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A Kikuchi–Fujimoto-betegség (histiocytás nekrotizáló lymphadenitis) egy autolimitált folyamat, melynek kiváltó tényezőihez soroljuk az Epstein–Barr-vírust, a humán herpeszvírust, a HIV-et, a B19 parvovírust, a paromyxovirusokat, a SARS-CoV-2-t, illetve a Toxoplasmát és a Yersiniát. A pontos diagnózis felállításához elengedhetetlen a nyirokcsomó-biopszia, melyet szövettani vizsgálat követ. Egy 45 éves nőbeteg igazolt SARS-CoV-2-fertőzést követően egyoldali nyaki nyirokcsomó-megnagyobbodással, lázzal, rekedtséggel, illetve nyelési nehezítettséggel érkezett ambulanciánkra. SARS-CoV-2-fertőzése a tünetek megjelenése előtt 1 hónappal kettős pozitív (orrgarati) gyorsteszt formájában került bizonyításra, melyet 2 hetes otthoni karantén követett. Felszabadító teszt nem készült, az ambulanter vizsgálat előtt végzett COVID–19 orrgarati gyorsteszt negatív eredményt produkált. A fizikális status felmérését osztályos felvétel követte, melynek során intravénás antibiotikumterápia indult (Augmentin, 3 × 1,2 g; Klion, 2 × 100 mg) szteroidterápiával párhuzamosan (Solu-Medrol, 2 × 125 mg). A nyaki-mellkasi CT jobb oldali retropharyngealis tályogot írt le, nyaki nyirokcsomó-megnagyobbodással párhuzamosan. Sürgős tracheotomiát, illetve nyaki feltárást végeztünk nyirokcsomó-biopsziával egybekötve. A feltárás során tályogra utaló jelet nem találtunk. A szövettani vizsgálat nekrotizáló lymphadenitist igazolt. Annak ellenére, hogy a betegség autolimitált, látható, hogy a fenti esetben a SARS-CoV-2-fertőzést követően kialakuló nyaki lymphadenopathia életet veszélyeztető állapot okozott, mely miatt légcsőmetszés, nyaki feltárás, illetve nyirokcsomó-biopszia volt szükséges a beteg állapotának javulásáért és betegségének pontos tisztázásáért. A kialakult szöveti exsudatum nyaki tályog képét utánozta a CT-felvételeken. Az általunk felkeresett, nagyszámú szakirodalmi közleményben hasonló beavatkozás nem került leírásra. A nyaki feltárás, a tracheotomia, illetve a nyaki nyirokcsomóknak mint ,,trigger” zónáknak az eltávolítása jelen esetünkben a teljes gyógyulást eredményezte. Fontos a SARS-CoV-2, illetve a Kikuchi–Fujimoto-betegség korrelációjának további megerősítése, pontosabb tisztázása. Orv Hetil. 2022; 163(27): 1061–1065.

Összefoglaló. A lateralis cysticus nyaki terimék két leggyakoribb oka a branchiogen cysta és a cysticus nyaki áttét. Az átfedő lokalizáció (a leggyakrabban a IIA nyaki régióban), a betegek életkora és az esetenként hirtelen kezdet alapján a két leggyakoribb ok differenciáldiagnózisa nagy kihívást jelenthet. Egy hirtelen fellépő fájdalmas, bal oldali nyaki duzzanattal, dysphagiával és lázzal jelentkező 72 éves férfi esetét ismertetjük. A nyak komputertomográfiás vizsgálata egy 6 cm legnagyobb átmérőjű, vastag falú, többrekeszes cysticus terimét igazolt. Infektív branchiogen cysta lehetőségére gondolva az elváltozást eltávolítottuk. A szövettan azonban p16-pozitív laphámrákot igazolt. A primer tumort végül az ipsilateralis tonsilla palatina állományában sikerült azonosítani. A beteg definitív radioterápiában részesült, és 18 hónappal a diagnózis után tumormentes. A nyaki cystákon, az infektív nyaki cystákon és a cysticus metastasisokon kívül a humán papillómavírussal összefüggő szájgarati laphámrákok infektív cysticus vagy necroticus metastasisait is figyelembe kell venni a lateralis cysticus nyaki terimék differenciáldiagnózisában. Orv Hetil. 2020; 162(15): 595–600. Summary. Branchial cleft cysts and cystic neck metastases are the two most common causes of cystic lateral neck masses. Based on the overlapping location (neck level IIA), patient age at onset and the occasionally sudden onset, their differential diagnosis is challenging. We present a 72-year-old male presenting with a suddenly emerging painful, left-sided neck swelling, dysphagia and fever. Computed tomography showed a 6 cm thick-walled multicystic mass. With the suspected diagnosis of an infected branchial cleft cyst, the lesion was removed. Histology confirmed p16 positive squamous cell carcinoma. Primary tumor was identified in the ipsilateral palatine tonsil. Definive radiotherapy was performed and the patient is free of disease at the 18-month follow-up. Beyond pure and infected branchial cleft cysts and pure cystic metastases, infected cystic or necrotic metastasis of human papillomavirus associated oropharyngeal squamous cell carcinoma should be included in the differential diagnosis of cystic lateral neck lesions. Orv Hetil. 2021; 162(15): 595–600.

The Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) is an autolimited process, which can be caused by viral agents like Epstein-Barr virus, human herpes virus, HIV, B19 parvovirus, paromyxoviruses, SARS-CoV-2, Toxoplasma and Yersinia. The correct diagnosis is based on histological findings. A 45-year-old female patient presented in our ambulatory room with a unilateral neck mass, fever, dysphonia and dysphagia. The patient was double-tested positive for SARS-CoV-2 approximately 1 month before the symptoms started. Before examination, the nasopharyngeal rapid test for SARS-CoV-2 resulted negative. After hospitalization, intravenous antibiotic (Augmentin, 3 x 1.2 g; Klion, 2 x 100 mg) and steroid (Solu-Medrol, 2 x 125 mg) therapy were administered. The neck and chest CT described a right-sided retropharyngeal abscess with bilateral neck lympadenopathy. Urgent tracheotomy, neck dissection and lymph node biopsy were made. The intraoperative findings excluded the presence of the abscess. The histological findings confirmed the necrotizing histiocytic lymphadenitis. Despite of the fact that the Kikuchi-Fujimoto disease is autolimited, we can see that, in this particular case, the lymphadenopathy after the SARS-CoV-2 infection caused a life-threatening situation. The formed extratissular liquid imitated the image of a retropharyngeal abscess. In the searched worldwide literature, similar intervention for this type of process was not described. Tracheotomy, neck dissection and removing the lymph nodes as ,,trigger zones used the full recovery of the patient. In the future, we consider important proving and clarifying the correlation between SARS-CoV-2 and Kikuchi-Fujimoto disease.A Kikuchi–Fujimoto-betegség (histiocytás nekrotizáló lymphadenitis) egy autolimitált folyamat, melynek kiváltó tényezőihez soroljuk az Epstein–Barr-vírust, a humán herpeszvírust, a HIV-et, a B19 parvovírust, a paromyxovirusokat, a SARS-CoV-2-t, illetve a

Absztrakt: A Parry–Romberg-szindróma ritka, lassan progrediáló, autolimitált betegség, melyet unilateralis arcfélatrophia jellemez. Általában gyerek-, fiatal felnőtt korban manifesztálódik. Az atrophia mértékének, illetve a társuló egyéb tünetek változatosságának következtében a betegség diagnózisa, a prognózis megítélése és a kezelés nagy kihívást jelent. Az esetbemutatás célja rávilágítani a diagnózis felállításának nehézségeire, bemutatni a beteg kivizsgálásának lépéseit, felhívni a figyelmet a műtét megfelelő időzítésének fontosságára, a hemifacialis atrophia mértékének megfelelő műtét kiválasztására, illetve a szindrómával gyakran előforduló betegségek keresésére. Orv Hetil. 2020; 161(28): 1181–1185.

Absztrakt: A szemgödörbe került idegen testek műtéti eltávolítására, az ezek során kialakult komplikációk kezelésére, illetve gyógyítására jelenleg Magyarországon nincs protokoll. Annak ellenére, hogy sokszor több szakma bevonása szükséges, orbitasebészeti centrum országosan nem került kialakításra. Kettős esetbemutatásunk célja rávilágítani a fenti esetek fontosságára, műtéti szemlélet kialakítására, illetve az esetleges komplikációk felismerésére, megoldására legfőképp szerves idegen testek esetén olyan esetben is, ha több fej-nyaki anatómiai régió érintett, létfontosságú szervekkel együtt. Orv Hetil. 2020; 161(21): 889–894.

Absztrakt: Az otosclerosis kizárólag az emberi temporalis csontban előforduló csontanyagcsere-megbetegedés, mely apró, gócszerű csontlaesiókat hoz létre az oticus kapszulában. A betegség tünetei leginkább a gócok elhelyezkedésétől függenek. Így, klinikai szempontból, a leginkább releváns a stapestalp fixációjával járó stapedialis otosclerosis, amely a legtöbbször jelentős fokú vezetéses hallászavarral jár. Sok esetben már az anamnesztikus adatok jellegzetességéből, a beteg életkorából és a fizikális vizsgálat semmitmondó leleteiből következtethetünk a stapesfixáció valószínűségére. Jóllehet preoperatív diagnózisunkat audiológiai tesztekkel, VEMP-vizsgálattal és különféle képalkotókkal tovább pontosíthatjuk, 100%-os diagnózist csak a műtét során eltávolított stapestalpak szövettani verifikálásával nyerhetünk. Orv Hetil. 2019; 160(51): 2007–2011.

Abstract: Introducing the diagnostic protocol and therapy of a rare disease reviewing the worldwide literature named as vagal paraganglioma is our main target. This type is specific for women of middle age, and it is appearing as a unilateral neck mass, with or without Fontaine’s sign. Giving a heavy aspect on the ear, nose and throat examination, the most important diagnostic tool is CT-angiography. Carefully looking at the size and relationship with the narrowing arteries, veins, nerves, muscles and bony structures (skull base, cervical spine), in most of the cases we choose the surgical procedure. Orv Hetil. 2019; 160(34): 1358–1362.

Abstract: Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular disease with a worldwide prevalence of 1 : 5000 – 1 : 10 000. Diagnosis is based on clinical Curacao criteria. Approximately 85% of HHT cases have heterozygous family-specific mutations in the ENG or ACVRL1 genes. Aim: We investigated 23 Hungarian HHT families, established the genetic diagnosis, executed family-screening and confirmed founder effects. Method: Probands were identified by the stratified population screening of the primary attendance area of our institution and from individuals contacting our study group voluntarily. Diagnosis is based on the otorhinolaryngological physical examination completed with characteristic telangiectasis sites, a visceral arteriovenous malformation screening and the sequence analysis of ENG and ACVRL1 genes. The family screening consists of physical examination and genetic screening for the family-specific mutation, followed by the arteriovenous malformation screening in patients with definite/suspected HHT and/or in individuals with the mutation. Results: Sixty-three individuals with family-specific mutations were identified in 22 families, 48 of them with definite and 12 with suspected HHT. Seven ENG and ACVRL1 mutations were detected, respectively; most of these are pathogenic. Three founder mutations were observed. One proband with definite HHT had wild-type alleles in all tested HHT-specific loci. Conclusions: The significance of genetic testing is confirming or excluding HHT in young asymptomatic individuals in families with pathogenic mutations. As ENG and ACVRL1 mutations result in overlapping fenotypes, the genetic testing lacks any prognostic value. The identification of founder effects might simplify the genetic diagnosis of new HHT patients from a given region. Orv Hetil. 2019; 160(18): 710–719.

Összefoglaló. A lateralis cysticus nyaki terimék két leggyakoribb oka a branchiogen cysta és a cysticus nyaki áttét. Az átfedő lokalizáció (a leggyakrabban a IIA nyaki régióban), a betegek életkora és az esetenként hirtelen kezdet alapján a két leggyakoribb ok differenciáldiagnózisa nagy kihívást jelenthet. Egy hirtelen fellépő fájdalmas, bal oldali nyaki duzzanattal, dysphagiával és lázzal jelentkező 72 éves férfi esetét ismertetjük. A nyak komputertomográfiás vizsgálata egy 6 cm legnagyobb átmérőjű, vastag falú, többrekeszes cysticus terimét igazolt. Infektív branchiogen cysta lehetőségére gondolva az elváltozást eltávolítottuk. A szövettan azonban p16-pozitív laphámrákot igazolt. A primer tumort végül az ipsilateralis tonsilla palatina állományában sikerült azonosítani. A beteg definitív radioterápiában részesült, és 18 hónappal a diagnózis után tumormentes. A nyaki cystákon, az infektív nyaki cystákon és a cysticus metastasisokon kívül a humán papillómavírussal összefüggő szájgarati laphámrákok infektív cysticus vagy necroticus metastasisait is figyelembe kell venni a lateralis cysticus nyaki terimék differenciáldiagnózisában. Orv Hetil. 2020; 162(15): 595-600. Summary. Branchial cleft cysts and cystic neck metastases are the two most common causes of cystic lateral neck masses. Based on the overlapping location (neck level IIA), patient age at onset and the occasionally sudden onset, their differential diagnosis is challenging. We present a 72-year-old male presenting with a suddenly emerging painful, left-sided neck swelling, dysphagia and fever. Computed tomography showed a 6 cm thick-walled multicystic mass. With the suspected diagnosis of an infected branchial cleft cyst, the lesion was removed. Histology confirmed p16 positive squamous cell carcinoma. Primary tumor was identified in the ipsilateral palatine tonsil. Definive radiotherapy was performed and the patient is free of disease at the 18-month follow-up. Beyond pure and infected branchial cleft cysts and pure cystic metastases, infected cystic or necrotic metastasis of human papillomavirus associated oropharyngeal squamous cell carcinoma should be included in the differential diagnosis of cystic lateral neck lesions. Orv Hetil. 2021; 162(15): 595-600.

Parry-Romberg syndrome is a rare, slowly progressive, autolimitated disease, characterized by unilateral facial atrophy. It is usually manifested in childhood and young adulthood. Because of the degree of atrophy and the variety of symptoms, the diagnosis, prognosis, and treatment of Parry-Romberg syndrome are a major challenge. The purpose of this case presentation is to highlight the difficulty of establishing the diagnosis, furthermore, to present the steps of examining the patient and to draw attention to the importance of proper timing of the surgery. Moreover, it wants to emphasize the importance of looking for diseases that often occur with the mentioned syndrome. Orv Hetil. 2020; 161(28): 1181-1185.

The surgical procedure of orbital foreign bodies with its complications is not yet solved in Hungary. Despite the fact that many specialities are involved, until the present day, an orbital surgical centre was not developed. The main goal of this case report is to highlight the importance of these events, to develop a surgical approach, to recognize and solve the complications if they are present even in the cases of organic foreign bodies affecting more head and neck anatomical regions and structures. Orv Hetil. 2020; 161(21): 889-894.

Otosclerosis is a bone remodeling disorder affecting exclusively the human temporal bone which causes small bony lesions in the otic capsule. The symptoms depend on the location and the extent of the otosclerotic foci. Hence, clinically the most relevant sign is the conductive hearing loss due to the stapedial otosclerosis with fixation of the stapes footplate. In many cases, the specific anamnestic features, the age of presentation and usually the absence of tympanic membrane pathology can provide a strong clinical suspicion for otosclerosis. Although audiometric and imaging examinations and VEMP testing can confirm our preoperative diagnosis, the histolopathologic examination of the removed stapes footplate is the most accurate way to determine the diagnosis. Orv Hetil. 2019; 160(51): 2007-2011.Absztrakt: Az otosclerosis kizárólag az emberi temporalis csontban előforduló csontanyagcsere-megbetegedés, mely apró, gócszerű csontlaesiókat hoz létre az oticus kapszulában. A betegség tünetei leginkább a gócok elhelyezkedésétől függenek. Így, klinikai szempontból, a leginkább releváns a stapestalp fixációjával járó stapedialis otosclerosis, amely a legtöbbször jelentős fokú vezetéses hallászavarral jár. Sok esetben már az anamnesztikus adatok jellegzetességéből, a beteg életkorából és a fizikális vizsgálat semmitmondó leleteiből következtethetünk a stapesfixáció valószínűségére. Jóllehet preoperatív diagnózisunkat audiológiai tesztekkel, VEMP-vizsgálattal és különféle képalkotókkal tovább pontosíthatjuk, 100%-os diagnózist csak a műtét során eltávolított stapestalpak szövettani verifikálásával nyerhetünk. Orv Hetil. 2019; 160(51): 2007–2011.

Abstract: Otosclerosis can be found exclusively in the human otic capsule of the temporal bone. Its etiology is still unknown. In the past decades, several potential etiopathogenetic factors have been revealed, however, most studies were based on otosclerotic patients diagnosed by clinical symptoms only. The current experience indicates that one third of this group suffer from non-otosclerotic stapes fixation. In our experimental series, we have diagnosed and classified otosclerotic patients based on histologic examination, and analyzed also the pathogenetic factors. Recent data demonstrate that measles virus and rs1800472 SNP of transforming growth factor beta 1 (TGFβ1) gene are marked obvious etiologic factors, which have no therapeutic consequences so far. Furthermore, we summarize the genetic and environmental factors to be found in the literature, which may play a fundamental role in the pathogenesis of otosclerosis. Orv Hetil. 2018; 159(30): 1215–1220.

Carotid body tumors (CBTs) are rare types of extra-adrenal paragangliomas, which originate from the neuroendocrine cells of the adventitial layer of carotid bifurcation. An 8-year-old girl was admitted to our department with left-sided and pulsating neck swelling, which progressively grew over several months. The patient had no family history of CBTs. Computed tomography (CT) and CT angiography (CTA) scans revealed a contrast material enhancing, hypervascularized mass involving the left carotid bifurcation, internal carotid artery (ICA), and external carotid artery (ECA), respectively. Preoperative embolization and surgical resection were performed. Histopathological examination later confirmed a benign CBT. Current follow-up examination revealed no evidence of residual or recurrent tumor. A systemic review of the literature indicates that early diagnosis, and experienced multi-disciplinary management is required in case of unilateral, resectable forms of CBTs with no distant metastasis, in order to provide a long-time survival of patients. Surgical intervention of unilateral, solitary CBTs with preoperative embolization is a relatively safe procedure, allowing complete tumor removal with minimal morbidity and low recurrence rate.

Hereditary haemorrhagic telangiectasia (HHT; Osler–Weber–Rendu disease) is an autosomal dominant vascular disease characterized by nosebleeds, mucocutaneous telangiectases, visceral arteriovenous malformations (AVM) and a first-degree relative with HHT. Diagnosis is definite if three or four criteria are present. This case report describes a 19-year-old male with incidentally detected polycythaemia and an associated soft-tissue opacity over the left lower lobe on his frontal chest radiogram. He had experienced dyspnoea on exertion since infancy and clubbing at physical examination. Polycythaemia vera, chronic obstructive pulmonary disease, sleep apnoea and cyanotic congenital heart disease were excluded. Chest computed tomography (CT) was initially refused by the patient, but 3 years later he presented with severe epistaxis. Considering the unvarying soft tissue mass and erythrocytosis, an HHT-associated pulmonary AVM (PAVM) was eventually confirmed by chest CT. A pathogenic family-specific ENG c.817-2 A>C mutation was detected in the patient. The large PAVM was successfully treated using AMPLATZER™ vascular plug embolization. A combination of the multisystemic nature of his symptoms, the age-related penetrance of HHT symptoms and insufficient patient compliance delayed the diagnosis of HHT in this current case.

Introducing the diagnostic protocol and therapy of a rare disease reviewing the worldwide literature named as vagal paraganglioma is our main target. This type is specific for women of middle age, and it is appearing as a unilateral neck mass, with or without Fontaine's sign. Giving a heavy aspect on the ear, nose and throat examination, the most important diagnostic tool is CT-angiography. Carefully looking at the size and relationship with the narrowing arteries, veins, nerves, muscles and bony structures (skull base, cervical spine), in most of the cases we choose the surgical procedure. Orv Hetil. 2019; 160(34): 1358-1362.Absztrakt: Esetbemutatásunkban a világviszonylatban is ritkának számító glomus vagale tumorok kivizsgálásáról, terápiájáról adunk összefogó képet. A jellemzően középkorú nőket érintő betegség unilaterálisan elhelyezkedő nyaki tumoros elváltozás képében jelenik meg, melyre nem minden esetben jellemző a felette érezhető pulzáció (Fontaine-jel), a glomus caroticum tumorokkal szemben. Nagy hangsúlyt fektetve a fül-orr-gégészeti fizikális vizsgálatra, a betegség pontos diagnózisát a CT-angiográfia adja meg. Figyelembe véve a kiterjedést, a szomszédos erekhez, idegekhez, izmokhoz, illetve csontszerkezetű képletekhez (koponyaalap, nyaki gerinc) való viszonyt, az esetek nagy részében sebészi beavatkozás mellett döntünk. A bemutatott beteg kezelése 2017 szeptemberében történt Osztályunkon. Orv Hetil. 2019; 160(34): 1358–1362.

Absztrakt

Roma are a socially and culturally distinct isolated population with genetically divergent subisolates, residing mainly across Central, Southern, and Eastern Europe. We evaluated the genetic etiology of hearing impairment (HI) in 15 Hungarian Roma families through exome sequencing. A family with autosomal dominant non-syndromic HI segregating a rare variant in the Calponin-homology 2 domain of PLS1, or Plastin 1 [p.(Leu363Phe)] was identified. Young adult Pls1 knockout mice have progressive HI and show morphological defects to their inner hair cells. There is evidence that PLS1 is important in the preservation of adult stereocilia and normal hearing. Four families segregated the European ancestral variant c.35delG [p.(Gly12fs)] in GJB2, and one family was homozygous for p.(Trp24*), an Indian subcontinent ancestral variant which is common amongst Roma from Slovakia, Czech Republic, and Spain. We also observed variants in known HI genes USH1G, USH2A, MYH9, MYO7A, and a splice site variant in MANBA (c.2158-2A>G) in a family with HI, intellectual disability, behavioral problems, and respiratory inflammation, which was previously reported in a Czech Roma family with similar features. Lastly, using multidimensional scaling and ADMIXTURE analyses, we delineate the degree of Asian/European admixture in the HI families understudy, and show that Roma individuals carrying the GJB2 p.(Trp24*) and MANBA c.2158-2A>G variants have a more pronounced South Asian background, whereas the other hearing-impaired Roma display an ancestral background similar to Europeans. We demonstrate a diverse genetic HI etiology in the Hungarian Roma and identify a new gene PLS1, for autosomal dominant human non-syndromic HI.

Our goal was to report a 44-year-old woman with carotid body tumor, and to give a brief and comprehensive presentation about the disease and summarize its complex management. Carotid body tumor is a rare, mostly sporadic, benign head and neck mass originating from the glomus caroticum. It occurs mostly in middle-aged women as a slowly growing, semifix, painless neck mass. The diagnosis is based upon the physical examination (pulsatile mass, Fontaine-sign) and - as the gold standard - CT-angiography. It should be established that preoperative embolisation by digital substraction angiography plays a crucial role in the treatment of carotid body tumors that should be followed by surgical removal. In case of inoperable/irresecable and residual tumors, radiotherapy is the treatment option. The patient was treated in our department in April 2017. Orv Hetil. 2018; 159(36): 1487-1492.Absztrakt: Célunk egy 44 éves nőbeteg esetének bemutatása kapcsán rövid és átfogó képet adni a glomus caroticum paragangliomájáról, diagnosztikájáról és komplex ellátásáról. A glomus caroticum paragangliomája a glomus caroticumból kiinduló ritka, többnyire sporadikusan megjelenő, jóindulatú fej-nyaki daganat. A legtöbbször középkorú nőbetegek érintettek; a nyak egyik oldalán jelentkező, igen lassan növekvő, szemifix, fájdalmatlan nyaki duzzanatként jelentkezik. Diagnosztikájában a fizikális vizsgálaton túl (pulzáció, Fontaine-jel) az arany standard a CT-angiográfia. Hangsúlyozzuk, hogy a glomus caroticum paragangliomájának terápiájában alapvető a preoperatív digitális szubsztrakciós angiográfia során elvégzett embolisatio, majd a tumor sebészi eltávolítása. Inoperabilitás és/vagy irreszekabilitás, illetve residualis tumor esetén a választandó terápia a sugárkezelés. A közleményben bemutatott beteget 2017 áprilisában kezeltük osztályunkon. Orv Hetil. 2018; 159(36): 1487–1492.

Otosclerosis can be found exclusively in the human otic capsule of the temporal bone. Its etiology is still unknown. In the past decades, several potential etiopathogenetic factors have been revealed, however, most studies were based on otosclerotic patients diagnosed by clinical symptoms only. The current experience indicates that one third of this group suffer from non-otosclerotic stapes fixation. In our experimental series, we have diagnosed and classified otosclerotic patients based on histologic examination, and analyzed also the pathogenetic factors. Recent data demonstrate that measles virus and rs1800472 SNP of transforming growth factor beta 1 (TGFβ1) gene are marked obvious etiologic factors, which have no therapeutic consequences so far. Furthermore, we summarize the genetic and environmental factors to be found in the literature, which may play a fundamental role in the pathogenesis of otosclerosis. Orv Hetil. 2018; 159(30): 1215-1220.Absztrakt: Az otosclerosis egy jelenleg is ismeretlen etiológiájú megbetegedés, mely kizárólagosan az emberi temporalis csont oticus kapszulájában mutatható ki. Az elmúlt évtizedekben számtalan etiopatogenetikai faktor lehetséges szerepe merült fel, azonban a legtöbb kísérletet klinikai tünetek alapján diagnosztizált otosclerosisos beteganyagon végezték, amelynek nagyjából egyharmada nem is otosclerosisos eredetű stapesfixáció. Kísérletsorozatainkban szövettani vizsgálat alapján diagnosztizáltuk és stadizáltuk az otosclerosisos betegcsoportot, és ezúton vizsgáltuk a lehetséges patogenetikai tényezőket. Kísérletes munkánknak köszönhetően mára egyértelmű etiológiai tényezőként tartják számon a kanyaróvírus-fertőzést és a transzformáló növekedési faktor-béta-1 (TGFβ1)-gén rs1800472-SNP-jét, melyeknek ez idáig még nincs terápiás konzekvenciájuk. Továbbá a jelen tanulmányban végigkövetjük az irodalomban fellelhető genetikai és környezeti tényezőket, melyek alapvető szerepet játszhatnak az otosclerosis patogenezisében. Orv Hetil. 2018; 159(30): 1215–1220.

The aim of this retrospective study was to compare the 3-month postoperative hearing results following laser stapedotomy with the use of NiTiBOND versus Nitinol prostheses (31 and 39 patients, respectively). The operations were performed between September 2012 and September 2014, and between March 2006 and December 2012 regarding NiTiBOND and Nitinol, respectively. Twenty of the consecutive 31 patients were female and 11 were male for NiTiBOND, while 11 were male and 28 were female for Nitinol. The mean age was 43.8 years (range 22–61) and 46.9 years (range 28–83) for NiTiBOND and Nitinol, respectively. No significant cochlear trauma was documented postoperatively. The mean air–bone gap (ABG) for the frequencies 0.5, 1, 2 and 3 kHz at the 3-month postoperative follow-up was 7.6 dB (SD 4.7), and 9.3 dB (SD 4.1) for NiTiBOND and Nitinol, respectively. The differences between the mean pre- (p = 0.179), and postoperative (p = 0.059) ABG of the two groups were not significant. ABG closure within 10 dB was achieved in 77.4 and 59 % for NiTiBOND and Nitinol, respectively, the difference was not significant (p = 0.10). Two cases of delayed facial paralysis occurred, 1 with Nitinol and 1 with the NiTiBOND. All patients attained an ABG

This prospective case review was performed with the aim to compare and asses the diagnostic values of cone-beam computed tomography (CBCT) and high-resolution computed tomography (HRCT) in the preoperative evaluation of otosclerosis. A total of 43 patients with histologically confirmed stapedial otosclerosis, who underwent unilateral stapedectomies were analyzed. Preoperative temporal bone CBCT and HRCT scans were performed in all cases. Both CBCT and HRCT imaging were characterized by a slice thickness of 0.4-0.625 mm and multiplanar image reconstruction. Histopathologic examination of the removed stapes footplates was performed in all cases. Findings of CBCT and HRCT were categorized according to the modified Marshall's grading system (fenestral or retrofenestral lesions). Histopathologic results were correlated with multiplanar reconstructed CBCT and HRCT scans, respectively. Negative control groups for CBCT (n = 36) and HRCT (n = 27) examinations consisted of patients, who underwent CBCT imaging due to various dental disorders or HRCT analysis due to idiopathic sudden sensorineural hearing loss. Histologically active foci of otosclerosis (n = 31, 72 %) were identified by both CBCT and HRCT in all cases with a sensitivity of 100 %. However, CBCT could not detect histologically inactive otosclerosis (n = 12, 23 %; sensitivity 0 %). In contrast, HRCT showed inactive otosclerosis with a sensitivity of 59.3 %. According to CBCT results, no retrofenestral lesions were found and the overall sensitivity for hypodense lesions was 61.37 %. In conclusion, CBCT is a robust imaging method in the detection of histologically active fenestral hypodense foci of otosclerosis with high sensitivity and radiologic specificity. In the light of these results, HRCT still remains the basic imaging method in the preoperative diagnosis of otosclerosis, since it has much greater sensitivity and specificity in the detection of retrofenestral hypodense lesions and histologically inactive otosclerotic foci in the oval window niche.

Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5 normal skin samples (retroauricular region) using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma.

The aim of this study was an evaluation of the mid-term hearing results after the implantation of a self-crimping heat memory Nitinol piston in stapes surgery. The 12-month postoperative results were compared with those at a minimum of 3 years (maximum 6.7, average 4.4 years). The medical records of all 44 patients who underwent surgery with a Nitinol piston for stapes fixation between November 2005 and January 2007 were evaluated retrospectively. The prostheses used in all cases measured either 4.5 or 4.75 × 0.6 mm. We hypothesized that the 12-month postoperative hearing results would be permanent after an average follow-up of 4.4 years. Thirty-two of the 44 consecutive patients were females and 12 were males. Their mean age was 40.4 years (range 27–69). All underwent a 12-month postoperative audiometric evaluation. 38 (30 females, 8 males, average age 45, range 28–77 years) of the 44 were available for mid-term 4.4-year (minimum 3 years, maximum 6.7 years) postoperative audiometric evaluation. The mean air–bone gap (ABG) for the frequencies 0.5, 1, 2 and 3 kHz at the 12-month postoperative follow-up was 11 dB (SD 4.1) and that after an average 4.4-year postoperative evaluation was 6.4 dB (SD 3.6). The mean decrease in ABG after 12 months was 19.5 dB, and that after the average 4.4 years was 21.3 dB. ABG closure within 10 dB was achieved in 77.2 % after 12 months and in 89.5 % after the average 4.4 years. No patient with an ABG > 20 dB was recorded after the average 4.4 years. The mean air conduction threshold at 4 kHz was examined pre and postoperatively so as to indicate any possible inner ear damage. At the 12-month follow-up, the difference between the pre and postoperative values was −2.5 dB, whereas after the average 4.4 years the difference was surprisingly +13 dB. The individual AC improvements were also demonstrated with the use of Amsterdam Hearing Evaluation Plots (AHEPs). The Nitinol prosthesis allowed excellent intraoperative handling and no postoperative complication was reported. As compared with conventional stapes prostheses, the Nitinol-based SMart prosthesis is a safe and reliable stapes prosthesis. Our mid-term audiometric evaluations revealed that the audiometric parameters demonstrated a hearing improvement between the postoperative 12-month and average 4.4-year examinations. We consider the elimination of manual crimping and the use of a “non-touch” hand-held laser technique has a positive impact on the mid-term audiometric results. Most of the previous studies presented only relatively short-term (from 6 weeks up to 6–12 months) audiometric evaluations. Complications are rare, but a longer follow-up is needed to establish the long-term stability.

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids (INCS) is a reliable option in the management of CRSwNP. INCS medication has been suspected to influence the presence and thickness of microbial biofilms and inflammatory cell patterns in CRSwNP. Two series of identical nasal polyps obtained from non-allergic patients with CRSwNP (n = 56), who underwent endoscopic sinus surgery (ESS), were processed to hematoxylin–eosin (H.E.) and Gram staining, respectively. Patients were recruited into three groups. Group A (n = 21) consisted of patients with continuous preoperative INCS treatment. In group B (n = 17), patients were never treated by INCS, while in group C (n = 18) INCS medication was stopped at least 6 months before ESS. Biofilm positivity varied from 76.4 to 88.8 % in different subject groups. These values and average thickness of biofilms did not reach statistically significant levels (Mann–Whitney’s U probe, p > 0.05) in different patient groups. In contrast, microscopic pattern and numbers of predominant inflammatory cell populations displayed obvious differences according to INCS treatment (Mann–Whitney’s U probe, p < 0.001). According to these observations, INCS treatment does not affect the presence and thickness of microbial biofilms in CRSwNP. In contrast, it has significant effects on the pattern of inflammatory cells infiltrating the subepithelial layer, which might result in beneficially altered extracellular matrix production and cytokine release.

INTRODUCTION Recent studies have reported genetic associations between with single nucleotide polymorphism (SNP) of the several genes of the renin-angiotensin-aldosterone (RAA) system in otosclerosis without the confirmation of RAA system expression in human stapes footplates. There are conflicting results. These results are conflicting because RAA system expression has been attributed exclusively to neural, vascular, and renal tissues, exclusively. MATERIALS AND METHODS Ankylotic stapes footplates (n = 20), cortical bone fragments (n = 10), and human kidney tissue specimens (n = 10) were processed to hematoxylin-eosin (HE) staining and RAA system-specific immunofluorescent assay (IFA), respectively. RESULTS Histologic diagnosis of otosclerosis was established in all ankylotic stapes footplates. Histologically active- (n = 13) and inactive (n = 7) foci of otosclerosis were consequently characterized by negative immunoreactions for renin, angiotensin converting enzyme (ACE), angiotensin-II (AT-II), and angiotensin-II receptor (AT-IIR), consequently. In cortical bones, a considerable RAA system expression was observed confirmed in the perivascular bone marrow progenitor cells. Kidney specimens, applied as positive controls, showed intense RAA system-specific immunoreactions. CONCLUSION Concerning current observations, the 4 studied members of RAA system that did not display active expression were not expressed at protein level in otosclerotic stapes footplates. This phenomenon was independent from the histologic activity of otosclerosis. Between these conditions, the etiologic role of RAA system is questionable in the pathogenesis of otosclerosis.

Genetic predisposition of otosclerosis has long been suspected, but unclarified. Unique coexpression pattern of measles virus receptor (CD46) splicing isoforms in the human otic capsule is assumed, since otosclerosis is a measles virus-associated organ-specific disease. In order to identify CD46 involved in the pathogenesis of otosclerosis, we used representative groups of histologically diagnosed otosclerotic, nonotosclerotic, and normal stapes footplates (n=109). Consecutive histopathological examinations and CD46-specific Western blot analysis were performed. Normal and nonotosclerotic stapes footplates showed consistent expression of the conventional c, d, e, f, and l CD46 isoforms. In contrast, four novel isoforms (os1–4) translated as intact proteins were additionally detected in each otosclerotic specimen. The study herein presented provides evidence for the otosclerosis-associated expression pattern of CD46. This finding might explain the organ-specific, virus-associated and autoimmune-inflammatory pathogenesis of otosclerosis. Regarding our current knowledge, this is the first report that confirms the presence of four new disease-specific protein variants of CD46.

Otosclerosis is a unique osseous remodeling disorder of the human temporal bone, which is also considered as a disease of measles virus-associated inflammatory-autoimmune reaction against the middle layer of the otic capsule: globuli interossei. Its preoperative diagnosis is rather difficult, and there is no consensus-based diagnostic protocol with enough high sensitivity and specificity for the clinical confirmation of the disease. On the other hand, the preoperative diagnosis or clinical diagnosis of otosclerosis was potentially important considering several differential diagnostic-, prognostic-, and legal-ethical factors and problems. At this time, combination of various well-defined and new preoperative diagnostic methods might serve a strong clinical suspicion for otosclerosis. This fact might provide the basis of diagnosis and helps to avoid unnecessary stapes surgeries, serious intraoperative complications, and “blinded surgeries”: explorative tympanostomies that are unacceptable for most of the patients with conductive hearing loss. In this chapter, an overview is provided about the potential preoperative diagnostic tools and their specificity and sensitivity levels in case of otosclerosis or non-otosclerotic stapes fixations. Finally, authors recommend a considerable preoperative diagnostic protocol for the confirmation or exclusion of otosclerosis.

The main goal of this report is to review our current knowledge about the etiopathogenesis of otosclerotic bone remodeling disorder focusing on measles virus infection. Otosclerosis is a disease of pathologically increased bone turnover of the human otic capsule; however, the etiopathogenesis remained unclear. Persisting measles virus infection, genetic predisposition, disturbed bone metabolism, inflammatory processes, autoimmunity, and hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. In the future, prospective studies based on comprehensive histopathologic, molecular biologic, and genetic analysis are necessary to get further information about the background of disease in order to clarify the role of measles in the etiopathogenesis and to find the most promising treatment option.

To estimate the correlations between high-resolution computed tomography (HRCT) scans, preoperative audiometric findings and histopathologic results in stapes ankylosis.Retrospective case review.Tertiary referral center.A total of 57 patients with stapes ankylosis, who underwent unilateral stapedectomies were analyzed.Diagnostic and therapeutic.Preoperative HRCT examinations were performed in all cases. Findings of HRCT were categorized according to Marshall's grading system. Preoperative air-bone gaps (ABGs) and bone conduction (BC) thresholds were determined. Stapes footplates removed surgically were processed using hematoxylin and eosin staining.Active otosclerosis (n = 29) was demonstrated by HRCT with a sensitivity of 76.31%, whereas its sensitivity to establish inactive otosclerosis (n = 13, 61.9%) and nonotosclerotic stapes fixations (n = 15, 51.7%) was much lower. Nonotosclerotic stapes fixations were characterized by pure conductive hearing loss that was not associated with HRCT findings. HRCT grades showed statistically significant association with BC levels at the averages of 0.5-1-2 kHz frequencies in the group of ears with inactive otosclerosis, exclusively (p0.05).HRCT is a reliable imaging method in the preoperative diagnosis of different types of stapes fixations. Imaging findings should be evaluated together with clinical history and audiometric data for obtaining as precise diagnosis for stapes fixation as possible.

This study is the first to establish that bone morphogenetic protein 5 (BMP5) plays a role in the pathogenesis of otosclerosis. These results confirm that elevated expression levels of BMPs, members of the transforming growth factor (TGF)-β superfamily, contribute to the pathologically increased bone turnover in early, active stages of otosclerosis.Otosclerosis is a complex bone remodeling disorder of the otic capsule, which might be characterized by increased expression of different types of BMPs. TGF-β and BMP are both members of the TGF-β superfamily and play a critical role in bone resorption and new bone formation. It has been suggested that BMP and its receptors may be involved in the pathologically increased bone turnover observed in otosclerosis.Fifty-one otosclerotic and 16 non-otosclerotic ankylotic stapes footplates were histologically analyzed: conventional hematoxylin-eosin staining and BMP2, 4, 5, and 7specific immunofluorescent assays were performed. Cortical bone fragments (n = 35) and incus specimens (n = 6) were used as negative controls.Active otosclerosis (n = 39) was characterized by increased expression of BMP2, 4, 5, and 7. Inactive cases of otosclerosis (n = 12) were characterized by negative immunoreaction for BMPs. Non-otosclerotic stapes specimens (n = 16) and negative controls (n = 41) showed negligible BMP expression. The BMP expression pattern showed a strong correlation with the histological activity of otosclerosis.

Objectives/Hypothesis: Biofilms might play a potential role in the pathogenesis and high recurrence rate of chronic rhinosinusitis with nasal polyposis (CRSwNP). Biofilm persistence has been thought to correlate with epithelial damage, subepithelial inflammatory cell infiltration, and tumor necrosis factor-α receptor (TNFR) expression in CRSwNP. Study Design: Case-control experimental study. Methods: A total of 36 patients with CRSwNP undergoing endoscopic sinus surgery were analyzed. The negative control group consisted of eight patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa samples applied as negative controls were processed by hematoxylin-eosin (HE) and Gram staining and TNFR-I and TNFR-II–specific immunofluorescent assay. Results: Biofilm was detected in 29 of 36 patients with CRSwNP and in none of the eight negative controls. Staining by HE showed strong correlation with the results of Gram staining protocol. In the biofilm-positive cases, TNFR-I and TNFR-II displayed homogeneous pattern of significantly increased epithelial expression compared to the biofilm-negative nasal polyps. In cases of biofilm absence, the expression pattern of TNF-α receptors was characterized by increased TNFR-II–specific immunoreaction. It was found that biofilm detectability corresponded to the integrity of nasal epithelium and to the dominant inflammatory cell type of the subepithelial layer. Conclusions: Persisting biofilms might increase the epithelial sensitivity against TNF-α that result in epithelium destruction. Coexistence of biofilms and increased TNFR expression might explain the inflammatory mucosal changes, functional disorders, and therapy resistance featuring CRSwNP. Laryngoscope,, 2012

Several studies have reported a potential genetic association between disease-specific single nucleotide polymorphism (SNPs) of RELN and otosclerosis and confirmed RELN expression in human stapes footplates. These are conflicting results, since RELN expression has been attributed exclusively to neural tissues and to odontoblasts. Otosclerosis is a disease of complex bone remodeling disorder, which is limited to the human otic capsule. Genetic predisposition has long been suspected, however, the pathogenesis remained unclear. Ankylotic stapes footplates (n = 85), cortical bone fragments (n = 4), hearing ossicles (n = 2) and human brain tissue specimens (n = 4) were processed to RELN-specific RT-PCR and reelin-specific immunofluorescent assay (IFA). The first group of ankylotic stapes footplates (n = 22) showed a consistent positive reaction against reelin by IFA; however, RELN-specific mRNA could not be detected in the second, RT-PCR group (n = 63). Brain specimens were characterized by robust expression of reelin (n = 2) and RELN-specific mRNA (n = 2). In case of bone-specific controls (n = 6), reelin/RELN expression was excluded obviously. Concerning current observations, RELN gene does not show active expression in adult stapes footplates. Since, the otic capsule surrounds a special neural structure (membranous labyrinth), reelin might play a coordinative role in the early embryonic stage of development. As being a part of the otic capsule, stapes footplate might be characterized by persisting reelin detectability without mRNA expression. Between these conditions, the etiologic role of RELN is questionable in the pathogenesis of otosclerosis.

Objectives To review our current knowledge of the etiopathogenesis of otosclerotic bone remodeling including genetics, viral infection, autoimmunity and inflammation and to discuss disease pathogenesis with relevance for pharmacotherapy. Systematic review methodology Relevant publications on the etiopathogenesis, molecular biology, genetics and histopathology of otosclerosis from 1984 to 2009 were analyzed. Results and conclusions Otosclerosis is a bone remodeling disorder of the human otic capsule, however, the etiopathogenesis remains unclear. Genetic predisposition, disturbed bone metabolism, persistent measles virus infection, autoimmunity, hormonal and environmental factors also may play contributing roles in the pathogenesis of otosclerosis. Since, diagnosis of otosclerosis is still based on histopathological examination of the removed stapes footplate, systemic prospective studies based on comprehensive histopathological and molecular biological analysis are necessary to get further information about the background of disease.

Hypothesis: Persistent measles virus infection of the otic capsule is suggested to be an etiologic factor in otosclerosis. Otosclerosis is a disease of complex unknown etiology causing progressive conductive and/or sensorineural hearing loss (HL). Background: Diagnostic methods of otosclerosis are sensitive to ossicular chain fixation with low specificity for otosclerotic stapes ankylosis. Methods: Nucleic acid was extracted from stapes footplates of clinically stapes fixation patients (N = 213). Measles virus nucleoprotein RNA was amplified by reverse-transcriptase polymerase chain reaction. Amplification results were correlated to histologic findings in 49 cases. Antimeasles IgG levels of all clinically stapes fixation as well as control sera specimens were measured by enzyme-linked immunosorbent assay. Results: Among clinically stapes fixation patients, 141 stapes footplates contained measles virus RNA. Among 49 histologic specimens, viral RNA was detectable only in histologically otosclerotic stapes footplates (n = 35). Histology for virus-negative footplates (n = 14) excluded otosclerosis. Antimeasles IgG levels were significantly lower in the sera of patients with virus-positive stapes than in control sera. Conclusions: Combination of decreased antimeasles IgG serum level and conductive HL has a great specificity and sensitivity as a diagnostic method in the preoperative evaluation of ossicular chain fixations otosclerosis. Low antimeasles IgG level indicates otosclerosis, whereas high level suggests nonotosclerotic ossicular chain fixations. Preoperative elucidation of the cause of a conductive HL may suggest optional medical treatment in preference to surgical methods.

Hypothesis Persistent measles virus infection of the otic capsule is presumed to be one of the etiologic factors in otosclerosis. The viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplates and reverse-transcriptase polymerase chain reaction amplification of the viral RNA. At present, histologic analysis of the removed stapes footplates is the only appropriate method of distinguishing otosclerotic and nonotosclerotic stapes fixations. Background The presence of measles virus was shown in otosclerotic patients by reverse-transcriptase polymerase chain reaction amplification of the viral RNA and detecting the viral proteins by immunohistochemistry. Methods Nucleic acids (mRNA, vRNA, and DNA) were extracted from ankylotic stapes footplates of stapes fixation patients (n = 44). Measles virus genomic nucleoprotein RNA was amplified by seminested reverse-transcriptase polymerase chain reaction. Amplification results were correlated to postoperative histologic findings. Results Measles virus RNA was detectable only in histologically otosclerotic stapes footplates (n = 32). Histology for virus-negative footplates (n = 12) excluded otosclerosis. Virus-negative stapes footplates showed annular calcification (n = 8), bone resorption with increased numbers of hemosiderophages (n = 2), and mononuclear cell infiltration with osteolysis (n = 2). Conclusion Stapes ankylosis is a heterogenous disease causing conductive hearing loss with different causes. Nonotosclerotic stapes fixations may belong to degenerative disorders with variable histopathology. Otosclerosis is an inflammatory disease resulting from persisting measles virus infection of the otic capsule.

Hypothesis: Otosclerosis is a disease of unknown etiology causing conductive or sensorineural hearing loss. Persistent measles virus infection of the otic capsule is considered to be one of the etiologic factors in otosclerosis. Background: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, on the types and features of paracrine cytokines in otosclerosis. Methods: Nucleic acid was extracted from stapes footplate samples of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. Tumor necrosis factor (TNF)-alpha mRNA expression was detected by RT-PCR in otosclerotic bone and was correlated with preoperative audiologic findings and measles virus positivity. Results: Among 154 clinically otosclerotic patients, 99 stapes footplate specimens contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. There was no detectable TNF-alpha mRNA expression in virus negative cases. Conclusion: The etiologic role of measles virus in the pathogenesis of otosclerosis should be considered. Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Virus-associated and virus-negative pathomechanisms of otosclerosis should be distinguished.

Tuberculosis remains one of the most challenging infectious diseases, which rarely manifests in the middle ear cleft exclusively. Typical symptoms of tuberculosis have become more and more confusing due to the genetic evolution of different Mycobacterium species. In the diagnosis of tuberculous otitis media (TOM), clinical suspicion plays a fundamental role, when topical and/or systemic antibiotic treatment cannot lead to improvement in ear discharge and inflammation. If there is no other reason of persisting otorrhea, microbiological sampling and culturing are the subsequent steps of diagnosis. These investigations, however, have low sensitivity; therefore a canal wall-up mastoidectomy is recommended, which includes the removal of necrotic bone and multiple histological sampling from various locations. Currently, histopathological analysis is the most robust and reliable method in the diagnosis of TOM. Tuberculin skin test, Mycobacterium-specific PCR and interferon-gamma release assay cannot distinguish between active, inactive or post-infective conditions. According to these considerations, these methods may serve as supplementary assays for the final diagnosis. Having the appropriate diagnosis after surgical intervention and laboratory analysis, medical management should be continued by anti-tuberculosis chemotherapy. Hereby, we demonstrate two cases with primary TOM and provide an overview of the literature in the light of diagnostic and therapeutic guidelines in the management of TOM.

Previous experiments suggested the possibility of a short-term sound stimulus-evoked and transient increase in DPOAE amplitudes. This phenomenon is possibly due to the complexity of the outer hair cells and their efferent control system and the different time scales of regulatory processes. A total of 100 healthy subjects ranging from 18 to 40 years of age with normal hearing and normal DPOAE values in the range of 781–4000 Hz were recruited in the study. Diagnostic DPOAE measurements were performed after short-term sound exposure. We proposed a 10 sec, 50 dB sound impulse as the most effective stimulus for clinical practice between 40 and 60 sec poststimulus time to detect the aforementioned transient DPOAE increase. We developed a procedure for detection of this transient increase in DPOAE by the application of a short-term sound exposure. The phenomenon was consistent and well detectable. Based on our findings, a new aspect of cochlear adaptation can be established that might be introduced as a routine clinical diagnostic tool. A mathematical model was provided that summarizes various factors that determine electromotility of OHCs and serves as a possible clinical application using this phenomenon for the prediction of individual noise susceptibility.

This retrospective case review was performed with the aim to asses the value of cone-beam computed tomography (CBCT) in the preoperative diagnosis of otosclerosis. A total of 32 patients with histologically confirmed stapedial otosclerosis, who underwent unilateral stapedectomies were analyzed. Preoperative temporal bone CBCT scans were performed in all cases. CBCT imaging was characterized by a slice thickness of 0.3 mm and multiplanar image reconstruction. Histopathologic examination of the removed stapes footplates was performed in all cases. Findings of CBCT were categorized according to Marshall's grading system (from grade 0 to grade 3). Histopathologic results were correlated to multiplanar reconstructed CBCT scans, respectively. Histologically active foci of otosclerosis (n = 21) were identified by CBCT in all cases with a sensitivity of 100 %. However, CBCT was unable to detect histologically inactive otosclerosis (n = 11, sensitivity = 0 %). According to CBCT scans, no retrofenestral lesions were found and all positive cases were recruited into the grade 1 group indicating solely fenestral lesions at the anterior pole of stapes footplates. In conclusion, CBCT is a reliable imaging method with considerably lower radiation dose than high-resolution CT (HRCT) in the preoperative diagnosis of otosclerosis. These results indicate that CBCT has high sensitivity and specificity in the detection of hypodense lesions due to histologically active otosclerosis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease that seems to be associated with the presence of microbial biofilms and corresponding subepithelial inflammatory reactions. Optical coherence tomography (OCT) might be applied to detect bacterial and fungal biofilms in patients with CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of six patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27 patients (81.5 %) with CRSwNP and in none of six negative controls. In our series, OCT scan showed an obvious association with the findings of H.E. and Gram staining and was allocated to be a good predictor of biofilm existence. On OCT images, biofilms were displayed as distinct superficial layers with high optical density. It was found that microscopic architecture of biofilms was strongly associated with the integrity of nasal mucosa and to the cellular pattern of subepithelial inflammatory reaction. This study confirmed the presence of microbial biofilms in patients with CRSwNP according to OCT scans and histological analysis. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected preoperatively. In conclusion, single application of OCT analysis or combination with conventional histological protocols provides a robust and reliable method for the detection of bacterial and fungal biofilms in CRSwNP. Level of evidence 3b, individual case–control study.

Objective. Adenoid hypertrophy is a common condition in childhood, which may be associated with recurring acute otitis media (RAOM), otitis media with effusion (OME), and obstructive sleep apnea syndrome (OSAS). These different clinical characteristics have some clinical overlap; however, they might be explained by distinct immunologic and infectious profiles and result in various histopathologic findings of adenoid specimens.Methods. A total of 59 children with adenoid hypertrophy undergoing adenoidectomy were studied. Three series of identical adenoid specimens were processed to hematoxylin-eosin (H.E.) and Gram staining and to respiratory virus specific real-time PCR, respectively.Results. According to the clinical characteristics, patients were recruited into three groups: RAOM (). Bacterial biofilms were detected in 21 cases, while at least one of the studied respiratory viruses was detected in 52 specimens. RAOM cases were significantly associated with biofilm existence (). In contrast, OME group was characterized by the absence of bacterial biofilm and by normal mucosa. Showing a statistically significant correlation, all OME cases were positive for human bocavirus (HBoV, ).Conclusions. Bacterial biofilms might contribute to the damage of respiratory epithelium and recurring acute infections resulting in RAOM. In OME cases persisting respiratory viruses, mainly HBoV, can cause subsequent lymphoid hyperplasia leading to ventilation disorders and impaired immunoreactivity of the middle ear cleft.

Biofilm-positive cases of chronic rhinosinusitis with nasal polyposis (CRSwNP) may form a separate clinical entity, which is characterized by high recurrence rates and resistance against different therapeutic strategies. This can be explained by a special immunologic phenotype. Biofilm existence has been supposed to correlate with increased amount of dendritic cells that are responsible for antigen presentation in CRSwNP. A total of 20 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of ten patients undergoing septoplasty without CRSwNP. Three series of individual nasal polyps and control specimens were processed to hematoxylin–eosin (HE) and Gram staining and to CD209-specific immunofluorescent assay, respectively. Biofilm was detected in 13 of 20 patients (65 %) with CRSwNP and in none of the ten negative controls. The subepithelial layer of biofilm-positive nasal polyps displayed a statistically significant (p < 0.001) increase in the numbers of CD209-expressing dendritic cells compared to biofilm-negative specimens. It was found that biofilm detectability showed strong correlation to the architecture of respiratory mucosa and to the dominant inflammatory cell type of the subepithelial layer. Persisting bacterial biofilms may affect the type of antigen presentation and consecutive immune reactions in the subepithelial layer of nasal mucosa. This phenomenon may result in different inflammatory pathways with specific cytokine profile compared to biofilm-negative cases. Co-existence of bacterial biofilms and dominant pattern of dendritic cells suggest a biofilm-associated immunologic phenotype in CRSwNP. This can explain the mucosal changes, functional disorders and therapy resistance featuring CRSwNP.

Objectives/Hypothesis: Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Although biofilms are characterized by an extremely high resistance against chemical and physical agents, low-frequency ultrasound (LFU) treatment has been suspected to be an efficient and safe method for biofilm disruption. Study Design: Basic science experimental study. Methods: A total of 10 patients with CRSwNP undergoing endoscopic sinus surgery were analyzed. Two series of identical nasal polyps (n = 20) were processed to hematoxylin-eosin (HE) and Gram staining and to continuous-wave LFU treatment (5 minutes, 0.4 MHz, 37°C), respectively. Results: Presence of microbial biofilms was confirmed in all patients with CRSwNP. HE staining showed a strong correlation with the results of Gram protocol in biofilm detection. In the LFU-treated group (n = 10), a significantly decreased inflammatory cell count was found in the subepithelial layer of nasal polyps (P < .001). In addition, bacterial biofilms were completely removed from the surface of the epithelial layer. Microscopic tissue injuries or significant temperature changes were not detected due to LFU treatment. Conclusions: Between in vitro conditions, LFU treatment appeared to be a reliable and microscopically safe method for the disruption of microbial biofilms in CRSwNP. These results may provide a basis for a prospective human study investigating the efficacy and safety of this therapeutic modality alone or in combination with antibiotics or topical steroids in biofilm-positive cases of CRSwNP. Laryngoscope, 2013

To review our current knowledge of the pathologic bone metabolism in otosclerosis and to discuss the possibilities of non-surgical, pharmacological intervention. Otosclerosis has been suspected to be associated with defective measles virus infection, local inflammation and consecutive bone deterioration in the human otic capsule. In the early stages of otosclerosis, different pharmacological agents may delay the progression or prevent further deterioration of the disease and consecutive hearing loss. Although effective anti-osteoporotic drugs have become available, the use of sodium fluoride and bisphosphonates in otosclerosis has not yet been successful. Bioflavonoids may relieve tinnitus due to otosclerosis, but there is no data available on long-term application and effects on sensorineural hearing loss. In the initial inflammatory phase, corticosteroids or non-steroidal anti-inflammatory drugs may be effective; however, extended systemic application may lead to serious side effects. Vitamin D administration may have effects on the pathological bone loss, as well as on inflammation. No information has been reported on the use of immunosuppressive drugs. Anti-cytokine targeted biological therapy, however, may be feasible. Indeed, one study on the local administration of infliximab has been reported. Potential targets of future therapy may include osteoprotegerin, RANK ligand, cathepsins and also the Wnt-β-catenin pathway. Finally, anti-measles vaccination may delay the progression of the disease and potentially decrease the number of new cases. In conclusion, stapes surgery remains to be widely accepted treatment of conductive hearing loss due to otosclerosis. Due to lack of solid evidence, the place of pharmacological treatment targeting inflammation and bone metabolism needs to be determined by future studies.