RESUMO
BACKGROUND: Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years. OBJECTIVE: We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway. METHODS: Recombinant major cat dander allergen Fel d 1 was fused to a translocation sequence (TAT) and to part of the human invariant chain, generating a modular antigen transporter (MAT) vaccine (MAT-Fel d 1). In a randomized double-blind trial ILIT with MAT-Fel d 1 in alum was compared with ILIT with placebo (saline in alum) in allergic patients (ClinicalTrials.govNCT00718679). RESULTS: ILIT with MAT-Fel d 1 elicited no adverse events. After 3 placebo injections within 2 months, nasal tolerance increased less than 3-fold, whereas 3 intralymphatic injections with MAT-Fel d 1 increased nasal tolerance 74-fold (P < .001 vs placebo). ILIT with MAT-Fel d 1 stimulated regulatory T-cell responses (P = .026 vs placebo) and increased cat dander-specific IgG(4) levels by 5.66-fold (P = .003). The IgG(4) response positively correlated with IL-10 production (P < .001). CONCLUSION: In a first-in-human clinical study ILIT with MAT-Fel d 1 was safe and induced allergen tolerance after 3 injections.
Assuntos
Alérgenos/administração & dosagem , Dessensibilização Imunológica , Glicoproteínas/administração & dosagem , Hipersensibilidade/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Alérgenos/efeitos adversos , Alérgenos/genética , Alérgenos/metabolismo , Animais , Formação de Anticorpos/efeitos dos fármacos , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/metabolismo , Gatos , Células Cultivadas , Feminino , Glicoproteínas/efeitos adversos , Glicoproteínas/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Imunoglobulina G/sangue , Injeções Intralinfáticas , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Engenharia de Proteínas , Proteínas Recombinantes de Fusão/genética , Testes Cutâneos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Adulto JovemRESUMO
BACKGROUND: Duty-cycled radiofrequency (DCRF) is increasingly used for ablation of atrial fibrillation (AF). Many patients also have atrial flutter (AFL). Recently, a linear multielectrode has been shown to create linear block at the cavotricuspid isthmus and in the left atrium (LA). OBJECTIVE: To map and ablate atypical AFL and atrial tachycardias (ATs) in the right and LA using a linear multielectrode with DCRF. METHODS: The linear multielectrode delivers DCRF at 20-45 W maximum in 1:1 unipolar/bipolar temperature-controlled mode. Target temperatures were manually titrated to 60 °C in the LA, if power >5W indicated adequate passive cooling. RESULTS: A total of 76 AT/AFL were targeted in 57 patients. Acute success was reached in 14/15 (93%) right AT, in 17/22 (77%) left atrial roof AFL, in 5/6 (83%) septal AFL, in 9/9 (100%) other left atrial AT, but only in 8/23 (35%) AFL from the mitral isthmus (which rose to 13/23 [57%] with additional use of irrigated radiofrequency). Nevertheless, freedom of AF/AFL 10 ± 6 months after a single procedure was documented in 92% of right AT, 71% of roof AFL, 73% for mitral AFL, and 60% of septal or other LA AT/AFL. No char formation was noted. However, frequent induction of AF and one case of asystole occurred during delivery of DCRF in a pacemaker patient. CONCLUSION: The linear multielectrode allows mapping and ablation of atypical AFL/AT. Freedom of AF/AT was reached in 60%-92% depending on localization and number of arrhythmias. Technical modifications will improve safety and efficacy.
Assuntos
Flutter Atrial/cirurgia , Ablação por Cateter/instrumentação , Taquicardia Atrial Ectópica/cirurgia , Adulto , Idoso , Ablação por Cateter/métodos , Eletrocardiografia , Feminino , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Duty-cycled (DC) radiofrequency ablation (RFA) for atrial fibrillation (AF) has been introduced, however, data on large patient series and comparison to conventional RFA are scarce. METHODS: Between 2006 and 2008 DC RFA was performed in 209 consecutive patients (143 (68%) paroxysmal and 66 (32%) persistent AF). As controls served 211 patients, 155 (73%) with paroxysmal and 56 (27%) with persistent AF (p=0.3). In DC RFA, the pulmonary veins (PV) were isolated followed by ablation at the septum and left atrium, if AF persisted. Conventional PV isolation was followed by anatomical lines at the roof and mitral isthmus. RESULTS: Freedom of paroxysmal AF was demonstrated after 1.08 DC RFA procedures per patient in 82% and after 1.19 conventional procedures in 87% after 8.5 ± 6.5 months (ns). In persistent AF, success rates were 79% after 1.35 DC RFA procedures and 80% after 1.34 conventional procedures after 11.5 ± 8.5 months (ns). The subgroup analysis of 119 patients with follow-up ≥ 12 months (17.5 [14.1-23.6] months) showed similar results. Left atrial flutter occurred in 3% and 8% after paroxysmal AF ablation (p < 0.05) and in 12% and 23% after persistent AF ablation (p=0.1). Multivariate predictors for success in both groups were age, left atrial size, presence of persistent vs. paroxysmal AF and previous pacemaker implantation, but not the ablation technique used. Non-fatal complications were seen in 2.8% with no differences between the groups. CONCLUSION: Outcome in DC RFA is similar to conventional RFA with a final success rate exceeding 80% in both paroxysmal and persistent AF in the absence of fatal complications.