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1.
Nature ; 610(7931): 290-295, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36224421

RESUMO

Delocalized Bloch electrons and the low-energy correlations between them determine key optical1, electronic2 and entanglement3 functionalities of solids, all the way through to phase transitions4,5. To directly capture how many-body correlations affect the actual motion of Bloch electrons, subfemtosecond (1 fs = 10-15 s) temporal precision6-15 is desirable. Yet, probing with attosecond (1 as = 10-18 s) high-energy photons has not been energy-selective enough to resolve the relevant millielectronvolt-scale interactions of electrons1-5,16,17 near the Fermi energy. Here, we use multi-terahertz light fields to force electron-hole pairs in crystalline semiconductors onto closed trajectories, and clock the delay between separation and recollision with 300 as precision, corresponding to 0.7% of the driving field's oscillation period. We detect that strong Coulomb correlations emergent in atomically thin WSe2 shift the optimal timing of recollisions by up to 1.2 ± 0.3 fs compared to the bulk material. A quantitative analysis with quantum-dynamic many-body computations in a Wigner-function representation yields a direct and intuitive view on how the Coulomb interaction, non-classical aspects, the strength of the driving field and the valley polarization influence the dynamics. The resulting attosecond chronoscopy of delocalized electrons could revolutionize the understanding of unexpected phase transitions and emergent quantum-dynamic phenomena for future electronic, optoelectronic and quantum-information technologies.

2.
Nature ; 593(7859): 385-390, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34012087

RESUMO

When intense lightwaves accelerate electrons through a solid, the emerging high-order harmonic (HH) radiation offers key insights into the material1-11. Sub-optical-cycle dynamics-such as dynamical Bloch oscillations2-5, quasiparticle collisions6,12, valley pseudospin switching13 and heating of Dirac gases10-leave fingerprints in the HH spectra of conventional solids. Topologically non-trivial matter14,15 with invariants that are robust against imperfections has been predicted to support unconventional HH generation16-20. Here we experimentally demonstrate HH generation in a three-dimensional topological insulator-bismuth telluride. The frequency of the terahertz driving field sharply discriminates between HH generation from the bulk and from the topological surface, where the unique combination of long scattering times owing to spin-momentum locking17 and the quasi-relativistic dispersion enables unusually efficient HH generation. Intriguingly, all observed orders can be continuously shifted to arbitrary non-integer multiples of the driving frequency by varying the carrier-envelope phase of the driving field-in line with quantum theory. The anomalous Berry curvature warranted by the non-trivial topology enforces meandering ballistic trajectories of the Dirac fermions, causing a hallmark polarization pattern of the HH emission. Our study provides a platform to explore topology and relativistic quantum physics in strong-field control, and could lead to non-dissipative topological electronics at infrared frequencies.

3.
Nature ; 569(7756): 383-387, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31092937

RESUMO

Future information technology demands ever-faster, low-loss quantum control. Intense light fields have facilitated milestones along this way, including the induction of novel states of matter1-3, ballistic acceleration of electrons4-7 and coherent flipping of the valley pseudospin8. These dynamics leave unique 'fingerprints', such as characteristic bandgaps or high-order harmonic radiation. The fastest and least dissipative way of switching the technologically most important quantum attribute-the spin-between two states separated by a potential barrier is to trigger an all-coherent precession. Experimental and theoretical studies with picosecond electric and magnetic fields have suggested this possibility9-11, yet observing the actual spin dynamics has remained out of reach. Here we show that terahertz electromagnetic pulses allow coherent steering of spins over a potential barrier, and we report the corresponding temporal and spectral fingerprints. This goal is achieved by coupling spins in antiferromagnetic TmFeO3 (thulium orthoferrite) with the locally enhanced terahertz electric field of custom-tailored antennas. Within their duration of one picosecond, the intense terahertz pulses abruptly change the magnetic anisotropy and trigger a large-amplitude ballistic spin motion. A characteristic phase flip, an asymmetric splitting of the collective spin resonance and a long-lived offset of the Faraday signal are hallmarks of coherent spin switching into adjacent potential minima, in agreement with numerical simulations. The switchable states can be selected by an external magnetic bias. The low dissipation and the antenna's subwavelength spatial definition could facilitate scalable spin devices operating at terahertz rates.

4.
Nature ; 562(7727): 396-400, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30258232

RESUMO

Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates1. Lightwave-driven currents have been assumed to be essential for high-harmonic generation in solids2-6, charge transport in nanostructures7,8, attosecond-streaking experiments9-16 and atomic-resolution ultrafast microscopy17,18. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators19-29 may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi2Te3. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.

5.
Nature ; 557(7703): 76-80, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29720633

RESUMO

As conventional electronics approaches its limits 1 , nanoscience has urgently sought methods of fast control of electrons at the fundamental quantum level 2 . Lightwave electronics 3 -the foundation of attosecond science 4 -uses the oscillating carrier wave of intense light pulses to control the translational motion of the electron's charge faster than a single cycle of light5-15. Despite being particularly promising information carriers, the internal quantum attributes of spin 16 and valley pseudospin17-21 have not been switchable on the subcycle scale. Here we demonstrate lightwave-driven changes of the valley pseudospin and introduce distinct signatures in the optical readout. Photogenerated electron-hole pairs in a monolayer of tungsten diselenide are accelerated and collided by a strong lightwave. The emergence of high-odd-order sidebands and anomalous changes in their polarization direction directly attest to the ultrafast pseudospin dynamics. Quantitative computations combining density functional theory with a non-perturbative quantum many-body approach assign the polarization of the sidebands to a lightwave-induced change of the valley pseudospin and confirm that the process is coherent and adiabatic. Our work opens the door to systematic valleytronic logic at optical clock rates.

6.
Nature ; 533(7602): 225-9, 2016 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-27172045

RESUMO

Ever since Ernest Rutherford scattered α-particles from gold foils, collision experiments have revealed insights into atoms, nuclei and elementary particles. In solids, many-body correlations lead to characteristic resonances--called quasiparticles--such as excitons, dropletons, polarons and Cooper pairs. The structure and dynamics of quasiparticles are important because they define macroscopic phenomena such as Mott insulating states, spontaneous spin- and charge-order, and high-temperature superconductivity. However, the extremely short lifetimes of these entities make practical implementations of a suitable collider challenging. Here we exploit lightwave-driven charge transport, the foundation of attosecond science, to explore ultrafast quasiparticle collisions directly in the time domain: a femtosecond optical pulse creates excitonic electron-hole pairs in the layered dichalcogenide tungsten diselenide while a strong terahertz field accelerates and collides the electrons with the holes. The underlying dynamics of the wave packets, including collision, pair annihilation, quantum interference and dephasing, are detected as light emission in high-order spectral sidebands of the optical excitation. A full quantum theory explains our observations microscopically. This approach enables collision experiments with various complex quasiparticles and suggests a promising new way of generating sub-femtosecond pulses.

7.
Thorac Cardiovasc Surg ; 70(8): 607-615, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35263792

RESUMO

OBJECTIVES: Type A aortic dissection with true lumen collapse and malperfusion downstream is associated with a devastating prognosis. This study compares the clinical outcomes of two operative strategies for this disease: hybrid approach of ascending aorta (and hemiarch replacement) supplemented with retrograde stenting of the descending aorta (thoracic endovascular aortic repair [TEVAR]) and standard ascending aorta (and hemiarch) replacement without stent placement. METHODS: From January 1, 2016 to December 31, 2019, 81 patients with type A aortic dissection were studied. The hybrid technique was applied in 30 patients (group 1), while 51 patients received standard surgical repair (group 2). Patient demographics, clinical and operative findings, postoperative outcome, follow-up interventions, and mid-term survival were analyzed. RESULTS: Baseline characteristics were similar among the groups, except that more preoperative malperfusion was evident in group 1. The postoperative incidence of visceral malperfusion (0 vs. 15.7%, p = 0.02) and low cardiac output syndrome requiring extracorporeal membrane oxygenation support (3.3 vs. 19.6%, p = 0.04) was significantly less in group 1. In-hospital mortality was also significantly lower in group 1 as in group 2 (13.3 vs. 33.3%, p = 0.04). At follow-up, the need for secondary endovascular stenting (3.3 vs. 7.8%, p = 0.65) and surgical aortic reintervention (6.7 vs. 2.0%, p = 0.55) was comparable. One-year, 2-year, and 3-year survival rates were 83.3, 83.3, and 62.5% in group 1, and 58.7, 58.7, and 52.6% in group 2 (p = 0.05), respectively. CONCLUSION: The combination of open surgical replacement of the ascending aorta (and hemiarch) with TEVAR of the descending aorta for true lumen compromise is a feasible treatment option for patients with type A aortic dissection and is associated with a better perioperative outcome and improved mid-term survival rate.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Resultado do Tratamento , Stents , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
8.
J Acoust Soc Am ; 150(2): 673, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34470279

RESUMO

Typically, the coding strategies of cochlear implant audio processors discard acoustic temporal fine structure information (TFS), which may be related to the poor perception of interaural time differences (ITDs) and the resulting reduced spatial hearing capabilities compared to normal-hearing individuals. This study aimed to investigate to what extent bilateral cochlear implant (BiCI) recipients can exploit ITD cues provided by a TFS preserving coding strategy (FS4) in a series of sound field spatial hearing tests. As a baseline, we assessed the sensitivity to ITDs and binaural beats of 12 BiCI subjects with a coding strategy disregarding fine structure (HDCIS) and the FS4 strategy. For 250 Hz pure-tone stimuli but not for broadband noise, the BiCI users had significantly improved ITD discrimination using the FS4 strategy. In the binaural beat detection task and the broadband sound localization, spatial discrimination, and tracking tasks, no significant differences between the two tested coding strategies were observed. These results suggest that ITD sensitivity did not generalize to broadband stimuli or sound field spatial hearing tests, suggesting that it would not be useful for real-world listening.


Assuntos
Implante Coclear , Implantes Cocleares , Localização de Som , Estimulação Acústica , Audição , Testes Auditivos , Humanos
9.
Immunol Invest ; 49(4): 365-385, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31535582

RESUMO

In cancer or hematologic disorders, chemokines act as growth- or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, -9, -10, CCL2, -5, and IL-12 in AML/MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blast-proportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, -9, -10 and lower release of CCL2 and -5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2-release at relapse were found compared to first diagnosis - pointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, -9, -10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and -5 but lower levels of CXCL8, -9, -10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, -9, -10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.


Assuntos
Citocinas/sangue , Leucemia Mieloide Aguda/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoterapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Transplante de Células-Tronco
10.
Arch Toxicol ; 94(6): 2239-2247, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32303803

RESUMO

Suicidal ingestion of organophosphorus (OP) or carbamate (CM) compounds challenges health care systems worldwide, particularly in Southeast Asia. The diagnosis and treatment of OP or CM poisoning is traditionally based on the clinical appearance of the typical cholinergic toxidrome, e.g. miosis, salivation and bradycardia. Yet, clinical signs might be inconclusive or even misleading. A current case report highlights the importance of enzymatic assays to provide rapid information and support clinicians in diagnosis and rational clinical decision making. Furthermore, the differentiation between OP and CM poisoning seems important, as an oxime therapy will most probably not provide benefit in CM poisoning, but-as every pharmaceutical product-it might result in adverse effects. The early identification of the causing agent and the amount taken up in the body are helpful in planning of the therapeutic regimen including experimental strategies, e.g. the use of human blood products to facilitate scavenging of the toxic agent. Furthermore, the analysis of biotransformation products and antidote levels provides additional insights into the pathophysiology of OP or CM poisoning. In conclusion, cholinesterase activities and modern analytical methods help to provide a more effective treatment and a thorough understanding of individual cases of OP or CM poisoning.


Assuntos
Acetilcolinesterase/sangue , Butirilcolinesterase/sangue , Inibidores da Colinesterase/intoxicação , Ensaios Enzimáticos Clínicos , Intoxicação por Organofosfatos/diagnóstico , Idoso de 80 Anos ou mais , Antídotos/uso terapêutico , Atropina/uso terapêutico , Biomarcadores/sangue , Reativadores da Colinesterase/uso terapêutico , Tomada de Decisão Clínica , Diagnóstico Diferencial , Proteínas Ligadas por GPI/sangue , Humanos , Antagonistas Muscarínicos/uso terapêutico , Cloreto de Obidoxima/uso terapêutico , Intoxicação por Organofosfatos/sangue , Intoxicação por Organofosfatos/tratamento farmacológico , Valor Preditivo dos Testes , Tentativa de Suicídio , Resultado do Tratamento
11.
BMC Med Educ ; 19(1): 353, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521146

RESUMO

BACKGROUND: Peer-assisted learning (PAL) is a common teaching and learning method in medical education worldwide. In the setting of skills laboratories (skills labs), student tutors are often employed as an equivalent alternative to faculty teachers. However, to the best of our knowledge, there is a lack of qualitative studies which explore the reasons for the personal commitment of student tutors. The aim of our study was to examine how undergraduate students experienced and evaluated their roles as skills lab student tutors, what their motivation was, and whether social and cognitive congruence played a role in their teaching experiences. METHODS: We conducted in-depth, semi-structured interviews with student tutors who were currently teaching in a skills lab. After the interviews had been transcribed verbatim, two independent investigators performed a qualitative content analysis according to Mayring. RESULTS: In total, we conducted nine interviews with student tutors. Our results revealed that all student tutors showed great enthusiasm and motivation for their jobs as peer teachers. One of the main motivating factors for student tutors to teach in a skills lab was the possibility to simultaneously share and improve their knowledge and expertise. In general, the participants of our study had high aspirations for their teaching. They found it particularly important to be empathetic with the student learners. At the same time, they thought they would personally benefit from their teaching activities and develop a certain expertise as student tutors. CONCLUSIONS: With the present study we are able to gain some insight into what motivates student tutors to teach in a skills lab and what kind of experiences they have. Our results provide an important input for the future training of highly qualified student tutors.


Assuntos
Educação de Graduação em Medicina/normas , Docentes de Medicina , Motivação , Estudantes de Medicina , Currículo , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Influência dos Pares , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Ensino
12.
J Mol Cell Cardiol ; 118: 159-168, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29614261

RESUMO

RATIONALE: Ca/calmodulin-dependent protein kinase II (CaMKII) was shown to increase diastolic sarcoplasmic reticulum (SR) Ca leak, which can result in delayed afterdepolarizations and triggered arrhythmias. Since increased CaMKII expression and activity has been mechanistically linked to arrhythmias in human heart failure (HF) and atrial fibrillation (AF), specific strategies aimed at CaMKII inhibition may have therapeutic potential. OBJECTIVE: We tested the antiarrhythmic and inotropic effects of a novel selective and ATP-competitive CaMKII inhibitor (GS-680). METHODS AND RESULTS: Trabeculae were isolated from right atrial appendage biopsies of patients undergoing cardiac surgery. Premature atrial contractions (PACs) were induced by stimulation with isoproterenol (ISO, 100 nM) at increased [Ca]o (3.5 mM). Interestingly, compared to vehicle, PACs were significantly inhibited by exposure to GS-680 (at 100 and 300 nM). GS-680 also significantly decreased early and delayed afterdepolarizations in isolated human atrial myocytes. Moreover, GS-680 (at 100 or 300 nM) significantly inhibited diastolic SR Ca leak, measured as frequency of spontaneous SR Ca release events (Ca sparks) in isolated human atrial myocytes (Fluo-4 loaded) similar to the well-established peptide CaMKII inhibitor AIP. In accordance, GS-680 significantly reduced CaMKII autophosphorylation (Western blot) but enhanced developed tension after 10 or 30 s pause of electrical stimulation (post-rest behavior). Surprisingly, we found a strong negative inotropic effect of GS-680 in atrial trabeculae at 1 Hz stimulation rate, which was not observed at 4 Hz and abolished by beta-adrenergic stimulation. In contrast, GS-680 did not impair systolic force of isolated ventricular trabeculae from explanted hearts of heart transplant recipients at 1 Hz, blunted the negative force-frequency relationship (1-3 Hz) and significantly increased the Ca transient amplitude. CONCLUSION: The novel ATP-competitive and selective CaMKII inhibitor GS-680 inhibits pro-arrhythmic activity in human atrium and improves contractility in failing human ventricle, which may have therapeutic implications.


Assuntos
Arritmias Cardíacas/enzimologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirrolidinas/farmacologia , Tiofenos/farmacologia , Arritmias Cardíacas/complicações , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Diástole/efeitos dos fármacos , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/química , Piridinas/química , Pirrolidinas/química , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo
13.
J Intern Med ; 283(2): 166-177, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29027756

RESUMO

BACKGROUND: Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic haematopoietic stem cell transplantation (HSCT). With new promising therapies, survival may improve for severe aGVHD. OBJECTIVES: We wanted to analyze the long-term outcome in patients who survive severe aGVHD. METHODS: This study was a landmark analysis of 23 567 patients with acute Leukaemia who survived for more than 6 months after HSCT, 2002-2014. Patients alive after severe aGVHD (n = 1738) were compared to controls. RESULTS: Patients with severe aGVHD had higher non-relapse mortality (NRM) and higher rate of extensive chronic GVHD (cGVHD) than the controls (P < 10-5 ). The probability of relapse was significantly lower in the severe aGVHD group, but Leukaemia-free survival (LFS) and overall survival were significantly lower than for the controls (P < 10-5 ). Five-year LFS in patients with severe aGVHD was 49%, as opposed to 61% in controls with no or mild GVHD and 59% in patients with moderate GVHD. CONCLUSIONS: HSCT patients who survive severe aGVHD have higher risk of developing extensive cGVHD, a higher NRM, a lower relapse probability, and lower LFS than other HSCT patients. This study is a platform for outcome analysis in patients treated with novel therapies for acute GVHD.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Análise de Sobrevida , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto Jovem
14.
J Intern Med ; 283(4): 371-379, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29214689

RESUMO

BACKGROUND: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). AIMS: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. MATERIALS AND METHODS: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. RESULTS: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). DISCUSSION AND CONCLUSION: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
15.
Eur Radiol ; 28(6): 2700-2707, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29372312

RESUMO

OBJECTIVES: To assess the additional diagnostic value of 18F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. METHODS: A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. RESULTS: A total of 26 patients underwent 18F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. CONCLUSIONS: These results demonstrate that 18F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. KEY POINTS: • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.


Assuntos
Adenoma/diagnóstico por imagem , Colina/análogos & derivados , Hiperparatireoidismo Primário/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adenoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Radioisótopos de Flúor , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Exame Físico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Cintilografia , Reoperação , Estudos Retrospectivos , Ultrassonografia
16.
Horm Metab Res ; 48(10): 623-629, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27607246

RESUMO

Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is characterized by cellular and humoral immunity leading to thyroid destruction. The impact of the humoral immunity on the risk to develop hypothyroidism has not exactly been defined yet. The aim of the present study was to investigate the association between thyroid antibody levels and the risk for developing hypothyroidism. In this retrospective study, 335 untreated AIT patients were enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg) antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels [p=0.0023; relative risk (95% confidence interval): 1.343 (1.108-1.627)] compared to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and between 100-500 IU/ml had no significantly different TSH levels. Presence of Tg-Abs alone or in combination with TPO-Abs did not help to increase the sensitivity to identify patients at risk. Long term follow-up of AIT patients with high TPO-Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range: 2.52±2.73 to 3.02±3.05 mIU/l; p=0.0420). Still, these patients remained euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated with a moderately increased risk of developing hypothyroidism.


Assuntos
Anticorpos Anti-Idiotípicos/sangue , Autoanticorpos/sangue , Autoantígenos/imunologia , Hipotireoidismo/sangue , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Tireoidite Autoimune/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Idiotípicos/imunologia , Autoanticorpos/imunologia , Autoantígenos/sangue , Feminino , Seguimentos , Humanos , Hipotireoidismo/etiologia , Iodeto Peroxidase/sangue , Proteínas de Ligação ao Ferro/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tireoidite Autoimune/complicações , Tireoidite Autoimune/imunologia , Adulto Jovem
17.
Horm Metab Res ; 48(12): 795-801, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27923250

RESUMO

Until recently, stimulating TSH receptor autoantibodies (sTRAbs) could only be measured by bioassays. A new assay system, which directly detects sTRAb in sera by applying bridge technology, has been established and is now available as automated chemiluminescence (bridge) immunoassay. We evaluated the automated bridge assay in clinical routine and compared it with a conventional automated TRAb assay (competition assay). Altogether, 226 Graves' disease (GD), 57 autoimmune thyroiditis, 74 non-autoimmune nodular goiter and 49 thyroid cancer patients, as well as 41 healthy controls were retrospectively evaluated. ROC plot analysis based on sera of newly diagnosed GD patients revealed an area under curve of 0.99 (95% CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest sensitivity (100%) and specificity (99%) were seen at a cut-off level of 0.55 IU/l. The calculated positive predictive value was 94%, whereas the negative was 100%. Applying a ROC plot-derived cut-off of≥0.30 IU/l, derived from sera of GD patients already receiving antithyroid drug therapy for≤6 months, the sensitivity was 99% whereas the specificity was 98%. Detailed comparison of both assay systems used revealed a slightly different distribution of sTRAb and TRAb. Measurement of sTRAb during follow-up revealed a steady decline over one year of follow-up. In summary, our results demonstrate that the new automated bridge assay system for detecting sTRAb has a high sensitivity and specificity for diagnosing GD and to discriminate from other thyroid diseases, respectively. Our study, however, does not provide full evidence that the bridge assay is specific for sTRAb only.


Assuntos
Autoanticorpos/biossíntese , Imunoensaio/métodos , Receptores da Tireotropina/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação , Feminino , Seguimentos , Doença de Graves/sangue , Doença de Graves/diagnóstico , Doença de Graves/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Tiroxina/sangue , Fatores de Tempo , Adulto Jovem
19.
Pol J Pathol ; 67(2): 172-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27543873

RESUMO

We present the case of a 62-year-old male patient with a three-month history of pain in the left shoulder. Magnetic resonance imaging of the left scapula showed an osteo-destructive lesion. H and E stained sections revealed a Langerhans cell sarcoma, and immunohistochemistry was performed additionally; CD68, CD163, CD14, fascin, HLA-DR, lysozyme, S100 CD1a and langerin showed a positive reaction, while CD20, CD30, CD34, CD31, pan-cytokeratin, AE/1AE3, SMA, desmin, EMA, ERG, INI-1, CD21, CD4, PLAP, MPO and CD117c were negative. We suggested palliative treatment with chemotherapy and radiation. The patient refused any treatment and died 2 weeks later.


Assuntos
Sarcoma de Células de Langerhans/patologia , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
20.
Z Geburtshilfe Neonatol ; 220(1): 35-8, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-26866691

RESUMO

INTRODUCTION: Staphylococcal scalded skin syndrome (SSSS) was often endemic in the past but is nowadays rare. The hematogeneous spread of exfoliative toxins A (ETA) or B (ETB) produced by specific Staphylococcus aureus strains causes a scald-like eruption with disseminated bullous lesions. CASE REPORT: A perioral impetigo lesion occurred on day 14 of life in a preterm male infant (1,065 g, 30 weeks of gestational age). Empiric antibiotic therapy with cefotaxime and vancomycin was given for 6 days and led to complete resolution. A Staphylococcus aureus strain was isolated. After a symptom-free interval a relapse was noted on day 26 of life. Despite restarting the antibiotic therapy immediately the initial lesion expanded, and disseminated flaccid blisters on an erythematous base appeared within a few hours. On histological examination the cleavage was in the level of the granular layer. There was no mucosal involvement, and the Nikolsky I sign was positive. The antibiotic therapy was changed to a combination of cefotaxime, flucloxacillin and clindamycin which rapidly stopped progression of the exfoliation. Supportive therapy included adequate analgesia, parenteral rehydration, and application of local antiseptics. The preterm infant completely recovered. In the primary lesion an ETA-producing Staphylococcus aureus strain was isolated. Nasal microtrauma by a nasogastric tube was assumed to have caused the fulminant disease. At the same time, no other Staphylococcus aureus infections were seen in our Department of Neonatology. DISCUSSION: According to the literature, the incidence of SSSS is higher in premature infants and newborns than in older children. Possible causes include lower antibody levels against exfoliative toxins and renal immaturity. Rapid diagnosis and immediate appropriate antibiotic therapy are essential to prevent secondary infection, dehydration with electrolyte disturbance, death, and endemic spread.


Assuntos
Antibacterianos/administração & dosagem , Dermatite Perioral/diagnóstico , Dermatite Perioral/tratamento farmacológico , Recém-Nascido de muito Baixo Peso , Síndrome da Pele Escaldada Estafilocócica/diagnóstico , Síndrome da Pele Escaldada Estafilocócica/tratamento farmacológico , Dermatite Perioral/microbiologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/microbiologia , Recém-Nascido Prematuro , Masculino , Síndrome da Pele Escaldada Estafilocócica/microbiologia , Resultado do Tratamento
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