[Introduction of fiberoptic endoscopic evaluation of swallowing and increase of the range of indications in our department]. / Fiberoszkóppal végzett funkcionális nyelésvizsgálat bevezetése és indikációs körének kiterjesztése klinikánkon.

Dysphagia is a disease resulting from preparatory or transport disorder of the swallowing process and it is divided into oropharyngeal and esophageal phases according to the site of the lesion. The ear, nose and throat assessment focuses on the oropharyngeal phase, but differential diagnosis, investigation, and treatment of the cause of dysphagia is often a complex task requiring multidisciplinary approach and collaboration. The method of fiberoptic endoscopic evaluation of swallowing (FEES) has been introduced at the Department of Ear, Nose and Throat and Head-Neck Surgery, University of Szeged, enabling the examination of otorhinolaryngological and neurological disorders of swallowing as well as objective analysis of patients' swallowing quality. The fiberoptic endoscopic evaluation of swallowing is a minimally invasive procedure that allows visualization of the oropharyngeal phase of swallowing. It can identify anatomical abnormalities or neurological disorders causing dysphagia, thus playing a significant role in later patient rehabilitation. We hereby present our experiences in examinations of patients who underwent partial laryngectomy and/or pharyngectomy due to head and neck tumors as well as of those who underwent airway surgery duo to upper airway stenosis. Thanks to our collaboration with the Neurology Department, we also share our experiences gained during the examinations of patients struggling with oropharyngeal swallowing problems of various neurological origins. Orv Hetil. 2023; 164(46): 1817-1823.

Extended partial laryngectomy with functional preservation using the rotational crico-thyrotracheopexy.

Objectives: Glottic tumors with infiltration of the anterior/posterior commissure, and lesions with subglottic, cricoid, or cricoarytenoid joint infiltration have been highly controversial in the past, from the perspective of oncological safety. Although conservation laryngeal resection options exist, most are limited by the extent of resection proscribed by the technique and the postoperative functional results. Oncologically speaking, extended vertical hemilaryngectomy is often the optimal solution. However, limited reconstruction methods often compel total laryngectomy. Methods: Eight patients with vocal fold malignancy, which infiltrated the anterior and sometimes the posterior commissure and with subglottic extension and resultant uni/bilateral vocal fold motion impairment, were treated by single stage extended vertical partial laryngectomy with rotational crico-thyrotracheopexy as a functional reconstruction of the laryngeal framework. Patients were evaluated with objective and subjective function tests. Results: Histologic examination demonstrated tumor-free margins in every case. Definitive decannulation was successful in all cases within 2 weeks. All patients had a stable and adequate airway during follow-up and reported socially acceptable voice. Oral feeding was possible in seven patients. Conclusion: Rotational crico-thyrotracheopexy, as a single stage reconstruction technique, is based on well-vascularized, readily available, appropriately shaped local tissues, without significant donor site morbidity or need for long-term stenting to reconstruct large laryngeal defects after extended vertical hemilaryngectomy for advanced unilateral glottic tumors and is applicable even with supra/subglottic invasion or infiltration of the contralateral vocal fold. An adequate airway can be achieved with socially acceptable voice and safe swallowing without compromising oncologic reliability. Level of Evidence: 4 (retrospective case series review).

Quality by design-based optimization of in situ ionic-sensitive gels of amoxicillin-loaded bovine serum albumin nanoparticles for enhanced local nasal delivery.

A recommended first-line acute bacterial rhinosinusitis (ABR) treatment regimen includes a high dose of orally administered amoxicillin, despite its frequent systemic adverse reactions coupled with poor oral bioavailability. Therefore, to overcome these issues, nasal administration of amoxicillin might become a potential approach for treating ABR locally. The present study aimed to develop a suitable carrier system for improved local nasal delivery of amoxicillin employing the combination of albumin nanoparticles and gellan gum, an ionic-sensitive polymer, under the Quality by Design methodology framework. The application of albumin nanocarrier for local nasal antibiotic therapy means a novel approach by hindering the nasal absorption of the drug through embedding into an in situ gelling matrix, further prolonging the drug release in the nasal cavity. The developed formulations were characterized, including mucoadhesive properties, in vitro drug release and antibacterial activities. Based on the results, 0.3 % w/v gellan gum concentration was selected as the optimal in situ gelling matrix. Essentially, each formulation adequately inhibited the growth of five common nasal pathogens in ABR. In conclusion, the preparation of albumin-based nanoparticles integrated with in situ ionic-sensitive polymer provides promising ability as nanocarrier systems for delivering amoxicillin intranasally for local antibiotic therapy.

Genetic Etiology of Nonsyndromic Hearing Loss in Hungarian Patients.

Hearing loss is the most prevalent sensory disorder worldwide. The majority of congenital nonsyndromic hearing loss (NSHL) cases are caused by hereditary factors. Previously, the majority of NSHL studies focused on the GJB2 gene; however, with the availability of next-generation sequencing (NGS) methods, the number of novel variants associated with NSHL has increased. The purpose of this study was to design effective genetic screening for a Hungarian population based on a pilot study with 139 NSHL patients. A stepwise, comprehensive genetic approach was developed, including bidirectional capillary sequencing, multiplex ligation-dependent probe amplification (MLPA), and an NGS panel of 108 hearing loss genes. With our results, a genetic diagnosis was possible for 92 patients. Sanger sequencing and MLPA identified the genetic background of 50% of these diagnosed cases, and the NGS panel identified another 16%. The vast majority (92%) of the diagnosed cases showed autosomal recessive inheritance and 76% were attributed to GJB2. The implementation of this stepwise analysis markedly increased our diagnostic yield and proved to be cost-effective as well.

Tilorone increases glucose uptake in vivo and in skeletal muscle cells by enhancing Akt2/AS160 signaling and glucose transporter levels.

Skeletal muscle plays a major role in whole-body glucose metabolism. Insulin resistance in skeletal muscle is characterized by decreased insulin-stimulated glucose uptake resulting from impaired intracellular trafficking and decreased glucose transporter 4 (GLUT4) expression. In this study, we illustrated that tilorone, a low-molecular-weight antiviral agent, improves glucose uptake in vitro and in vivo. Tilorone increased bone morphogenetic protein (BMP) signaling in C2C12 myoblasts, the transcription of multiple BMPs (BMP2, BMP4, BMP7, and BMP14), Smad4 expression, and the phosphorylation of BMP-mediated Smad1/5/8. The activation of Akt2/AS160 (TBC1D4) signaling, the critical regulator of GLUT4 translocation, was also increased, as well as the levels of GLUT4 and GLUT1, leading to enhanced uptake of the radioactively labeled glucose analog 18 F-fluoro-2-deoxyglucose (18 FDG). However, this excess glucose content did not result in increased ATP formation by mitochondrial respiration; both basal and ATP-linked respiration were diminished, thereby contributing to the induction of AMPK. In differentiated myotubes, AS160 phosphorylation and 18 FDG uptake also increased. Moreover, tilorone administration further increased insulin-stimulated phosphorylation of Akt2 and glucose uptake of myotubes indicating an insulin-sensitizing effect. Importantly, during in vivo experiments, the systemic administration of tilorone resulted in increased 18 FDG uptake of skeletal muscle, liver, and adipose tissue in C57BL/6 mice. Our results provide new perspectives for the treatment of type 2 diabetes, which has a limited number of treatments that regulate protein expression or translocation.

[Subcutaneous and intramuscular heterotopic calcification of the neck 42 years after radiotherapy]. / Subcutan és intramuscularis heterotop kalcifikáció a nyakon 42 évvel a sugárkezelést követoen.

Radiotherapy-induced heterotopic tissue calcification is an exceedingly rare complication in the head and neck region. We report a patient with extensive, radiotherapy-induced, combined subcutaneous and intramuscular, heterotopic calcification of the neck. An 80-year-old male presented with a 2-month history of severe dysphagia and a painful ulcer on the neck 42 years after salvage total laryngectomy following radiotherapy (total dose: 80 Gy) for a T3N0M0 glottic squamous cell carcinoma. We excluded recurrence or secondary malignancy by biopsy and performed computed tomography, which revealed subcutaneous and intramuscular calcification in the area of the skin ulcer and close to the hypopharyngeal wall, moreover, total occlusion of the common carotid and vertebral arteries bilaterally. Surgical correction involved removing the calcified lesions and closure using fasciocutaneous flap transposition. The patient has been asymptomatic for the past 48 months. Radiotherapy plays an essential role in the treatment of patients with head and neck squamous cell carcinoma. Distorted postoperative anatomy, excessive scar formation, radiotherapy-induced fibrosis as well as skin and subcutaneous tissue calcification can present as atypical findings. Orv Hetil. 2023; 164(10): 383-387.

Self-Assembling Injectable Hydrogel for Controlled Drug Delivery of Antimuscular Atrophy Drug Tilorone.

A two-component injectable hydrogel was suitably prepared for the encapsulation and prolonged release of tilorone which is an antimuscular atrophy drug. The rapid (7-45 s, depending on the polymer concentration) in situ solidifications of the hydrogel were evoked by the evolving Schiff-base bonds between the aldehyde groups of modified PVA (4-formyl benzoate PVA, PVA-CHO, 5.9 mol% functionalization degree) and the amino groups of 3-mercaptopropionate chitosan (CHIT-SH). The successful modification of the initial polymers was confirmed by both FTIR and NMR measurements; moreover, a new peak appeared in the FTIR spectrum of the 10% w/v PVA-CHO/CHIT-SH hydrogel at 1647 cm-1, indicating the formation of a Schiff base (-CH=N-) and confirming the interaction between the NH2 groups of CHIT-SH and the CHO groups of PVA-CHO for the formation of the dynamic hydrogel. The reaction between the NH2 and CHO groups of the modified biopolymers resulted in a significant increase in the hydrogel's viscosity which was more than one thousand times greater (9800 mPa·s) than that of the used polymer solutions, which have a viscosity of only 4.6 and 5.8 mPa·s, respectively. Furthermore, the initial chitosan was modified with mercaptopropionic acid (thiol content = 201.85 ± 12 µmol/g) to increase the mucoadhesive properties of the hydrogel. The thiolated chitosan showed a significant increase (~600 mN/mm) in adhesion to the pig intestinal membrane compared to the initial one (~300 mN/mm). The in vitro release of tilorone from the hydrogel was controlled with the crosslinking density/concentration of the hydrogel; the 10% w/v PVA-CHO/CHIT-SH hydrogel had the slowest releasing (21.7 h-1/2) rate, while the 2% w/v PVA-CHO/CHIT-SH hydrogel had the fastest releasing rate (34.6 h-1/2). Due to the characteristics of these hydrogels, their future uses include tissue regeneration scaffolds, wound dressings for skin injuries, and injectable or in situ forming drug delivery systems. Eventually, we hope that the developed hydrogel will be useful in the local treatment of muscle atrophy, such as laryngotracheal atrophy.

Peritonsillar abscess: an 8-year retrospective, culture based evaluation of 208 cases.

Introduction. Peritonsillar abscess (PTA) is a common infection which requires surgical intervention and suitable antibiotic therapy.Hypotheses/Gap Statement. Beside Streptococcus pyogenes and Fusobacterium necrophorum several other mostly anaerobic bacteria can be cultured from the properly taken pus samples of PTA, the clinical significance of which is still not fully understood.Aim. This study focused on the culture-based microbiological evaluation of PTA cases, compared to surgical intervention and empirical antibiotic management.Methodology. A retrospective analysis of PTA cases was performed between 2012 and 2019. Data about the aerobic and anaerobic culture results of the samples taken during different surgical interventions were summarized and the coverage of the empirically selected antibiotics was evaluated. The patient's history, the development of complications and the recurrence rate were also evaluated.Results. The microbiological culture results were available for 208 of 320 patients with clinically diagnosed PTA. Incision and drainage (I and D) and immediate tonsillectomy were the leading surgical interventions. Ninety-five Fusobacterium species (including 44 Fusobacterium necrophorum), 52 Actinomyces species and 47 Streptococcus pyogenes were obtained from PTA samples alone or together with polymicrobial flora. S. pyogenes (33.7 %, n=28) and F. necrophorum (22.9 %, n=19) were the dominating pathogens in the 83 monobacterial PTA samples. In >60 % of the patients polymicrobial infection was demonstrated, involving a great variety of anaerobic bacteria. In 22 out of 42 cases where intravenous cefuroxime was empirically started, the therapy should be changed to properly cover the culture-proven anaerobic flora. There were no serious complications, abscess recurrence was detected in two cases (0.96 %).Conclusion. PTAs are often polymicrobial infections including a great variety of anaerobes. Targeted antibiotic therapy, in conjunction with adequate surgical drainage eliminating the anaerobic milieu, can accelerate the healing process and radically reduce the complication and recurrence rate.

[Minimally invasive surgery for motility disorders of the oesophagus]. / A nyelocso motilitási betegségeinek minimálisan invazív sebészete

Introduction and aims. We present our experience with minimally invasive surgery for pharyngoesophageal (Zenker) diverticulums, epiphrenic diverticulums and achalasia cardiae focusing on the perioperative features and patients' quality of life. Patients and methods. Between 1 January 2003 and 31 December 2020, patients were selected with a symptom-causing Zenker diverticulum, epiphrenic diverticulum and achalasia cardiae. In 17 cases, transoral stapler diverticulostomy, in 23 cases transcervical diverticulectomy and cricomyotomy were done because of Zenker diverticulum, in 14 cases, laparoscopic transhiatal surgery was performed because of epiphrenic diverticula, while in 63 cases, laparoscopic Heller­Dor operation were carried out because of achalasia cardiae. Perioperative results, the quality of life outcomes of various surgeries were evaluated in mid- and long-term. Results/conclusions. The surgeries were performed with minimal blood loss, zero mortality and low morbidity. According to our result, the two different surgical approaches in the therapy of Zenker's diverticulum, the laparoscopic Heller­Dor procedure applied in the management of epiphrenic diverticulas and achalasia cardiae are safe and effective operations. In the long term, the symptom control in patients after minimally invasive surgeries is sufficient and only a small percentage of the patients may require additional medication therapy and/or reintervention due to persistent complaints.

Use of Self-Assembled Colloidal Prodrug Nanoparticles for Controlled Drug Delivery of Anticancer, Antifibrotic and Antibacterial Mitomycin.

Herein we present the synthesis of a polymeric prodrug nanomaterial capable of spontaneous, self-assembled nanoparticle formation and of the conjugation (encapsulation) of drugs with amino and/or carboxyl and/or hydroxyl groups via ester and/or amide linkage. Mitomycin C (MMC) a versatile drug with antibiotic, antibacterial and antineoplastic properties, was used to prove this concept. The in vitro drug release experiments showed a fast release for the pure MMC (k = 49.59 h-n); however, a significantly lower MMC dissolution rate (k = 2.25, 1.46, and 1.35 h-n) was obtained for the nanoparticles with increased cross-link density (3, 10, 21%). The successful modification and conjugation reactions were confirmed using FTIR and EDX measurements, while the mucoadhesive properties of the self-assembled particles synthesized in a simple one-pot reaction were proved by rheological measurement. The prepared biocompatible polymeric prodrugs are very promising and applicable as a drug delivery system (DDS) and useful in the area of cancer treatment.

A new method of preoperative assessment of correct electrode array alignment based on post-operative measurements in a cochlear implanted cohort.

PURPOSE: During cochlear implantation surgery, a range of complications may occur such as tip fold-over. We recently developed a method to estimate the insertion orientation of the electrode array. The aim of the study was to determine the optimal angle of orientation in a cohort of cochlear implanted patients. METHODS: On eighty-five CT scans (80 uncomplicated insertions and 5 cases with tip fold-over), location of the electrode array's Insertion Guide (IG), Orientation marker (OM) and two easily identifiable landmarks (the round window (RW) and the incus short process (ISP)) were manually marked. The angle enclosed by ISP-RW line and the Cochlear™ Slim Modiolar electrode array's OM line determined the electrode array insertion angle. RESULTS: The average insertion angle was 45.0-47.2° ± 10.4-12° SD and was validated with 98% confidence interval. Based on the measurements obtained, patients' sex and age had no impact on the size of this angle. Although the angles of the tip fold-over cases (44.9°, 46.9°, 34.2°, 54.3°, 55.9°) fell within this average range, the further it diverted from the average it increased the likelihood for tip fold-over. CONCLUSION: Electrode array insertion in the individually calculated angle relative to the visible incus short process provides a useful guide for the surgeon when aiming for the optimal angle, and potentially enhances good surgical outcomes. Our results show that factors other than the orientation angle may additionally contribute to failures in implantation when the Slim Modiolar electrode is used.

Postoperative respiratory complications in children with obstructive sleep apnoea syndrome.

Objective: We aimed to prospectively assess the effect of comorbidities on the occurrence of postoperative respiratory complications (PoRCs) after adenotonsillectomy in children with obstructive sleep apnoea syndrome (OSA) and whether otherwise healthy children need a higher level of postoperative monitoring. Methods: 577 children who had OSA and underwent adenotonsillectomy were enrolled. The effects of demographics, comorbidities and OSA on PoRCs were investigated with logistic regression analysis. Results: The PoRC rate was 4.3%. Postoperative oxygen desaturations were more marked in patients with comorbidities (p = 0.005). The presence of comorbidity increased the risk of PoRCs (odds ratio 4.234/3.226-5.241, 95% confidence intervals, p < 0.001). There was no difference in apnoea-hypopnoea index (AHI) values between comorbid patients with and without PoRCs [8.2 (3.8-50.2) vs 14.3 (11.7-23.3)]. (p = 0.37). In the group of patients without comorbidities, PoRCs were associated with a higher AHI [14.7 (3.4-51.3) vs 3.9 (2.0- 8.0), p < 0.001]. Conclusions: Comorbidities are more closely linked with PoRCs than OSA severity. In patients without comorbidity, PoRCs are associated with OSA severity and usually occur within the first 2 hours after the intervention.

Long-term results of slide laryngotracheoplasty for congenital subglottic stenosis in newborns and infants.

OBJECTIVES: Slide laryngotracheoplasty is an effective, single-step procedure without tracheostomy and stenting for treating high-grade congenital subglottic stenosis in neonates and infants. Long-term outcomes were evaluated to assess the reliability of the procedure performed in this age of rapid development of the laryngeal structures. METHODS: We report five children who underwent slide laryngotracheoplasty before the age of 4 months, each with >3 years follow-up. Increases of length and bodyweight were systematically assessed. Breathing, swallowing, voice, and overall satisfaction was assessed by a quality of life questionnaire. Voice quality was objectively evaluated by measuring shimmer, jitter, fundamental frequency, and the harmonics-to-noise ratio. RESULTS: All patients had a stable and adequate airway during follow-up without any additional open airway surgery. The patients' voices were physiological, and the intervention had no negative impact on speech development. Swallowing function was optimally retained, and the patients' bodyweight gain and length were satisfactory. During at least 3 years of observation, the anastomosis remained stable and grew dynamically with the patient. CONCLUSIONS: Slide laryngotracheoplasty (as a single-step procedure) provides an adequate airway without tracheostomy, grafting, or stenting with good long-term functional results in selected neonates and infants with congenital subglottic stenosis.

Application of a modified Kleinsasser laryngoscope in two cases / Módosított Kleinsasser-laringoszkóp bemutatása két eset kapcsán

In cases of transoral laryngeal and hypopharyngeal surgeries, the exploration of these relatively narrow anatomical regions is paramount. The conventional operational endoscopes allow the visualization of the surgical field, but - due to their structure - are not optimal regarding the coordination and simultaneous moving of microsurgical instruments. Furthermore, the relatively great distance between the surgical microscope and the endoscope has a negative impact on the illumination of the surgical area and the physical characteristics of the laser beam. The authors introduce a modified laryngoscope used in the field of laryngeal and hypopharyngeal surgery. The openings in the sides of the endoscope allow the lateral insertion of microsurgical devices, while the distance between the microscope and the target area can be significantly reduced. The endoscope is presented in addition to a tongue base and a glottic surgery. The introduced operational endoscope allows optimal exploration of the area of interest, the free and simultaneous moving of the microsurgical instruments, and the optimal usage of the laser beam.

Pediatric morphometric study to guide the optimized implantation of the Osia® 2 implant system.

PURPOSE: Continuous technological advances result in the availability of new bone conduction hearing implants, of which their suitability for pediatric patients is of major concern. The CochlearTMOsia® 2 is a new active osseointegrated steady-state implant system that uses digital piezoelectric stimulation to treat hearing loss. The implant in the United States was approved for patients aged 12 years and above, whereas the CE mark is independent of age, the only requirement is body weight of at least 7 kg. Therefore, further clinical studies are required to assess device characteristics in younger patients. The aim of our study was to perform a morphometric study among 5-12-year-old children, and to develop a surgical protocol for Osia 2 system implantation based on these findings. METHODS: We examined retrospectively cranial CT scans of 5-12-year-old patients from our clinical database. We measured the bone and soft-tissue thickness in the region of interest, and the position of the sigmoid sinus. 3D printed temporal bones were also used for planning. RESULTS: Soft-tissue thickness varied between 3.2 ± 0.5 mm and 3.6 ± 0.6 mm and bone thickness varied between 3.5 ± 1.1 mm and 4.7 ± 0.3 mm. The sigmoid sinus was located 1.3 ± 0.2 cm posterior to the ear canal, and the anterior distance was 4.8 ± 0.9 to 7.1 ± 1.1 mm. CONCLUSIONS: Our morphometric studies showed that patients aged 5-12 have different anatomical dimensions compared to adults, but that implantation of the Osia 2 system is feasible in these patients using an altered implant positioning recommended by our data. The Cochlear™ Osia® 2 is, therefore, an option for hearing rehabilitation in younger pediatrics.

Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors.

Skeletal muscle demonstrates a high degree of regenerative capacity repeating the embryonic myogenic program under strict control. Rhabdomyosarcoma is the most common sarcoma in childhood and is characterized by impaired muscle differentiation. In this study, we observed that silencing the expression of syndecan-4, the ubiquitously expressed transmembrane heparan sulfate proteoglycan, significantly enhanced myoblast differentiation, and fusion. During muscle differentiation, the gradually decreasing expression of syndecan-4 allows the activation of Rac1, thereby mediating myoblast fusion. Single-molecule localized superresolution direct stochastic optical reconstruction microscopy (dSTORM) imaging revealed nanoscale changes in actin cytoskeletal architecture, and atomic force microscopy showed reduced elasticity of syndecan-4-knockdown cells during fusion. Syndecan-4 copy-number amplification was observed in 28% of human fusion-negative rhabdomyosarcoma tumors and was accompanied by increased syndecan-4 expression based on RNA sequencing data. Our study suggests that syndecan-4 can serve as a tumor driver gene in promoting rabdomyosarcoma tumor development. Our results contribute to the understanding of the role of syndecan-4 in skeletal muscle development, regeneration, and tumorigenesis.

Open, prospective, multicenter study on postoperative intranasal phototherapy in nasal polyposis.

BACKGROUND: The therapeutic effect of ultraviolet (UV) light is generally attributed to its immunosuppressive and immunomodulatory effects. Since chronic inflammation is the major factor in the development of nasal polyposis, we have previously used mixed ultraviolet-visible light (mUV-VIS, Rhinolight®) phototherapy for the treatment of nasal polyps. AIMS: In the present open, multicenter study, our aim was to delineate whether mUV-VIS applied postoperatively in vivo together with intranasal steroid treatment could reduce the recurrence of nasal polyps. METHODS: After functional endoscopic sinus surgery, one group of patients received mUV-VIS light together with standard intranasal steroid (mometason furoate 2 × 200 µg) application for a 12-week treatment period, whereas the other patient group obtained only intranasal steroid for the same duration. We recorded nasal endoscopy images and obtained demographical and clinical data, total nasal score (TNS), and nasal obstruction symptom evaluation (NOSE). We performed acoustic rhinometry and measured nasal inspiratory peak flow. Follow-up was 12 months. RESULTS: We found that the recurrence of nasal polyps was significantly diminished, and based on video-endoscopic measurements, the size and grade of recurrent polyps were significantly smaller in the phototherapy-receiving group. Nasal obstruction values and NOSE were significantly better throughout the follow-up period in the mUV-VIS light-treated group than in the intranasal steroid monotreatment group. CONCLUSIONS: Rhinophototherapy together with standard nasal steroid application may have a supportive role in the treatment of recurrent bilateral nasal polyps.