Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients. Trattamento chirurgico degli schwannomi vestibolari: risultati su una serie di 1006 pazienti

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare l’evoluzione negli esiti chirurgici dell’exeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente l’asportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dell’ultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado HouseBrackmann), con una variazione tra il primo e l’ultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione dell’udito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). L’udito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nell’ultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dell’asportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione dell’udito, le perdite di liquido cefalorachidiano, principalmente grazie all’esperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall’ esperienza maturata sulle lesioni di piccole dimensioniThe management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team's experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

Anatomical and functional results of ossiculoplasty using titanium prosthesis

Titanium ossicular chain replacement prosthesis is often used for rehabilitation of the columellar effect in otologic surgeries. This retrospective study aims to analyse the anatomical and functional results of surgeries in which a titanium prosthesis was used. Two hundred and eighty procedures in 256 patients operated on in a tertiary referral center were analysed. Aetiologies, preoperative audiograms, peropera-tive data and postoperative outcomes at 2 and 12 months postoperatively were reviewed. Chronic suppurative otitis media with or without cholesteatoma was the main aetiology (89%). There was no difference in anatomical results between partial and total ossicular replacement prosthesis, with an overall dislocation rate of 6%, and an overall extrusion rate of 3%. Regarding functional results, a postoperative air-bone gap ≤ 20 dB was achieved in 65% of cases, with a better result for partial compared to total ossiculoplasty (p = 0.02). A significant difference in air bone gap closure was found when comparing aetiologies, with a higher air-bone gap closure in malformation cases compared to chronic suppurative otitis media with cholesteatoma or retraction cases (p = 0.03). Ossiculoplasty using titanium prosthesis is a safe and effective procedure for rehabilitation of hearing loss, which allows reaching an air-bone gap ≤ 20 dB in the majority of patients

Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients = Trattamento chirurgico degli schwannomi vestibolari: Risultati su una serie di 1006 pazienti

The management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team’s experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

3D curved multiplanar cone beam CT reconstruction for intracochlear position assessment of straight electrodes array. A temporal bones and patients study

A retrospective review of post-op cone beam CT (CBCT) of 8 adult patients and 14 fresh temporal bones that underwent cochlear implantation with straight flexible electrodes array was performed to determine if the position of a long and flexible electrodes array within the cochlear scalae could be reliably assessed with CBCT. An oto-radiologist and two otologists examined the images and assessed the electrodes position. The temporal bone specimens underwent histological analysis for confirm the exact position. The position of the electrodes was rated as scala tympani, scala vestibule, or intermediate position for the electrodes at 180°, 360° and for the apical electrode. In the patient group, for the electrodes at 180° all observers agreed for scala tympani position except for 1 evaluation, while a discrepancy in 3 patients both for the 360° and for the apical electrode assessment were found. In five temporal bones the evaluations were in discrepancy for the 180° electrode, while at 360° a disagreement between raters on the scalar positioning was seen in six temporal bones. A higher discrepancy between was found in assessment of the scalar position of the apical electrode (average pairwise agreement 45.4%, Fleiss k = 0.13). A good concordance was found between the histological results and the consensus between raters for the electrodes in the basal turn, while low agreement (Cohen’s k 0.31, pairwise agreement 50%) was found in the identification of the apical electrode position confirming the difficulty to correct identify the electrode position in the second cochlear turn in temporal bones. In conclusion, CBCT is a reliable radiologic exam to correctly evaluate the position of a lateral wall flexible array in implanted patients using the proposed imaging reconstruction method, while some artefacts impede exact evaluation of the position of the apical electrode in temporal bone and other radiological techniques should be preferred in ex vivo studies

ACTA OTORHINOLARYNGOLOGICA ITALICA

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare levoluzione negli esiti chirurgici dellexeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente lasportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dellultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado House- Brackmann), con una variazione tra il primo e lultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione delludito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). Ludito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nellultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dellasportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione delludito, le perdite di liquido cefalorachidiano, principalmente grazie allesperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall esperienza maturata sulle lesioni di piccole dimensioni

Ricostruzione multiplanare 3D di immagini cone beam per lidenficazione della posizione degli impianti cocleari. Studio su ossi temporali e pazienti impiantati

Questo studio riporta unanalisi retrospettica delle immagini cone beam CT effettuate su 8 pazienti adulti sottoposti ad impianto cochleare MedEl flex 28 e su 14 ossi temporali impiantati con lo stesso tipo di array portaelettrodi. Lo scopo dello studio é di determinare laffidabilità della metodica cone beam CT nella valutazione della posizione intracocleare degli elettrodi in impianti che si posizionano lungo la parete laterale del lume cocleare, quindi non perimodiolari la cui posizione é più facilmente identificabile. Un otoradiologo e due otologi hanno analizzato le immagini e assegnato la posizione per ciascun elettrodo localizzato nella regione dei 180° e dei 360° del primo giro cocleare e per lelettrodo apicale scegliendo tra scala timpanica, vestibulare o posizione intermedia Lanalisi istologica ha successivamente confermato lesatta posizione negli ossi temporali. Nel gruppo dei pazienti per lelettrodo a 180° i tre esperti concordavano sulla posizione in scala timpanica in tutti eccetto un paziente, mentre una discordanza nella valutazione era presente in 3 pazienti per gli elettrodi a 360° e per gli elettrodi apicali. Negli ossi temporali in 5 casi era presente una discordanza per lelettrodo a 180°, mentre a 360° sei valutazioni erano discordanti tra i valutatori. Una disdcordanza tra le valutazioni più elevata veniva trovata per la la posizione dellelettrodo apicale (concordanza valutatori 45.4%, Fleiss k = 0,13). Un buon grado di concordanza veniva trovato tra i risultati istologici e le valutazioni tra i valutatori per gli elettrodi localizzati nel giro basale; un grado più basso esisteva per la posizione degli elettrodi apicali (concordanza valutatori 50%, Cohens k = 0,31) confermando la difficoltà nella corretta valutazione della posizione degli elettrodi nella regione più apicale negli ossi temporali. In conclusione, le immagini cone beam postoperatorie analizzate con la metodica della ricostruzione multiplanare 3D rappresentano una metodica affidabile per lo studio della posizione intracocleare degli elettrodi a posizionamento laterale nei pazienti impiantati. La corretta identificazione del posizionamento dellelettrodo piu apicale risulta difficile su osso temporale per la presenza di un artefatto più importante o per la minore resistenza delle strutture della parete laterale della coclea (legamento spirale, membrane basilare) nel preparato istologico (osso temporale fresco/congelato) che è responsabile di un maggior numero di traslocazioni dalla rampa timpanica alla rampa vestibolare e di localizzazioni intermedie più difficilmente interpretabili

The treatment of polycythaemia vera: an update in the JAK2 era

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases

Gap Junction Mediated Intercellular Metabolite Transfer in the Cochlea Is Compromised in Connexin30 Null Mice

Connexin26 (Cx26) and connexin30 (Cx30) are two major protein subunits that co-assemble to form gap junctions (GJs) in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG) among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a novel pathogenesis process in the cochlea for Cx-mutation-linked deafness

Nod2 Mediates Susceptibility to Yersinia pseudotuberculosis in Mice

Nucleotide oligomerisation domain 2 (NOD2) is a component of the innate immunity known to be involved in the homeostasis of Peyer patches (PPs) in mice. However, little is known about its role during gut infection in vivo. Yersinia pseudotuberculosis is an enteropathogen causing gastroenteritis, adenolymphitis and septicaemia which is able to invade its host through PPs. We investigated the role of Nod2 during Y. pseudotuberculosis infection. Death was delayed in Nod2 deleted and Crohn's disease associated Nod2 mutated mice orogastrically inoculated with Y. pseudotuberculosis. In PPs, the local immune response was characterized by a higher KC level and a more intense infiltration by neutrophils and macrophages. The apoptotic and bacterial cell counts were decreased. Finally, Nod2 deleted mice had a lower systemic bacterial dissemination and less damage of the haematopoeitic organs. This resistance phenotype was lost in case of intraperitoneal infection. We concluded that Nod2 contributes to the susceptibility to Y. pseudotuberculosis in mice

CARD15/NOD2 Is Required for Peyer's Patches Homeostasis in Mice

BACKGROUND: CARD15/NOD2 mutations are associated with susceptibility to Crohn's Disease (CD) and Graft Versus Host Disease (GVHD). CD and GVHD are suspected to be related with the dysfunction of Peyer's patches (PP) and isolated lymphoid follicles (LFs). Using a new mouse model invalidated for Card15/Nod2 (KO), we thus analysed the impact of the gene in these lymphoid formations together with the development of experimental colitis. METHODOLOGY/PRINCIPAL FINDINGS: At weeks 4, 12 and 52, the numbers of PPs and LFs were higher in KO mice while no difference was observed at birth. At weeks 4 and 12, the size and cellular composition of PPs were analysed by flow cytometry and immunohistochemistry. PPs of KO mice were larger with an increased proportion of M cells and CD4(+) T-cells. KO mice were also characterised by higher concentrations of TNFalpha, IFNgamma, IL12 and IL4 measured by ELISA. In contrast, little differences were found in the PP-free ileum and the spleen of KO mice. By using chamber experiments, we found that this PP phenotype is associated with an increased of both paracellular permeability and yeast/bacterial translocation. Finally, KO mice were more susceptible to the colitis induced by TNBS. CONCLUSIONS: Card15/Nod2 deficiency induces an abnormal development and function of the PPs characterised by an exaggerated immune response and an increased permeability. These observations provide a comprehensive link between the molecular defect and the Human CARD15/NOD2 associated disorders: CD and GVHD