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1.
Opt Lett ; 49(7): 1684-1687, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38560836

RESUMEN

Dual-comb spectroscopy in the ultraviolet (UV) and visible would enable broad bandwidth electronic spectroscopy with unprecedented frequency resolution. However, there are significant challenges in generation, detection, and processing of dual-comb data that have restricted its progress in this spectral region. In this work, we leverage robust 1550 nm few-cycle pulses to generate frequency combs in the UV-visible. We combine these combs with a wavelength multiplexed dual-comb spectrometer and simultaneously retrieve 100 MHz comb-mode-resolved spectra over three distinct harmonics at 386, 500, and 760 nm. The experiments highlight the path to continuous dual-comb coverage spanning 200-750 nm, offering extensive access to electronic transitions in atoms, molecules, and solids.

2.
Int J Immunogenet ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898624

RESUMEN

Narcolepsy is a sleep disorder caused by an apparent degeneration of orexin/hypocretin neurons in the lateral hypothalamic area and a subsequent decrease in orexin/hypocretin levels in the cerebrospinal fluid. Narcolepsy is classified into type 1 (NT1) and type 2 (NT2). While genetic associations in the human leukocyte antigen (HLA) region and candidate autoantibodies have been investigated in NT1 to imply an autoimmune origin, less is known about the pathogenesis in NT2. Twenty-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-DRB3, -DRB4, -DRB5, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01 (odds ratio [OR]: 9.15; p = 8.31 × 10-4) and HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB4*01:03:01, -DRB1*04:01:01, -DQA1*03:02//03:03:01, -DQB1*03:01:01 (OR: 23.61; p = 1.58 × 10-4) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (n = 5) that was associated with the extended HLA-DQB1*06:02:01 haplotype (p = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (p = .8524). We confirmed the previous association of NT1 with HLA-DQB1*06:02:01 extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with HLA-DQB1*06:02:01 was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.

3.
Eur J Immunol ; 51(1): 247-249, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32671842

RESUMEN

Increased incidence of narcolepsy type 1 (NT1) was observed following Pandemrix®-vaccination, initiated as a preventive measure against the 2009 Influenza pandemic. Here, single cell analysis was conducted to suggest a lower number of CD8+ CD27+ T cells among these patients. These findings provide understanding into the autoimmune pathogenesis of NT1.


Asunto(s)
Vacunas contra la Influenza/efectos adversos , Narcolepsia/etiología , Narcolepsia/inmunología , Algoritmos , Basófilos/inmunología , Linfocitos T CD8-positivos/clasificación , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Citometría de Flujo , Cadenas beta de HLA-DQ/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Hermanos , Análisis de la Célula Individual
4.
Int J Immunogenet ; 49(5): 333-339, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35959717

RESUMEN

Multiple sclerosis (MS) is a chronic neurological disease believed to be caused by autoimmune pathogenesis. The aetiology is likely explained by a complex interplay between inherited and environmental factors. Genetic investigations into MS have been conducted for over 50 years, yielding >100 associations to date. Globally, the strongest linkage is with the human leukocyte antigen (HLA) HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype. Here, high-resolution sequencing of HLA was used to determine the alleles of DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1 and DPB1 as well as their extended haplotypes and genotypes in 100 Swedish MS patients. Results were compared to 636 population controls. The heterogeneity in HLA associations with MS was demonstrated; among 100 patients, 69 extended HLA-DR-DQ genotypes were found. Three extended HLA-DR-DQ genotypes were found to be correlated to MS; HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype together with (A) HLA-DRB4*01:01:01//DRB4*01:01:01:01-DRB1*07:01:01-DQA1*02:01//02:01:01-DQB1*02:02:01, (B) HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01, and (C) HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01. At the allelic level, HLA-DRB3*01:01:02 was considered protective against MS. However, when combined with HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01, this extended haplotype was considered a predisposing risk factor. This highlights the limitations as included with investigations of single alleles relative to those of extended haplotypes/genotypes. In conclusion, with 69 genotypes presented among 100 patients, high-resolution sequencing was conducted to underscore the wide polymorphisms present among MS patients. Additional studies in larger cohorts will be of importance to define MS among the patient group not associated with HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01.


Asunto(s)
Esclerosis Múltiple , Antígenos HLA , Cadenas alfa de HLA-DQ/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB3/genética , Cadenas HLA-DRB5/genética , Haplotipos , Humanos , Esclerosis Múltiple/genética , Suecia
5.
Minim Invasive Ther Allied Technol ; 31(6): 909-916, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34915823

RESUMEN

BACKGROUND: We aimed to evaluate the outcomes of transapical and transaortic transcatheter aortic valve replacement (TAVR) in high-risk patients who were not suitable for transfemoral access and had a logistic EuroSCORE-I ≥ 25% and Society of Thoracic Surgeons (STS) score >6%. 'STS/ACC TAVR In-Hospital Mortality Risk App' was evaluated. MATERIAL AND METHODS: Between January 2016 and May 2020, 126 patients at very high risk for aortic valve replacement underwent transapical (n = 121) or transaortic (n = 5) transcatheter aortic valve replacement. TAVR was performed using SAPIEN 3™ or ACURATE TA™ prosthesis. RESULTS: The logistic EuroSCORE-I was 40.6 ± 14.0%, the STS-score 7.9 ± 4.6%, and STS/ACC-score 8.4 ± 3.4%. Valve implantation was successful in all patients. Operative, in-hospital and 30-days mortality, were 0, 7.9, and 13.5%, respectively. Survival was 72% at one year and 48% at four years. Expected/observed in-hospital mortality was 1.0 for the STS-score and 1.06 for the STS/ACC-score. Renal failure, low ejection fraction, and postoperative acute kidney injury, hemorrhage, and vascular complications were identified as independent predictors for 30-day mortality. CONCLUSIONS: Transapical and transaortic TAVR in high-risk patients unsuitable for transfemoral access is still a reasonable alternative in these patients. STS and STS/ACC-score appear to be highly accurate in predicting in-hospital mortality in high-risk patients undergoing TAVR.


Asunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
6.
J Card Surg ; 36(4): 1226-1231, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33491207

RESUMEN

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) techniques are increasingly being adopted into clinical routine for various risk groups. Coronary artery disease (CAD) is seen in up to 75% of patients with severe aortic valve stenosis (AS) presenting with typical angina pectoris. Due to high mortality rates and procedural complications in these patients, a hybrid concept of simultaneous transaortic TAVI and off-pump coronary artery bypass (OPCAB) can be a feasible treatment option. METHODS: Between April 2014 and July 2020, 10 consecutive high-risk patients underwent concomitant transaortic TAVI and OPCAB at our institution. All indications were discussed in Heart Team and decisions were made based on patients' comorbidities and complexity of CAD. The study endpoints were 30-day mortality, device success, and development of postoperative adverse events defined by the Valve Academic Research Consorium. RESULTS: The mean age of the patients was 77.9 ± 7.1 years old. All patients presented with multiple comorbidities (mean logistic EuroSCORE 26.5 ± 12.3%, median EuroSCORE II 5.13% [interquartile range 4.2-9.5], mean STS-Score 6.04 ± 1.6%). Five patients (50%) presented with porcelain aorta. No conversion to conventional procedures was needed. 30-day mortality occurred in one patient (10%). Complete revascularization was achieved in seven (70%) of the patients. Device success rate was 100%. No paravalvular leakage was detected. No stroke, myocardial infarction or vascular complications were observed. CONCLUSIONS: A hybrid approach combining transaortic TAVI and OPCAB might be a safe and feasible method of treatment in high-risk patients presenting with severe AS and CAD who are not eligible for conventional surgical or interventional solutions.


Asunto(s)
Estenosis de la Válvula Aórtica , Puente de Arteria Coronaria Off-Pump , Enfermedad de la Arteria Coronaria , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Factores de Riesgo , Resultado del Tratamiento
7.
Medicina (Kaunas) ; 57(12)2021 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-34946276

RESUMEN

Background and Objectives: Permanent pacemaker implantation (PPI) is frequently required following transcatheter aortic valve replacement (TAVR). Dual antiplatelet therapy (DAPT) or oral anticoagulation therapy (OAK) is often necessary in these patients since they are at higher risk of thromboembolic events due to TAVR implantation, high incidence of coronary artery diseases (CAD) with the necessity of coronary intervention, and high rate of atrial fibrillation with the need of stroke prevention. We sought to evaluate the safety, efficiency, and clinical outcomes of early PPI following TAVR using the PlasmaBlade™ (Medtronic Inc., Minneapolis, MN, USA) pulsed electron avalanche knife (PEAK) for bleeding control in patients under DAPT or OAK. Materials and Methods: This retrospective single-center study included patients who underwent PPI after transfemoral TAVR (TF) at our center between December 2015 and May 2020. All PPI were performed using the PlasmaBlade™ Device. Results: The overall PPI rate was 14.1% (83 of 587 patients; 82.5 ± 4.6 years; 45.8% male). The PPI procedures were used to treat high-grade atrioventricular block (81.9%), severe sinus node dysfunction (13.3%), and alternating bundle branch block (4.8%). At the time of the procedure, 35 (42.2%) patients received DAPT, and 48 (57.8%) patients received OAK (50% with vitamin K antagonist (VKA) and 50% with novel oral anticoagulants (NOAK)). One device-pocket hematoma treated conservatively occurred in a patient (1.2%) receiving NOAK. Two re-operations were necessary in patients due to immediate lead dislocation (2.4%). Conclusions: The results of this study illustrate that the use of PlasmaBlade™ for PPI in patients after a TAVR who require antithrombotic treatment is feasible and might result into lower rates of severe bleeding complications compared to rates reported in the literature. Use of the PlasmaBlade device may be considered in this specific group of patients because of their high risk of bleeding.


Asunto(s)
Hemorragia/prevención & control , Marcapaso Artificial , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Válvula Aórtica/cirugía , Femenino , Hemorragia/epidemiología , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
8.
Scand J Immunol ; 91(4): e12864, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32056243

RESUMEN

Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin-producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®-vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two-step approach to identify autoantigens in patients that acquired NT1 after Pandemrix®-vaccination. Using arrays of more than 9000 full-length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first-degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and α-MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix®-induced NT1.


Asunto(s)
Autoanticuerpos/sangre , Autoantígenos/análisis , Vacunas contra la Influenza/efectos adversos , Narcolepsia/inmunología , Análisis por Matrices de Proteínas/métodos , Autoantígenos/inmunología , Femenino , Humanos , Masculino
9.
Opt Lett ; 45(9): 2660-2663, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32356840

RESUMEN

We report an all-fiber approach to generating sub-2-cycle pulses at 2 µm and a corresponding octave-spanning optical frequency comb. Our configuration leverages mature erbium:fiber laser technology at 1.5 µm to provide a seed pulse for a thulium-doped fiber amplifier that outputs 330 mW average power at a 100 MHz repetition rate. Following amplification, nonlinear self-compression in fiber decreases the pulse duration to 9.5 fs, or 1.4 optical cycles. The spectrum of the ultrashort pulse spans from 1 to beyond 2.4 µm and enables direct measurement of the carrier-envelope offset frequency. Our approach employs only commercially available fiber components, resulting in a design that is easy to reproduce in the larger community. As such, this system should be useful as a robust frequency comb source in the near-infrared or as a pump source to generate mid-infrared frequency combs.

10.
Opt Lett ; 45(13): 3677-3680, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32630928

RESUMEN

We demonstrate mid-infrared (MIR) frequency combs at 10 GHz repetition rate via intra-pulse difference-frequency generation (DFG) in quasi-phase-matched nonlinear media. Few-cycle pump pulses (≲15fs, 100 pJ) from a near-infrared electro-optic frequency comb are provided via nonlinear soliton-like compression in photonic-chip silicon-nitride waveguides. Subsequent intra-pulse DFG in periodically poled lithium niobate waveguides yields MIR frequency combs in the 3.1-4.8 µm region, while orientation-patterned gallium phosphide provides coverage across 7-11 µm. Cascaded second-order nonlinearities simultaneously provide access to the carrier-envelope-offset frequency of the pump source via in-line f-2f nonlinear interferometry. The high-repetition rate MIR frequency combs introduced here can be used for condensed phase spectroscopy and applications such as laser heterodyne radiometry.

11.
Phys Rev Lett ; 124(13): 133904, 2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32302192

RESUMEN

The mid-infrared atmospheric window of 3-5.5 µm holds valuable information regarding molecular composition and function for fundamental and applied spectroscopy. Using a robust, mode-locked fiber-laser source of <11 fs pulses in the near infrared, we explore quadratic (χ^{(2)}) nonlinear optical processes leading to frequency comb generation across this entire mid-infrared atmospheric window. With experiments and modeling, we demonstrate intrapulse difference frequency generation that yields few-cycle mid-infrared pulses in a single pass through periodically poled lithium niobate. Harmonic and cascaded χ^{(2)} nonlinearities further provide direct access to the carrier-envelope offset frequency of the near infrared driving pulse train. The high frequency stability of the mid-infrared frequency comb is exploited for spectroscopy of acetone and carbonyl sulfide with simultaneous bandwidths exceeding 11 THz and with spectral resolution as high as 0.003 cm^{-1}. The combination of low noise and broad spectral coverage enables detection of trace gases with concentrations in the part-per-billion range.

12.
BMC Cardiovasc Disord ; 20(1): 267, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493384

RESUMEN

BACKGROUND: Parameters that mark the timing of left ventricular (LV) reverse remodeling following transcatheter aortic valve replacement (TAVR) are incompletely defined. This study aims to identify the dynamics of LV strain derived from speckle tracking echocardiography in a cohort of patients with severe aortic stenosis (AS) who underwent TAVR and its correlation with postprocedural outcomes. METHODS: We selected 150 consecutive patients (82 ± 4 years old, STS score 6.4 ± 6.2) who underwent transfemoral TAVR between 07/2016 and 12/2017 at our tertiary care center. All patients were evaluated at baseline, 1 week after TAVR, and 3 months following TAVR. RESULTS: The global longitudinal strain (GLS) 1 week following TAVR was comparable to that at baseline (- 15,9 ± 4.3 vs - 16.8 ± 4.1; p = NS) but significantly improved at 3 months following TAVR (- 15.9 ± 4.3% vs. -19.5 ± 3.5%; p < 0.001). No significant changes in global circumferential strain (GCS) and global radial strain (GRS) were detectable. The ejection fraction was significantly improved 1 week after the TAVR procedure. The baseline GLS correlated directly with the complication rate (R = 0.36, p = 0.005). The linear regression analysis showed that the main predictors of the improvement in the GLS at 3 months in our cohort were baseline GRS and GCS. CONCLUSION: GLS improves at 3 months after TAVR, while LV ejection fraction does not show a substantial change, signaling an early recovery of LV longitudinal function after the intervention. Additionally, GLS has a direct correlation with the postprocedural outcomes. GLS improvement might emerge as a valuable parameter for a tailored follow-up in TAVR patients.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Volumen Sistólico , Reemplazo de la Válvula Aórtica Transcatéter , Función Ventricular Izquierda , Remodelación Ventricular , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Femenino , Humanos , Masculino , Recuperación de la Función , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
13.
Eur J Vasc Endovasc Surg ; 58(6): 822-830, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31628049

RESUMEN

OBJECTIVES: Distal stent graft induced new entry (dSINE) is a rare complication associated with acute and chronic dissections after thoracic endovascular aortic repair (TEVAR) and is linked to a high re-intervention rate. The potential predicting risk factors for dSINE and long term outcome of patients after re-intervention were analysed. METHODS: This single centre, retrospective study included patients undergoing TEVAR. Multivariable analysis was used to test important interventional parameters such as distal oversizing (dOS), taper ratio (TR), angle between distal stent graft and aorta, acute dissection and stent graft length. Re-intervention characteristics were analysed and further long term follow up after re-intervention were evaluated. RESULTS: One hundred and eighty-five patients were analysed with acute (n = 77) and chronic (n = 108) dissections after TEVAR with an average follow up of 68.9 ± 32.5 months. During follow up, 12 (6.5%) patients developed dSINE after a median of 22.2 ± 20.7 months. Acute dissection was identified as a major predicting factor for dSINE development (15.8 fold increased odds), followed by increased dOS and TR. The re-intervention rate was higher in the dSINE group (83% vs. 20%, p = .001), but results indicated that no further re-intervention was needed and no new endoleak development occurred up to a mean follow up of 60.7 ± 54.8 months. No dSINE was seen in association with tapered stent grafts. CONCLUSIONS: Acute aortic dissection was found to be the major predicting factor for dSINE development, followed by increased dOS and TR. The use of tapered stent grafts might be beneficial for patients with high expected dOS and TR. In the rare case of dSINE occurrence, even when re-intervention is required, the long term prognosis is good.


Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Endofuga/epidemiología , Procedimientos Endovasculares/efectos adversos , Stents/efectos adversos , Anciano , Disección Aórtica/mortalidad , Aneurisma de la Aorta Torácica/mortalidad , Implantación de Prótesis Vascular/instrumentación , Endofuga/etiología , Endofuga/cirugía , Procedimientos Endovasculares/instrumentación , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
14.
Echocardiography ; 36(1): 28-37, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30484901

RESUMEN

OBJECTIVES: To evaluate the impact of baseline left ventricular ejection fraction (LVEF) and its interaction with low-gradient aortic stenosis (LGAS) on all-cause mortality after transfemoral aortic valve implantation (TF-TAVI). METHODS: We reviewed mortality data of 624 consecutive single center TF-TAVI patients and categorized LVEF according to current ASE/EACVI recommendations (normal, mildly-, moderately-, and severely abnormal). RESULTS: Baseline LVEF was normal in 336 (53.8%), mildly abnormal in 160 (25.6%), moderately abnormal in 91 (14.6%), and severely abnormal in 37 (5.9%) patients, and 1-year mortality was 19%, 17%, 23%, and 43% (P = 0.002), respectively. Patients with LGAS had a similar 1-year mortality compared to those without LGAS in groups with normal (19% vs 19%, P = 0.899) and mildly abnormal LVEF (16% vs 17%, P = 0.898). One-year mortality of patients with LGAS was significantly greater than in those without LGAS in presence of moderately abnormal LVEF (31% vs 11%, P = 0.022), and it was numerically greater than in those without LGAS in presence of severely abnormal LVEF (48% vs 25%, P = 0.219). In multivariate analysis, only the combination of moderately/severely abnormal LVEF and LGAS predicted increased 1-year mortality (HR: 2.12, 95% CI: 1.4-3.2, P < 0.001). Other variables, including EuroSCORE I did not affect this result. CONCLUSIONS: Moderately/severely abnormal LVEF (≤40%) at baseline is associated with increased mortality after TF-TAVI, especially when the mean transvalvular aortic gradient is <40 mm Hg (LGAS), while outcomes in patients with normal and mildly abnormal LVEF are comparable regardless of the pressure gradient across the native aortic valve. (DRKS00013729).


Asunto(s)
Estenosis de la Válvula Aórtica/complicaciones , Ecocardiografía/métodos , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/fisiopatología , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Disfunción Ventricular Izquierda/complicaciones , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/mortalidad
15.
J Autoimmun ; 50: 99-106, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24485154

RESUMEN

Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1 antibodies and TRIB2 autoantibody levels particularly among the youngest narcolepsy patients (r = 0.819, p < 0.001). In conclusion, following the 2009 influenza pandemic vaccination, A/H1N1 antibody levels were associated with young age-at-onset narcolepsy patients positive for HLA-DQB1*06:02. The possibility that TRIB2 is an autoantigen in narcolepsy remains to be clarified. We could verify autoantibody responses against TRIB2 which needs to be determined in larger patient cohorts and control populations.


Asunto(s)
Anticuerpos Antivirales/sangre , Autoanticuerpos/sangre , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Péptidos y Proteínas de Señalización Intracelular/inmunología , Narcolepsia/inducido químicamente , Adolescente , Adulto , Anciano , Proteínas Quinasas Dependientes de Calcio-Calmodulina , Niño , Preescolar , Femenino , Expresión Génica , Glutamato Descarboxilasa/antagonistas & inhibidores , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/inmunología , Cadenas beta de HLA-DQ/genética , Cadenas beta de HLA-DQ/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Persona de Mediana Edad , Narcolepsia/diagnóstico , Narcolepsia/genética , Narcolepsia/inmunología , Pandemias/prevención & control , Suecia , Vacunación/efectos adversos
16.
J Endovasc Ther ; 21(1): 79-84, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24502487

RESUMEN

PURPOSE: To compare complication rates of a collagen-based vascular closure device (VCD) in patients with vs. without significant peripheral artery disease (PAD). METHODS: A total of 382 patients (268 men; mean age 64.6±10.8 years) undergoing either an endovascular procedure of the lower limb (PAD group, n=132) or a percutaneous coronary intervention (PCI group, n=250) via a common femoral artery access were enrolled in this prospective study if hemostasis was achieved using the collagen-based Angio-Seal. In the PCI group, significant PAD was excluded by measurement of the ankle-brachial index. In-hospital major complications (bleeding, large hematoma, pseudoaneurysm, vessel occlusion, dissection) were recorded. RESULTS: Similar and low rates of major complications were observed in both arms of the study: 2 (1.5%) major complications in the PAD group and 3 (1.2%) in the PCI group (p=1.0). There was no significant difference in efficacy of the VCDs in the groups (PAD group 99.2% vs. 100% in PCI group, p=0.35). CONCLUSION: Our study shows no significant differences in the rate of major complications after utilization of a collagen-based VCD for femoral artery access site closure in patients with severe lower limb PAD compared to those without; however, complications in the PAD group tended to be more severe, with the need for surgical repair.


Asunto(s)
Colágeno/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Procedimientos Endovasculares/efectos adversos , Arteria Femoral/lesiones , Hemorragia/prevención & control , Técnicas Hemostáticas/instrumentación , Hemostáticos/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Intervención Coronaria Percutánea/efectos adversos , Enfermedad Arterial Periférica/terapia , Lesiones del Sistema Vascular/terapia , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico , Diseño de Equipo , Femenino , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Estudios Prospectivos , Punciones , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Lesiones del Sistema Vascular/diagnóstico , Lesiones del Sistema Vascular/etiología
17.
J Heart Valve Dis ; 23(5): 537-44, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25799701

RESUMEN

BACKGROUND AND AIM OF THE STUDY: The aim of this prospective study was to determine the impact of plasma B-type natriuretic peptide (BNP) on long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: TAVI was performed either transfemorally or transaxillary using either the CoreValve prosthesis or Edwards SAPIEN prosthesis in 226 patients with symptomatic severe aortic valve stenosis and at high surgical risk. The examinations included measurements of plasma BNP and echocardiography before and at 30 days after TAVI. The primary study end-point was death from any cause after TAVI; the secondary end-point was defined as cardiovascular death. RESULTS: During a mean follow up of 728 ± 549 days, 72 patients died; 52 deaths were cardiovascular-related. Those patients who died had higher preprocedural plasma BNP levels compared to those who survived (1,305 ± 1,238 pg/ml versus 716 ± 954 pg/ml; p < 0.001). Plasma BNP was the strongest independent predictor of all-cause mortality (BNP > 475 pg/ml, hazard risk [HR] 3.049; 95% confidence interval [CI] 1.804-5.151; p < 0.001) and cardiovascular mortality (BNP > 475 pg/ml, HR 3.479; 95% CI 1.817-6.662; p < 0.001). In surviving patients, plasma BNP levels were decreased by 30 days after TAVI (pre-TAVI 874 ± 1,122 pg/ml; post TAVI 471 ± 569 pg/ml; p < 0.001). A plasma BNP level > 328 pg/ml at 30 days postoperatively was also associated with all-cause mortality (HR 8.125; 95% CI 3.097-21.318; p < 0.001). CONCLUSION: In patients undergoing TAVI, plasma BNP is the strongest independent predictor of all-cause mortality and cardiovascular mortality. Plasma BNP levels at 30 days after TAVI may provide prognostic information that should, potentially, lead to a more intensive therapy of these patients.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Péptido Natriurético Encefálico/sangre , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Biomarcadores/sangre , Causas de Muerte , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Masculino , Análisis Multivariante , Pronóstico , Estudios Prospectivos
18.
Front Pediatr ; 12: 1386513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699153

RESUMEN

Objective: To screen a general pediatric population for type 1 diabetes (T1D), celiac disease (CD), and autoimmune thyroid disease (AITD) after home capillary sampling. Methods: Swedish schoolchildren between 6-9 years and 13-16 years of age were invited to screening by taking a capillary sample at home. Samples were returned by mail and assessed for autoantibodies associated with T1D, CD, and AITD. Persistently autoantibody-positive children were referred for clinical follow-up. Results: Of 19,593 invited, 3,527 (18.0%) consented to participate and 2,315/3,527 (65.6%) returned a blood sample of sufficient volume. Hemolysis occurred in 830/2,301 (36.1%) samples. After exclusion of 42 children with previously known T1D, CD, or AITD, and two autoantibody-positive children who declined a confirmatory sample, 2,271/19,593 (11.6%) were included. 211/2,271 (9.3%) had persistent autoantibodies: 60/2,271 (2.6%) with T1D autoantibodies, 61/2,271 (2.7%) with CD autoantibodies, and 99/2,271 (4.4%) with AITD autoantibodies; 9/2,271 (0.4%) were autoantibody positive for ≥1 disease. After clinical follow-up, 3/2,271 (0.1%) were diagnosed with T1D, 26/2,271 (1.1%) with CD, and 6/2,271 (0.3%) with AITD. Children with a first-degree relative (FDR) with T1D, CD, and/or AITD, had higher occurrence of autoantibodies compared to children without an FDR (63/344, 18.3%, vs. 148/1,810, 8.2%) (p < 0.0001, OR 2.52, 95% CI 1.83-3.47), and higher occurrence of screening-detected diagnosis (14/344, 4.1%, vs. 21/1,810, 1.2%) (p < 0.0001, OR 3.61, 95% CI 1.82-7.18). Half of these children screened positive for another disease than the FDR. Conclusion: Screening for T1D, CD, and AITD by home capillary sampling in a Swedish general pediatric population detected autoimmunity in 9.3% and undiagnosed disease in 1.5%.

19.
EBioMedicine ; 104: 105144, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723553

RESUMEN

BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity. METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented. FINDINGS: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC. INTERPRETATION: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes. FUNDING: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.


Asunto(s)
Autoanticuerpos , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Femenino , Masculino , Niño , Preescolar , Lactante , Transportador 8 de Zinc/inmunología , Sensibilidad y Especificidad , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/inmunología , Glutamato Descarboxilasa/inmunología , Curva ROC , Tamizaje Masivo/métodos
20.
Exp Clin Endocrinol Diabetes ; 131(9): 456-462, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37380031

RESUMEN

Autoimmune thyroid disease (AITD) may be detected prior to clinical symptoms through the presence of autoantibodies against thyroid peroxidase (TPOab), thyroglobulin (TGab), or both.The present study aimed to develop a novel radiobinding assay (RBA) for TPOab and to determine the prevalence of TPOab and TGab in the Swedish population.Patient samples from 27 newly diagnosed Graves' disease patients in longitudinal follow-up and 124 AITD autoantibody-positive children in prospective follow-up for increased risk of type 1 diabetes were included to validate the novel RBA for TPO. The results of RBA were compared with those obtained by commercial radioimmunoassay (RIA) and electrochemiluminescence (ECL). Furthermore, 476 serum samples from adult blood donors and 297 from 13-year-old school children were analyzed for the presence of TPOab and TGab.Receiver operating characteristics analysis for the novel TPOab resulted in an area under curve (AUC) value of 0.82 (p<0.0001), a sensitivity of 77.8%, and a specificity of 91.9% in adult blood donors, and an AUC value of 0.70 (p<0.0001), a sensitivity of 53.2% and a specificity of 95.3% in the 13-year-old school children, respectively. TPOab levels in RBA correlated with both ECL (r=0.8950, p<0.0001) and RIA (r=0.9295, p<0.0001). The prevalence of TPOab and TGab was 6.3% and 7.6% in adult blood donors and 2.9 and 3.7% in 13-year-old school children.In conclusion, a novel RBA for the determination of TPOab was developed and validated with current methodologies. This study also reports an increasing prevalence of thyroid autoantibodies from adolescence to adulthood.


Asunto(s)
Enfermedad de Hashimoto , Tiroglobulina , Adulto , Niño , Adolescente , Humanos , Yoduro Peroxidasa , Autoanticuerpos , Prevalencia , Suecia/epidemiología , Estudios Prospectivos
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