Comparison of transnasal esophagoscopy and sedated esophagogastroduodenoscopy in the assessment of laryngopharyngeal reflux.

OBJECTIVE: Transnasal esophagoscopy (TNE) in the awake patient and esophagogastroduodenoscopy (EGD) in sedation are both used in the assessment of laryngopharyngeal reflux (LPR). The objective of this study was to compare these two endoscopic methods in contributing to the diagnosis of LPR. METHODS: This study included 54 patients presenting with signs and symptoms suspicious for LPR, which were examined both by TNE and EGD. The contribution of each method to the diagnosis of LPR was evaluated separately and then compared with each other. RESULTS: In detecting LPR, TNE showed a significant higher sensitivity (94% vs. 60%) and accuracy (93% vs. 59%) than EGD, but their specificity was equal (50% each). The most common pathologic findings in both methods were a hiatal hernia (70% vs. 48%) and gaping cardia (69% vs. 24%), followed by peptic esophagitis (41% vs. 24%). CONCLUSION: The value of EGD is limited in the workup of LPR, as sedation tends to mask the subtle findings in this kind of reflux disease.

A novel scoring system for evaluating laryngopharyngeal reflux.

OBJECTIVE: Although laryngopharyngeal reflux (LPR) is a common condition in daily practice, no gold standard exists for its diagnosis. The objective of this study was to establish a simple and reliable scoring system for evaluating LPR consisting of both subjective and objective criteria. METHODS: This retrospective study includes 124 patients presenting with symptoms of LPR. In all patients, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH monitoring (PHM) and transnasal oesophagoscopy (TNE) were performed and rated in a special scoring system. RESULTS: A Horvath Score of 4-5 for severe LPR was found in 76 patients (61%), a score of 2-3 for non-severe LPR in 38 patients (31%) and a score of 0-1 for non-existing LPR in 10 patients (8%) by combining the 4 validated diagnostic methods. CONCLUSION: The proposed scoring system qualifies as a simple and reliable tool for evaluating LPR in daily practice, directly impacting patient management.

Evaluation of ultrasound and fine-needle aspiration in the assessment of head and neck lesions.

PURPOSE: Neck masses of uncertain character need further investigation through imaging and tissue sampling. This is the most extensive study in the literature of clinician-operated ultrasound and fine-needle aspiration (US + FNA) of the head and neck with histological verification, itemized into organ system. The purpose of the present study was to comprehensively evaluate the combination of US + FNA in the assessment of various kinds of head and neck lesions in the hand of the clinician in one single study. METHODS: A total of 408 histologically verified head and neck lesions in 376 consecutive patients undergoing all three diagnostic steps (US, FNA, US + FNA) were included. Excisional biopsy or core-needle biopsy served as a gold standard. US and FNA were evaluated alone and in combination to distinguish between malignant and benign lesions as well as to establish an approximate and specific diagnosis. Each calculation was itemized by organ system. RESULTS: In detecting malignancy, US + FNA showed a significantly higher accuracy (97% vs 86% and 92%) than US and FNA alone. An approximate diagnosis was established in 93%, and a specific diagnosis in 88%, which was significantly better than that of US and FNA alone. CONCLUSION: US + FNA is suited for an efficient evaluation of head and neck masses. This combined method should be the first line of investigation in such lesions before any other imaging and/or sampling methods. While discrepancies in diagnostic findings potentially occur, the key is the interpretation of the package (US and cytologic findings, clinical information) made in one consultation by one clinician to proceed in proper decision making regarding an adequate treatment plan. Consequently US + FNA belong to the standard armamentarium of the otolaryngologist.

Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells.

Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin-embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site.

Activin signaling disruption in the cochlea does not influence hearing in adult mice.

Activin, a member of the TGF-F superfamily, was found to play an important role in the development, repair and apoptosis of different tissues and organs. Accordingly, activin signaling is involved in the development of the cochlea. Activin binds to its receptor ActRII, then dimerizes with ActRI and induces a signaling pathway resulting in gene expression. A study reported a case of fibrodysplasia ossificans progressiva with an unusual mutation in the ActRI gene leading to sensorineural hearing loss. This draws attention to the role of activin and its receptors in the developed cochlea. To date, only the expression of ActRII is known in the adult mammalian cochlea. In this study, we present for the first time the presence of activin A and ActRIB in the adult cochlea. Transgenic mice with postnatal dominant-negative ActRIB expression causing disruption of activin signaling in vivo were used for assessing cochlear morphology and hearing ability through the auditory brainstem response (ABR) threshold. Nonfunctioning ActRIB did not affect the ABR thresholds and did not alter the microscopic anatomy of the cochlea. We conclude, therefore, that activin signaling is not necessary for hearing in adult mice under physiological conditions but may be important during and after damaging events in the inner ear.

The Thyrohyoid Syndrome: Promoting Awareness with a Case Report and Systematic Review of the Literature.

OBJECTIVE: Neck pain is commonly referred to an ENT specialist and can be caused by the little-known inflammatory condition of the lateral thyrohyoid ligament. The pathophysiology of this condition is believed to be inflammation subsequent to over-exertion or cervical trauma. Typically, patients present with chronic unilateral neck pain. Elicitation of localized tenderness over the axis of the lateral thyrohyoid ligament on palpation is a key finding for its diagnosis. We present an unusual case with an acute course and subcutaneous inflammation and discuss its management in an effort to raise awareness for this often-misdiagnosed syndrome. METHODS: A systematic literature research on PubMed was performed selecting patients with a definitive diagnosis of thyrohyoid syndrome or lateral thyrohyoid ligament syndrome. RESULTS: We collected 54 cases from three studies. This condition is an important differential diagnosis for acute or chronic antero-lateral or unilateral neck pain. CONCLUSION: No specific radiological findings are defined and a CT scan is therefore not necessary for its diagnosis, but ultrasound is a useful tool to primarily assess any neck lesion. Once the diagnosis is made, a local infiltration of steroids is the most sustainable treatment option and relapse prevention.

Evaluation of Oropharyngeal pH-Monitoring in the Assessment of Laryngopharyngeal Reflux.

BACKGROUND: Laryngopharyngeal reflux (LPR) is a prevalent disorder. The aim of the present retrospective cohort study was to evaluate oropharyngeal pH-monitoring using a novel scoring system for LPR. METHODS: In a total of 180 consecutive patients with possible LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring and transnasal esophagoscopy were carried out for further investigation. RESULTS: In our series, 99 (55%) patients had severe LPR, 29 (16%) cases presented with moderate and 23 (13%) with mild severity, 9 (5%) subjects revealed neutral values, and 7 (4%) individuals were alkaline, while 13 (7%) patients had no LPR. In detecting LPR, the sensitivity, specificity and accuracy of oropharyngeal pH-monitoring was 95%, 93% and 94%, respectively. CONCLUSION: Oropharyngeal pH-monitoring is a reliable tool in the assessment of LPR, but the pH graphs have to be precisely analyzed and interpreted in context with other validated diagnostic tests.

Value of Transnasal Esophagoscopy in the Workup of Laryngo-Pharyngeal Reflux.

BACKGROUND: Laryngopharyngeal reflux (LPR) can display a variety of symptoms, and upper endoscopy is occasionally used for its investigation. The aim of the present study was to determine the value of transnasal esophagoscopy (TNE) in the workup of LPR. METHODS: In 200 consecutive patients with suspected LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring (PHM) and transnasal esophagoscopy (TNE) were carried out and rated according to the Horvath Score. RESULTS: In the investigation of LPR, TNE showed a sensitivity, specificity and accuracy of 96%, 85% and 95%, respectively. The most common pathologic TNE findings in LPR patients were an insufficient cardia, hiatal hernia, lymphoid follicles and visible reflux. CONCLUSIONS: TNE is a supportive method in the workup of LPR, which can display the underlying pathology and directly affect therapeutic decisions.

Smell and taste loss in COVID-19 patients: assessment outcomes in a Victorian population.

Background: It has been noted that olfactory and gustatory disturbances may precede or accompany the typical features of COVID-19, such as fever and cough. Hence, a high index of suspicion is required when patients report sudden loss of smell or taste, in order to facilitate timely diagnosis and isolation.Aims/objectives: The aim of this study was to assess the frequency of olfactory and gustatory disturbances in COVID-19 positive patients from a cohort representative of Melbourne, Australia.Methods: A retrospective descriptive study was conducted on patients who tested positive for COVID-19. Standardised phone consultations and online follow-up questionnaires were performed to assess clinical features of COVID-19, with a focus on smell and taste disorders.Results: The most frequent symptoms experienced were taste and smell disturbances with 74% experiencing either smell or taste disturbance or both. Post-recovery, 34% of patients continued to experience ongoing hyposmia and 2% anosmia, whereas 28% continued to suffer from hypogeusia or ageusia.Conclusion and significance: This study presents the high rates of improvement of both olfactory and gustatory disturbance in a short-lived period. It also highlights the importance of these symptoms in prompting appropriate testing, quarantine precautions, initiate early olfactory retraining and the potential for continued sensory disturbance.

Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K-Akt pathway.

Gentamicin is a widely used antibiotic for the treatment of gram-negative bacterial infections; however, its use often results in significant and permanent hearing loss. Hearing loss resulting from hair cell (HC) degeneration affects millions of people worldwide, and one major cause is the loss of sensory HCs in the inner ear due to aminoglycoside exposure. Strategies to overcome the apparently irreversible loss of HCs in mammals are crucial for hearing protection. Here, we report that the somatostatin analog pasireotide protects mouse cochlear HCs from gentamicin damage using a well-established in vitro gentamicin-induced HC loss model and that the otoprotective effects of pasireotide are due to Akt up-regulation via the PI3K-Akt signal pathway activation. We demonstrate active caspase signal in organ of Corti (OC) explants exposed to gentamicin and show that pasireotide treatment activates survival genes, reduces caspase signal, and increases HC survival. The neuropeptide somatostatin and its selective analogs have provided neuroprotection by activating five somatostatin receptor (SSTR1-SSTR5) subtypes. Pasireotide has a high affinity for SSTR2 and SSTR5, and the addition of SSTR2- and SSTR5-specific antagonists leads to a loss of protection. The otoprotective effects of pasireotide were also observed in a gentamicin-injured animal model. In vivo studies have shown that 13 days of subcutaneous pasireotide application prevents gentamicin-induced HC death and permanent hearing loss in mice. Auditory brainstem response analysis confirmed the protective effect of pasireotide, and we found a significant threshold shift at all measured frequencies (4, 8, 16, 24, and 32 kHz). Together, these findings indicate that pasireotide is a novel otoprotective peptide acting via the PI3K-Akt pathway and may be of therapeutic value for HC protection from ototoxic insults.

Functional and morphological analysis of different aminoglycoside treatment regimens inducing hearing loss in mice.

Aminoglycoside ototoxicity is common in clinical practice but reliable protective agents currently do not exist. Aminoglycoside regimens causing ototoxicity in different laboratory animals are under investigation. The assessment method used most commonly to determine auditory effects is the auditory brainstem response (ABR). Distortion product otoacoustic emissions (DPOAE) have been used less frequently. A precise recommendation on the specific method to assess peripheral auditory function before and after aminoglycoside toxicity in mice does not exist. In order to evaluate various mouse models for ototoxic injury caused by various aminoglycoside regimens, there is a need for performing preliminary tests in small cohorts before large experiments. The aim of our study was to investigate different aminoglycoside regimens that cause substantial ototoxic damage in vivo. Aminoglycosides are safe and produce a detectable hearing threshold shift in a small cohort of mice that can be used as a model for preliminary tests. Different ototoxic regimens were assessed by ABR and DPOAE measurements pre- and post-treatment. Further, the sensory cell loss was quantified by counting hair cells in the cochlea. It was revealed that an ototoxic regimen with kanamycin twice daily for 15 consecutive days is safe, well tolerated and produces an early significant hearing threshold shift detected by DPOAE in a small cohort of mice. The study compared ABR and DPOAE in mentioned regimens for the first time and illustrated that DPOAE is well suited for detecting hearing threshold shifts in high frequencies before ABR threshold shifts occur in accordance with predominating outer hair cell damage mainly in the basal turn of the cochlea.

Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice.

Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain.

Salmonella enterica Subspecies diarizonae Maxillary Sinusitis in a Snake Handler: First Report.

In this study, we report the first case of reptile-associated maxillary sinusitis due to Salmonella enterica subspecies diarizonae in a snake handler and the third case of salmonella-associated sinusitis worldwide. The case highlights the potential of respiratory transmission and atypical salmonellosis presentations.