Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: results from the global valve-in-valve registry.

BACKGROUND: Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. METHODS AND RESULTS: The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. CONCLUSIONS: The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

UNLABELLED: Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7-7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4-5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46-103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1-2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION: clinicaltrials.gov NTC02092116.

Le reflux gastro-oesophagien de l'enfant: indications chirurgicales, techniques et suivi.

Contexte: Présent sous forme physiologique chez environ 60% des nourrissons normaux de moins de quatre mois, le reflux gastro-oesophagien (RGO) n'est symptomatique que chez 10% d'entre eux. Il est également plus fréquent chez les enfants atteints de troubles neurologiques quelque soit leur âge. Non traité, il peut avoir des conséquences graves (oesophagite, sténose peptique, endobrachyoesophage (Barrett) puis adénocarcinome de l'oesophage). Il s'agit donc d'un problème qu'il faut savoir détecter et traiter précocement. Les signes et symptômes du RGO sont multiples et varient en fonction de l'âge. Ils ne se limitent pas au seul vomissement. Le traitement initial du RGO chez l'enfant est médical. En cas d'échec de celui-ci ou dans certaines indications (comme les RGO récidivants, les malformations congénitales, les anomalies morphologiques ou les pathologies neurologiques) un traitement chirurgical est nécessaire. L'évolution des traitements conservateurs et des techniques chirurgicales lors de ces dernières années en font un bon sujet pour une étude rétrospective. Objectif: Le but de cette étude est de mettre en évidence dans une population d'enfants ayant bénéficié d'une cure chirurgicale anti-reflux la fréquence relative des symptômes selon la pathologie initiale de l'enfant, puis de préciser le choix de traitement et sa durée. Nous analyserons également les risques d'échec qui s'y rapportent. Ces conclusions devraient nous permettre de proposer un algorithme décisionnel de prise en charge du RGO de l'enfant en pré et post-opératoire. Méthodologie: Étude rétrospective sur 9 ans se basant sur les dossiers médicaux-chirurgicaux de 132 enfants opérés d'un reflux gastro-oesophagien dans le Service de Chirurgie Pédiatrique du Centre Hospitalier Universitaire Vaudois (CHUV) par le Professeur Olivier Reinberg et son équipe entre le 1er janvier 2003 et le 31 décembre 2012. Résultats: Sur les 132 enfants, 93 ont bénéficié d'une fundoplicature selon Toupet, 34 selon Nissen et 5 selon Dor. 57% des enfants présentant un déficit neurologique ont été opérés selon la technique de Nissen contre 7% des enfants "sains". Les taux de démontage et de récidive sont respectivement 5.4% et 3.5 % pour la technique selon Toupet et 2.9% et 0% pour la technique de Nissen. Le taux de démontage global de la fundoplicature est de 4.6% (N=6) Conclusions: La fundoplicature est une méthode de choix pour les enfants chez qui tous les autres traitements ont échoué ou chez qui la présence concomitante du RGO et des comorbidités est délétère à une croissance harmonieuse. Grâce à la chirurgie, la qualité de vie d'au moins 95% des enfants est grandement améliorée après la disparition de symptômes quotidiens et qui peuvent donner lieu à des complications graves.

Complicações do tratamento laparoscópico da doença do refluxo gastroesofágico: experiência com 600 casos

O objetivo do presente estudo é apresentar as complicações que ocorreram em seiscentos pacientes consecutivos com doença do refluxo gastroesofágico submetidos à fundoplicatura laparoscópica. O procedimento de Nissen-Rosetti (fundoplicatura de 360°) foi realizado em 587 pacientes (97,8%) e o de Toupet (fundoplicatura de 270°) em 13 (2,2%). Oitenta e um pacientes também foram submetidos à colecistectomia no mesmo ato operatório, e um a diverticulectomia faringoesofágica cervical com miotomia cricofaringeana. Trinta e nove pacientes tinham operação prévia no abdome superior. O período de internação hospitalar variou de 12 horas a 23 dias, com média de 1,2 dias. A via de acesso foi convertida em laparotomia em dez pacientes (1,7%). A principal causa de conversão foi a presença de aderências. A complicação intra- operatória mais freqüente foi pneumotórax, que foi observado em oito pacientes. Todos os pneumotóraces ocorreram nos cem primeiros casos. Cinco pacientes apresentaram hemorragia significante, sendo que dois deles necessitaram laparotomia para controle do sangramento. Úlcera gástrica foi diagnosticada em sete pacientes. Um paciente etilista morreu de pancreatite aguda e outro de síndrome de disfunção de múltiplos órgãos e sistemas conseqüente à perfuração gástrica. Outras complicações importantes foram: dois abscessos intra-abdominais, uma perfuração esofágica, uma sepse secundária à perfuração gástrica, um choque hemorrágico e uma obstrução gástrica secundária à herniação da fundoplicatura. Concluímos que a taxa de complicações da fundoplicatura laparoscópica é baixa e diminui significativamente com a experiência do cirurgião.

Tratamento cirúrgico do refluxo gastroesofágico na esclerodermia

OBJETIVO: A esclerodermia é caracterizada pelo aumento fibrótico do tecido conectivo. O envolvimento esofágico atinge 75 a 90% dos pacientes. O receio em se construir uma válvula em um esôfago hipotônico levou às operações de ressecção, que têm morbidade significante. Posteriormente, estudos com técnicas anti-refluxo demonstraram regressão dos sintomas em 69 a 75% dos pacientes. MÉTODO: Sete pacientes femininas (32 a 59 anos, seguimento entre seis e 48 meses) com esclerodermia apresentavam pirose e havia disfagia em seis casos. Quatro pacientes com estenoses necessitaram dilatações. Quatro pacientes foram submetidas à técnica de Nissen modificada e três pacientes à técnica de Lind, por via laparoscópica. Houve uma conversão. RESULTADOS: Todas obtiveram alguma melhora clínica, exceto uma em que houve migração da válvula. Quatro pacientes ficaram com Visick grau I (58%), uma com grau II (14%), uma com grau III (14%) e uma com grau IV (14%). Não houve retardo importante do esvaziamento esofágico à cintilografia, e os exames não demonstraram mais estenoses. CONCLUSÃO: O tratamento cirúrgico anti-refluxo é eficaz em regredir os sintomas da DRGE na esclerodermia, sem comprometer a função esofágica. As ressecções são indicadas para falha do tratamento inicial, pacientes com estenoses graves ou lesões malignas.

Curva de aprendizado na fundoplicatura laparoscópica durante a residência médica em cirurgia geral

OBJETIVO: A fundoplicatura laparoscópica a 360º é o tratamento de escolha para pacientes com doença do refluxo gastroesofágico que não respondem bem ao tratamento clínico. Este artigo demonstra a curva de aprendizado durante a Residência Médica em Cirurgia Geral. MÉTODO: Foi realizada uma análise retrospectiva de 60 pacientes submetidos à fundoplicatura laparoscópica durante o período de março a outubro de 2005. Os pacientes foram divididos em dois grupos: 30 casos iniciais que foram comparados aos 30 casos subseqüentes. As variáveis analisadas incluíram: tempo operatório, taxa de conversão, complicações e tempo de hospitalização. RESULTADOS: A fundoplicatura laparoscópica foi realizada em 18 homens e 42 mulheres, com idade média de 48,3 anos. Comparando os dois grupos, houve diferença estatisticamente significativa no tempo operatório total (92,7 vs. 76,7 minutos, p=0,003), no tempo operatório para a operação de Nissen-Rossetti (86,7 vs. 68,4 minutos, p=0,00006) e no tempo para a liberação dos vasos gástricos curtos (22 vs. 13,1 minutos, p=0,00005). As complicações intra-operatórias foram maiores no primeiro grupo de pacientes, mas a diferença não foi estatisticamente significativa (p=0,2). Todos os procedimentos foram concluídos com sucesso por vídeo-laparoscopia em ambos os grupos, e a mortalidade foi nula nesta série. A alta hospitalar ocorreu em média no primeiro dia de pós-operatório em ambos os grupos (p=0,06). CONCLUSÃO: A fundoplicatura laparoscópica pode ser realizada com segurança por um cirurgião em formação, sob supervisão direta de um titular, com mínima morbidade para os pacientes. A curva de aprendizado foi demonstrada, avaliando-se principalmente, o tempo operatório do procedimento.

Genetic diversity among proso millet (Panicum miliaceum) biotypes assessed by AFLP technique

The Amplified Fragment Length Polymorphism (AFLP) technique was used to access genetic diversity between three domestic and nine wild proso millet biotypes from the United States and Canada. Eight primer combinations detected 39 polymorphic DNA fragments, with the genetic distance estimates among biotypes ranging from 0.02 to 0.04. Colorado-Weld County black seeded and Wyoming-Platte County were the most distinct biotypes according to the dissimilarity level. A UPGMA cluster analysis revealed two distinct groups of proso millet without any geographic association. Six weed biotypes exhibiting some characters of cultivated plants were grouped together with domesticated biotypes of proso millet while the three typical wild phenotypes were clearly clustered into another group according to AFLP markers.

Eficacia de la melatonina en insomnio primario en el adulto mayor: revisión sistemática de la literatura

Introducción: La melatonina, una sustancia cronobiótica endógena, es cada vez más empleada para el manejo de los problemas del sueño en adultos mayores por su aparente eficacia y buen perfil de eventos adversos. En este sentido, se intentó evaluar la eficacia de la melatonina en el tratamiento del insomnio primario en el adulto mayor (≥55 años) comparado con benzodiacepinas, zopiclona y placebo a la luz de la evidencia disponible en los últimos cinco años. Métodos: Revisión sistemática de la literatura. Resultados: En comparación con placebo, al parecer la melatonina mejora la calidad y los hábitos de sueño, no así la latencia de inicio de sueño en mediciones subjetivas ni objetivas (polisomnografía); a diferencia de otros medicamentos hipnóticos, no altera la arquitectura del sueño ni genera síntomas diurnos. Conclusiones: No se encontró evidencia que soporte el uso de melatonina en adultos mayores de 55 años para la reducción de la latencia de sueño, aumento del tiempo total de sueño, mejoría de la eficiencia del sueño, disminución de despertares nocturnos o mejoría de la calidad de sueño. Es necesario adelantar más estudios en comparación con placebo y otros medicamentos.

ENABLE: a wrist worn device with integrated accessible services to support old people living independently and safely at home

This RTD project, 2007-2009, is partly funded by the European Commission, in Framework Programme 6. It aims to assist elderly people for living well, independently and at case. ENABLE will provide a number of services for elderly people based on the new technology provided by mobile phones. The project is developing a Wrist unit with both integrated and external sensors, and with a radio frequency link to a mobile phone. Dedicated ENABLE software running on the wrist unit and mobile phone makes these services fully accessible for the elderly users. This paper outlines the fundamental motivation and the approach which currently is undertaken in order to collect the more detailed user needs and requirements. The general architecture and the design of the ENABLE system are outlined.

Mediterranean cyclones and windstorms in a changing climate

Changes in the frequency and intensity of cyclones and associated windstorms affecting the Medi-terranean region simulated under enhanced Greenhouse Gas forcing conditions are investigated. The analysis is based on 7 climate model integrations performed with two coupled global models (ECHAM5 MPIOM and INGV CMCC), comparing the end of the twentieth century and at least the first half of the twenty-first century. As one of the models has a considerably enhanced resolution of the atmosphere and the ocean, it is also investigated whether the climate change signals are influenced by the model resolution. While the higher resolved simulation is closer to reanalysis climatology, both in terms of cyclones and windstorm distributions, there is no evidence for an influence of the resolution on the sign of the climate change signal. All model simulations show a reduction in the total number of cyclones crossing the Mediterranean region under climate change conditions. Exceptions are Morocco and the Levant region, where the models predict an increase in the number of cyclones. The reduction is especially strong for intense cyclones in terms of their Laplacian of pressure. The influence of the simulated positive shift in the NAO Index on the cyclone decrease is restricted to the Western Mediterranean region, where it explains 10–50 % of the simulated trend, depending on the individual simulation. With respect to windstorms, decreases are simulated over most of the Mediterranean basin. This overall reduction is due to a decrease in the number of events associated with local cyclones, while the number of events associated with cyclones outside of the Mediterranean region slightly increases. These systems are, however, less intense in terms of their integrated severity over the Mediterranean area, as they mostly affect the fringes of the region. In spite of the general reduction in total numbers, several cyclones and windstorms of intensity unknown under current climate conditions are identified for the scenario simulations. For these events, no common trend exists in the individual simulations. Thus, they may rather be attributed to long-term (e.g. decadal) variability than to the Greenhouse Gas forcing. Nevertheless, the result indicates that high-impact weather systems will remain an important risk in the Mediterranean Basin.

Cyclones causing wind storms in the Mediterranean: characteristics, trends and links to large-scale patterns

A climatology of cyclones with a focus on their relation to wind storm tracks in the Mediterranean region (MR) is presented. Trends in the frequency of cyclones and wind storms, as well as variations associated with the North Atlantic Oscillation (NAO), the East Atlantic/West Russian (EAWR) and the Scandinavian variability pattern (SCAND) are discussed. The study is based on the ERA40 reanalysis dataset. Wind storm tracks are identified by tracking clusters of adjacent grid boxes characterised by extremely high local wind speeds. The wind track is assigned to a cyclone track independently identified with an objective scheme. Areas with high wind activity – quantified by extreme wind tracks – are typically located south of the Golf of Genoa, south of Cyprus, southeast of Sicily and west of the Iberian Peninsula. About 69% of the wind storms are caused by cyclones located in the Mediterranean region, while the remaining 31% can be attributed to North Atlantic or Northern European cyclones. The North Atlantic Oscillation, the East Atlantic/West Russian pattern and the Scandinavian pattern all influence the amount and spatial distribution of wind inducing cyclones and wind events in the MR. The strongest signals exist for the NAO and the EAWR pattern, which are both associated with an increase in the number of organised strong wind events in the eastern MR during their positive phase. On the other hand, the storm numbers decrease over the western MR for the positive phase of the NAO and over the central MR during the positive phase of the EAWR pattern. The positive phase of the Scandinavian pattern is associated with a decrease in the number of winter wind storms over most of the MR. A third of the trends in the number of wind storms and wind producing cyclones during the winter season of the ERA40 period may be attributed to the variability of the North Atlantic Oscillation.