Carotid artery revascularisation following neck irradiation: immediate and long-term results.

OBJECTIVE: Carotid artery stenosis is a complication of neck irradiation. We describe the immediate and long-term results of surgical treatment. METHODS: This was a retrospective single centre study. From 1996 to 2009, 24 consecutive patients who had in the past received neck radiation therapy (mean 12 years, 1-41 years) underwent 27 primary carotid artery revascularisation procedures. Six patients (23%) had previous radical neck dissection, three permanent tracheostomies and one cervicoplasty with pectoral muscle flap. Indications for surgery included symptomatic (five transient ischaemic attacks (TIAs), four strokes; 34%) and asymptomatic (18 patients, 66%) stenosis. Four patients had occlusion of the contralateral carotid. General anaesthesia without shunting was used with measurement of stump pressure. Carotid interposition bypass grafting included 23 vein grafts and three polytetrafluoroethylene (PTFE) grafts. RESULTS: No perioperative deaths or central neurological events occurred. Three patients suffered transient cranial nerve injuries. Eleven patients died during follow-up, mean interval of 28 months (range 6-120 months), of causes unrelated to surgery. Five patients had recurrent bypass stenosis with one TIA and one stroke. All other surviving patients remained asymptomatic. CONCLUSION: Despite no comparative study as evidence, we think that the perioperative risk of stroke is at least comparable with the risk encountered for angioplasty procedures.

Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France.

BACKGROUND: Cryopyrin-associated periodic syndromes (CAPS) consist of a continuum of autoinflammatory diseases caused by a defect in interleukin 1ß regulation. Although symptoms may vary widely, the discovery, in 2001, of the gene involved (NLRP3) has dramatically helped diagnosis. OBJECTIVES: To define the spectrum and prevalence of NLRP3 mutations in France and to delineate initial criteria before molecular analysis. METHODS: Retrospective review (2001-9) of genetic analysis data and request forms of patients living in France with an NLRP3 mutation since the set up of CAPS molecular diagnosis by the three French laboratories providing this test (GenMAI network). RESULTS: Over 800 analyses of this gene have been conducted, identifying 135 cases with an NLRP3 mutation (55 probands; 33 multiplex families); the estimated prevalence in France was equal to 1/360 000. A total of 21 different sequence variants were detected, among which four are common and nine are new mutations. CONCLUSIONS: Although the number of NLRP3 test requests has doubled over the past 5 years, genetic screening has not contributed to enhanced detection of new index cases each year. There are two possible reasons for this: (i) no clinical prerequisite for genetic diagnosis and (ii) few new large families are now identified (unlike the initial study based on a selection by linkage). A set of initial clinical criteria have been drawn up which it is recommended should be fulfilled before a patient is tested: at least three recurrent bouts, age at disease onset < 20 years and elevated levels of C-reactive protein, especially in individuals with urticaria and moderate fever.

Mutations in NALP12 cause hereditary periodic fever syndromes.

NALP proteins, also known as NLRPs, belong to the CATERPILLER protein family involved, like Toll-like receptors, in the recognition of microbial molecules and the subsequent activation of inflammatory and immune responses. Current advances in the function of NALPs support the recently proposed model of a disease continuum bridging autoimmune and autoinflammatory disorders. Among these diseases, hereditary periodic fevers (HPFs) are Mendelian disorders associated with sequence variations in very few genes; these variations are mostly missense mutations whose deleterious effect, which is particularly difficult to assess, is often questionable. The growing number of identified sporadic cases of periodic fever syndrome, together with the lack of discriminatory clinical criteria, has greatly hampered the identification of new disease-causing genes, a step that is, however, essential for appropriate management of these disorders. Using a candidate gene approach, we identified nonambiguous mutations in NALP12 (i.e., nonsense and splice site) in two families with periodic fever syndromes. As shown by means of functional studies, these two NALP12 mutations have a deleterious effect on NF-kappaB signaling. Overall, these data identify a group of HPFs defined by molecular defects in NALP12, opening up new ways to manage these disorders. The identification of these first NALP12 mutations in patients with autoinflammatory disorder also clearly demonstrates the crucial role of NALP12 in inflammatory signaling pathways, thereby assigning a precise function to this particular member of an emerging family of proteins whose putative biological properties are currently inferred essentially through in vitro means.

Dramatic improvement in survival after lung transplantation over time: a single center experience.

Lung transplantation (LT) is a recognized procedure for selected patients with end-stage respiratory failure. We performed 123 LT, including 32 single lung, 84 double lung, and 7 heart-lung transplantations in 48 patients with chronic obstructive pulmonary disease (COPD), 13 patients with pulmonary hypertension (PH), 33 with cystic fibrosis (CF), and 29 with interstitial lung disease (ILD) between July 1990 and January 2008. Survival was compared for periods before and after December 2001. The mean age of patients was 44.4 years (range 16-66.5 years); 84 (69%) were men. Before LT, 1 second forced expiratory volume was 28.7% +/- 18.1% and PaCO(2) = 6.3 kPa. Fifty-five patients were on noninvasive ventilation. Cold ischemia time was 320 +/- 91 minutes. Cardiopulmonary bypass (CPB) was used in 77 patients (64%). There were 18 early surgical reinterventions, 8 extracorporeal membrane oxygenations, and 38 bronchial stent insertions among 206 at-risk bronchial sutures. Crude survivals were 69%, 58%, 41%, and 18% at 1, 2, 5, and 10 years, respectively. Comparing before (n = 70 with 15 CF) vs after December 2001 (n = 53 with 17 CF), survivals were 63% vs 78%, 51% vs 71%, and 33% vs 60% at 1, 2, and 5 years, respectively (P = .01) and for CF patients, 52% vs 100%, 52% vs 94%, and 25% vs 94% at 1, 2, and 5 years, respectively (P = .005). There was significant improvement in survival before and after 2001 in 123 LT and particularly among CF patients. Improvement in survival after LT may be related to the sum of numerous changes in our practice since December 2001, including the use of pulmonary rehabilitation pre-LT, extracellular pneumoplegia, statins, macrolides for chronic rejection, monitoring of Epstein-Barr blood load, changes in maintenance immunosuppressants, as well as position movement up the coordinator nurse and learning curve.

Good speech recognition and quality-of-life scores after cochlear implantation in patients with DFNA9.

OBJECTIVE: To compare audiometric and quality-of-life results in DFNA 9 patients who received a cochlear implant with cochlear implant patients with adult-onset progressive sensorineural hearing loss. STUDY DESIGN: Prospective comparative design; results were collected cross-sectionally. SETTING: Tertiary referral center. PATIENTS: Eleven DFNA 9 patients were included in the study as well as a comparative group of 39 post-lingually deafened cochlear implant subjects with adult-onset progressive sensorineural hearing loss. INTERVENTIONS: All patients received a cochlear implant. Subjects were implanted with either the Nucleus 24 M/RCS or Med-el Combi 40+ cochlear implant systems implementing the SPEAK, ACE, or CIS+ coding strategies. MEAN OUTCOME MEASURES: Speech recognition was determined by means of phonetically balanced monosyllabic word lists. The Hearing Handicap Inventory for Adults, the Glasgow Benefit Inventory, and the Scale for the Prediction of Hearing Disability in Sensorineural Hearing Loss were used to quantify the quality of life. RESULTS: The results show that the speech perception and the quality of life of the DFNA 9 patients do not differ significantly from the control group (p=0.179; p=0.56). CONCLUSION: In spite of the fact that DFNA 9 is a disease that is known to involve cochlear dendrites, cochlear implantation is a good option for treatment of deafness in DFNA 9.

Cochlear implantation: a bionic system to restore hearing in severely hearing impaired patients.

CI replaces and functionally bypasses the inner haircells of the cochlea. Candidate selection is not merely based on non-aided auditory thresholds, but aided speech recognition tests in quite and in noise after a rehabilitation period may be decisive, besides a comprehensive selection process including general health, imaging, learning and cognitive skills, supportive aspect of the environment. The vast majority of severely or profoundly hearing impaired persons can benefit from CI. CI restores hearing of adults to a level allowing normal conversation, using the telephone and even understanding in a limited amount of background noise. Congenitally severely or profoundly hearing impaired children implanted before the age of 2 years, will outperform patients operated at a later age, allowing to follow mainstream education. CI is not just a technique, but the driving force behind an elaborate care-programme for the severely hearing impaired patient.