Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study

Background: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. Methods: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. Results: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Conclusions: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years

How to deal with large airways stenosis

Institutul National de Pneumologie "Marius Nasta", București, România, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaManagementul stenozelor traheale rămâne o provocare terapeutică, necesitând un abord multidisciplinar. Orice leziune simptomatica ce limitează activitatea curentă a unui pacient trebuie abordată chirurgical, cel mai eficient tratament fiind rezecția traheală cu anastomoză. Cauza principala a stenozelor benigne este lezarea traheală post-intubație. Tumorile primitive traheale sunt rare, iar abordul chirurgical este de elecție. În cancerul tiroidian cu invazie traheală se practică rezecția ”în bloc’’ cu anastomoză termino-terminală. Opțiunile de tratament non-chirurgical (dilatațiile repetate, tratamentul laser, stentarea prelungită) sunt indicate doar la pacienți atent selecționați și sunt folosite în principal doar pentru stabilizarea stenozei până la tratamentul chirurgical. Evaluarea preoperatorie a pacienților cu stenoză traheală include fibrobronhoscopia pentru a determina gradul de afectare a căilor aeriene si examenul CT toracic pentru decelarea metastazelor la distanță, în cazul neoplaziilor. Abordul chirurgical se face prin: cervicotomie simplă, cervicotomie cu sternotomie parțială superioară sau toracotomie. Pacienții sunt inițial intubați cu o sondă endotraheala de calibru mic, până când traheea este expusă în plagă și disecată circumferențial, cu păstrarea nervilor laringei recurenți. În timpul rezecției și anastomozei pacientul este ventilat prin plagă cu ajutorul unei sonde de intubație poziționată în traheea distală. În cazul unei leziuni la nivelul treimei medii sau inferioare a traheei, se folosește ventilatia în jet cu frecvență înalta. Este foarte important ca anastomoza să nu fie realizată în tensiune deoarece dehiscentele pot fi fatale. Manevrele de relaxare traheala precum disectia anterioara a traheei și flexia cervicală permit o rezecție de până la 8 cartilagii traheale (4 cm) fără complicații. * * * The management of tracheal stenosis remains a challenge, requiring a multidisciplinary team. Any lesion that produces symptoms that limit patient activity should be considered for surgery. The most effective treatment is the tracheal resection with reconstruction. The main cause of benign stenosis is postintubation tracheal injury. Primary tracheal tumors are rare, but surgery gives the best local control. In tracheal involvement by thyroid cancer we perform ‘en-bloc’ resection with primary end-to-end anastomosis. Non-operative treatments (dilation, laser treatment, prolonged stenting) are indicated in selected patients and are mainly used to stabilize the stenosis before surgery. Preoperative assessment included brobchoscopy and CT-scan to evaluate the extent of the airway involvement and distant metastases if present. We use as surgical approach: cervical collar incision, cervical incision with partial sternal split or thoracotomy. The patients are intubated initially with a small caliber endotracheal tube until the trachea is exposed and circumferentially dissected, sparing the inferior laryngeal nerves. During resection and anastomosis the patients are kept ventilated by means of a distal intubation tube. In cases with lesions of the middle and lower third of the trachea we use high frequency jet ventilation. It is very important to have a tension-free anastomosis as anastomotic leakage can be fatal in most cases. Releasing maneuvers such as anterior dissection of the trachea and cervical flexion allows a total length of eight tracheal cartilages (4 cm in length) to be resected with no complications