BACKGROUND: Balloon catheters facilitate pulmonary vein (PV) isolation, but current technology is limited by either a single ablative element, potentially leading to over-ablation of thin and under-ablation of thick tissue, or prolonged procedure times. Visualized by electroanatomical mapping, a novel compliant radiofrequency balloon catheter with 10 irrigated, flexible electrodes can simultaneously and independently deliver energy. Herein, we evaluated the feasibility, safety, and short-term efficacy of this radiofrequency balloon in a multicenter, single-arm, first-in-human study. METHODS: Paroxysmal atrial fibrillation patients underwent PV isolation with the radiofrequency balloon delivered over-the-wire with a deflectable 13.5F sheath. Radiofrequency energy is delivered simultaneously from all electrodes-up to 30 s posteriorly and 60 s anteriorly. Esophageal temperature was monitored in all patients; the esophagus was also mechanically deviated in 10 patients. RESULTS: At 4 sites, 39 patients were treated by 9 operators. The radiofrequency balloon isolated all targeted PVs (152/152), 79.6% with a single application. Electrical reconnection occurred in only 7/150 PVs (4.7%) on adenosine/isoproterenol challenge. Mean procedure, balloon dwell, and fluoroscopy times were 101.6, 40.5, and 17.4 min, respectively. Esophagogastroduodenoscopy revealed asymptomatic esophageal erythema in 5 patients. Phrenic nerve palsy occurred in a patient in whom phrenic pacing was inadvertently omitted. At 3 months, imaging revealed no PV stenosis, and early atrial arrhythmia recurrence occurred in only 10/39 (25.6%) patients. CONCLUSIONS: The compliant radiofrequency balloon can directionally tailor energy delivery for efficient, effective, and reasonably safe acute PV isolation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: ISRCTN 11764506.

• MeSH
• akční potenciály MeSH
• časové faktory MeSH
• design vybavení MeSH
• fibrilace síní diagnóza   patofyziologie   chirurgie   MeSH
• katetrizační ablace škodlivé účinky   přístrojové vybavení   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pooperační komplikace etiologie   MeSH
• prospektivní studie MeSH
• recidiva MeSH
• senioři MeSH
• srdeční frekvence * MeSH
• srdeční katetrizace škodlivé účinky   přístrojové vybavení   MeSH
• srdeční katétry * MeSH
• venae pulmonales patofyziologie   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

• MeSH
• Collesova fraktura * diagnóza   chirurgie   MeSH
• fraktury vřetenní kosti diagnóza   chirurgie   MeSH
• intraartikulární fraktury diagnóza   klasifikace   MeSH
• klasifikace * metody   MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• multicentrické studie jako téma MeSH
• poranění zápěstí diagnóza   klasifikace   MeSH
• radius zranění   MeSH
• statistika jako téma MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Contact force (CF) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation. This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation. METHODS AND RESULTS: A total of 300 patients with symptomatic, drug-refractory, paroxysmal atrial fibrillation were enrolled in a prospective, multicenter, randomized, controlled trial and randomized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter (control). The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months. The primary safety end point included device-related serious adverse events. End points were powered to show noninferiority. All pulmonary veins were isolated in both groups. Effectiveness was achieved in 67.8% and 69.4% of subjects in the CF and control arms, respectively (absolute difference, -1.6%; lower limit of 1-sided 95% confidence interval, -10.7%; P=0.0073 for noninferiority). When the CF arm was stratified into optimal CF (≥90% ablations with ≥10 g) and nonoptimal CF groups, effectiveness was achieved in 75.9% versus 58.1%, respectively (P=0.018). The primary safety end point occurred in 1.97% and 1.40% of CF patients and control subjects, respectively (absolute difference, 0.57%; upper limit of 1-sided 95% confidence interval, 3.61%; P=0.0004 for noninferiority). CONCLUSIONS: The CF ablation catheter met the primary safety and effectiveness end points. Additionally, optimal CF was associated with improved effectiveness. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01278953.

• MeSH
• fibrilace síní diagnóza   chirurgie   MeSH
• katetrizační ablace škodlivé účinky   metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• perikarditida diagnóza   etiologie   MeSH
• převodní systém srdeční abnormality   MeSH
• prospektivní studie MeSH
• senioři MeSH
• srdeční arytmie diagnóza   etiologie   MeSH
• srdeční katetrizace škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population. METHODS: We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. RESULTS: The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P=0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. CONCLUSIONS: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.).

• MeSH
• analýza přežití MeSH
• antigeny CD274 metabolismus   MeSH
• antigeny CD279 imunologie   MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• imunoglobulin G MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• nádory plic farmakoterapie   mortalita   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   MeSH
• senioři MeSH
• spinocelulární karcinom farmakoterapie   mortalita   MeSH
• taxoidy škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Cieľ Chromozómové prestavby zahŕňajúce gén tyrozínkinázy receptoru ROS1 boli nedávno popísané v podskupine nemalobunkových karcinómov pľúc (NSCLC). Pretože o týchto tumoroch sa vie málo, skúmali sme klinické charakteristiky a výsledky liečby u pacientov s NSCLC a prestavbou ROS1. Pacienti a metódy Použitím metódy fluorescenčnej in situ hybridizácie (FISH) sme urobili skríning ROS1 u 1 073 pacientov s NSCLC a hľadali sme súvislosť prítomnosti prestavby ROS1 s klinickými charakteristikami, celkovým prežitím, a ak bol dostupný, so stavom prestavby ALK. Štúdie in vitro zistili u buniek s prestavbou ROS1 odpoveď na tyrozínkinázový inhibítor crizotinib. Klinická odpoveď na crizotinib u jedného pacienta s NSCLC a prestavbou ROS1 bola skúmaná ako súčasť rozšírenej kohorty fázy I. Výsledky Zo skríningu 1 073 tumorov bola pomocou FISH zistená prestavba ROS1 u 18 (1,7 %), u 31 (2,9 %) bola prestavba ALK. V porovnaní s ROS1-negatívnou skupinou boli pacienti s prestavbami ROS1 signifi kantne mladší a častejšie boli celoživotní nefajčiari (obe p < 0,001). Všetky z ROS1- -pozitívnych tumorov boli adenokarcinómy, s tendenciou k vyššiemu gradingu. V ROS1-pozitívnej a ROS1-negatívnej skupine nebol zistený rozdiel v celkovom prežití. V bunkovej línii NSCLC HCC78 s prestavbou ROS1 a v 293 bunkách s transfekciou CD74-ROS1 sa dokázala citlivosť na crizotinib. U pacienta liečeného crizotinibom sa dosiahlo zmenšenie nádoru s takmer kompletnou odpoveďou. Záver Prestavba ROS1 predstavuje molekulárny podtyp NSCLC s osobitými klinickými charakteristickými vlastnosťami podobnými tým, ktoré sa pozorujú u pacientov NSCLC s prestavbou ALK. Crizotinib preukazuje aktivitu in vitro i prvé dôkazy o klinickej aktivite u NSCLC s prestavbou ROS1.

• MeSH
• adenokarcinom MeSH
• analýza přežití MeSH
• biologické markery * MeSH
• buněčné linie * účinky léků   MeSH
• dospělí MeSH
• etnicita MeSH
• fúze genů MeSH
• genová přestavba MeSH
• hybridizace in situ fluorescenční MeSH
• klinické zkoušky, fáze I jako téma MeSH
• kouření MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádory plic genetika   MeSH
• nemalobuněčný karcinom plic * genetika   terapie   MeSH
• plošný screening MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• statistika jako téma MeSH
• techniky in vitro MeSH
• tyrosinkinasy * antagonisté a inhibitory   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

• Publikační typ
• abstrakt z konference MeSH

Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS: We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS: Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS: Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

• MeSH
• analýza podle původního léčebného záměru MeSH
• B-lymfocyty účinky léků   MeSH
• cyklofosfamid škodlivé účinky   terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• financování organizované MeSH
• glukokortikoidy škodlivé účinky   terapeutické užití   MeSH
• granulomatóza s polyangiitidou farmakoterapie   MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• indukce remise MeSH
• kombinovaná farmakoterapie MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• methylprednisolon MeSH
• mikroskopická polyangiitida MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• nádory epidemiologie   MeSH
• prednison terapeutické užití   MeSH
• protilátky proti cytoplazmě neutrofilů krev   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH

Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage. OBJECTIVE: To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation. DESIGN: Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003. SETTING: An integrated health care delivery system. PATIENTS: 13 559 adults with nonvalvular atrial fibrillation. MEASUREMENTS: Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism. RESULTS: Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used. LIMITATIONS: Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable. CONCLUSION: Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation. PRIMARY FUNDING SOURCE: National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

• MeSH
• antikoagulancia aplikace a dávkování   MeSH
• fibrilace síní komplikace   MeSH
• financování organizované MeSH
• intrakraniální krvácení prevence a kontrola   MeSH
• ischemie mozku prevence a kontrola   MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• sekundární prevence MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tromboembolie prevence a kontrola   MeSH
• věkové faktory MeSH
• warfarin aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH