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1.
Crit Care ; 24(1): 244, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448380

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients. METHODS: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 µg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy. RESULTS: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 µg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p <  0.001] were significantly associated with in-hospital mortality. CONCLUSIONS: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients. CLINICAL TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

2.
Blood Adv ; 4(6): 997-1005, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32176765

RESUMO

Cold agglutinin disease (CAD) causes predominantly extravascular hemolysis and anemia via complement activation. Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s. We aimed to evaluate the safety and efficacy of long-term maintenance treatment with sutimlimab in patients with CAD. Seven CAD patients treated with sutimlimab as part of a phase 1B study were transitioned to a named patient program. After a loading dose, patients received biweekly (once every 2 weeks) infusions of sutimlimab at various doses. When a patient's laboratory data showed signs of breakthrough hemolysis, the dose of sutimlimab was increased. Three patients started with a dose of 45 mg/kg, another 3 with 60 mg/kg, and 1 with a fixed dose of 5.5 g every other week. All CAD patients responded to re-treatment, and sutimlimab increased hemoglobin from a median initial level of 7.7 g/dL to a median peak of 12.5 g/dL (P = .016). Patients maintained near normal hemoglobin levels except for a few breakthrough events that were related to underdosing and which resolved after the appropriate dose increase. Four of the patients included were eventually treated with a biweekly 5.5 g fixed-dose regimen of sutimlimab. None of them had any breakthrough hemolysis. All patients remained transfusion free while receiving sutimlimab. There were no treatment-related serious adverse events. Overlapping treatment with erythropoietin, rituximab, or ibrutinib in individual patients was safe and did not cause untoward drug interactions. Long-term maintenance treatment with sutimlimab was safe, effectively inhibited hemolysis, and significantly increased hemoglobin levels in re-exposed, previously transfusion-dependent CAD patients.

3.
Crit Care Med ; 48(4): 459-465, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32205591

RESUMO

OBJECTIVE: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients. DESIGN: Retrospective observational study. SETTING: Adult surgical, anesthesiologic, and medical ICUs of a university hospital. PATIENTS: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949-0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384-1.665 per log µg/L]; p < 0.001). CONCLUSIONS: This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.

4.
J Cancer Res Clin Oncol ; 146(4): 1065-1077, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32076823

RESUMO

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults. METHODS: Patients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded. RESULTS: The study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17-87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (p = 0.077). Platelets under 20*109/l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival. CONCLUSION: Close multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.


Assuntos
Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Adulto Jovem
6.
Mov Disord ; 35(4): 650-661, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31951049

RESUMO

BACKGROUND: There is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes. OBJECTIVE: To develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes. METHODS: The Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts). RESULTS: Cognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P < 0.001). Individual Progressive Supranuclear Palsy Clinical Deficits Scale items correlated well with similar constructs in existing scales. Internal consistency (Cronbach's alpha: 0.75), inter-rater reliability (0.96), and test-retest stability (0.99) were acceptable. The PSP-CDS showed significant 12-month change (baseline, 8.6 ± 3.6; follow-up: 10.8 ± 3.6; annualized difference: 3.4 ± 3.4; n = 49; P < 0.0001). Sample sizes required per arm for a two-arm, 1-year follow-up therapeutic trial to detect 50% change in Progressive Supranuclear Palsy Clinical Deficits Scale progression was estimated to be 65 (two-sided, two-sample t test). CONCLUSION: The Progressive Supranuclear Palsy Clinical Deficits Scale is a rapidly completed, clinimetrically sound scale for clinical care and research involving PSP. © 2020 International Parkinson and Movement Disorder Society.

7.
Neuropsychologia ; 139: 107297, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31830484

RESUMO

Spatial neglect is a debilitating neurological disorder marked by reduced exploration of contralesional space. We developed an intervention in which eye movements to and within one half of a search display were reduced over the course of several hundred trials. The aim of this study was to determine whether this intervention had an effect on the deployment of attention of healthy participants as a first step towards application in patients. The participants carried out a visual search task during which the stimuli in one half of the search display were removed whenever the participants made eye movements towards it. The stimuli in the other half were unaffected by eye movements. Indeed, this led to a steady relative decrease in fixations within the affected half over the course of the intervention. In five experiments, the performance in different spatial attention paradigms was measured before and after this intervention. In two visual search paradigms (feature and conjunction search), exploration of the affected half decreased compared to the unaffected half. In a Posner task with exogenous cues, a partial effect of the intervention was found. However, an attempt at replicating this effect was not successful. The fifth experiment showed that performance in a line bisection paradigm was not significantly influenced by the intervention. To conclude, the intervention showed the potential to influence the behavior of healthy participants in overt attentional exploration tasks.

8.
BMJ Open ; 9(10): e032695, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666276

RESUMO

INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated. METHODS AND ANALYSIS: The HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité - Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine. ETHICS AND DISSEMINATION: The institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité - Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03510650.

9.
Vision (Basel) ; 3(3)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31735837

RESUMO

Ganel, Freud, Chajut, and Algom (2012) demonstrated that maximum grip apertures (MGAs) differ significantly when grasping perceptually identical objects. From this finding they concluded that the visual size information used by the motor system is more accurate than the visual size information available to the perceptual system. A direct comparison between the accuracy in the perception and the action system is, however, problematic, given that accuracy in the perceptual task is measured using a dichotomous variable, while accuracy in the visuomotor task is determined using a continuous variable. We addressed this problem by dichotomizing the visuomotor measures. Using this approach, our results show that size discrimination in grasping is in fact inferior to perceptual discrimination therefore contradicting the original suggestion put forward by Ganel and colleagues.

10.
Shock ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626037

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the ICU is challenged by the clinical overlap with sepsis. Here, we analyze HLH patients to better understand its clinical presentation, diagnosis and treatment. METHODS: For the purpose of this retrospective observational study, we searched for suspected and diagnosed adult HLH of all patients admitted to at least one adult surgical, anesthesiological or medical ICU between January 2006 and August 2018 at the university hospital Charité - Universitätsmedizin Berlin. All cases were reviewed by two HLH experts, who confirmed or declined the diagnosis. RESULTS: Of 6340 ICU patients with ferritin measurement, 40 suffered from HLH (0.63%). Of these, in-hospital mortality was 60.0% over all cases, which was highest in malignancy-associated HLH (71.4%). Infections were identified as most common triggers (42.5%). A variety of 19 different treatment strategies were applied. Non-survivors showed higher ferritin at diagnosis compared to survivors (p = 0.021), which was also seen in multivariable analyses. A minimum ferritin of 4083 µg/L after diagnosis was most predictive for 30-day mortality (AUC 0.888, 95% CI 0.771-1.000; sensitivity 93.8%, specificity 78.9%). CONCLUSIONS: Mortality in adult HLH patients in the ICU is high, particularly in malignancy-associated HLH. Infections are the most frequent HLH triggers in critically ill patients. At present, there is no standardized treatment for HLH in adult patients available. Assessment of ferritin is valuable for diagnosis, prognosis, and treatment monitoring. TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

11.
Neurocase ; 25(6): 243-250, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31532322

RESUMO

We describe a patient with acute herpes simplex encephalitis with left-hemispheric hippocampal, parahippocampal and insular lesions. Although prototypic language areas were unaffected, the patient suffered from an inability to name objects or animals displayed on pictures. This deficit was transient and gradually disappeared 8 weeks after the initial diagnosis. Our findings are in line with a previous report showing similar deficits in a patient with a comparable lesion pattern and support the hypothesis that left insular lesions can produce severe naming deficits. Using FDG-PET we ruled out that functional deactivation in classical language areas account for the observed naming deficits.

12.
J Psychosom Res ; 122: 36-38, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31126409

RESUMO

OBJECTIVE: We aimed to determine the prevalence of posttraumatic stress disorder (PTSD) 12 months after transient ischemic attack (TIA). METHOD: TIA patients of our previous investigation (examined 3 months after the event) were again examined 12 months after the diagnosis. PTSD and associated variables were assessed via self-rating instruments. RESULTS: Eighty-four patients were included in the analyses. Twelve months after TIA the prevalence of probable PTSD was reduced (8.3%) compared to that found 3 months after TIA (29.6%). Coping assessed 3 months after TIA predicted long-term PTSD severity. CONCLUSION: Although the prevalence of probable PTSD decreased 12 months after experiencing a TIA compared to 3 months after TIA, prevalence of probable PTSD is still increased relative to that in the general population.

13.
J Cancer Res Clin Oncol ; 145(6): 1645-1650, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941573

RESUMO

PURPOSE: The advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR-ABL1 transcripts by real-time quantitative PCR every 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR4, MR4.5, MR5) maintain remission after treatment stop, assessment of DMR is crucial. However, systematically collected molecular data, monitored with sensitive standardized assays, are not available outside clinical trials. METHODS: Data were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after > 2 years of TKI therapy were evaluated for DMR by local laboratories as well as standardized EUTOS laboratories. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out. RESULTS: Between 2014 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR-ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n = 197 (6.51%); MMR, n = 496 (16.40%); MR4, n = 685 (22.64%); MR4.5, n = 937 (30.98%); MR5, n = 710 (23.47%). With a Cohen's kappa coefficient of 0.708, a substantial agreement between EUTOS-certified and local laboratories was shown. CONCLUSIONS: Multicenter DMR assessment is feasible in the context of real-life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients' molecular response during or after TKI therapy.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Inibidores de Proteínas Quinases/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente) , Humanos , Laboratórios/normas , Laboratórios/estatística & dados numéricos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mieloide de Fase Crônica/sangue , Pessoa de Meia-Idade , Sistema de Registros , Adulto Jovem
14.
Psychol Res ; 2019 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-30778763

RESUMO

In their Perception-Action Model (PAM), Goodale and Milner (1992) proposed functionally independent and encapsulated processing of visual information for action and perception. In this context, they postulated that visual input for action is processed in an automatized and analytic manner, which renders visuomotor behaviour immune to perceptual interferences or multitasking costs due to sharing of cognitive resources. Here, we investigate the well-known Garner Interference effect under dual- and single-task conditions in its classic perceptual form as well as in grasping. Garner Interference arises when stimuli are classified along a relevant dimension (e.g., their length), while another irrelevant dimension (e.g., their width) has to be ignored. In the present study, participants were presented with differently sized rectangular objects and either grasped them or classified them as long or short via button presses. We found classical Garner Interference effects in perception as expressed in prolonged reaction times when variations occurred also in the irrelevant object dimension. While reaction times during grasping were not susceptible to Garner Interference, effects were observed in a number of measures that reflect grasping accuracy (i.e., poorer adjustment of grip aperture to object size, prolonged adjustment times, and increased variability of the maximum hand opening when irrelevant object dimensions were varied). In addition, multitasking costs occurred in both perception and action tasks. Thus, our findings challenge the assumption of automaticity in visuomotor behaviour as proposed by the PAM.

15.
Blood ; 133(9): 893-901, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30559259

RESUMO

Cold agglutinin disease is a difficult-to-treat autoimmune hemolytic anemia in which immunoglobulin M antibodies bind to erythrocytes and fix complement, resulting in predominantly extravascular hemolysis. This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease participated in the phase 1b component of a first-in-human trial. Patients received a test dose of 10-mg/kg sutimlimab followed by a full dose of 60 mg/kg 1 to 4 days later and 3 additional weekly doses of 60 mg/kg. All infusions were well tolerated without premedication. No drug-related serious adverse events were observed. Seven of 10 patients with cold agglutinin disease responded with a hemoglobin increase >2 g/dL. Sutimlimab rapidly increased hemoglobin levels by a median of 1.6 g/dL within the first week, and by a median of 3.9 g/dL (interquartile range, 1.3-4.5 g/dL; 95% confidence interval, 2.1-4.5) within 6 weeks (P = .005). Sutimlimab rapidly abrogated extravascular hemolysis, normalizing bilirubin levels within 24 hours in most patients and normalizing haptoglobin levels in 4 patients within 1 week. Hemolytic anemia recurred when drug levels were cleared from the circulation 3 to 4 weeks after the last dose of sutimlimab. Reexposure to sutimlimab in a named patient program recapitulated the control of hemolytic anemia. All 6 previously transfused patients became transfusion-free during treatment. Sutimlimab was safe, well tolerated, and rapidly stopped C1s complement-mediated hemolysis in patients with cold agglutinin disease, significantly increasing hemoglobin levels and precluding the need for transfusions. This trial was registered at www.clinicaltrials.gov as #NCT02502903.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Complemento C1s/antagonistas & inibidores , Hemólise/efeitos dos fármacos , Índice de Gravidade de Doença , Idoso , Anemia Hemolítica/etiologia , Anemia Hemolítica Autoimune/complicações , Complemento C1s/imunologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
16.
Materials (Basel) ; 11(9)2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30149568

RESUMO

The high-temperature creep behavior of a rafted [001] oriented AM1 Ni-based single crystal superalloy was investigated during in situ creep tests on synchrotrons. Experiments were performed at constant temperatures under variable applied stress in order to study the response (plastic strain, load transfer) to stress jumps. Using two different diffraction techniques in transmission (Laue) geometry, it was possible to measure the average lattice parameters of both the γ matrix and the γ ' rafts in the [100] direction at intervals shorter than 300 s. The absolute precision with both diffraction techniques of the constrained transverse mismatch (in the rafts' plane) is about 10-5. After stress jumps, special attention is given to the evolution of plastic strain within the γ channels. The relaxation of the Von Mises stress at leveled applied stress shows evidence of dislocation multiplication within the γ channels. From the analysis, we showed an interaction between plastic stress and dislocation density of the γ phase.

17.
Conscious Cogn ; 64: 72-83, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093260

RESUMO

The Perception-Action Model (PAM) considers the visual system to be divided into two streams defined by their specific functions, a ventral stream for vision and a dorsal stream for action. In this study we investigated two behavioral paradigms which according to PAM represent the two contrasting functions of the ventral and dorsal stream, namely bisection and obstacle-avoidance, respectively. It is an assumption of PAM that while ventral stream processing is ultimately linked with processing in other cognitive systems, dorsal stream processing is insulated from cognition. Accordingly it can be expected that a secondary task will interfere with bisection but not with obstacle-avoidance. We tested this prediction using a rapid serial visual presentation task as our secondary task (RSVP). Contrary to expectations we found significant interference for both bisection and obstacle-avoidance. Our findings suggest that dorsal-stream processing is not insulated from cognitive processes.


Assuntos
Cognição/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas , Vias Visuais , Adulto Jovem
18.
Shock ; 50(2): 149-155, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30010630

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis in adults (aHLH) is a rare life-threatening hyperinflammatory syndrome caused by excessive activation of macrophages and CD8+ T-cells. Due to the clinical overlap with severe sepsis, aHLH often remains undiagnosed resulting in poor outcome. Here, we present a retrospective study of incidence, clinical findings, and the outcome of aHLH in intensive care units (ICUs). METHODS: This retrospective analysis was performed at the university hospital Charité - Universitätsmedizin Berlin. We gathered data from 556 out of 46,532 patients admitted to our anesthesiological ICUs between 2006 and 2013, who had at least one plasma ferritin measurement during ICU treatment, and were at least 18 years old. Of these, 244 patients with ferritin at least 500 µg/L and available datasets of at least 4 HLH-2004 criteria were included. HLH-2004 diagnostic criteria and the recently published HScore were used. An aHLH expert team retrospectively reviewed the potential aHLH cases. RESULTS: Seventy-one of the included 244 patients died; 9 out of the 244 patients were retrospectively classified as aHLH of whom 4 patients had died (44.4%). Two of the 9 aHLH patients had been correctly diagnosed and had received specific aHLH treatment. Thus, 7 out of 9 patients (77.8%) remained undetected. ICU patients with at least 1 captured ferritin value and hyperferritinemia showed an aHLH rate of 3.7%, which rises up to 5.6% when only deceased patients are considered. Mortality in this selected cohort is 44.4%. CONCLUSIONS: Overall, 7 out of 9 patients (77.8%) suffering from aHLH remained undiagnosed. Awareness of this life-threatening syndrome, especially in ICUs, should be raised. The inclusion of ferritin into the admission lab panel for ICU is warranted.Clinical trial registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016. As this is a retrospective study, trial registration was after final data collection date.


Assuntos
Cuidados Críticos , Bases de Dados Factuais , Ferritinas/sangue , Unidades de Terapia Intensiva , Linfo-Histiocitose Hemofagocítica , Adulto , Idoso , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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