Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, chronic multisystemic disease which, depending on its severity, can lead to considerable physical and cognitive impairment, ...loss of ability to work and the need for nursing care including artificial nutrition and, in very severe cases, even death.The aim of this D-A-CH (Germany, Austria, Switzerland) consensus statement is 1) to summarize the current state of knowledge on ME/CFS, 2) to highlight the Canadian Consensus Criteria (CCC) as clinical criteria for diagnostics with a focus on the leading symptom post-exertional malaise (PEM) and 3) to provide an overview of current options and possible future developments, particularly with regard to diagnostics and therapy. The D-A-CH consensus statement is intended to support physicians, therapists and valuer in diagnosing patients with suspected ME/CFS by means of adequate anamnesis and clinical-physical examinations as well as the recommended clinical CCC, using the questionnaires and other examination methods presented. The overview of the two pillars of therapy for ME/CFS, pacing and symptom-relieving therapy options, is intended not only to provide orientation for physicians and therapists, but also to support decision-makers from healthcare policy and insurance companies in determining which therapy options should already be reimbursable by them at this point in time for the indication ME/CFS.
Zusammenfassung
Myalgische Enzephalomyelitis/Chronisches Fatigue-Syndrom (ME/CFS) ist eine schwere, chronische Multisystemerkrankung, die je nach Ausprägung zu erheblichen körperlichen und kognitiven ...Einschränkungen, zum Verlust der Arbeitsfähigkeit bis hin zur Pflegebedürftigkeit einschließlich künstlicher Ernährung und in sehr schweren Fällen sogar zum Tod führen kann. Das Ziel dieses D-A-CH-Konsensusstatements ist es, 1) den aktuellen Wissensstand zu ME/CFS zusammenzufassen, 2) in der Diagnostik die kanadischen Konsensuskriterien (CCC) als klinische Kriterien mit Fokus auf das Leitsymptom post-exertionelle Malaise (PEM) hervorzuheben und 3) vor allem im Hinblick auf Diagnostik und Therapie einen Überblick über aktuelle Optionen und mögliche zukünftige Entwicklungen aufzuzeigen. Das D-A-CH-Konsensusstatement soll Ärzt:innen, Therapeut:innen und Gutachter:innen dabei unterstützen, Patient:innen mit Verdacht auf ME/CFS mittels adäquater Anamnese und klinisch-physikalischen Untersuchungen sowie der empfohlenen klinischen CCC zu diagnostizieren und dabei die präsentierten Fragebögen sowie die weiteren Untersuchungsmethoden zu nutzen. Der Überblick über die zwei Säulen der Therapie bei ME/CFS, Pacing und die symptomlindernden Therapieoptionen sollen nicht nur Ärzt:innen und Therapeut:innen zur Orientierung dienen, sondern auch Entscheidungsträger:innen aus der Gesundheitspolitik und den Versicherungen darin unterstützen, welche Therapieoptionen bereits zu diesem Zeitpunkt bei der Indikation „ME/CFS“ von diesen erstattbar sein sollten.
Abstract Objectives Myelodysplastic syndromes (MDS) are typical diseases of the elderly. The clinical outcome of a well-characterized cohort of patients with MDS was analyzed for prevalence and ...impact of comorbidities to establish the basis for tailored treatment algorithms. Focus was on age- and sex-related differences. Material and Methods The hematopoietic cell transplantation-comorbidity index (HCT-CI) was assessed in 616 well-defined patients from the Austrian MDS platform (median age: 71 years). Results Most patients displayed one (24.5%) or more (23.7%) comorbidities. The highest frequencies were observed for cardiovascular disease (28.4%), diabetes (12.2%), and prior tumors (9.9%). Comorbidities were more frequent (mean number: 0.92 vs. 0.74 male vs. female; p = 0.030) and more severe in men than in women (mean HCT-CI score: 1.41 vs. 1.09 male vs. female; p = 0.016). Elderly patients (65 + years) showed a higher prevalence of comorbidities than younger patients (HCT-CI score: 1.52, mean in 65 +, vs. 0.24 and 0.76 in < 45 years and 46–65 years, respectively) (p < 0.001). These differences were most pronounced for cardiovascular disease, diabetes, and prior tumors (p < 0.001). Presence of cardiac arrhythmia or prior solid tumor was significantly associated with shorter overall survival (p = 0.023, 0.024, respectively). Moreover, HCT-CI risk grouping remained an independent prognostic parameter for survival in multivariate analysis. Conclusions Comorbidities impact clinical outcome in elderly patients with MDS. Distinct diseases cluster in an age- and sex-related manner, which may have clinical implications when designing individualized therapies. Comorbidities should be evaluated with established scores and integrated in decision making.
To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues ...allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the
cluster extending over 10 Mb in placenta.
Objective
Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the ...size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile.
Methods
Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent‐retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6‐second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI).
Results
A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6ml (interquartile range = 0–16). Ischemic core volumes correlated with 27‐hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6‐second lesion volumes correlated with 27‐hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow‐up Tmax > 6‐second volume (ie, predicted infarct volume) correlated with the 27‐hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13ml.
Interpretation
Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27‐hour infarct volume in acute stroke patients who were treated with reperfusion therapies. ANN NEUROL 2016;79:76–89
Improved pose estimation using a novel self-encoded marker for optical prospective motion correction in neuro-MRI. In vivo experiments show enhanced image quality using the pose estimates of ...self-encoded marker compared to checkerboard marker for motion correction.
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► We introduce a novel marker design for optical prospective motion correction in MRI. ► Embedded codes on this marker allow an independent identification of features. ► Without the need of all features visible to the camera the tracking range is extended. ► The novel marker shows an improved accuracy compared to a checkerboard marker. ► These improvements result in enhanced image quality in performed in vivo experiments.
The tracking and compensation of patient motion during a magnetic resonance imaging (MRI) acquisition is an unsolved problem. For brain MRI, a promising approach recently suggested is to track the patient using an in-bore camera and a checkerboard marker attached to the patient’s forehead. However, the possible tracking range of the head pose is limited by the fact that the locally attached marker must be entirely visible inside the camera’s narrow field of view (FOV). To overcome this shortcoming, we developed a novel self-encoded marker where each feature on the pattern is augmented with a 2-D barcode. Hence, the marker can be tracked even if it is not completely visible in the camera image. Furthermore, it offers considerable advantages over the checkerboard marker in terms of processing speed, since it makes the correspondence search of feature points and marker-model coordinates, which are required for the pose estimation, redundant. The motion correction with the novel self-encoded marker recovered a rotation of 18° around the principal axis of the cylindrical phantom in-between two scans. After rigid registration of the resulting volumes, we measured a maximal error of 0.39
mm and 0.15° in translation and rotation, respectively. In in vivo experiments, the motion compensated images in scans with large motion during data acquisition indicate a correlation of 0.982 compared to a corresponding motion-free reference.
Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated ...user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the 'allelome' by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.
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