The influence of clinical characteristics on prism adaptation training in visuospatial neglect: A post-hoc analysis of a randomized controlled trial.

Previous studies indicate that the effect of prism adaptation training (PAT) on unilateral neglect may depend on clinical characteristics. In this explorative work, we re-analyzed data from a previously conducted randomized controlled trial (N = 23) to investigate whether age, etiology, severity of motor impairments, and visual field deficits affect the efficacy of PAT. Additionally, we reviewed PAT studies that reported lesion maps and distinguished responders from non-responders. We transferred these maps into a common standard brain and added data from 12 patients from our study. We found patients suffering from subarachnoid bleeding appeared to show stronger functional recovery than those with intracranial hemorrhage or cortical infarction. Furthermore, patients with visual field deficits and those with more severe contralateral motor impairments had larger after-effect sizes but did not differ in treatment effects. In addition, patients with parietal lesions showed reduced recovery, whereas patients with lesions in the basal ganglia recovered better. We conclude that PAT (in its current form) is effective when fronto-subcortical areas are involved but it may not be the best choice when parietal regions are affected. Overall, the present work adds to the understanding on the effects of clinical characteristics on PAT.

Can auditory cues improve visuo-spatial neglect? Results of two pilot studies.

Although neglect is known to be a multimodal deficit, current interventions often address the visual modality only. Experimental studies, however, found that neglect patients can partially overcome their spatial inattention temporarily when being exposed to auditory cues that move towards the neglected side of space. Two pilot studies investigated the impact of dynamic auditory cueing on egocentric neglect severity in a clinical-therapeutic setting. In both studies, the patient groups received 15 sessions of intervention. Study 1, designed as double-blinded trial with a historical control group, targeted severely impaired early-acute patients who listened to music or audio books which were presented as moving dynamically from right to left. Results showed a reduction in egocentric neglect severity that persisted after therapy termination in the intervention but not in the historical control group. In study 2, based on the comparison with reported effect sizes of previous studies, dynamic meaningful auditory cues and optokinetic stimulation were combined in a computer-based training. Both studies found a significant reduction of neglect severity. Results provide evidence for the reduction of egocentric neglect severity after repetitive auditory cueing therapy in both severely and moderately impaired patients. Our promising findings should be verified thoroughly in randomized-controlled trials.

Capillary Refill-The Key to Assessing Dermal Capillary Capacity and Pathology in Optical Coherence Tomography Angiography.

BACKGROUND/OBJECTIVES: Standard optical coherence tomography angiography (OCTA) has been limited to imaging blood vessels actively undergoing perfusion, providing a temporary picture of surface microvasculature. Capillary perfusion in the skin is dynamic and changes in response to the surrounding tissue's respiratory, nutritional, and thermoregulatory needs. Hence, OCTA often represents a given perfusion state without depicting the actual extent of the vascular network. Here we present a method for obtaining a more accurate anatomic representation of the surface capillary network in human skin using OCTA, along with proposing a new parameter, the Relative Capillary Capacity (RCC), a quantifiable proxy for assessing capillary dilation potential and permeability. METHODS: OCTA images were captured at baseline and after compression of the skin. Baseline images display ambient capillary perfusion, while images taken upon capillary refill display the network of existing capillaries at full capacity. An optimization-based automated vessel segmentation method was used to automatically analyze and compare OCTA image sequences obtained from two volunteers. RCC was then compared with visual impressions of capillary viability. RESULTS: Our OCTA imaging sequence provides a method for mapping cutaneous capillary networks independent of ambient perfusion. Differences between baseline and refill images clearly demonstrate the shortcomings of standard OCTA imaging and produce the RCC biometric as a quantifiable proxy for assessing capillary dilation potential and permeability. CONCLUSION: Future dermatological OCTA diagnostic studies should implement the Capillary Refill Methods over standard imaging techniques and further explore the relevance of RCC to differential diagnosis and dermatopathology. Lasers Surg. Med. © The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Combined OCT distance and FBG force sensing cannulation needle for retinal vein cannulation: in vivo animal validation.

PURPOSE: Retinal vein cannulation is an experimental procedure during which a clot-dissolving drug is injected into an obstructed retinal vein. However, due to the fragility and minute size of retinal veins, such procedure is considered too risky to perform manually. With the aid of surgical robots, key limiting factors such as: unwanted eye rotations, hand tremor and instrument immobilization can be tackled. However, local instrument anatomy distance and force estimation remain unresolved issues. A reliable, real-time local interaction estimation between instrument tip and the retina could be a solution. This paper reports on the development of a combined force and distance sensing cannulation needle, and its experimental validation during in vivo animal trials. METHODS: Two prototypes are reported, relying on force and distance measurements based on FBG and OCT A-scan fibres, respectively. Both instruments provide an 80 [Formula: see text] needle tip and have outer shaft diameters of 0.6 and 2.3 mm, respectively. RESULTS: Both prototypes were characterized and experimentally validated ex vivo. Then, paired with a previously developed surgical robot, in vivo experimental validation was performed. The first prototype successfully demonstrated the feasibility of using a combined force and distance sensing instrument in an in vivo setting. CONCLUSION: The results demonstrate the feasibility of deploying a combined sensing instrument in an in vivo setting. The performed study provides a foundation for further work on real-time local modelling of the surgical scene. This paper provides initial insights; however, additional processing remains necessary.

A cell culture model for investigation of synapse influenceability: epigenetics, expression and function of gene targets important for synapse formation and preservation in SH-SY5Y neuroblastoma cells differentiated by retinoic acid.

SH-SY5Y neuroblastoma cells are frequently used for different neuronal cell culture models. As there is no "gold-standard", miscellaneous protocols exist to differentiate these cells into a neuronal cell type. Here, the aim was to find a differentiation condition making cells suitable for investigation of influenceability of synapses by environmental conditions in pharmacologic experiments. For this purpose, effects on synapse molecules should be somehow rateable and cells should be usable for functional analysis like calcium imaging. A system like this is desirable for example in basic research concerning schizophrenia, depression, autism or neurodegeneration as synaptic plasticity and neuronal maturation are known to have a significant impact in these diseases. Cells grown on laminin-coated glass cover slips and treated with 50 µM retinoic acid (RA) turned out to show most convincing morphological signs of neuronal differentiation and attached strongly to the ground, thereby also fulfilling preconditions for functional analysis. Systematic characterisation of this differentiation condition in comparison to non-treated controls revealed lower methylation rates and higher expression of most candidate molecules relevant for formation, preservation and function of synapses as well as differential function. In conclusion, this combination of differentiation strategy and markers seems to be a suitable system to estimate synapse modifications in basic research as it could help to identify possible dedifferentiating effects. To our knowledge, differentiation of SH-SY5Y has not been described as systematic before regarding comprehensiveness of the set of investigated synapse molecules and coverage of applied methods spanning from epigenetics to protein function. Furthermore, this is the first time that SH-SY5Y cells were differentiated on glass cover slips to an extent making them suitable for investigation of synapse molecules as part of stable intercellular connections in downstream functional analyses.

Imaging for planning of transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) has proven to be the standard of care for patients with prohibitive and high operative risk; today, it is considered a reasonable alternative to surgical aortic valve replacement in intermediate-risk patients. As indications for TAVI move toward patients at lower risk, safety aspects are becoming even more important. Furthermore, adequate patient selection is key for predictable procedural success with minimal complications, translating into an optimal clinical outcome. Decisions on valve type and size as well as on the access route are based on multimodality imaging including echocardiography, multislice computed tomography, and cardiac catheterization with peripheral angiography. This combination of multiple imaging modalities provides the best picture of a patient's anatomical and physiological suitability for the TAVI procedure. Yet, the reliability of preprocedural imaging is influenced by the quality of the images, which should be as high as possible, and both image acquisition and interpretation should be performed in a standardized manner. This article provides a concise overview of standardized multimodality imaging for the preprocedural planning and assessment of patients undergoing TAVI.

THRIVE score predicts clinical and radiological outcome after endovascular therapy or thrombolysis in patients with anterior circulation stroke in everyday clinical practice.

BACKGROUND AND PURPOSE: Based on the data of several trials the Totaled Health Risks in Vascular Events (THRIVE) score has been shown to predict outcome after either intravenous thrombolysis (IVT) or endovascular therapy (ET) in acute stroke patients. It is unknown whether the THRIVE score can also predict outcome in everyday clinical practice. Using our prospectively obtained stroke database the utility of the THRIVE score to predict clinical and radiological outcome in everyday clinical practice was analysed. METHODS: The relationships between THRIVE and good outcome (modified Rankin Scale ≤ 2 at discharge), poor outcome (modified Rankin Scale 5-6), in-hospital death, symptomatic intracranial haemorrhage (SICH) as well as infarct size were examined in patients with distal intracranial carotid artery, M1 and M2 occlusions after either IVT or ET. RESULTS: From January 2008 to October 2016 a total of 546 patients were treated with IVT and 492 patients received ET with stent retrievers (with or without IVT). In both treatment groups the THRIVE score predicted clinical outcome (Mantel-Haenszel chi-squared tests for trend P < 0.001 for good outcome, P < 0.001 for poor outcome and P < 0.001 for in-hospital death). In the ET group the THRIVE score remained an independent predictor of outcome after controlling for recanalization. The THRIVE score was associated with the infarct size after IVT or ET, whereas it did not predict SICH rates in either treatment group. CONCLUSIONS: In everyday clinical practice the THRIVE score strongly predicts clinical outcome and the extent of ischaemia after ET or IVT in patients with anterior circulation large vessel occlusions.

Impact of ASPECTS on computed tomography angiography source images on outcome after thrombolysis or endovascular therapy in large vessel occlusions.

BACKGROUND AND PURPOSE: Endovascular therapy (ET) is superior to intravenous thrombolysis (IVT) in selected patients with anterior circulation large vessel occlusions. However, it is unclear if this positive effect also applies to patients with extensive early ischaemic changes. The aim of this study was to analyze the impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on the CT angiography source images (SI) on outcome after ET or IVT. METHODS: Using our prospectively obtained stroke database and the admission SI-ASPECTS divided into three groups (0-5, 6-7 and 8-10), primarily the rates of good outcome [modified Rankin Scale (mRS) ≤2 at discharge] after either ET (n = 255) or IVT (n = 479) were compared. RESULTS: A favorable SI-ASPECTS (8-10) was present in 501 patients, 132 patients had a moderately favorable SI-ASPECTS (6-7) and 101 patients had an unfavorable SI-ASPECTS (0-5). Irrespective of the treatment modality, no patient with an unfavorable SI-ASPECTS had a good outcome and 38% died during hospital stay. Whilst significantly more patients with a favorable SI-ASPECTS had a good outcome after ET than after IVT (51% vs. 35%, P < 0.01), there was only a non-significant trend towards a good outcome after ET than after IVT in patients with a moderately favorable ASPECTS (25% vs. 14%, P = 0.1). CONCLUSION: Patients with extensive early ischaemic changes on CT scans (SI- ASPECTS ≤5) might not profit from ET. The impact of ET on outcome in patients with moderately favorable SI-ASPECTS should be addressed in further trials.

The effect of rotating random dot motion on visuospatial line orientation in patients with right-sided stroke.

Spatial deficits are frequent after brain damage, particularly right hemisphere stroke. Visual judgments of line orientation (LINE) are often impaired after right parietal lesions. Perception of line orientation is an important visuoperceptual component of visuoconstructive capacities. Yet, little is known about modulating factors in LINE and effective treatments are rare for this disorder. Studies in patients with spatial neglect show that horizontal random dot motion (RDM) significantly modulates horizontal spatial disorders, both transiently and permanently after treatment. In the current study, we investigated whether rotational RDM modulates judgements in an oblique LINE task in 20 patients with right-hemispheric first ever stroke (10 of them with a disorder in LINE and 10 without such a disorder), and 10 healthy, age-matched subjects. Subjects were tested under three experimental conditions: (1) with a static background of small white dots, (2) with slow clockwise or (3) counterclockwise circular RDM of these background stimuli, while they performed the LINE task. In the baseline condition with static background, the impaired patient group showed a significant counterclockwise tilt. Clockwise rotating RDM normalized this deficit transiently but completely, while counterclockwise rotating RDM slightly aggravated it, though not significantly. Tilts in the LINE task were significantly correlated with left visuospatial neglect. Similar but much smaller effects were obtained in the spatially unimpaired patients and the normal controls. These results show that rotational RDM modulates deficits of line orientation in patients with right-sided stroke, possibly by influencing higher spatial representations devoted to the perception of oblique lines.

Rotational coherent dot movement normalizes spatial disorientation of the subjective visual vertical in patients with rightsided stroke.

Studies in healthy individuals indicate a significant influence of rotating visual motion on judgments of the subjective visual vertical (SVV). Moreover, sensory stimulation manoeuvres like horizontal coherent dot movement significantly modulate horizontal spatial deficits in patients with rightsided stroke. Here, we investigated whether rotational coherent dot movement (RCDM) modulates spatial orientation deficits of the SVV in the roll plane in right hemispheric stroke. We tested the perceptual judgment of the SVV in 20 patients with right-hemispheric, first ever stroke (10 of them with a disorder of the SVV and 10 without a disorder), and 10 healthy, age-matched subjects under three experimental conditions: (1) with a static background of small white dots, (2) with slow clockwise or (3) counterclockwise circular RCDM of these background stimuli. In the baseline condition with static background, the impaired patient group showed a counterclockwise tilt of the SVV. Clockwise RCDM normalized this deficit completely, while with counterclockwise RCDM a slight aggravation was observed. Similar but quantitatively much smaller effects were obtained in the SVV-unimpaired patients and the healthy individuals. These results demonstrate a strong modulatory effect of RCDM on the SVV in patients with a tilt of the SVV due to right-sided stroke. RCDM thus appears to influence higher spatial representations devoted to visuospatial perception of the SVV. Possible mechanisms as well as clinical implications for therapy of visuospatial disorientation (self-orientation in space) after stroke are discussed.

On the relation between self-reported cognitive fatigue and the posterior hypothalamic-brainstem network.

BACKGROUND AND PURPOSE: Various causes have been suggested for multiple sclerosis (MS) related fatigue. Hypothalamus-brainstem fibres play a role in sleep-wake regulation and in hypothalamic deactivation during inflammatory states. Hence, they may play a role for experiencing fatigue by changing bottom-up hypothalamic activation. METHODS: Multiple sclerosis patients with and without self-reported cognitive fatigue and healthy controls were analysed with respect to the integrity of hypothalamus-brainstem fibres using diffusion-tensor imaging based tractography, focusing on the anterior, medial and posterior hypothalamic areas, controlling for clinical impairment and excluding participants with depressive mood. RESULTS: Multiple sclerosis patients without self-reported cognitive fatigue showed increased axial and radial diffusivity levels specifically for fibres connecting the right posterior hypothalamus with the right locus coeruleus, but not for the medial hypothalamus and the corpus callosum. Moreover, there were no differences between MS patients with and without fatigue in brain atrophy and lesion load, which could explain our results. CONCLUSION: Multiple sclerosis patients not experiencing fatigue show increased axial and radial diffusivity for fibres connecting the posterior hypothalamus and the brainstem, which might prevent bottom-up activation of the posterior hypothalamus and therefore downregulation of structures responsible for wakefulness and exploratory states of mind.

Brain structure, cognition and negative symptoms in schizophrenia are associated with serum levels of polysialic acid-modified NCAM.

The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell-cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder.

[Declared dead? Recommendations regarding integrated care from the perspective of German statutory health insurance]. / Totgesagte leben länger : Empfehlungen zur Integrierten Versorgung aus Sicht der gesetzlichen Krankenkassen.

The traditional separation of health care into sectors in Germany causes communication problems that hinder continuous, patient-oriented care. This is most evident in the transition from inpatient to outpatient care. That said, there are also breaks in the flow of information, a lack of supply, or even incorrect information flowing within same-sector care. The transition from a division of functions into sectors to a patient-oriented process represents a change in the paradigm of health care that can only be successfully completed with considerable effort. Germany's statutory health insurance (SHI) funds play a key role here, as they are the contracting parties as well as the financiers of integrated care, and are strategically located at the center of the development process.The objective of this article is to explore how Germany's SHI funds view integrated care, what they regard as being the drivers of and barriers to transitioning to such a system, and what recommendations they can provide with regard to the further development of integrated care. For this purpose semi-structured interviews with board members and those responsible for implementing integrated care into the operations of ten SHI funds representing more than half of Germany's SHI-insured population were conducted. According to the interviewees, a better framework for integrated care urgently needs to be developed and rendered more receptive to innovation.Only in this way will the widespread stagnation of the past several years be overcome. The deregulation of § 140a-d SGB V and the establishment of a uniform basis for new forms of care in terms of a new innovation clause are among the central recommendations of this article. The German federal government's innovation fund was met with great hope, but also implied risks. Nonetheless, the new law designed to strengthen health care overall generated high expectations.

[Economic Evaluation of Integrated Care Systems - Scientific Standard Specifications, Challenges, Best Practice Model]. / Ökonomische Erfolgsmessung von integrierten Versorgungsnetzen - Gütekriterien, Herausforderungen, Best-Practice-Modell.

PURPOSE: Transparency of economic performance of integrated care systems (IV) is a basic requirement for the acceptance and further development of integrated care. Diverse evaluation methods are used but are seldom openly discussed because of the proprietary nature of the different business models. The aim of this article is to develop a generic model for measuring economic performance of IV interventions. METHODS: A catalogue of five quality criteria is used to discuss different evaluation methods -(uncontrolled before-after-studies, control group-based approaches, regression models). On this -basis a best practice model is proposed. RESULTS: A regression model based on the German morbidity-based risk structure equalisation scheme (MorbiRSA) has some benefits in comparison to the other methods mentioned. In particular it requires less resources to be implemented and offers advantages concerning the relia-bility and the transparency of the method (=important for acceptance). Also validity is sound. Although RCTs and - also to a lesser -extent - complex difference-in-difference matching approaches can lead to a higher validity of the results, their feasibility in real life settings is limited due to economic and practical reasons. That is why central criticisms of a MorbiRSA-based model were addressed, adaptions proposed and incorporated in a best practice model: Population-oriented morbidity adjusted margin improvement model (P-DBV(MRSA)). CONCLUSION: The P-DBV(MRSA) approach may be used as a standardised best practice model for the economic evaluation of IV. Parallel to the proposed approach for measuring economic performance a balanced, quality-oriented performance measurement system should be introduced. This should prevent incentivising IV-players to undertake short-term cost cutting at the expense of quality.

Microanatomy of the tympanic membrane in chronic myringitis obtained with optical coherence tomography.

A microscope-based optical coherence tomography (OCT) device was used to assess the microanatomy of the tympanic membrane in patients with chronic myringitis. A prospective study was designed for this purpose. OCT measurements of the tympanic membrane were done on 11 patients with myringitis with a microscope-based spectral domain OCT system. The in vivo findings were compared with those findings of a control group consisting of 36 patients with retraction pockets or atrophic tympanic membranes (n = 13), myringosclerosis (n = 12) and perforations (n = 11). In active chronic myringitis, the thickness of the tympanic membrane is increased compared to healthy membranes and to other pathological conditions of the tympanic membrane. Consistent changes of the microanatomy of the tympanic membrane were found in chronic myringitis with OCT. Serial OCT measurements revealed no biofilm suspicious findings in all patients with active chronic myringitis. Intraoperative and in vivo OCT measurements may help to detect microanatomical changes of the tympanic membrane in chronic myringitis and in other conditions of the tympanic membrane.

Compassionate use of the self-expandable medtronic CoreValve prosthesis for the treatment of pure aortic regurgitation in a patient at prohibitive risk for surgical valve replacement.

Transcatheter aortic valve implantation (TAVI) is a viable treatment option for high- and prohibitive-risk patients with severe, calcified pure or predominant aortic valve stenosis, but not for pure aortic valve regurgitation. In fact, the use of TAVI for this indication is even considered unlikely due to the lack of calcium which appears essential for anchoring the stent-valve and prevents dislocation. We report a case of a patient with severe, symptomatic pure aortic regurgitation, and a history of two previous open-heart surgeries who was successfully treated by compassionate use implantation of an oversized Medtronic CoreValve prosthesis as an ultima ratio treatment option.