A Multidisciplinary Skull Base Board for Tumour and Non-Tumour Diseases: Initial Experiences.

The skull base is the area where various cancerous and non-cancerous diseases occur and represents the intersection of several medical fields. The key is an integrated treatment by specialists of multiple disciplines. We prospectively analysed patients with a skull base disease between August 2022 and 2023 and presented to the Multidisciplinary Skull Base Board (MDT-SB), which takes place once a month hybridly (in-person and remotely). Thirty-nine patients (median age of 58.2 years) were included, of which twelve (30.8%) had a benign tumour, twelve (30.8%) had a malignant tumour, five had an infection (12.8%), and ten (25.6%) had other diseases. For each patient, at least two otorhinolaryngologists, a neurosurgeon, and a neuroradiologist, as well as an infectious disease specialist, a paediatrician, an oculoplastic surgeon, a maxillofacial surgeon, and a pathologist were involved in 10%, 8%, 8%, 3%, and 3% of cases, respectively. In fifteen patients (38%), the MDT-SB suggested surgical treatment; in fourteen (36%), radiological follow-ups; in five (13%), non-surgical treatments; in two, conservative treatments (5%); in two (5%), surgical and conservative treatments; and in one (3%), a biopsy. Non-cancerous and cancerous diseases of the skull base in adults and children should be presented to the MDT-SB, which consists of at least an otolaryngologist, a neurosurgeon, and a neuroradiologist.

Sinonasal Orbital Apex Syndrome, Horner Syndrome and Pterygopalatine Fossa Infection: A Case Report and Mini-Review.

This paper presents a literature review and a case of an 83-year-old otherwise healthy female patient with a history of recent syncope, a sudden-onset right-sided temporal headache, diplopia, and vision loss. An exam revealed right-sided upper eyelid ptosis, myosis, vision loss, ophthalmoplegia, and a positive relative afferent pupillary defect on the right eye. CT showed sphenoid sinus opacification, eroded lateral sinus wall, Vidian canal, disease extension to the posterior ethmoid air cells, orbital apex, medial orbital wall, and pterygopalatine fossa. An orbital apex syndrome (Jacod's syndrome), Horner syndrome, and pterygopalatine fossa infection were diagnosed due to the acute invasive fungal sinusitis developed from a sphenoid sinus fungal ball. The patient was treated with antimicrobial therapy and transnasal endoscopic surgery twice to decompress the orbital apex, drain the abscess and obtain specimens for analysis. The right-sided ptosis, visual loss, ophthalmoplegia, and headache resolved entirely. No immune or comorbid diseases were identified, microbiological and histopathological analyses were negative, and MRI could not be performed on the presented patient. For that reason, the diagnostic procedure was non-standard. Nevertheless, the treatment outcome of this vision and life-threatening disease was satisfactory. Treating the fungal ball in an older or immunocompromised patient is essential to prevent invasive fungal rhinosinusitis and fatal complications.

Atypical Skull-Base Osteomyelitis: Comprehensive Review and Multidisciplinary Management Viewpoints.

Atypical skull-base osteomyelitis is a rare but fatal disease that usually involves infection of the ethmoid, sphenoid, occipital, or temporal bones that form the skull base. Unlike typical (so-called otogenic), atypical skull-base osteomyelitis has no otogenic cause. Instead, some authors call atypical skull-base osteomyelitis sinonasal, since the infection most often originates from the nose and paranasal sinuses. Diagnosing and treating this disease is challenging. To assist in managing atypical skull-base osteomyelitis, a review of the most recent literature, with patient cases and multidisciplinary perspectives from otolaryngologists, neurosurgeons, radiologists, infectious disease specialists, pathologists, and clinical microbiologists, is provided in this paper.

Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review.

The preparation of autologous platelet and extracellular vesicle-rich plasma (PVRP) has been explored in many medical fields with the aim to benefit from its healing potential. In parallel, efforts are being invested to understand the function and dynamics of PVRP that is complex in its composition and interactions. Some clinical evidence reveals beneficial effects of PVRP, while some report that there were no effects. To optimize the preparation methods, functions and mechanisms of PVRP, its constituents should be better understood. With the intention to promote further studies of autologous therapeutic PVRP, we performed a review on some topics regarding PVRP composition, harvesting, assessment and preservation, and also on clinical experience following PVRP application in humans and animals. Besides the acknowledged actions of platelets, leukocytes and different molecules, we focus on extracellular vesicles that were found abundant in PVRP.

Management of Choanal Atresia: National Recommendations with a Comprehensive Literature Review.

Choanal atresia is the most common congenital anatomical abnormality of the nasal cavities, manifested with a clinical picture of neonatal respiratory distress. The treatment requires interdisciplinary management based mainly on tertiary referral centre experiences. However, there is a lack of high-quality evidence in the available literature. Recommendations were prepared based on a systematic review of the supporting literature: on a website survey addressed to the participating authors consisting of 28 questions and on five live meetings. The initial response to the recommendations was determined at their presentation at the sectional meeting of the section for otorhinolaryngology of the Slovenian Medical Association. Then, reactions from the professional public were accepted until the recommendations were presented at the Expert Council for Otorhinolaryngology of the Slovenian Medical Association. A systematic literature review identified eight systematic reviews or meta-analyses and four randomized controlled clinical trials. Thirty-four recommendations for diagnosis, treatment and postoperative management were consolidated. The paper presents the proposal and first Slovenian recommendations for treating patients with choanal atresia. They are based on foreign medical institutions' published literature and our clinical experience. They represent the basic requirements of diagnostics and may represent an essential guide in treatment.

Appropriate Vestibular Stimulation in Children and Adolescents-A Prerequisite for Normal Cognitive, Motor Development and Bodily Homeostasis-A Review.

The structural development of the vestibular part of the inner ear is completed by birth but its central connections continue to develop until adolescence. Their development is dependent on vestibular stimulation-vestibular experience. Studies have shown that vestibular function, modulated by experience and epigenetic factors, is not solely an instrument for body position regulation, navigation, and stabilization of the head and images but also influences cognition, emotion, the autonomous nervous system and hormones. To emphasize the importance of appropriate vestibular stimulation, we present a literature review of its effect on bodily homeostasis, cognition and emotion.

Vector-Borne Tularemia: A Re-Emerging Cause of Cervical Lymphadenopathy.

Tularemia is a zoonosis caused by the highly invasive bacterium Francisella tularensis. It is transmitted to humans by direct contact with infected animals or by vectors, such as ticks, mosquitos, and flies. Even though it is well-known as a tick-borne disease, it is usually not immediately recognised after a tick bite. In Slovenia, tularemia is rare, with 1-3 cases reported annually; however, the incidence seems to be increasing. Ulceroglandular tularemia is one of its most common forms, with cervical colliquative lymphadenopathy as a frequent manifestation. The diagnosis of tularemia largely relies on epidemiological information, clinical examination, imaging, and molecular studies. Physicians should consider this disease a differential diagnosis for a neck mass, especially after a tick bite, as its management significantly differs from that of other causes. Tularemia-associated lymphadenitis is treated with antibiotics and surgical drainage of the colliquated lymph nodes. Additionally, tularemia should be noted for its potential use in bioterrorism on behalf of the causative agents' low infectious dose, possible aerosol formation, no effective vaccine at disposal, and the ability to produce severe disease. This article reviews the recent literature on tularemia and presents a case of an adult male with tick-borne cervical ulceroglandular tularemia.

Indicators of pediatric peripheral vestibular disorder: A retrospective study in a tertiary referral center.

OBJECTIVES: This study aims to present characteristics of pediatric patients with peripheral vertigo and dizziness and their clinical workup results in the tertiary otorhinolaryngology center. We wanted to investigate whether the detailed history could replace the extensive vestibular testing and whether the clinical presentation could guide the first contact physician to appropriately directed specialist referral. METHODS: Retrospective case review of consecutive pediatric vertigo and dizziness patients referred to the tertiary otorhinolaryngology center from 2015 to 2020. The data about the signs and symptoms of vertigo and dizziness and the results of audiological and vestibular tests were collected. RESULTS: Of 257 children aged 10.9±4.3 years (R: 1-17 years), 32 (12.5%) had peripheral, and 49 (19%) had central vertigo and dizziness. Acute vestibulopathy was diagnosed in 22/257 (8.5%) children, sudden sensorineural hearing loss and benign paroxysmal positional vertigo in 5/257 (2%) children each. 60% of children with peripheral vertigo and dizziness had emesis, and 55.6% had nausea. 8% of children had spontaneous horizontal-rotatory nystagmus that followed Alexander's law. Goodman and Kruskal's л for determining whether the type of nystagmus could predict the type of vertigo and dizziness (central or peripheral) was 0.481 (p = 0.001). 12/26 (60%) of children with peripheral vertigo and dizziness had emesis compared to 14 (30.04%) children without emesis, a difference in proportions of 0.296 (p = 0.024, chi-square test of homogeneity). Binomial logistic regression to ascertain the effects of duration, nausea and emesis on the likelihood of the presence of peripheral vertigo was statistically significant (χ2(3) = 10.626, p = 0.014). CONCLUSION: Unlike adults, peripheral vestibular causes of vertigo and dizziness in children may be rare but have the same typical signs and symptoms. The detailed history and careful clinical examination are crucial in differentiating between peripheral and central causes. This guides the first contact physician for further referral to appropriate specialists included in a multidisciplinary workup. Namely, nausea, emesis, horizontal nystagmus and a longer duration of symptoms in a child with vertigo and dizziness indicate a peripheral etiology. Therefore, a referral to an otorhinolaryngologist is reasonable.

Clinical Implementation of Platelet- and Extracellular Vesicle-Rich Product Preparation Protocols.

Extracellular vesicles (EVs) are considered essential mediators of regenerative roles of autologous platelet- and extracellular vesicle-rich plasma (PVRP) and platelet- and extracellular vesicle-rich gel (PVRG). PVRP and PVRG are novel blood-derived products gaining attraction in regenerative medicine. However, despite their reported good efficacy, their preparation protocols are too time-consuming. Moreover, patient-tailored preparation protocols are desired to optimize platelet and EV count in PVRP and PVRG. This article presents the clinical implementation of one-step, patient-tailored erythrocyte sedimentation rate (ESR)-based, PVRP and PVRG preparation protocols through the presentation of three cases: (1) large chronic tympanic membrane (TM) perforation, (2) osteoradionecrosis of the lateral skull base, and (3) cerebrospinal fluid (CSF) leak in the sphenoid sinus. These were treated with PVRP and PVRG, prepared according to our preclinically constructed mathematical sedimentation model of cells and EVs based on the patient's ESR. (1) TM healed completely after the treatment with 3.6 mL of PVRP and PVRG (high platelet and EV protocol). The speech discrimination score and air conduction pure tone average improved from 75% to 95% and from 65 to 25 dB, respectively. (2) The osteoradionecrotic surface area decreased from 46 to 18 cm2, and infection was eradicated after six applications of 13-65 mL of PVRG ("half-volume" protocol). (3) No CSF leak recurrence was detected after surgical closure with 30 mL of PVRG postoperatively. Reproducible preparation protocols proved effective, safe, fast, and straightforward enough for the surgical staff to prepare PVRP and PVRG intraoperatively. To alleviate preparation, a calculator is provided. This pilot study presents a sound basis for further studies, which are needed to assess the therapeutic effect of PVRP and PVRG. Impact statement We introduce a clinical implementation of a patient-tailored, erythrocyte sedimentation rate-based platelet- and extracellular vesicle-rich plasma (PVRP) and gel (PVRG) preparation protocol based on a mathematical model. Products proved beneficial in wound healing and were, to our knowledge, used for the first time in the treatment of osteoradionecrosis of the lateral skull base. Furthermore, this reproducible preparation protocol is fast and straightforward to implement in clinical practice. A calculator is provided to alleviate PVRP and PVRG preparation for various clinical scenarios.

Malignant Syphilis in a Female Patient: A Case Report and Mini-Review.

Malignant syphilis (MS) is a rare form of secondary syphilis with grotesque skin lesions, systemic manifestation and life-threatening complications. This article presents a case of MS in an immunocompetent 41-year-old female, who initially manifested with a generalized nonpruritic erythematous rash and systemic symptoms. She was mistreated for generalized impetigo and hepatitis attributed to chronic alcoholism. After partial recovery and a 3-month latent period, she developed infiltrated plaques with crusts on the trunk, head and neck; pharyngitis and laryngeal lesions; generalized lymphadenopathy and nonspecific systemic symptoms. Serologic tests confirmed syphilis, and cerebrospinal fluid analyses indicated the presence of anti-treponemal antibodies. Urine drug screening was positive for cannabinoids. The polymerase chain reaction from skin biopsy samples identified T. pallidum, confirmed with Warthin-Starry staining. Immunohistochemical analysis was uncharacteristic. Tertiary syphilis, neurosyphilis, ocular syphilis and otosyphilis were excluded. However, the patient was treated for neurosyphilis with benzylpenicillin (18 million IU intravenously daily, 14 days) and corticosteroids. No Jarisch-Herxheimer reaction occurred. Ten months after treatment, residual scars were visible, and 1 year later, she attempted suicide. Since MS can resemble other diseases, it should be suspected in a mentally ill patient with chronic drug abuse, systemic nonspecific manifestations and dermatological abnormalities, including the head and neck region.

Enrichment of plasma in platelets and extracellular vesicles by the counterflow to erythrocyte settling.

In order to prepare optimal platelet and extracellular vesicle (EV)-rich plasma for the treatment of chronic temporal bone inflammation, we studied effects of centrifugation parameters on redistribution of blood constituents in blood samples of 23 patients and 20 volunteers with no record of disease. Concentrations of blood cells and EVs were measured by flow cytometry. Sample content was inspected by scanning electron microscopy. A mathematical model was constructed to interpret the experimental results. The observed enrichment of plasma in platelets and EVs after a single spin of blood depended on the erythrocyte sedimentation rate, thereby indicating the presence of a flow of plasma that carried platelets and EVs in the direction opposite to settling of erythrocytes. Prolonged handling time correlated with the decrease of concentration of platelets and larger EVs in platelet and EV-rich plasma (PVRP), R = -0.538, p = 0.003, indicating cell fragmentation during the processing of samples. In further centrifugation of the obtained plasma, platelet and EV enrichment depended on the average distance of the sample from the centrifuge rotor axis. Based on the agreement of the model predictions with observations, we propose the centrifugation protocol optimal for platelet and EV enrichment and recovery in an individual sample, adjusted to the dimensions of the centrifuge rotor, volume of blood and erythrocyte sedimentation rate.[Figure: see text].

Autologous Platelet- and Extracellular Vesicle-Rich Plasma Is an Effective Treatment Modality for Chronic Postoperative Temporal Bone Cavity Inflammation: Randomized Controlled Clinical Trial.

PURPOSE: To determine the efficacy of autologous platelet- and extracellular vesicle-rich plasma (PVRP) to treat chronic postoperative temporal bone cavity inflammation (CPTBCI) after exhausting surgical and standard conservative therapies. MATERIALS AND METHODS: Patients were randomly allocated to treatment with PVRP (PVRP group) or standard conservative methods (control group) in a setting of four once-monthly checkups and subsequent follow-up. The treatment outcome was measured with the Chronic Otitis Media Questionnaire-12 (COMQ-12), CPTBCI focus surface area, and CPTBCI symptom-free time after the fourth checkup. RESULTS: Eleven patients from each group completed the trial; 95% of patients suffered from chronically discharging mastoid cavity (the type of CPTBCI). Within four checkups, the COMQ-12 score decreased statistically significantly in the PVRP group (p < 0.001) but not in the control group (p = 0.339). The CPTBCI foci surface area decreased statistically significantly between the first and second checkups (p < 0.0005) but not between other checkups (p > 0.05) in the PVRP group. No statistically significant differences in CPTBCI foci surface area were detected between checkups in the control group (p = 0.152). Nine patients from the PVRP group and three patients from the control group were CPTBCI symptom-free at the fourth checkup. The median symptom-free time was 9.2 months (95% CI [7.4, 11.9]) in the PVRP group. Cumulatively, 49% of patients in the PVRP group remained CPTBCI symptom-free for 12.7 months after the fourth checkup. CONCLUSION: Autologous PVRP represents a novel additional and successful treatment modality for a chronically discharging radical mastoid cavity when the surgical and standard conservative treatment methods have been exhausted. TRIAL NUMBER: https://clinicaltrials.gov (NCT04281901).

Unraveling the Etiology of Pediatric Vertigo and Dizziness: A Tertiary Pediatric Center Experience.

Background and Objectives: Numerous authors have reported that the commonest type of vertigo in children is migraine-associated vertigo (vestibular migraine and benign paroxysmal vertigo of childhood-BPV). We aimed to provide the possible etiological background of vertigo and dizziness in Slovenian children. Materials and Methods: A retrospective case series of pediatric vertigo and dizziness children referred to the tertiary pediatric otorhinolaryngology center from 2015 to 2020. Children received a complete audiological and vestibular workup and were referred to pediatric specialists depending on the clinical presentation. Results: Of 257 children (42% male, 58% female) aged 1-17 years (M = 10.9, SD = 4.3 years) in 19.1% vertigo and dizziness were classified as central, in 12.4% as a peripheral vestibular, in 10.9% as a hemodynamic, in 5.8% as a psychological and none as visual by pediatric neurologists, otorhinolaryngologists, cardiologists, psychologists or ophthalmologists, respectively. 40.8% (20) children with central vertigo had BPV (7.8% of all children) and 8.2% (4) migrainous vertigo. In 43.6% (112 children), the etiology remained unclassified. Conclusions: After a thorough multidisciplinary workup, the etiology of vertigo and dizziness was unraveled in the majority of children referred to our tertiary otorhinolaryngology center. The most common cause was central; however, in a considerable number, the etiology remained unclassified. The latter could be attributed to the self-limiting nature of vertigo spells. Hence, a child presenting with dizziness and vertigo requires a multidisciplinary approach, in which referral to a neurologist is, in most cases, essential.

The importance of flaps in reconstruction of locoregionally advanced lateral skull-base cancer defects: a tertiary otorhinolaryngology referral centre experience.

BACKGROUND: The aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer. PATIENTS AND METHODS: The retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made. RESULTS: Twelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive. CONCLUSIONS: Favourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.

Slovenian Cross-Cultural Adaptation and Validation of Health-Related Quality of Life Measures for Chronic Otitis Media (COMQ-12), Vertigo (DHI, NVI) and TINNITUS (THI).

PURPOSE: To provide physicians and patients with the tools needed to evaluate patients' problems and health-related quality of life by cross-culturally adapting and validating the Chronic Otitis Media Questionnaire 12 (COMQ-12), the Dizziness Handicap Inventory (DHI), the Neuropsychological Vertigo Inventory (NVI) and the Tinnitus Handicap Inventory (THI). MATERIALS AND METHODS: COMQ-12, DHI, NVI and THI were translated into the Slovenian language and completed by patients treated at our department for chronic otitis media, vertigo or tinnitus. The control group for each questionnaire consisted of healthy volunteers. Internal consistency, test-retest reliability, discriminant validity, diagnostic accuracy and cut-off value were determined for each questionnaire. RESULTS: Test-retest reliability was excellent for DHI (ICC A=0.946) and NVI (p=0.315, ICC A=0.975), good to excellent for COMQ-12 (p=0.680, ICC A=0.858) and satisfactory for THI (p=0.120). Discriminant validity was confirmed for each questionnaire (p>0.05) using the Mann-Whitney U test (COMQ-12, DHI, THI) or the Welch t-test (NVI). COMQ-12 had acceptable (α=0.796) and DHI (α=0.910), NVI (α=0.950) and THI (α=0.924) perfect internal consistency. COMQ-12 and DHI had excellent, NVI acceptable and THI perfect diagnostic accuracy (AUC=0.987, AUC=0.999, AUC=0.781 and AUC=1.000 respectively). Cut-off values determined by Youden's index were 7, 7, 9 and 56 for COMQ-12, THI, DHI and NVI, respectively. CONCLUSION: Slovenian COMQ-12, DHI, NVI and THI are a valid and accurate tool for the diagnosis and measurement of health-related quality of life in patients with chronic otitis media, vertigo and tinnitus. They could aid general practitioners, occupational health specialists, neurologists and otorhinolaryngologists.

The Outcome of Prompt Concomitant Single-Dose High-Concentration Intratympanic and Tapered Low-Dose Oral Systemic Corticosteroid Treatment for Sudden Deafness.

OBJECTIVES: To investigate the efficacy of prompt concomitant corticosteroid treatment with single application of high-concentration intratympanic (IT) dexamethasone and tapered low-dose systemic methylprednisolone of an idiopathic sudden sensorineural hearing loss (ISSNHL). MATERIALS AND METHODS: Between September 2017 and September 2019, 86 adult patients met the criteria for the diagnosis of ISSNHL at baseline evaluation. The patients received immediate concomitant treatment with single high-concentration (24 mg/mL) IT dexamethasone and low-dose (48 mg) oral methylprednisolone for 1 week followed by tapered doses. Improvement in pure-tone average (PTA) and word recognition score (WRS) was determined after 1 and 6 months. RESULTS: A total of 63 patients met the requirements for the analysis. PTA improved in 71% and WRS improved in 59% of patients with ISSNHL. PTA and WRS were statistically significantly different at different time points during the intervention (p<0.0005). Hearing improved in all measured frequencies from 125 to 8000 Hz until the second follow-up. In 65.4% of patients with tinnitus, the WRS has improved compared with 27.3% without tinnitus (p<0.05). In 69.2% of patients without vertigo, the WRS has improved compared with 41.7% with vertigo (p<0.05). CONCLUSION: Prompt concomitant single high-concentration IT and low-dose systemic corticosteroid treatment is efficient in recovering hearing loss and speech discrimination in ISSNHL. Tinnitus positively predicts hearing outcome. Vertigo negatively predicts speech discrimination recovery.

Applicability of extracellular vesicles in clinical studies.

BACKGROUND: Extracellular vesicles (EVs) are submicron cellular fragments that mediate intercellular communication. EVs have in the last decade attracted major interest as biomarkers or platforms for biomarkers of health and disease. To better understand the reasons why despite great expectations and considerable effort, EV-based methods have not yet been introduced into clinical practice, we present a systematic analysis of published results of clinical studies. MATERIALS AND METHODS: Clinical studies on populations of body fluid samples, published from 2010 to including 2015, applying centrifugation of fluid human samples with centrifuge accelerations up to about 25 000 g and flow cytometry for detection of EVs were analysed with respect to statistical significance (p), statistical power (P), clinical significance (CS), defined as the difference between the means divided by the sum of standard deviations, and size of the populations (Nmin ), defined as the number of samples in the smaller group. RESULTS: Final analysis included 65 publications with 716 comparisons reporting 308 (43%) statistically significant differences (P < 0·05), 242 (34%) had statistical power P > 0·8 and 88 (12%) had clinical importance CS > 1·96. None of comparison with CS > 1·96 included populations in which the smaller group consisted of 50 or more samples. CONCLUSIONS: To fulfil claimed expectations for EV-based methods as promising diagnostic tools, more evidence on EV-based mechanisms of diseases should be gathered. Also, the methods of EV harvesting and assessment should be improved to yield better repeatability and thus allow clinical studies with larger number of samples.