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"Schenk, Thomas"
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Binocular rivalry reveals differential face processing in congenital prosopagnosia
Congenital Prosopagnosia (CP) is an innate impairment in face perception with heterogeneous characteristics. It is still unclear if and to what degree holistic processing of faces is disrupted in CP. Such disruption would be expected to lead to a focus on local features of the face. In this study, we used binocular rivalry (BR) to implicitly measure face perception in conditions that favour holistic or local processing. The underlying assumption is that if stimulus saliency affects the perceptual dominance of a given stimulus in BR, one can deduce how salient a stimulus is for a given group (here: participants with and without CP) based on the measured perceptual dominance. A further open question is whether the deficit in face processing in CP extends to the processing of the facial display of emotions. In experiment 1, we compared predominance of upright and inverted faces displaying different emotions (fearful, happy, neutral) vs. houses between participants with CP (N = 21) and with normal face perception (N = 21). The results suggest that CP observers process emotions in faces automatically but rely more on local features than controls. The inversion of faces, which is supposed to disturb holistic processing, affected controls in a more pronounced way than participants with CP. In experiment 2, we introduced the Thatcher effect in BR by inverting the eye and mouth regions of the presented faces in the hope of further increasing the effect of face inversion. However, our expectations were not borne out by the results. Critically, both experiments showed that inversion effects were more pronounced in controls than in CP, suggesting that holistic face processing is less relevant in CP. We find BR to be a useful implicit test for assessing visual processing specificities in neurological participants.
Journal Article
Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry
PurposeHemophagocytic 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.MethodsPatients 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.ResultsThe 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.ConclusionClose 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.
Journal Article
Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore
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.
Journal Article
ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia
Gene mutations independent of BCR::ABL1 have been identified in newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase, whereby mutations in epigenetic modifier genes were most common. These findings prompted the systematic analysis of prevalence, dynamics, and prognostic significance of such mutations, in a clinically well-characterized patient population of 222 CML patients from the TIGER study (CML-V) by targeted next-generation sequencing covering 54 myeloid leukemia-associated genes. In total, 53/222 CML patients (24%) carried 60 mutations at diagnosis with ASXL1 being most commonly affected (n = 20). To study mutation dynamics, longitudinal deep sequencing analysis of serial samples was performed in 100 patients after 12, 24, and 36 months of therapy. Typical patterns of clonal evolution included eradication, persistence, and emergence of mutated clones. Patients carrying an ASXL1 mutation at diagnosis showed a less favorable molecular response to nilotinib treatment, as a major molecular response (MMR) was achieved less frequently at month 12, 18, and 24 compared to all other patients. Patients with ASXL1 mutations were also younger and more frequently found in the high risk category, suggesting a central role of clonal evolution associated with ASXL1 mutations in CML pathogenesis.
Journal Article
Ponatinib for CML patients in routine clinical practice: the PONDEROSA study
Ponatinib, a third-generation tyrosine kinase inhibitor, is effective in patients with chronic myeloid leukemia (CML), particularly in cases of resistance or
BCR::ABL1
T315I mutation. However, arterial occlusive events (AOEs) remain an important safety concern. The PONDEROSA registry evaluated ponatinib use under routine clinical conditions in Germany and the Czech Republic. This observational cohort study included 99 adult CML patients treated with ponatinib; patient recruitment took place between 2015 and 2022 at 31 centers. The median follow-up was 22 months (range: 1–83). Among the 99 patients (median age 54 years at CML diagnosis), 91.9% were in chronic phase, 4.0% in accelerated phase, and 4.0% in blast phase. The T315I BCR::ABL1 mutation was detected in 19.2%. Ponatinib starting doses were 45 mg/day (32.3%), 30 mg/day (37.3%), or 15 mg/day (29.3%). Adverse events (AEs) were recorded in 64.6% of patients. Severe cardiovascular or cerebrovascular events occurred in 12.1% of patients, with no fatal events observed. Ponatinib was discontinued in 31.3% of patients, mainly due to intolerance or lack of response. 58.6% of patients achieved or maintained at least a major molecular response (MMR), compared to 19.0% at baseline. Disease progression was observed in 14.1% of patients, and 8.1% underwent allogeneic stem cell transplantation. The estimated 2-year progression-free survival and overall survival rates were 84.4% and 85.7%, respectively. The PONDEROSA study confirms the clinical effectiveness of ponatinib in routine practice. Individualized dosing strategies are essential to balance efficacy and cardiovascular safety. Ponatinib remains a valuable bridging therapy for patients requiring allogeneic transplantation.
Journal Article
Influence of transfusions, hemodialysis and extracorporeal life support on hyperferritinemia in critically ill patients
Ferritin is the major iron storage protein and an acute phase reactant. Hyperferritinemia is frequently seen in the critically ill where it has been hypothesized that not only underlying conditions but also factors such as transfusions, hemodialysis and extracorporeal life support (ECLS) lead to hyperferritinemia. This study aims to investigate the influence of transfusions, hemodialysis, and ECLS on hyperferritinemia in a multidisciplinary ICU cohort. This is a post-hoc analysis of a retrospective observational study including patients aged [greater than or equal to] 18 years who were admitted to at least one adult ICU between January 2006 and August 2018 with hyperferritinemia [greater than or equal to] 500 [mu]g/L and of [greater than or equal to] 14 days between two ICU ferritin measurements. Patients with hemophagocytic lymphohistiocytosis (HLH) were excluded. To identify the influence of transfusions, hemodialysis, and ECLS on ferritin change, multivariable linear regression analysis with ferritin change between two measurements as dependent variable was performed. A total of 268 patients was analyzed. Median duration between measurements was 36 days (22-57). Over all patients, ferritin significantly increased between the first and last measurement (p = 0.006). Multivariable linear regression analysis showed no effect of transfusions, hemodialysis, or ECLS on ferritin change. Changes in aspartate aminotransferase (ASAT) and sequential organ failure assessment (SOFA) score were identified as influencing factors on ferritin change [unstandardized regression coefficient (B) = 2.6; (95% confidence interval (CI) 1.9, 3.3); p < 0.001 and B = 376.5; (95% CI 113.8, 639.1); p = 0.005, respectively]. Using the same model for subgroups of SOFA score, we found SOFA platelet count to be associated with ferritin change [B = 1729.3; (95% CI 466.8, 2991.9); p = 0.007]. No association of ferritin change and in-hospital mortality was seen in multivariable analysis. The present study demonstrates that transfusions, hemodialysis, and ECLS had no influence on ferritin increases in critically ill patients. Hyperferritinemia appears to be less the result of iatrogenic influences in the ICU thereby underscoring its unskewed diagnostic value.
Journal Article
Trait mindfulness is primarily associated with depression and not with fatigue in multiple sclerosis (MS): implications for mindfulness-based interventions
Objectives
Persons with MS (PwMS) often display symptoms of depression and fatigue. Mindfulness-based interventions are known to counteract these symptoms. However, to-date the exact relations between trait mindfulness, depression and fatigue remain to be examined. Fatigue is generally regarded as a symptom immanent to the disease and as a direct neurobiological consequence of increased cytokine levels and cortical atrophy. In depression on the other hand, psychosocial factors in the context of adaptation difficulties are probably of higher relevance. Hence, one may argue that mindfulness, as a trait that promotes successful adaption, may show a strong negative association with depression and a relatively minor negative association with fatigue in PwMS.
Methods
In the current study, the association between self-reported trait mindfulness, fatigue and depression was examined in a sample of 69 PwMS.
Results
Trait mindfulness showed highly significant negative correlations with both, depression and fatigue. Mediation analyses however, revealed that depression mediated the relation between mindfulness and fatigue.
Conclusion
It may be concluded that in PwMS, trait mindfulness shows a genuine negative association with depression, but that it is only secondarily associated with fatigue. Implications for mindfulness-based interventions in MS are discussed. Based on the results of the current study, it may be feasible to promote the acceptance of default fatigue symptoms, instead of an actual reduction of fatigue symptoms.
Journal Article
The Effect of Gaze Position on Reaching Movements in an Obstacle Avoidance Task
Numerous studies have addressed the issue of where people look when they perform hand movements. Yet, very little is known about how visuomotor performance is affected by fixation location. Previous studies investigating the accuracy of actions performed in visual periphery have revealed inconsistent results. While movements performed under full visual-feedback (closed-loop) seem to remain surprisingly accurate, open-loop as well as memory-guided movements usually show a distinct bias (i.e. overestimation of target eccentricity) when executed in periphery. In this study, we aimed to investigate whether gaze position affects movements that are performed under full-vision but cannot be corrected based on a direct comparison between the hand and target position. To do so, we employed a classical visuomotor reaching task in which participants were required to move their hand through a gap between two obstacles into a target area. Participants performed the task in four gaze conditions: free-viewing (no restrictions on gaze), central fixation, or fixation on one of the two obstacles. Our findings show that obstacle avoidance behaviour is moderated by fixation position. Specifically, participants tended to select movement paths that veered away from the obstacle fixated indicating that perceptual errors persist in closed-loop vision conditions if they cannot be corrected effectively based on visual feedback. Moreover, measuring the eye-movement in a free-viewing task (Experiment 2), we confirmed that naturally participants' prefer to move their eyes and hand to the same spatial location.
Journal Article
Mindfulness training during brief periods of hospitalization in multiple sclerosis (MS): beneficial alterations in fatigue and the mediating role of depression
Objectives
Persons with MS (PwMS) are frequently affected by fatigue and depression. Mindfulness-based interventions may reduce these symptoms in PwMS and consequently their application has been extended to various settings. Only few efforts have been made to explore effects of short-term mindfulness training during brief periods of hospitalization. In the current study, the feasibility and potential effects of short-term mindfulness training on depression, fatigue, rumination and cognition were explored in PwMS in an acute-care hospital setting. Based on previous work, it was further examined whether the relation between trait mindfulness and fatigue prior to and following the intervention was mediated by depression and whether a mediation effect was also observable throughout the intervention.
Methods
A short-term mindfulness training protocol was developed, tailored to the requirements of the acute-care setting. Subsequently, 30 PwMS were recruited sequentially and received mindfulness training during the routine clinical process (median duration in hospital: eight days, number of sessions: four). Participants completed relevant self-report measures (depression, fatigue, rumination) and a neuropsychological assessment before and after training.
Results
Participants reported significantly increased trait mindfulness and decreased depression and fatigue following the intervention. Respective change scores were highly correlated so that increased trait mindfulness was associated with decreased symptoms. In the rumination domain, patients reported a tendency for an increased adaptive ability to engage in distractive behavior during arising negative mood. Other measures of trait rumination and cognition remained relatively stable. Results of the mediation analyses indicated that depression mediated the negative relationship between trait mindfulness and fatigue symptoms at pre and post assessments. With regards to the change scores, an association between mindfulness and cognitive fatigue ceased to be significant when depression was controlled, albeit in this case, the mediation effect did not reach significance.
Conclusion
Results of the current study indicate that short-term mindfulness training during brief periods of hospitalization may be beneficial for PwMS. They further complement previous work by identifying depression as a potential mediator of the antagonistic relationship between mindfulness and fatigue. Based on the current exploratory study, future trials are warranted to address this mechanism of mindfulness training in more detail.
Journal Article