Morphometrische Analyse des Azinus der humanen Lunge mittels synchrotron-basierter Mikro-Computertomographie

In der vorliegenden Arbeit wurde erstmals ein vollständiger dreidimensionaler Datensatz des Azinus der humanen Lunge mittels der Synchrotron-basierten Mikro-CT-Technik erstellt und anschließend eine quantitative Untersuchung der Strukturen des Azinus durchgeführt. Eine humane Lunge wurde durch die Beatmung mit Formalindampf in Inspirationsstellung fixiert und in einem 64-Zeilen Computertomographen gescannt. Die anschließend ausgestanzten Proben (N = 12, Durchmesser = 8 mm, Höhe = 10 mm) wurden mit Osmiumtetroxid kontrastverstärkt und mit einer Auflösung von 3,9 µm3 Voxelgröße in einem Mikro-CT mit Synchrotronstrahlenquelle gescannt. Mit einem automatisierten „Tree-Analysis“ Softwareprogramm konnten 8 Azini aus dem Volumendatensatz segmentiert werden. Die Morphometrischen Daten wurden mit dem Softwareprogramm ANALYZE 9.0 erhoben. Die Atemwege innerhalb der Azini verzweigten sich über 11 Generationen. Das mittlere Azinusvolumen wurde mit 131,3 ± 29,2 mm3 berechnet und die mittlere Oberfläche des Azinus betrug 1012 ± 26 cm2. Der Innere Durchmesser verringerte sich ausgehend von dem Bronchiolus terminalis von 0,66 ± 0,04 mm auf 0,34 ± 0,06 mm (P < 0,001) und blieb nach der siebten Generation konstant (P < 0,5). Die Länge der einzelnen Generationen variierte zwischen 0,52 und 0,93 mm und zeigte keine signifikanten Unterschiede zwischen der zweiten und elften Generation. Der Verzweigungswinkel der „Tochteräste“ schwankte zwischen 113º und 134º ohne signifikante Unterschiede zwischen den Generationen (P < 0,3). Die in vorangegangenen Arbeiten gezeigten Ergebnisse bezüglich der Morphometrie des humanen Azinus basieren auf den Methoden der Histomorphometrie. Diese arbeitet gewebedestruktiv und stellt lediglich Rückschlüsse von zweidimensionalen Serienschnitten auf dreidimensionale Strukturen her. Unsere Arbeit zeigt die Möglichkeit der quantitativen Erfassung der Strukturen des Azinus anhand eines vollständigen Volumendatensatzes unter Verwendung der Synchrotron- basierten Mikro-CT- Technik.Structural data about the human lung fin structure are mainly based on stereological methods applied to serial sections. As these methods utilize 2D images, which are often not contiguous, they suffer from inaccuracies which are overcome by analysis of 3D micro-CT images of the never-sectioned specimen. The purpose of our study was to generate a complete data set of the intact three-dimensional architecture of the human acinus using high resolution synchrotron-based micro-CT (synMCT). A human lung was inflation-fixed by formaldehyde ventilation and then scanned in a 64-slice CT over its apex to base extent. Lung samples (8-mm diameter, 10 mm height, N = 12) were punched out, stained with osmium tetroxide, and scanned using synMCT at (4 µm)3 voxel size. The lung functional unit (acinus, N = 8) was segmented from the 3D tomographic image using an automated tree-analysis software program. Morphometric data of the lung were analyzed by ANOVA. Intra-acinar airways branching occurred over 11 generations. The mean acinar volume was 131, 3 ± 29, 2 mm3 (range 92, 5- 171, 3 mm3) and the mean acinar surface was calculated with 1012 ± 26 cm2. The airway internal diameter (starting from the bronchiolus terminalis) decreases distally from 0,66 ± 0,04 mm to 0,34 ± 0,06 mm (P < 0,001) and remains constant after the seventh generation (P < 0,5). The length of each generation ranges between 0, 52 and 0, 93 mm and did not show significant differences between the second and eleventh generation. The branching angle between daughter branches varies between 113-degree and 134-degree without significant differences between the generations (P < 0, 3). This study demonstrates the feasibility of quantitating the 3D structure of the human acinus at the spatial resolution readily achievable using synMCT

Association of extent of resection on recurrence-free survival and functional outcome in vestibular schwannoma of the elderly

BackgroundDespite the ongoing debate on the risk–benefit ratio of vestibular schwannoma (VS) treatment options, watchful observation and radiation are usually favored in the elderly (&gt;65 years). If surgery is inevitable, a multimodal approach after deliberate subtotal resection has been described as a valid option. The relationship between the extent of resection (EOR) of surgical and functional outcomes and recurrence-free survival (RFS) remains unclear. This present study aims to evaluate the functional outcome and RFS of the elderly in relation to the EOR.MethodsThis matched cohort study analyzed all consecutive elderly VS patients treated at a tertiary referral center since 2005. A separate cohort (&lt;65 years) served as a matched control group (young). Clinical status was assessed by the Charlson Comorbidity Index (CCI), the Karnofsky Performance (KPS), and the Gardner and Robertson (GR) and House &amp; Brackmann (H&amp;B) scales. RFS was evaluated by Kaplan–Meier analysis using contrast-enhanced magnetic resonance imaging to identify tumor recurrence.ResultsAmong 2,191 patients, 296 (14%) patients were classified as elderly, of whom 133 (41%) were treated surgically. The elderly were characterized by a higher preoperative morbidity and worse gait uncertainty. Postoperative mortality (0.8% and 1%), morbidity (13% and 14%), and the functional outcome (G&amp;R, H&amp;B, and KPS) did not differ between the elderly and the young. There was a significant benefit in regard to the preoperative imbalance. Gross total resection (GTR) was accomplished in 74% of all cases. Lower grades of the EOR (subtotal and decompressive surgery) raised the incidence of recurrence significantly. Mean time to recurrence in the surgELDERLY was 67.33 ± 42.02 months and 63.2 ± 70.98 months in the surgCONTROL.ConclusionsSurgical VS treatment aiming for complete tumor resection is feasible and safe, even in advanced age. A higher EOR is not associated with cranial nerve deterioration in the elderly compared to the young. In contrast, the EOR determines RFS and the incidence of recurrence/progression in both study cohorts. If surgery is indicated in the elderly, GTR can be intended safely, and if only subtotal resection is achieved, further adjuvant therapy, e.g., radiotherapy, should be discussed in the elderly, as the incidence of recurrence is not significantly lower compared to the young

Assessment of 24-hour physical behaviour in children and adolescents via wearables: a systematic review of free-living validation studies

Objectives: Studies that assess all three dimensions of the integrative 24-hour physical behaviour (PB) construct, namely, intensity, posture/activity type and biological state, are on the rise. However, reviews on validation studies that cover intensity, posture/activity type and biological state assessed via wearables are missing. Design: Systematic review. The risk of bias was evaluated by using the QUADAS-2 tool with nine signalling questions separated into four domains (ie, patient selection/study design, index measure, criterion measure, flow and time). Data sources: Peer-reviewed validation studies from electronic databases as well as backward and forward citation searches (1970–July 2021). Eligibility criteria for selecting studies: Wearable validation studies with children and adolescents (age <18 years). Required indicators: (1) study protocol must include real-life conditions; (2) validated device outcome must belong to one dimension of the 24-hour PB construct; (3) the study protocol must include a criterion measure; (4) study results must be published in peer-reviewed English language journals. Results: Out of 13 285 unique search results, 76 articles with 51 different wearables were included and reviewed. Most studies (68.4%) validated an intensity measure outcome such as energy expenditure, but only 15.9% of studies validated biological state outcomes, while 15.8% of studies validated posture/activity type outcomes. We identified six wearables that had been used to validate outcomes from two different dimensions and only two wearables (ie, ActiGraph GT1M and ActiGraph GT3X+) that validated outcomes from all three dimensions. The percentage of studies meeting a given quality criterion ranged from 44.7% to 92.1%. Only 18 studies were classified as ‘low risk’ or ‘some concerns’. Summary: Validation studies on biological state and posture/activity outcomes are rare in children and adolescents. Most studies did not meet published quality principles. Standardised protocols embedded in a validation framework are needed

Assessment of 24-hour physical behaviour in children and adolescents via wearables: a systematic review of free-living validation studies.

Objectives Studies that assess all three dimensions of the integrative 24-hour physical behaviour (PB) construct, namely, intensity, posture/activity type and biological state, are on the rise. However, reviews on validation studies that cover intensity, posture/activity type and biological state assessed via wearables are missing. Design Systematic review. The risk of bias was evaluated by using the QUADAS-2 tool with nine signalling questions separated into four domains (ie, patient selection/study design, index measure, criterion measure, flow and time). Data sources Peer-reviewed validation studies from electronic databases as well as backward and forward citation searches (1970-July 2021). Eligibility criteria for selecting studies Wearable validation studies with children and adolescents (age <18 years). Required indicators: (1) study protocol must include real-life conditions; (2) validated device outcome must belong to one dimension of the 24-hour PB construct; (3) the study protocol must include a criterion measure; (4) study results must be published in peer-reviewed English language journals. Results Out of 13 285 unique search results, 76 articles with 51 different wearables were included and reviewed. Most studies (68.4%) validated an intensity measure outcome such as energy expenditure, but only 15.9% of studies validated biological state outcomes, while 15.8% of studies validated posture/activity type outcomes. We identified six wearables that had been used to validate outcomes from two different dimensions and only two wearables (ie, ActiGraph GT1M and ActiGraph GT3X+) that validated outcomes from all three dimensions. The percentage of studies meeting a given quality criterion ranged from 44.7% to 92.1%. Only 18 studies were classified as 'low risk' or 'some concerns'. Summary Validation studies on biological state and posture/activity outcomes are rare in children and adolescents. Most studies did not meet published quality principles. Standardised protocols embedded in a validation framework are needed. PROSPERO registration number CRD42021230894

Quality Evaluation of Free-living Validation Studies for the Assessment of 24-Hour Physical Behavior in Adults via Wearables: Systematic Review.

BACKGROUND Wearable technology is a leading fitness trend in the growing commercial industry and an established method for collecting 24-hour physical behavior data in research studies. High-quality free-living validation studies are required to enable both researchers and consumers to make guided decisions on which study to rely on and which device to use. However, reviews focusing on the quality of free-living validation studies in adults are lacking. OBJECTIVE This study aimed to raise researchers' and consumers' attention to the quality of published validation protocols while aiming to identify and compare specific consistencies or inconsistencies between protocols. We aimed to provide a comprehensive and historical overview of which wearable devices have been validated for which purpose and whether they show promise for use in further studies. METHODS Peer-reviewed validation studies from electronic databases, as well as backward and forward citation searches (1970 to July 2021), with the following, required indicators were included: protocol must include real-life conditions, outcome must belong to one dimension of the 24-hour physical behavior construct (intensity, posture or activity type, and biological state), the protocol must include a criterion measure, and study results must be published in English-language journals. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool with 9 questions separated into 4 domains (patient selection or study design, index measure, criterion measure, and flow and time). RESULTS Of the 13,285 unique search results, 222 (1.67%) articles were included. Most studies (153/237, 64.6%) validated an intensity measure outcome such as energy expenditure. However, only 19.8% (47/237) validated biological state and 15.6% (37/237) validated posture or activity-type outcomes. Across all studies, 163 different wearables were identified. Of these, 58.9% (96/163) were validated only once. ActiGraph GT3X/GT3X+ (36/163, 22.1%), Fitbit Flex (20/163, 12.3%), and ActivPAL (12/163, 7.4%) were used most often in the included studies. The percentage of participants meeting the quality criteria ranged from 38.8% (92/237) to 92.4% (219/237). On the basis of our classification tree to evaluate the overall study quality, 4.6% (11/237) of studies were classified as low risk. Furthermore, 16% (38/237) of studies were classified as having some concerns, and 72.9% (173/237) of studies were classified as high risk. CONCLUSIONS Overall, free-living validation studies of wearables are characterized by low methodological quality, large variability in design, and focus on intensity. Future research should strongly aim at biological state and posture or activity outcomes and strive for standardized protocols embedded in a validation framework. Standardized protocols for free-living validation embedded in a framework are urgently needed to inform and guide stakeholders (eg, manufacturers, scientists, and consumers) in selecting wearables for self-tracking purposes, applying wearables in health studies, and fostering innovation to achieve improved validity

Quality Evaluation of Free-living Validation Studies for the Assessment of 24-Hour Physical Behavior in Adults via Wearables: Systematic Review

Background: Wearable technology is a leading fitness trend in the growing commercial industry and an established method for collecting 24-hour physical behavior data in research studies. High-quality free-living validation studies are required to enable both researchers and consumers to make guided decisions on which study to rely on and which device to use. However, reviews focusing on the quality of free-living validation studies in adults are lacking. Objective: This study aimed to raise researchers’ and consumers’ attention to the quality of published validation protocols while aiming to identify and compare specific consistencies or inconsistencies between protocols. We aimed to provide a comprehensive and historical overview of which wearable devices have been validated for which purpose and whether they show promise for use in further studies. Methods: Peer-reviewed validation studies from electronic databases, as well as backward and forward citation searches (1970 to July 2021), with the following, required indicators were included: protocol must include real-life conditions, outcome must belong to one dimension of the 24-hour physical behavior construct (intensity, posture or activity type, and biological state), the protocol must include a criterion measure, and study results must be published in English-language journals. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool with 9 questions separated into 4 domains (patient selection or study design, index measure, criterion measure, and flow and time). Results: Of the 13,285 unique search results, 222 (1.67%) articles were included. Most studies (153/237, 64.6%) validated an intensity measure outcome such as energy expenditure. However, only 19.8% (47/237) validated biological state and 15.6% (37/237) validated posture or activity-type outcomes. Across all studies, 163 different wearables were identified. Of these, 58.9% (96/163) were validated only once. ActiGraph GT3X/GT3X+ (36/163, 22.1%), Fitbit Flex (20/163, 12.3%), and ActivPAL (12/163, 7.4%) were used most often in the included studies. The percentage of participants meeting the quality criteria ranged from 38.8% (92/237) to 92.4% (219/237). On the basis of our classification tree to evaluate the overall study quality, 4.6% (11/237) of studies were classified as low risk. Furthermore, 16% (38/237) of studies were classified as having some concerns, and 72.9% (173/237) of studies were classified as high risk. Conclusions: Overall, free-living validation studies of wearables are characterized by low methodological quality, large variability in design, and focus on intensity. Future research should strongly aim at biological state and posture or activity outcomes and strive for standardized protocols embedded in a validation framework. Standardized protocols for free-living validation embedded in a framework are urgently needed to inform and guide stakeholders (eg, manufacturers, scientists, and consumers) in selecting wearables for self-tracking purposes, applying wearables in health studies, and fostering innovation to achieve improved validity

Ambulatory assessment for physical activity research. State of the science, best practices and future directions

Technological and digital progress benefits physical activity (PA) research. Here we compiled expert knowledge on how Ambulatory Assessment (AA) is utilized to advance PA research, i.e., we present results of the 2nd International CAPA Workshop 2019 "Physical Activity Assessment - State of the Science, Best Practices, Future Directions" where invited researchers with experience in PA assessment, evaluation, technology and application participated. First, we provide readers with the state of the AA science, then we give best practice recommendations on how to measure PA via AA and shed light on methodological frontiers, and we furthermore discuss future directions. AA encompasses a class of methods that allows the study of PA and its behavioral, biological and physiological correlates as they unfold in everyday life. AA includes monitoring of movement (e.g., via accelerometry), physiological function (e.g., via mobile electrocardiogram), contextual information (e.g., via geolocation-tracking), and ecological momentary assessment (EMA; e.g., electronic diaries) to capture self-reported information. The strengths of AA are data assessment that near real-time, which minimizes retrospective biases in real-world settings, consequentially enabling ecological valid findings. Importantly, AA enables multiple assessments across time within subjects resulting in intensive longitudinal data (ILD), which allows unraveling within-person determinants of PA in everyday life. In this paper, we show how AA methods such as triggered e-diaries and geolocation-tracking can be used to measure PA and its correlates, and furthermore how these findings may translate into real-life interventions. In sum, AA provides numerous possibilities for PA research, especially the opportunity to tackle within-subject antecedents, concomitants, and consequences of PA as they unfold in everyday life. In-depth insights on determinants of PA could help us design and deliver impactful interventions in real-world contexts, thus enabling us to solve critical health issues in the 21st century such as insufficient PA and high levels of sedentary behavior. (DIPF/Orig.

Elevated frequencies of leukemic myeloid and plasmacytoid dendritic cells in acute myeloid leukemia with the FLT3 internal tandem duplication

Some 30% of acute myeloid leukemia (AML) patients display an internal tandem duplication (ITD) mutation in the FMS-like tyrosine kinase 3 (FLT3) gene. FLT3-ITDs are known to drive hematopoietic stem cells towards FLT3 ligand independent growth, but the effects on dendritic cell (DC) differentiation during leukemogenesis are not clear. We compared the frequency of cells with immunophenotype of myeloid DC (mDC: Lin−, HLA-DR+, CD11c+, CD86+) and plasmacytoid DC (pDC: Lin−, HLA-DR+, CD123+, CD86+) in diagnostic samples of 47 FLT3-ITD− and 40 FLT3-ITD+ AML patients. The majority of ITD+ AML samples showed high frequencies of mDCs or pDCs, with significantly decreased HLA-DR expression compared with DCs detectable in ITD− AML samples. Interestingly, mDCs and pDCs sorted out from ITD+ AML samples contained the ITD insert revealing their leukemic origin and, upon ex vivo culture with cytokines, they acquired DC morphology. Notably, mDC/pDCs were detectable concurrently with single lineage mDCs and pDCs in all ITD+ AML (n = 11) and ITD− AML (n = 12) samples analyzed for mixed lineage DCs (Lin−, HLA-DR+, CD11c+, CD123+). ITD+ AML mDCs/pDCs could be only partially activated with CD40L and CpG for production of IFN-α, TNF-α, and IL-1α, which may affect the anti-leukemia immune surveillance in the course of disease progression