Referred otalgia: Common causes and evidence-based strategies for assessment and management.

OBJECTIVE: To provide family physicians and general otolaryngologists with a practical, evidence-based, and comprehensive approach to the management of patients presenting with suspected referred otalgia. SOURCES OF INFORMATION: The approach described is a review based on the authors' clinical practices along with research and clinical review articles published between 2000 and 2020. MEDLINE and PubMed were searched using the terms otalgia, referred otalgia, and secondary otalgia. Current guidelines for the management of referred otalgia were also reviewed. MAIN MESSAGE: Otalgia is defined as pain localized to the ear. It is one of the most common head and neck presentations in primary care, otolaryngology, and emergency medicine. Secondary otalgia arises from nonotologic pathology and represents nearly 50% of otalgia cases. Otalgia in the absence of other otologic symptoms is highly indicative of a secondary cause. A thorough assessment of patients presenting with referred otalgia requires an understanding of the possible causes of this condition, including dental and oral mucosal pathologies, temporomandibular joint disorders, cervical spine pathology, sinusitis, upper airway infection, and reflux, as well as head and neck malignancy. This paper aims to highlight the most common causes of referred otalgia, their presentations, and initial options for assessment and management. CONCLUSION: The prevalence of referred otalgia makes this an important condition for family physicians to be able to assess, manage, and triage based on patient presentation and examination. Understanding the common causes of referred otalgia will help reduce wait times for specialist assessment and allow ease and speed of access to management options for patients in community clinics.

Otalgie référée: Causes habituelles et stratégies d'évaluation et de prise en charge fondées sur des données probantes.

OBJECTIF: Présenter aux médecins de famille et aux otorhinolaryngologistes généraux une approche pratique, exhaustive et fondée sur des données probantes pour la prise en charge des patients chez qui l'on soupçonnne une otalgie référée. SOURCES DE L'INFORMATION: L'approche décrite est une revue qui se fonde sur les pratiques cliniques des auteurs, et sur des articles de recherche et des revues cliniques publiés entre 2000 et 2020. Une recension a été effectuée dans MEDLINE et PubMed à l'aide des expressions en anglais otalgia, referred otalgia et secondary otalgia. Les lignes directrices actuelles sur la prise en charge de l'otalgie référée ont aussi été passées en revue. MESSAGE PRINCIPAL: L'otalgie désigne une douleur localisée à l'oreille. Il s'agit de l'une des présentations liées à la tête et au cou les plus fréquentes en soins primaires, en otorhinolaryngologie et en médecine d'urgence. L'otalgie secondaire découle d'une pathologie non otologique, et près de 50 % des cas d'otalgie lui sont attribuables. L'otalgie sans autres symptômes otologiques évoque fortement une cause secondaire. Une évaluation rigoureuse des patients qui présentent une otalgie référée nécessite une bonne compréhension des causes possibles de ce problème, notamment des pathologies dentaires et des muqueuses buccales, des troubles de l'articulation temporo-mandibulaire, des pathologies de la colonne cervicale, de la sinusite, des infections des voies aériennes supérieures et du reflux, de même que des cancers de la tête et du cou. Cet article a pour but de mettre en évidence les causes les plus fréquentes d'une otalgie référée, leurs caractéristiques, et les options initiales pour l'évaluation et la prise en charge. CONCLUSION: La prévalence de l'otalgie référée fait en sorte qu'il importe que les médecins de famille soient en mesure d'évaluer, de prendre en charge et de trier les patients d'après la présentation et l'examen. Une bonne compréhension des causes courantes de l'otalgie référée aide à réduire le temps d'attente avant une évaluation spécialisée, et permet de faciliter et d'accélérer l'accès par les patients à des options de prise en charge dans les cliniques communautaires.

Sensitivity and Specificity of US and CT as Diagnostic Tools for Pediatric Lateral Neck Abscesses.

OBJECTIVE: Ultrasound (US) and computed tomography (CT) are commonly used in the diagnosis of pediatric neck abscesses. The objective of this study is to determine the sensitivity and specificity of US and CT in the diagnosis of pediatric lateral neck abscesses, with a secondary objective of evaluating the association of specific clinical features with a positive US or CT scan. STUDY DESIGN: Retrospective review of pediatric patients admitted to a tertiary care center from January 1, 2011, to December 31, 2020, with neck abscesses. SETTING: Tertiary care center. METHODS: The sensitivity and specificity of US and CT were calculated by comparing imaging performed within 24 h of incision and drainage (I&D). Multiple regression was used to evaluate the association of clinical features with a true positive US or CT. RESULTS: There were 171 patients included in this study, with a median age of 1.5 years (interquartile range [IQR]: 1-5 years). I&D was done in 156 patients (91.2%), while 15 (8.8%) were treated with antibiotics. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US were 69.5%, 80%, 96.6%, and 24.2%. The sensitivity, specificity, PPV, and NPV of neck CT were 95.5%, 80%, 95.5%, and 57.1%. Length of symptoms, skin erythema, and fluctuance were not significantly associated with a positive US (F(3, 82) = 0.24, p = .9, R2 = 0.01) or CT scan (F(3, 30) = 0.84, p = .5, R2 = 0.08). CONCLUSION: Neck US has a low sensitivity for diagnosing pediatric neck abscesses, when compared to CT, but remains a useful initial investigation given its high PPV. Clinicians should have a low threshold for pursuing CT if there is a high suspicion of abscess formation. LEVEL OF EVIDENCE: Level 4.

Developing an Objective Structured Assessment of Technical Skills (OSATS) for Microlaryngoscopy.

BACKGROUND: Microlaryngoscopy is a basic technical skill in Oto-HNS. It is essential for residency programs to have a competency-based assessment tool to evaluate residents' performance of this procedure. An Objective Structured Assessment of Technical Skills (OSATS) is a procedure-specific assessment, which consists of the following: (a) Operation-Specific Checklist and (b) Global Rating Scale (GRS). OBJECTIVE: The objective of this study was to create an OSATS for adult microlaryngoscopy. METHODS: This was a prospective study, with an initial qualitative phase for OSATS development (Phase I), and a clinical pilot phase (Phase II). In Phase I, interviews were conducted with three laryngologists to establish a stepwise description of adult microlaryngoscopy and review a previously validated GRS for relevance to microlaryngoscopy. Responses were used to create a framework for the OSATS. The OSATS was then presented to Oto-HNS residents and laryngologists in an alternating fashion, for review of clarity and relevance. A pilot study was then performed to evaluate the resident performance of adult microlaryngoscopy. Multiple regression analysis was carried out to investigate whether training level, case complexity, and previous OSATS exposure could predict participant scores. RESULTS: Phase I of this study led to the creation of a 34-item OSATS. The pilot study (N = 28 procedures) revealed that training level was significantly correlated with increased OSATS scores. There was no statistically significant correlation between case complexity and resident scores. Assessors reported the perceived utility of the OSATS and intent for use in residency training. CONCLUSION: Application of the proposed OSATS will allow for competency-based assessment of the resident performance of microlaryngoscopy. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2719-2724, 2023.

Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.

Immunotherapy is considered a promising approach for cancer treatment. An important strategy for cancer immunotherapy is the use of cancer vaccines, which have been widely used for cancer treatment. Despite the great potential of cancer vaccines for cancer treatment, their therapeutic effects in clinical settings have been limited. The main reason behind the lack of significant therapeutic outcomes for cancer vaccines is believed to be the immunosuppressive tumor microenvironment (TME). The TME counteracts the therapeutic effects of immunotherapy and provides a favorable environment for tumor growth and progression. Therefore, overcoming the immunosuppressive TME can potentially augment the therapeutic effects of cancer immunotherapy in general and therapeutic cancer vaccines in particular. Among the strategies developed for overcoming immunosuppression in TME, the use of toll-like receptor (TLR) agonists has been suggested as a promising approach to reverse immunosuppression. In this paper, we will review the application of the four most widely studied TLR agonists including agonists of TLR3, 4, 7, and 9 in cancer immunotherapy.

Enhanced anticancer potency with reduced nephrotoxicity of newly synthesized platin-based complexes compared with cisplatin.

As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, 1HNMR, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC50 (200-1.75 µM). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC50 = 2.3 µM) than cisplatin (IC50 = 107 µM) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth.

Development of a patient reported outcome instrument for chronic sialadenitis.

BACKGROUND: Sialendoscopy assisted treatments are a minimally invasive management modality for chronic sialadenitis. Clinicians report improved patient quality of life (QoL) following sialendoscopy assisted treatments, but there exist gaps in current literature about patient reported outcomes (PROs). PROs are outcome measures developed based on patient perceptions. OBJECTIVE: The objective of this study was to create a PRO instrument for chronic sialadenitis, to assess the efficacy of sialendoscopy assisted treatments in improve patients' QoL. DESIGN: This four-phase qualitative study employed grounded theory methodology and a modified Delphi technique. In Phase I, ten patients were interviewed to identify the QoL domains impacted by chronic sialadenitis. In Phase II, these QoL domains were presented to a focus group of different chronic sialadenitis patients, who were asked to rank them by order of importance. A conceptual framework of QoL domains impacted by chronic sialadenitis was created based on patient consensus. Itemization of the PRO questionnaire was done by a focus group of four Otolaryngologists in phase III. Lastly, the questionnaire was completed in Phase IV by cognitive interviewing of five new chronic sialadenitis patients; ensuring ease of understanding and clarity. RESULTS: Patients identified 15 domains of QoL impacted by chronic sialadenitis, divided into three sub-scales: physical symptoms, psychosocial symptoms, and activity restriction. These domains provided the basis for creation of a 22-item PRO questionnaire, with a Likert-type response scale. CONCLUSION: Clinical application of the novel questionnaire produced by this study will allow for a patient-centered assessment of the patient reported effectiveness of sialendoscopy assisted therapies for management of chronic sialadenitis. Level of evidence Level V.

Dietary Patterns Prior to Pregnancy and Associations with Pregnancy Complications.

Few studies have explored pre-pregnancy diet and its relationship with pregnancy outcomes. The objectives of this study were to: (1) derive pre-pregnancy dietary patterns for women enrolled in a prospective cohort in the province of Alberta, Canada; (2) describe associations between dietary patterns and socio-demographic characteristics; and (3) describe associations between dietary patterns and pregnancy complications. Upon enrolment into the Alberta Pregnancy Outcomes and Nutrition (APrON) study (median age of gestation, 17 weeks), women (n = 1545) completed a validated 142-item food frequency questionnaire recording food and beverages consumed "in the 12 months prior to pregnancy". Other assessments included pre-pregnancy body mass index (BMI), gestational weight gain, gestational hypertension, gestational diabetes, and socio-demographic characteristics. Dietary patterns were derived using principal components analysis. Scores were calculated to represent adherence with each dietary pattern retained. Four dietary patterns were retained, accounting for 22.9% of the variation in the overall diet. Dietary patterns were named the "healthy", "meat and refined carbohydrate", "beans, cheese and salad" or "tea and coffee" patterns. Higher "healthy" pattern scores prior to pregnancy were associated with lower odds of developing gestational hypertension during pregnancy (adjusted Odds Ratio (OR): 0.6, 95% Confidence Intervals (CI): 0.4, 0.9). Diet prior to pregnancy is an important target for interventions and may reduce the likelihood of developing complications such as gestational hypertension during pregnancy.

Paraoxonase 1 (PON1)-L55M among common variants in the coding region of the paraoxonase gene family may contribute to the glycemic control in type 2 diabetes.

OBJECTIVE: Genome studies have shown that the genes encoding paraoxonase 1 (PON1) and PON2 are associated with glucose metabolism. The goal of this study was to simultaneously evaluate the association between functional variants in PON1 and PON2 genes and susceptibility for type 2 diabetes (T2D) and determine whether they can affect glycemic control. METHODS: We performed a case-control study with 145 newly diagnosed patients with T2D and 148 controls. The common variants including PON1-Q192R, PON1-L55M and PON2-S311C were genotyped by PCR-based RFLP. A mismatch-PCR/RFLP was applied for genotyping the PON2-A148G variant. RESULTS: The variant PON1-Q192R in males (OR = 2.55, 95%CI 1.16-5.69, p = 0.023) and PON2-A148G in females (OR = 1.56, 95%CI 1.00-2.44, p = 0.059) were associated with T2D. Compared with the LL genotypes of PON1-L55M, HbA1c levels were significantly lower in the LM genotypes (p = 0.01) and MM genotypes (p = 0.032) in patients. Multiple linear regression analyses showed that among the study variants only the PON1-L55M variant as an independent variable significantly associated with glycemic control. This variant significantly influenced glycemic control in patients with poor glycemic control so that it was better with the following order: LL < LM < MM. Based on gamma correlation, there was a significant inverse association between the number of M alleles of the PON1-L55M and HbA1c levels (r = -0.261, p = 0.001). CONCLUSIONS: Sex should be considered a confounding variable in association studies on the variants PON1-Q192R and PON2-A148G in T2D. Patients sharing the 55 M allele were prone to having good glycemic control. Our findings provide genetic evidence that the PON1-L55M variant may be a factor contributing to glycemic control.

Nanotoxicology: advances and pitfalls in research methodology.

As research progresses, nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite this rise, their potential risks to human health, together with environmental issues, has led to increasing concerns regarding their use. As such, a comprehensive understanding of the interactions that occur at the nano-bio interface is required in order to design safe, reliable and efficient NPs for biomedical applications. To this end, extensive studies have been dedicated to probing the factors that define various properties of the nano-bio interface. However, the literature remains unclear and contains conflicting reports on cytotoxicity and biological fates, even for seemingly identical NPs. This uncertainty reveals that we frequently fail to identify and control relevant parameters that unambiguously and reproducibly determine the toxicity of nanoparticles, both in vitro and in vivo. An effective understanding of the toxicological impact of NPs requires the consideration of relevant factors, including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects and personalized protein corona. In this review, we discuss the factors that play a critical role in nano-bio interface processes and nanotoxicity. A proper combinatorial assessment of these factors substantially changes our insight into the cytotoxicity, distribution and biological fate of NPs.