Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells.

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.

Sinonasal Hamartoma and Chronic Laryngeal Edema Causing Severe Dyspnea.

Background: Sinonasal hamartomas, according to the 5th edition of the World Health Organisation classification of head and neck tumours are divided into respiratory epithelial adenomatoid hamartoma (REAH), seromucinous hamartoma and chondromesenchymal hamartoma. Seromucinous hamartoma are benign proliferations of small eosinophilic glands surrounded by fibrous stroma and cuboidal cells. Hamartomas of the nasal cavity and paranasal sinuses are rare entities, clinically presenting as sinonasal polyposis. Case Presentation: A 79- year-old female patient was referred to our emergency room due to severe dyspnea. Anterior rhinoscopy revealed unilateral greyish polypoid mass obstructing the middle, inferior and common nasal meatus. Systemic corticosteroids and oxygen therapy were administered under observation. Computerized tomographic imaging of the paranasal sinuses with contrast on all three planes showed an opacified polypoid mass in all meatus and the maxillary, anterior ethmoidal and sphenoidal sinus posteriorly extending to the choanae. On the coronal plane a widening of the olfactory clefts about 12 mm was described. FESS visualized that the polypoid mass originated from the posterior septum and extended to all meatus anteriorly and to the choanae posteriorly. The polypoid lesion was endoscopically completely excised. Histopathological analysis revealed a seromucinous hamartoma. Conclusion: Seromucinous hamartoma are rare benign tumors of the sinonasal region with potential of malignant alteration. Unfortunately, they share symptoms and clinical appearance with other benign conditions of the sinonasal region. Therefore, it is even more important to consider them as a differential diagnose.

Gray-Level Co-occurrence Matrix Analysis of Nuclear Textural Patterns in Laryngeal Squamous Cell Carcinoma: Focus on Artificial Intelligence Methods.

Gray-level co-occurrence matrix (GLCM) and discrete wavelet transform (DWT) analyses are two contemporary computational methods that can identify discrete changes in cell and tissue textural features. Previous research has indicated that these methods may be applicable in the pathology for identification and classification of various types of cancers. In this study, we present findings that squamous epithelial cells in laryngeal carcinoma, which appear morphologically intact during conventional pathohistological evaluation, have distinct nuclear GLCM and DWT features. The average values of nuclear GLCM indicators of these cells, such as angular second moment, inverse difference moment, and textural contrast, substantially differ when compared to those in noncancerous tissue. In this work, we also propose machine learning models based on random forests and support vector machine that can be successfully trained to separate the cells using GLCM and DWT quantifiers as input data. We show that, based on a limited cell sample, these models have relatively good classification accuracy and discriminatory power, which makes them suitable candidates for future development of AI-based sensors potentially applicable in laryngeal carcinoma diagnostic protocols.

Ramsay Hunt Syndrome with Pharyngolaryngeal Involvement Mimicking Acute Stroke: A Case Report.

Ramsay Hunt syndrome is a clinical manifestation of the reactivation of latent varicella zoster virus in the geniculate ganglion after acute infection. It is commonly associated with an acute peripheral facial nerve paralysis, auricular vesicular eruption and acute sensorineural hearing loss. However, in some rare cases the involvement of other cranial nerves, especially the glossopharyngeal and vagal is described. We present a 56-year-old male patient who was diagnosed with acute pharyngitis. Two days later, the patient developed dysarthria, hoarseness, and left side facial weakness. Considering a patient's history of cardiovascular events, the acute stroke was suspected. Magnetic resonance imaging ruled out an acute cerebrovascular accident. The patient's otalgia aggravated and he reported hearing loss. Clinical examination revealed facial paralysis affecting the left side of the face, erythematous rash on the left auricle, multiple vesicles present on patient's left tympanic membrane, ulcerous lesion on the left side of the soft palate and ipsilateral velopharyngeal palsy. Indirect laryngoscopy revealed ulcerous lesions in the left side of the epiglottis and left vocal cord paralysis. The patient was diagnosed with Ramsay Hunt syndrome with cranial polyneuropathy. Oral acyclovir and oral prednisolone were administered. Seven months after discharge, facial paralysis improved to lower grade and flexible laryngoscopy showed that the left vocal cord had resumed normal movement. Ramsay Hunt syndrome can be accompanied by involvement of other cranial nerves. Previous history of hypertensive crises and myocardial infarction may influence a diagnosis of Ramsay Hunt syndrome, especially when it has atypical presentation. However, this diagnosis should be considered in patients with unilateral multiple cranial nerve palsies.

Emergency Tracheostomy Due to a Myasthenic Crisis in a Post-COVID Patient: Report of a Case.

Myasthenia gravis is an autoimmune disorder caused by the production of antibodies that block either acetylcholine receptors or structural receptors of the neuromuscular junction. There is expanding evidence that novel coronavirus (2019-nCoV) disease can lead to the development of an autoimmune response. Myasthenic crisis, a life-threatening respiratory muscle weakness severe enough to necessitate intubation or tracheostomy, can be a potential complication of myasthenia gravis. In this report, we describe the case of a 57-year-old man with acute respiratory insufficiency requiring emergency tracheostomy. His health condition rapidly deteriorated 1 week after initiating systemic corticosteroid treatment for a suspected adult-onset asthma exacerbation. The patient had a history of COVID-19 infection and thymectomy, which were noted in his medical records. Serological testing and electrodiagnostic evaluation confirmed the diagnosis of myasthenia gravis. The patient was treated with plasma exchange, continuous neostigmine infusion, and prednisone. He was successfully decannulated and discharged with anticholinesterase inhibitors and long-term immunosuppression therapy. It is important to consider neurological disorders in the differential diagnosis for patients presenting with respiratory insufficiency, particularly during the COVID-19 pandemic.

Late diagnosis of a submandibular gland carcinoma in Covid-19 pandemic.

The Covid-19 pandemic has created exceptional challenges for patients and medical care systems. Among many factors influencing postponed cancer diagnosis, mask-wearing created difficulties in initial diagnosis of head and neck tumours. This report features a patient who had been covering a submandibular tumour under a surgical mask for more than 6 months. He visited his general practitioner due to a significant weight loss, but he neither took his mask off, nor was he asked to do so. When he reported to our emergency room, we noticed a massive ulcerous mass in the right submandibular region. Histological examination confirmed primary squamocellular carcinoma of submandibular salivary gland. During the Covid-19 pandemic, significant clinical observations may be missed if a surgical mask or respirator are not removed during examination with the potential for increased incidence of medical malpractice claims.

Vagus Nerve Schwannoma Mimicking a Lateral Neck Cyst.

Schwannomas are benign tumors originating from Schwann cells of the myelin sheath. The cystic appearance of a cervical vagal schwannoma is an extremely rare finding, with few patients reported in the literature. A 60-year-old female patient was seen at our service for a slow-growing, 9 × 6 cm left-sided cystic neck mass. Preoperative clinical and computed tomography evaluation suggested a diagnosis of a lateral neck cyst. The surgical exploration through the lateral cervicotomy revealed a large cystic mass and clearly identified that the tumor was originating from the left vagal nerve. The histopathologic analysis confirmed the diagnosis of schwannoma. Although uncommon, vagal schwannoma with pronounced cystic component should be included in the differential diagnosis of the cystic neck swellings.

Spontaneous true aneurysm of the superficial temporal artery presenting as an asymptomatic forehead mass.

Superficial temporal artery aneurysms are rare; when they do occur, they are usually associated with head trauma. Spontaneous true aneurysms of the superficial temporal artery are extremely rare. They are classified as true aneurysms when all three layers of the vessel are found to be involved on histologic examination. Therapeutic options include conservative management, image-guided embolization, and surgical excision. We report a case of an extracranial spontaneous aneurysm of the frontal branch of the superficial temporal artery. A 20-year-old man presented with an asymptomatic, pulsatile, 1-cm forehead mass that had gradually increased in size. The aneurysm was evaluated by clinical examination and three-dimensional computed tomographic angiography. Complete resection was performed with local anesthesia. Histologic examination revealed that the aneurysm involved all three layers of the blood vessel: the tunica intima, tunica media, and tunica adventitia. No atherosclerotic changes or inflammatory cells were found. To the best of our knowledge, this is only the third reported case of a histologically verified spontaneous aneurysm of the frontal branch of the superficial temporal artery. Awareness of this rare pathology in the differential diagnosis of a forehead mass may facilitate diagnosis and prevent complications.

Giant Vertebrobasilar Fusiform Aneurysm as a Cerebellopontine Angle Mass.

INTRODUCTION: According to the literature, a fusiform aneurysm located in the cerebellopontine angle (CPA) is an extremely rare condition. CASE OUTLINE: We report a case of a 59-year-old patient with initial dizziness and left-sided sensorineural hearing loss that had gradually developed over six months. Vertebrobasilar fusiform aneurysm, with intraluminal thrombus, which was displaced to the right cerebellopontine angle, creating mass effect, was diagnosed using brain magnetic resonance imaging and magnetic resonance angiography. CONCLUSION: Atherosclerosis may be the essential factor in the pathogenesis of a fusiform aneurysm of the basilar artery, especially in elderly patients. The best treatment option is yet to be determined, but in soite of numerous previous large studies, personalized approach is probably the best.

Randomized prospective trial of hyperbaric oxygen therapy and intratympanic steroid injection as salvage treatment of sudden sensorineural hearing loss.

OBJECTIVE: To compare the effects of hyperbaric oxygen (HBO) and intratympanic (IT) steroid injection on hearing after the failure of primary treatment in patients with idiopathic sudden sensorineural hearing loss (ISSHL). STUDY DESIGN: A prospective randomized trial. SETTING: Tertiary referral center. PATIENTS: Fifty patients with failure of primary therapy for ISSHL. INTERVENTION(S): After primary treatment with systemic steroids and failure of therapy, defined as less than 10-dB hearing gain, 50 patients were enrolled in the study and received either hyperbaric oxygen or intratympanic steroid treatment. The patients were not matched and not similar. MAIN OUTCOME MEASURE(S): Hearing gain at 0.25, 0.5, 1, 2, and 4 kHz after treatment. RESULTS: There were significant differences between hearing thresholds at all frequencies before and after the HBO treatment. Similarly, there were significant differences between hearing thresholds at most frequencies (except 2 kHz) before and after the treatment in the IT group. The subgroups of patients with pure tone average less than 81 dB and were younger than 60 years had better response to HBO treatment than those with profound deafness and in the elderly. CONCLUSION: HBO and IT steroid therapy could be successfully used as salvage therapies in patients with sudden deafness. Further study is needed to demonstrate superiority of one of the treatments.

External ear canal cholesteatoma after ventilation tube insertion and mastoidectomy.

INTRODUCTION: Etiopathogenetically, there are two types of chollesteatomas: congenital, and acquired. Numerous theories in the literature try to explain the nature of the disease, however, the question about cholesteatomas remain still unanswered. The aim of the study was to present a case of external ear canal cholesteatoma (EEC) developed following microsurgery (ventilation tube insertion and mastoidectomy), as well as to point ant possible mechanisms if its development. CASE REPORT: A 16-year-old boy presented a 4-month sense of fullness in the ear and otalgia on the left side. A year before, mastoidectomy and posterior atticotomy were performed with ventilation tube placement due to acute purulent mastoiditis. Diagnosis was based on otoscopy examination, audiology and computed tomography (CT) findings. CT showed an obliterative soft-tissue mass completely filled the external ear canal with associated erosion of subjacent the bone. There were squamous epithelial links between the canal cholesteatoma and lateral tympanic membrane surface. They originated from the margins of tympanic membrane incision made for a ventilation tube (VT) insertion. The position of VT was good as well as the aeration of the middle ear cavity. The tympanic membrane was intact and of normal appearance without middle ear extension or mastoid involvement of cholesteatoma. Cholesteatoma and ventilation tube were both removed. The patient recovered without complications and shortly audiology revealed hearing improving. Follow-up 2 years later, however, showed no signs of the disease. CONCLUSION: There could be more than one potential delicate mechanism of developing EEC in the ear with VT insertion and mastoidectomy. It is necessary to perform routine otologic surveillance in all patients with tubes. Affected ear CT scan is very helpful in showing the extent of cholesteatoma and bony defects, which could not be assessed by otoscopic examination alone.

Management of complication from temporal bone fractures.

The objective of the study is to review clinical findings and outcomes in patients with temporal bone fractures, and to show an incidence and management of complications. It is the retrospective clinical study and the study took place at tertiary referral center. Fifty-two patients with temporal bone fractures. Data were collected from patients' charts and clinical review. Patients were classified into five groups according to the CT scan. The primary endpoint of study was to show management of possible complication from temporal bone fractures and to analyze association with intracranial injuries. The second endpoint was to show incompleteness of traditionally classification of fracture type. Of the 52 patients with 54 fractures, 27 (50%) had longitudinal fractures, 4 (7.4%) had transverse fractures, 17 (31.5%) had temporal squama-mastoid fractures, 4 (7.4%) had mixed fractures and 2 (3.7%) had isolated meatal fracture. Fifty-eight percent of patients had at least one intracranial pathologic finding, of which 11% had two or more. Persistent conductive hearing loss was noted in 8 of 16 affected patients. The facial paralysis occurred in seven patients. One patient had benign paroxysmal positional vertigo developed 3 weeks after injury. In conclusion, rarely temporal bone fractures are isolated injures. The squama-mastoid fracture in most cases associated with intracranial injuries. Coordination between the neurosurgeon and otologist is essential in the care of such patients. Further large studies will be done to give a more complete classification of temporal bone fractures which will include all fracture patterns and predict clinical outcome.

Unusual presentation of nodular fasciitis as a rapidly growing haemorrhagic temporal mass.

Nodular fasciitis (NF), also called proliferative or infiltrative fasciitis is considered to be a benign reactive process of the soft tissues (subcutaneous tissue, muscle or fascia) rather than a true neoplasm. Although the extremities are the most common sites, it may arise anywhere in the body. Local excision presents the main treatment. This study presents a case of NF with a unique clinical presentation, an acute subcutaneous temporal hemorrhagic growth. Because temporal NF is more often dermally situated than NF involving other anatomic sites, it may present with superficial ulceration or bleeding and appear clinically unusual. Nodular fasciitis should be considered in the differential diagnosis of other benign or malignant tissue masses involving the temporal area.

[Rare extracranial localizations of the head and neck schwannomas].

INTRODUCTION: Schwannomas are tumors of neurogenic origin, that arise from Schwann cells which surround peripheral, cranial and autonomic nerves. Schwannomas account for only 5% of all benign soft tissue tumors, and 25-45% of extracranial schwannomas are present in the head and neck region. They are usually classified according to the nerve of origin and the site within the head and neck. CASE REPORT: We presented extremely rare extracranial localizations of schwannomas and discussed about diagnosis and management of these tumors. CONCLUSION: Schwannomas are slow-growing tumors and late symptoms appearance may cause a delay in diagnosis and treatment of patients with these tumors. An appropriate diagnostic protocol is indispensable tool in performing a differential diagnosis of malignant from benign lesions. Choice of surgical approach depends on schwannomas localization.

Vocal fold mucosa "blue lines" observed on contact telescopy at Reinke's edema.

Reinke's space is a highly specific structure critical for the function of the vocal fold, involved in a majority of pathological changes of the larynx. The aim of the study was to contribute to the understanding of edematous areas of vocal fold mucosa in patients with Reinke's edema using contact telescopy (ConTel). The edematous tissue which could be identified grossly by microlaryngoscopy under general anesthesia was stained topically with methylene blue and then examined using ConTel. The observed changes on contact images were further correlated with corresponding histological sections of biopsied edematous tissue. In patients with Reinke's edema examined using ConTel, we observed longitudinal arranged mucosal "blue lines" (BL). In the histological sections of edematous tissue showing the BL on ConTel, we almost regularly observed well-developed hollow spaces in subepithelia. Also, they were regularly oriented from the middle of the membranous portion of the vocal fold toward the arcuate line distributed almost parallel to the free edge of the vocal fold. BL were a specific feature of Reinke's edema as they were not found in control groups with normal vocal fold mucosa and with vocal fold polyps. For the first time we are describing a new superficial morphological feature of Reinke's edema. The BL could present epithelial ConTel markers of the area between two enlarged neighboring subepithelial crevices of Reinke's space, as indicated on histological sections. Further characterization of BL is required for the understanding of their role in Reinke's edema.

Cyclin D1 immunoreactivity in meningiomas.

OBJECTIVE: Cyclin D1 is an important nuclear protein required for progression of cells through the G1 phase of the cell cycle. The proliferative potential of meningiomas has been studied using various proliferative markers. However, there have been only few published studies evaluating Cyclin D1 immunoreactivity in meningiomas. PURPOSE OF THE STUDY: The aim of our study was to analyze the Cyclin D1 expression in meningiomas and correlate it both with proliferation markers Ki67 and PCNA, and with meningiomas of WHO grade. MATERIAL AND METHODS: We evaluated immunoreactivity for proliferative markers (Cyclin D1, Ki-67, and PCNA) in a consecutive series of 64 meningioma samples obtained from patients who underwent surgical resection because of cerebral or spinal meningiomas. Immunohistochemical staining with Ki-67, PCNA, and Cyclin D1 was performed using the microwave processing procedure and LSAB+ methodology. The number of positive cells for each antibody has been determined and shown in percentage in relation to 1000 counted cells. RESULTS: All meningioma samples showed immunostaining for Ki-67, PCNA, and Cyclin D1 antibodies. The Cyclin D1 scores exhibited a close correlation with Ki-67 and PCNA immunostaining (P < 0.01). Some meningiomas (15 cases) showed a combination of nuclear and cytoplasmatic (fine granular) Cyclin D1 immunoreactivity. All proliferative indexes have been in positive correlation with meningioma grade. CONCLUSION: Our comparative study of proliferative markers in meningiomas demonstrated Cyclin D1 as a very useful proliferative marker in meningiomas.