes the definition of persistent idiopathic facial pain and its pathophysiology, clinical features, demographics, lack of findings on physical examination, use of imaging modalities and consultations, differential diagnosis, treatment, and prognosis within the framework of an holistic approach.

Complementary and integrative treatments: balance disorders.

This article presents an overview of balance disorders for the practicing otolaryngologist. The demographics of balance disorders, anatomy and physiology of human balance, clinical features, differential diagnosis, and treatment, within the framework of an holistic approach, are discussed.

Complementary and integrative treatments: rhinosinusitis.

Rhinosinusitis is characterized by inflammation of the mucosa involving the paranasal sinuses and the nasal cavity and is one of the most common health care problems, with significant impairment of quality of life. There is a growing amount of interest in the use of complementary and integrative medicine for the treatment of rhinosinusitis. This article focuses on an integrative approach to rhinosinusitis.