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Scapular notching is a radiographic finding associated with the use of a reverse shoulder prosthesis. The morphological characteristics of the glenoid neck have been scarcely explored as a relevant factor in relation to scapular notching. The objective of this study is to measure the length of the glenoid neck in a three-dimensional CT reconstruction of a healthy population and to simulate the scapular notching free range of motion for the "long neck" and for the "short neck" groups.CT scans of 214 shoulders were reviewed, excluding incomplete, poor quality, or altered studies. 100 CT scans were finally processed. The mean age was 51.7 years (SD 19.4; range, 15-84 years), with 49 female and 51 male patients. For each of the scapulae, four morphometric measurements were obtained: anterior glenoid neck (AGN), middle glenoid neck (MGN), posterior glenoid neck (PGN) and alternative posterior glenoid neck (aPGN). Using 3D software, we simulated a reverse shoulder prosthesis, and the scapular notching free range of motion was registered. Differences between measurements were evaluated with an unpaired t-test using StataIC16®. P-values0.05 were considered significant. The intraobserver and interobserver correlation was evaluated with the intraclass correlation coefficient.The AGN measured 7.43 ± 2.52 mm (range, 1.72-13.3 mm); MGN measured 8.05 mm ± 1.93 (range, 2.92-13.2 mm); PGN measured 7.26 ± 2.6 mm (range, 2-13.4 mm); and aPGN measured 8.97 ± 2.3 mm (range, 4.08-15.4 mm). The scapular notching free range of motion for the "long neck" group was 74.98° ± 7.35 (range, 55-83°) and for the "short neck" group, it was 62.93° ± 6.84 (range, 45-70°) (p = 0.0004).Measurement of posterior glenoid neck length exhibits excellent reliability and reproducibility, as well as being associated to the scapular notching free range of motion.Basic, retrospective, CT images research.

Objective In the evaluation of oropharyngeal dysphagia, instrumental procedures, for example, flexible endoscopic evaluation of swallowing or videofluoroscopic swallowing study, are essential to improve diagnostic accuracy for salient findings such as penetration, aspiration, or pharyngeal residue. To date, it is unclear which of the 2 methods represents the diagnostic gold standard. The aim of this study, therefore, was to compare videofluoroscopy and swallowing endoscopy during a simultaneous swallowing examination in a large cohort of patients with oropharyngeal dysphagia. Designs Prospective observational study. Setting and participants In this study, 49 patients with oropharyngeal dysphagia (mean age 70.0 ± 10.8 years) were evaluated using simultaneous swallowing endoscopy and videofluoroscopy. Furthermore, the effect of narrow-band imaging in swallowing endoscopy on the assessment of penetration and aspiration was investigated in a subgroup of 19 patients. Measures The Penetration-Aspiration Scale and the Yale Pharyngeal Residue Severity Rating Scale were rated independently based on both modalities. Results Both modalities showed a high correlation between penetration, aspiration, and pharyngeal residue. Causes for a higher score on the Penetration-Aspiration Scale in videofluoroscopy were intradeglutitive events that were not visible in swallowing endoscopy or false-positive events because of the loss of the lateral dimension in videofluoroscopy. A typical reason for a higher score on this scale in swallowing endoscopy was the better visualization of the anatomical structures. Narrow-band imaging in swallowing endoscopy resulted in a higher score on the Penetration-Aspiration Scale for liquids and semisolids in individual cases, although overall there was no statistically significant difference between scores using white light or narrow-band imaging. Conclusions and Implications Videofluoroscopy and swallowing endoscopy may equally be considered as a diagnostic gold standard for oropharyngeal dysphagia regarding penetration, aspiration, and pharyngeal residue. Narrow-band imaging may increase the sensitivity for penetration and aspiration in individual cases.

Several tricuspid annuloplasty (TA) techniques are used for concomitant repair of functional tricuspid regurgitation (TR). This study compared the midterm clinical and valvular outcome among 3 annuloplasty techniques.TA was performed in 307 patients (aged 75.9 ± 10.4 years) with a rigid ring (RA) in 184, a flexible band (FA) in 80, or a suture annuloplasty (SA) in 43. Study end points were survival and recurrence of TRgrade 2 at 5 years.TA was performed concomitantly to mitral valve surgery in 136 patients (44.3%), aortic valve surgery in 18 (5.9%), coronary artery bypass grafting in 13 (4.2%), or a combined procedure in 140 (45.6%). Most had TRgrade 2 (78.5%), without significant differences between the TA groups (P = .878). Within a median follow-up of 3.4 years (interquartile range, 2.2-5.0 years), the 5-year survival was 80.1% ± 3.4% for RA, 83.5% ± 4.7% for FA, and 85.1% ± 6.5% for SA (P = .471). Independent risk factors for late mortality were renal impairment (hazard ratio [HR], 2.83; 95% CI, 1.16-6.89; P = .022), diabetes (HR, 2.10; 95% CI, 1.07-4.11; P = .030), and severe right ventricular dysfunction by tricuspid annulus plane systolic excursion10 mm (HR, 11.52; 95% CI, 4.98-26.66; P.001). Pulmonary hypertension was nearly significant (HR, 1.92; 95% CI, 0.98-3.74; P = .057). The cumulative incidence of TR recurrence at 5 years was 15.9%, 19.4%, and 21.1% for RA, FA, and SA, respectively (P = .342). Severe pulmonary hypertension (HR, 2.64; 95% CI, 1.38-5.07; P = .003), preoperative TR grade (HR, 1.82; 95% CI, 1.01-3.27; P = .046), and residual TRgrade 2 at discharge (HR, 3.38; 95% CI, 1.64-6.96; P = .001) were predictive for later TR recurrence, regardless of the annuloplasty technique.This study demonstrates that advanced pathophysiological right circulatory impairment, such as severe pulmonary hypertension and right ventricular dysfunction, affects the midterm survival and TR recurrence rate more than the annuloplasty technique used for concomitant repair of functional TR.

Objectives Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. Methods We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the “COSYCONET” COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu’s method, k-means clustering, texture analysis, and 80th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. Results All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p r = 0.72, p p Emph (r = 0.70 to 0.75, p Emph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = − 0.54 to − 0.41, p Conclusion QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu’s method for future clinical studies in COPD. Key Points • QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT. • The extent of QDP from DCE-MRI corresponds to the combined extent of PRMEmph and PRMfSAD from CT. • Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

Collaboration and decision-making of humans usually entails logical reasoning that is expressed through discussions and individual arguments. Where collaborative work uses geo-spatial information and where decision-making has a spatial connotation, argumentation will include geographical references. Argumentation maps have been developed to support geographically referenced discussions and provide a visual access to debates in domains such as urban planning. The concept of argumentation maps provides for explicit links between arguments and the geographic objects they refer to. These geo-argumentative relations do not only allow for cartographic representation of arguments, but also support the querying of both, space and discussion. Combinations of spatial queries and retrieval of linked arguments provide a powerful way of analyzing and summarizing the current state of a debate. In this chapter, we provide an overview of the original argumentation model and we discuss related research and application development. We also link argumentation mapping to related concepts in geographic visualization, spatial decision support systems, and public participation GIS under the umbrella of collaborative GIS. Geographic Information Systems, Public Participation GIS, Collaborative GIS, Spatial Decision Support Systems, Argumentation Maps, Spatial Planning, User Interface.

Extreme hot weather is a threat to public health, and it is anticipated that the number of hot days and the duration of extreme heat events will increase with climate change. Already, heat-related illness and mortality is the dominant natural hazard in many countries. While everybody is at risk to varying degrees, there are known factors relating to heat exposure and sensitivity that make some population groups more vulnerable than others. The objective of this paper is to assess carto-graphic design decisions in creating heat vulnerability maps, and how they may affect the usefulness of different map types. Spatial patterns of heat vulnerability were visualized using maps representing individual exposure and sensitivity indicators, composite vulnerability indices, and geographical hot spots of vulnerability. The composite indices were calculated using the ordered weighted averaging (OWA) multi-criteria analysis method. Hot spots were determined using local indicators of spatial association (LISA). This study is part of an ongoing project which aims to identify vulnerable populations within the City of Toronto, Canada, in order to support targeted response and mitigation. The maps were found to be a valuable addition to the hot weather planning toolkit supporting neighbor-hood-level interventions.KEYWORDS: Climate change, cluster maps, geographic information systems, heat-related illness, multi-criteria analysis, vulnerability index

This paper presents a spatial decision support tool that implements the Ordered Weighted Averaging (OWA) method. OWA is a family of multicriteria evaluation operators characterised by two sets of weights: criterion importance weights and order weights. We propose a highly interactive way of choosing, modifying, and fine-tuning the decision strategy defined by the order weights. This exploratory approach to OWA is supported by a graphical representation of the operator's behaviour in terms of decision risk and tradeoff/dispersion between criteria. Our prototype implementation is based on the CommonGIS software, and thus, Web-enabled and working with vector data. We successfully demonstrate online, exploratory support of spatial decision strategies using a data set of skiing resorts in Wallis, Switzerland.This is a post-peer-review, pre-copyedit version of an article published in Journal of Geographical Systems. The final authenticated version is available online at: http://dx.doi.org/10.1007/s101090300095

Commonly used GIS combination operators such as Boolean conjunction/disjunction and weighted linear combination can be generalized to the ordered weighted averaging (OWA) family of operators. This multicriteria evaluation method allows decision-makers to define a decision strategy on a continuum between pessimistic and optimistic strategies. Recently, OWA has been introduced to GIS-based decision support systems. We propose to extend a previous implementation of OWA with linguistic quantifiers to simplify the definition of decision strategies and to facilitate an exploratory analysis of multiple criteria. The linguistic quantifier-guided OWA procedure is illustrated using a dataset for evaluating residential quality of neighborhoods in London, Ontario. This is a post-peer-review, pre-copyedit version of an article published in Journal of Geographical Systems. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10109-005-0159-2

When faced with important decisions, we tend to base our decision-making on a rational framework, which often includes multiple decision criteria. Spatial decision problems have been characterized as a set of geographically defined decision alternatives (locations) with associated criterion values (e.g., Malczewski 1999). Within Geographic Information Systems (GIS), multi-criteria decision analyses (MCDA) tools have been used for decision support in environmental, transportation, and urban/regional planning, in waste management, as well as in hydrology, agriculture, and forestry, to name but a few areas of application (Malczewski 2006). Often, MCDA tools are only loosely coupled with GIS software (e.g., calculations completed in a spreadsheet) or take the form of custom implementations in a GIS scripting/programming environment. Few GIS vendors have integrated generic MCDA functionality in their products, with the notable exceptions of Idrisi’s Multi-Criteria Evaluation module and ArcGIS’ Overlay Toolset. Both of these operate on raster data layers using map algebra operations to combine cell values into an evaluation score for each candidate location (raster cell). In this technical note, we present “MCDA4ArcMap”, an open-source tool for MCDA and geovisualization of vector data in Arc-Map. The analytical functionality of the tool includes three MCDA methods: weighted linear combination (WLC), ordered weighted averaging (OWA), and a local variant of WLC (LWLC). WLC corre-sponds to the weighted overlay tool that readers may know from ArcGIS. As an extension of the criterion importance weighting in WLC, the OWA method allows the decision-maker to specify a de-gree of risk in their approach to decision-making. OWA has been implemented previously in Idrisi (Jiang & Eastman 2000). The recently proposed LWLC (Malczewski 2011) adjusts criterion impor-tance weights with regards to the local range of criterion values. Criterion weights are increased in a neighbourhood, if their local range is large relative to their global range in the study area, or decreased if the local range is relatively small. This approach ad-heres to the range-sensitivity principle that stipulates that criterion weights should depend on the ranges of criterion values occurring in a specific decision problem.

This paper explores the spatial aspects of GIS-based multi-criteria evaluation. We provide a systematic account of geographically defined decision criteria based on three classes of spatial relations: location, proximity, and direction. We also discuss whether the evaluation score of a decision alternative should be directly influenced by neighbouring scores and outline a methodology for distance-based adjustment of evaluation scores. A home buyer case study is employed to demonstrate how spatial criteria can be included in a spatial decision support system and to investigate the effect of geographically adjusting the evaluation scores of decision alternatives. The case study demonstrates how spatial criteria can be presented to decision-makers and their effects be observed in the decision outcome. Further, the spatial adjustment of evaluation scores using the performance of neighbouring properties smoothes the distribution of scores across the study area and allows decision-makers to consider a location’s environment. Keywords: Multi-Criteria Evaluation, Residential Real-Estate Choice, Spatial Decision Support Systems, Spatial Relations.

Argumentation Maps support participants in geographically referenced debates as they occur, for example, as part of urban planning processes. In a quasi-naturalistic case study, 11 student participants discussed planning issues on the University of Toronto downtown campus. The analysis of this case study focuses on general usability aspects of an Argumentation Map prototype, such as cost of entry, efficiency, interactivity, and connectivity. By applying usability analysis methods from the field of human-computer interaction, we evaluate the learnability, memorability, and user satisfaction with this tool’s functionality. Our findings indicate that the participants were generally satisfied, but we include specific suggestions for improving the functionality of Argumentation Maps, e.g., with respect to map navigation, display of discussion contributions, and online status of participants. On a more general level, this case study contributes to the methods spectrum of research into participatory spatial decision support systems as an example of user testing in a realistic decision-making context.

1. Introduction Spatial planning deals with the problem of distributing the limited resource "space" among different uses and users. It can be highly challenging to find a balanced land-use pattern, for example in urban agglomerations. Different interest groups such as residents, industry, and ecologists will claim different desirable land-uses for a given area. Spatial planning is also about locating unwanted land-use such as waste facilities. In this case, interest groups (e.g. city councils, neighbourhood organizations) and individuals will fight nearby locations. This situation is known as the NIMBY problem: “Not In My BackYard!” In democratic societies, decisions such as those in spatial planning are made by political representatives in cooperation with public administration and residents. The final decision will usually be based on a number of consecutive prior decisions, or choices, which are made by different groups of stakeholders. At any of these decision levels, there are two important methods to reach a conclusion: consensus finding, or voting. Both will be preceded by more or less intensive discussions and argumentation. The ultimate goal of discussions is to achieve sustainable development by integrating the objectives of diverse stakeholders. Thus, we argue that discussions are a crucial element of spatial planning procedures and are to be integrated with planning and decision support techniques. Discussions will have diverse formats in different planning projects. For example, the number of participants may vary from only two to hundreds and more; participants may get together or stay separated in space and/or time; discussion may be un-moderated, or moderated and structured. Nevertheless, discussion contributions (statements, messages, arguments, articles) in spatial planning will commonly contain a spatial reference. This does allow to link discussion support to spatially enabled decision support techniques as argued in this chapter. In section 2, we will review general theories on argumentation and introduce major concepts of computer-supported cooperative work. Next, geographically referenced discourse will be analysed in more detail leading to the argumentation map model (section 3). Section 4 develops use cases for GIS-based discussion support, and section 5 presents some existing applications. Finally, we will speculate about future developments in computer support for discussions in spatial planning (section 6).

BACKGROUND AND AIMS we know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function. METHODS patients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination. RESULTS 1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p

The prognostic value of the present definition of microradicality in colon cancer is poorly understood, especially considering the vast influence it has in rectal cancer prognosis.This study aimed to investigate whether the risk of recurrence after complete mesocolic excision for stage III colon cancer is associated with the distance from tumor tissue to resection margin and whether the location of the involved margin is of any significance.A prospective cohort of patients was stratified into 2 groups to distinguish between direct margin invasion (0-mm resection margin) and a ≤1-mm resection margin without direct invasion or 3 groups to distinguish between the location of margin involvement (lateral tumor resection margin, central vascular ligation margin, and nonperitonealized mesocolic resection margin). Patients with microradical resections were used as a control group.We included all patients undergoing elective complete mesocolic excision for International Union Against Cancer stage III colon cancer at Nordsjællands Hospital between January 1, 2008, and December 31, 2016.A total of 276 patients met all inclusion criteria and none of the exclusion criteria.Primary outcome was risk of recurrence after 3.2 years.A total of 41 patients (15%) had a nonmicroradical resection. The 3.2-year cumulative incidence of recurrence for a 0-mm margin was 43% and 24% for a ≤1-mm margin without direct invasion, corresponding with an HR of 4.3 (p = 0.0146) and 1.3 (p = 0.474). The location of the involved margin showed no significant differences.This was a single-center study containing a limited number of patients with a nonmicroradical resection with a risk of type II error.We found no increased risk of recurrence for a ≤1-mm margin without direct invasion, indicating that the present classification of microradicality might not be justified if an intact posterior mesocolic fascia without invasion of tumor tissue is present. See Video Abstract at http://links.lww.com/DCR/B625.ANTECEDENTES:El valor pronóstico de la definición actual de microrradicalidad en el cáncer de colon es poco conocido, especialmente considerando la gran influencia que tiene en el pronóstico del cáncer de recto.OBJETIVO:Este estudio tiene como objetivo investigar si el riesgo de recurrencia después de la escisión mesocólica completa (CME) para el cáncer de colon en estadio III está asociado con la distancia desde el tejido tumoral hasta el margen de resección y si la localización del margen afectado tiene alguna importancia.DISEÑO:Una cohorte prospectiva de pacientes se estratificó en dos grupos para distinguir entre la invasión del margen directo (margen de resección de 0 mm) y un margen de resección ≤1 mm sin invasión directa, o tres grupos para distinguir entre la localización de la afectación del margen (resección lateral del margen del tumor, margen de ligadura vascular central y margen de resección mesocólica no peritonizada). Los pacientes con resecciones microrradicales se utilizaron como grupo control.ENTORNO CLÍNICO:Incluimos a todos los pacientes sometidos a CME electiva por cáncer de colon en estadio III de la UICC en el Hospital Nordsjællands, Dinamarca, entre el 1 de enero de 2008 y el 31 de diciembre de 2016.PACIENTES:Un total de 276 pacientes cumplieron todos los criterios de inclusión y ninguno de los criterios de exclusión.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el riesgo de recurrencia después de 3 · 2 años.RESULTADOS:Un total de 41 (15%) pacientes tuvieron una resección no microrradical. La incidencia acumulada de recurrencia a los 3,2 años para un margen de 0 mm fue del 43% y del 24% para un margen ≤1 mm sin invasión directa, lo que corresponde a un cociente de riesgo de 4,3 (p = 0,0146) y 1,3 (p = 0,474) respectivamente. La localización del margen afectado no mostró diferencias significativas.LIMITACIONES:Estudio unicéntrico con un número limitado de pacientes con resección no microrradical con riesgo de error tipo II.CONCLUSIONES:No encontramos un mayor riesgo de recurrencia para un margen ≤1 mm sin invasión directa, lo que indica que la clasificación actual de microrradicalidad podría no estar justificada si está presente una fascia mesocólica posterior intacta sin invasión del tejido tumoral. Consulte Video Resumen en http://links.lww.com/DCR/B625. (Traducción-Dr Yazmin Berrones-Medina).

Advancements in user interface technologies and demands of design engineering led to increasing implementation of large and mostly flat interactive surfaces in automotive. Recent discussions in the context of in-vehicle usage of touchscreens advocate for the use of haptic feedback to restore the explore- and feel-qualities typically experienced in traditional physical button interfaces that contribute to intuitive, eyes-free, and tactually rich interactions. Haptic technologies that include a friction modulation approach seem especially promising to convey a high-quality feeling. This research reports an experience-oriented evaluation of an electrostatic friction haptic display in an in-vehicle direct touch interaction context. The evaluation was based on an automotive multitask setting (primary driving-task and secondary target-selection-task) with a 2 × 2 feedback modality design (factors haptic/audio with levels absent/present). The objective variables (response time, errors, and performance on the primary task) did not differ between feedback modalities. Any additional feedback to a visual baseline enhanced the user experience, with the multimodal feedback being preferred by most participants. Surface haptics was perceived as a novel yet unexpected type of haptic feedback. We discuss the implications for the haptic design of programmable friction displays and provide an initial set of guidelines for this innovative technology.

In the last 2 decades, an increasing understanding of pathophysiological mechanisms in chronic rhinosinusitis (CRS) opened an avenue from phenotyping to endotyping, from eosinophilic inflammation to type 2 immunity, and from the ventilation and drainage paradigm to the mucosal concept for therapeutic considerations. With the advent of type 2 endotyping and targeted biomarkers, precise endotype-driven therapeutic options are possible including biologics and adapted surgical approaches. We here aim to focus on the complexity and heterogeneity of the features of CRS endotypes, especially for those with nasal polyps, including its history, latest developments, clinical associations, and endotype-driven solutions. In order to better manage uncontrolled severe CRS in clinical practice, medical decisions based on a profound understanding of the pathology and immunology of this heterogeneous disease, aiding a precision-medicine based approach for patient's treatment, are pivotal.

ZusammenfassungRadio- und Chemotherapie stellen sowohl als definitiver Therapieansatz als auch im adjuvanten Setting wesentliche Bestandteile der Behandlung von malignen Kopf-Hals-Tumoren dar. Der Behandlungserfolg ist hier wesentlich abhängig von Auswahl und Dosierung der verwendeten Substanzen sowie vom spezifischen radiotherapeutischen Setting in Bezug auf Fraktionierung, Therapiegesamtdauer und Bestrahlungstechnik.Hinzu kommen Untersuchungen zur immunologisch basierten Therapie und strahlentherapeutischen Modifikation durch Evaluation der Partikeltherapie innerhalb oder additiv zu etablierten Behandlungskonzepten. Die Therapie HPV-induzierter Tumoren stellt aufgrund der differenten Tumorbiologie und des damit verbundenen verbesserten Gesamtüberlebens eine weitere aktuell untersuchte therapeutische Herausforderung dar.

Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL).Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL.DemTect scores were =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment.We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.

Background: The Lichtenstein repair has long been heralded as the gold standard for unilateral primary inguinal hernias. However, minimally invasive surgery (MIS) repairs have gained popularity ove...

This article reviews the current epidemiology of central nervous system tumors. Population-level basic epidemiology, nationally and internationally, and current understanding of germline genetic risk are discussed, with a focus on known and well-studied risk factors related to the etiology of central nervous system tumors.

Purpose Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This study investigated the utilization of QA among randomized controlled trials that involve radiotherapy (RT). Methods and Materials We searched ClinicalTrials.gov in February 2020 for all phase III oncology randomized clinical trials (RCTs). These trials were screened for RT-specific RCTs that had published primary trial results. Information regarding QA in each trial was collected from the study publications and trial protocol if available. Two individuals independently performed trial screening and data collection. Pearson’s Chi-square tests analyses were used to assess factors that were associated with QA inclusion in RT trials. Results Forty-two RCTs with RT as the primary intervention or as a mandatory component of the protocol were analyzed; the earliest was started in 1994 and one trial was still active though not recruiting. Twenty-nine (69%) trials mandated RT quality assurance (RTQA) practices as part of the trial protocol, with 19 (45%) trials requiring institutional credentialing. Twenty-one (50%) trials published protocol deviation outcomes. Clinical trials involving advanced radiation techniques (IMRT, VMAT, SRS, SBRT) did not include more RTQA than trials without these advanced techniques (73% vs. 65%, p=0.55). Trials that reported protocol deviation outcomes were associated with mandating RTQA in their protocols as compared to trials that did not report these outcomes (100% vs. 38%, p Conclusions There is a lack of RTQA utilization and transparency in RT clinical trials. It is imperative for RT trials to include increased QA for safe, consistent, and high-quality RT planning and delivery.

Background Sexual dysfunction is a common side effect of medical therapy for benign prostatic hyperplasia (BPH), whereas prostatic urethral lift (PUL) offers safe and effective relief of lower urinary tract symptoms while preserving sexual function. Objective To compare the long-term impact on sexual health of PUL or daily medical therapy of doxazosin or finasteride alone or in combination in BPH patients. Design, setting, and participants This was a comparative analysis of sexual function outcomes from PUL studies (L.I.F.T. [n = 107], Crossover [n = 42], and MedLift [n = 39]) and the Medical Therapy of Prostatic Symptoms (MTOPS) trial. The men included were sexually active with International Prostate Symptom Score ≥13, Qmax ≤12 ml/s, and prostate volume 30–80 cm3. MTOPS subjects completed the Brief Male Sexual Function Inventory, while PUL subjects completed the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. Outcome measurements and statistical analysis Mean percentage changes from baseline in erectile, ejaculatory, and sexual satisfaction domains were compared at 12, 24, 36, and 48 mo. Results and limitations PUL significantly improved erectile function through 24 mo, and ejaculatory function and sexual satisfaction across all time points. Medical therapy did not improve sexual function at any time point. Finasteride significantly decreased erectile function at 48 mo, and combined therapy significantly reduced ejaculatory function at 12 and 24 mo. Comparatively, PUL was superior to finasteride in preserving erectile function at 24 and 48 mo, and superior to doxazosin and combined therapy at 12 mo. PUL outperformed all three medical therapies at all time points in improving ejaculatory function and sexual satisfaction. Limitations include the use of distinct patient-reported questionnaires and narrowed data on comorbidities that influence male sexual function. Conclusions Indirect comparison reveals that PUL is superior to BPH medical therapy in preserving erectile and ejaculatory function and sexual satisfaction. Patient summary In our non–head-to-head study, only patients undergoing PUL for an enlarged prostate experienced improvements in sexual health. Conversely, patients on medical therapy experienced worsening of erectile and ejaculatory function.

BACKGROUND CONTEXT: Lumbar interbody fusion is an effective treatment for unstable spinal segments. However, the time needed to establish a solid bony interbody fusion between the two vertebrae may be longer than twelve months after surgery. During this time window, the instrumented spinal segment is assumed to be at increased risk for instability related complications such as cage migration or subsidence. It is hypothesized that the design of new interbody cages that enable direct osseointegration of the cage at the vertebral endplates, without requiring full bony fusion between the two vertebral endplates, might shorten the time window that the instrumented spinal segment is susceptible to failure.PURPOSE: To quantify the bone ingrowth and resulting segmental stability during consolidation of lumbar interbody fusion using two different cage types.STUDY DESIGN: Preclinical ovine model.METHODS: Seven skeletally mature sheep underwent bi-segmental lumbar interbody fusion surgery with one conventional polyether ether ketone (PEEK) cage, and one newly developed trussed titanium (TT) cage. After a postoperative time period of 13 weeks, non-destructive range of motion testing and histological analysis were performed. Additionally, sample specific finite element (FE) analysis was performed to predict the stability of the interbody fusion region alone.RESULTS: Physiological movement of complete spinal motion segments did not reveal significant differences between the segments operated with PEEK and TT cages. The onset of creeping substitution within the cage seemed to be sooner for PEEK cages, which led to significantly higher bone volume over total volume (BV/TV) compared to the TT cages. TT cages showed significantly more direct bone to implant contact (BIC). Although the mean stability of the interbody fusion region alone was not statistically different between the PEEK and TT cages, the variation within the cage types illustrated an all-or-nothing response for the PEEK cages while a more gradual increase in stability was found for the TT cages.CONCLUSIONS: Spinal segments operated with conventional PEEK cages were not different from those operated with newly developed TT cages in terms of segmental stability but did show a different mechanism of bone ingrowth and attachment. Based on the differences in development of bony fusion, we hypothesize that TT cages might facilitate increased early segmental stability by direct osseointegration of the cage at the vertebral endplates without requiring complete bony bridging through the cage.CLINICAL SIGNIFICANCE: Interbody cage type affects the consolidation process of spinal interbody fusion. Whether different consolidation processes of spinal interbody fusion result in clinically significant differences requires further investigation.

Introduction Mycobacterium genavense is a fastidious slow growing mycobacterium (SGM) that causes disseminated infections in immunocompromised hosts. It has been described in HIV-positive individuals and increasingly in patients without HIV. The infections are difficult to treat and the optimal antimycobacterial regimen is still unknown. Methods An individual patient data meta-analysis was conducted aiming at including all hitherto published cases of infection with M. genavense. Clinical manifestations, microbiological data, dispositions and immunosuppression were recorded. Antimycobacterial therapies and mortality were analysed by logistic regression and time-to-event analysis. Results We included 223 patients with infection due to M. genavense published from 1992-2021. While the majority was HIV positive (n=223, 76.7 %), 52 patients were non-HIV-patients (23.3 %), 36 of whom received immunosuppressive therapy (69 %). We could confirm the bacterium's tropism for the gastrointestinal tract with abdominal pain, hepato-/splenomegaly and abdominal lymphadenopathy being major clinical manifestations. More than 90 % of patients received antimycobacterial therapy. The regimens consisted mainly of macrolides, rifamycins and ethambutol. Overall mortality was high, but in logistic regression and time-to-event analysis a macrolide containing regimen was associated with better outcomes. Conclusion In this first individual patient data meta-analysis of infections with M. genavense we confirm its tropism for the gastrointestinal tract. The high overall mortality underlines the clinical relevance of infection with this bacterium for the individual patient. In addition, our data give a hint that a macrolide containing regimen is associated with better survival.

Objective: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. Methods: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (

Context The role of a placebo response in the management of overactive bladder (OAB) remains unclear. Objective The aim of this review is to methodically study the placebo response extracted from the control arms of randomized clinical trials assessing therapy in patients with OAB. Evidence acquisition Medline (PubMed), The Cochrane Library, EMBASE, and Scopus were searched to identify randomized controlled trials (RCTs) published until September 2019. Randomized placebo-controlled trials investigating oral drug therapy for OAB were included. The articles were critically appraised by two reviewers. The primary outcomes were the placebo response in the main patient-reported urinary outcomes together with assessing the impact of patient demographic factors on the placebo response. Evidence synthesis The initial search resulted in 1982 records after reviewing the titles and abstracts, and reference lists of other systematic reviews; 57 studies with an overall estimated 12 901 patients were included in the meta-analysis. The included studies were of overall high/acceptable quality. The standardized mean difference was −0.45 (95% confidence interval [CI] −0.51 to −0.40; p Conclusions Placebo has a statistically significant effect on improving symptoms and signs associated with OAB; this effect is age dependent. However, there is no consensus on what change of OAB symptoms and signs is clinically meaningful for the affected patient. Taken together, the placebo response seems to be non-negligible in OAB, supporting the need for placebo control in RCTs. Patient summary Placebo is an inert treatment method often used in clinical research for comparison with active treatment. However, studies show that placebo has an effect of its own. A placebo response means the total improvement resulting from receiving a placebo. In our study, placebo had a significant role in improving the symptoms of overactive bladder.

This paper presents DistRDF2ML, the generic, scalable, and distributed framework for creating in-memory data preprocessing pipelines for Spark-based machine learning on RDF knowledge graphs. This framework introduces software modules that transform large-scale RDF data into ML-ready fixed-length numeric feature vectors. The developed modules are optimized to the multimodal nature of knowledge graphs. DistRDF2ML provides aligned software design and usage principles as common data science stacks that offer an easy-to-use package for creating machine learning pipelines. The modules used in the pipeline, the hyper-parameters and the results are exported as a semantic structure that can be used to enrich the original knowledge graph. The semantic representation of metadata and machine learning results offers the advantage of increasing the machine learning pipelines’ reusability, explainability, and reproducibility. The entire framework of DistRDF2ML is open source, integrated into the holistic SANSA stack, documented in scala-docs, and covered by unit tests. DistRDF2ML demonstrates its scalable design across different processing power configurations and (hyper-)parameter setups within various experiments. The framework brings the three worlds of knowledge graph engineers, distributed computation developers, and data scientists closer together and offers all of them the creation of explainable ML pipelines using a few lines of code.

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene–environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: “young” individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider “young” patients with COPD those patients in the age range of 20–50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.

Background There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. Purpose To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. Study type Prospective non-randomized diagnostic study. Population Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference. Field strength/sequence Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T1 (TE) mapping at TE1-5 = 70 μsec, 500 μsec, 1200 μsec, 1650 μsec, and 2300 μsec. Assessment Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. Statistical tests Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value Results Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . Data conclusion In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. Level of evidence 2 TECHNICAL EFFICACY: Stage 1.

Background Appendectomies in children and adolescents are performed in Germany in pediatric surgical (PS) or general surgical hospitals (GS). The aim of this study is to evaluate whether the surgery in a PS or GS hospital has an influence on the postoperative course after appendectomy in children and adolescents. Materials and methods Nationwide routine data from children and adolescents aged 1-17 y insured by the Local Health Insurance Fund who underwent appendectomy between 2014 and 2016 were analyzed (cohort study). Descriptive statistics were calculated both overall and in the two groups (PS and GS). Patients were additionally examined by age (1-5, 6-12, and 13-17 y), treatment (laparoscopic, open surgical, and conversion), and appendicitis type (nonacute: K36/K37/K38/R10, acute simple: K35.30/K35.8, and acute complex: K35.2/K35.31/K35.32). The influence of surgeon specialization on 90-d secondary surgery and 90-d general complications was assessed by multiple logistic regression. Results Altogether, 25,065 patients who underwent surgery in 83 PS and 906 GS hospitals were included. Logistic regression analysis revealed that PS was associated with a reduced risk of interventions in the 1-5- and 6-12-y age groups (odds ratio: 0.44, 0.62). Acute complex appendicitis, comorbidities, and open surgery significantly increased the risk for reintervention. PS was associated with an increased risk for complications in the 13-17-y age group (odds ratio: 1.66). Conclusions PS and GS hospitals provided safe appendectomies in children and adolescents with low reintervention and complication rates. PS hospitals demonstrated advantages for patients in the 1-5- and 6-12-y age groups and GS hospitals for patients 13-17 y.

We performed a post hoc analysis of data from phase 3 and 4 studies to evaluate the efficacy of silodosin 8mg in patients with severe lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). The presence of two or more of the following criteria was adopted to define severity: total International Prostate Symptom Score (IPSS) 20-35, quality of life (QoL) score 5-6, maximum urinary flow

Idiopathic inflammatory myopathy (IIM) can present with dysphagia as a leading or only symptom. In such cases, diagnostic evaluation may be difficult, especially if serological and electromyographical findings are unsuspicious. In this observational study we propose and evaluate a diagnostic algorithm to identify IIM as a cause of unexplained dysphagia.Over a period of 4 years, patients with unexplained dysphagia were offered diagnostic evaluation according to a specific algorithm: The pattern of dysphagia was characterized by instrumental assessment (swallowing endoscopy, videofluoroscopy, high-resolution manometry). Patients with an IIM-compatible dysphagia pattern were subjected to further IIM-focused diagnostic procedures, including whole-body muscle magnetic resonance imaging, electromyography, creatine kinase blood level, IIM antibody panel and, as a final diagnostic step, muscle biopsy. Muscle biopsies were taken from affected muscles. In cases where no other muscles showed abnormalities, the cricopharyngeal muscle was targeted.Seventy-two patients presented with IIM-compatible dysphagia as a leading or only symptom. As a result of the specific diagnostic approach, 19 of these patients were diagnosed with IIM according to the European League Against Rheumatism (EULAR) criteria. Eighteen patients received immunomodulatory therapy as a result of the diagnosis. Of 10 patients with follow-up swallowing examination, dysphagia improved in three patients after therapy, while it remained at least stable in six patients.Idiopathic inflammatory myopathy constitutes a potentially treatable etiology in patients with unexplained dysphagia. The diagnostic algorithm presented in this study helps to identify patients with an IIM-compatible dysphagia pattern and to assign those patients for further IIM-focused diagnostic and therapeutic procedures.

Background/aim: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. Materials and methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.

Purpose This study aims to assess the results, rebubbling rate, and graft survival after Descemet membrane endothelial keratoplasty (DMEK) with regard to the number and type of previous glaucoma surgeries. Methods This is a clinical retrospective review of 1845 consecutive DMEK surgeries between 07/2011 and 08/2017 at the Department of Ophthalmology, University of Cologne. Sixty-six eyes were included: group 1 (eyes with previous glaucoma drainage devices (GDD); n = 27) and group 2 (eyes with previous trabeculectomy (TE); n = 39). Endothelial cell loss (ECL), central corneal thickness, graft failure, rebubbling rate, and best spectacle-corrected visual acuity (BSCVA) up to 3 years after DMEK were compared between subgroups of patients with different numbers of and the two most common types of glaucoma surgeries either GDD or TE or both. Results Re-DMEK rate due to secondary graft failure was 55.6% (15/27) in group 1 and 35.9% in group 2. The mean graft survival time in group 1 was 25 ± 11 months and 31.3 ± 8.6 months in group 2 (p = 0.009). ECL in surviving grafts in group 1 was 35% (n = 13) at 6 months, 36% at 12 months (n = 8), and 27% (n = 4) at 2 years postoperatively. In group 2, ECL in surviving grafts was 41% (n = 10) at 6 months, 36% (n = 9) at 12 months, and 38% (n = 8) at 2 years postoperatively. Rebubbling rate in group 1 was 18.5% (5/27) and 35.9% (14/39) in group 2 (p = 0.079). Conclusion Eyes with previous GDD had no higher risk for an increased rebubbling rate but a higher risk for a re-DMEK due to secondary graft failure with a mean transplant survival time of about 2 years. Compared to eyes with preexisting glaucoma drainage device, eyes after trabeculectomy had less secondary graft failures and a longer mean graft survival rate.

This paper investigates statistical reproducibility of the [Formula: see text]-test. We formulate reproducibility as a predictive inference problem and apply the nonparametric predictive inference method. Within our research framework, statistical reproducibility provides inference on the probability that the same test outcome would be reached, if the test were repeated under identical conditions. We present an nonparametric predictive inference algorithm to calculate the reproducibility of the [Formula: see text]-test and then use simulations to explore the reproducibility both under the null and alternative hypotheses. We then apply nonparametric predictive inference reproducibility to a real-life scenario of a preclinical experiment, which involves multiple pairwise comparisons of test groups, where different groups are given a different concentration of a drug. The aim of the experiment is to decide the concentration of the drug which is most effective. In both simulations and the application scenario, we study the relationship between reproducibility and two test statistics, the Cohen’s [Formula: see text] and the [Formula: see text]-value. We also compare the reproducibility of the [Formula: see text]-test with the reproducibility of the Wilcoxon Mann–Whitney test. Finally, we examine reproducibility for the final decision of choosing a particular dose in the multiple pairwise comparisons scenario. This paper presents advances on the topic of test reproducibility with relevance for tests used in pharmaceutical research.

Objectives To examine association between post-prostatectomy incontinence (PPI) severity and weight changes before and after restoration of continence via artificial urinary sphincter (AUS). Methods Single surgeon, retrospective review of urologic prosthetic surgery (UPS) after radical prostatectomy (RP). A cohort of post-RP inflatable penile prosthesis (IPP) patients served as a surgical control. Body Mass Index (BMI) and total body weight were assessed pre and post-UPS. Multivariable linear regression was utilized to assess BMI changes post-UPS. Results 187 AUS and 63 IPP patients met selection criteria. Greater PPI severity was associated with faster BMI gain after RP (coeff. 0.14 kg/m2, P = 0.03, per pad used) and magnitude of incontinence improvement (mean reduction in daily pad use) after AUS insertion was associated with greater BMI reduction at 12 months post-UPS (coeff. - 0.13 kg/m2, P = 0.04). On multivariable regression, AUS insertion was associated with a decrease in BMI by - 2.83 kg/m2 12 months post-UPS (P = 0.02). Twelve months post-UPS, men with AUS exhibited a mean BMI reduction of -1.0 kg/m2 compared to a mean BMI increase in the IPP cohort of 0.4 kg/m2 (P 5% body weight) at 12 months post-UPS (31.8% vs 8.3%, P Conclusion Severe PPI appears to be associated with weight gain and correction of PPI via AUS insertion with weight loss.

Current risk-adjusted models for donor lung use and lung graft survival do not include donor critical care data. We sought to identify modifiable donor physiologic and mechanical ventilation parameters that predict donor lung use and lung graft survival. This is a prospective observational study of donors after brain death (DBDs) managed by 19 Organ Procurement Organizations from 2016 to 2019. Demographics, mechanical ventilation parameters, and critical care data were recorded at standardized time points during donor management. The lungs were transplanted from 1811 (30%) of 6052 DBDs. Achieving ≥7 critical care endpoints was a positive predictor of donor lung use. After controlling for recipient factors, donor blood pH positively predicted lung graft survival (OR 1.48 per 0.1 unit increase in pH) and the administration of dopamine during donor management negatively predicted lung graft survival (OR 0.19). Tidal volumes ≤8 ml/kg predicted body weight (OR 0.65), and higher positive end-expiratory pressures (OR 0.91 per cm H2 O) predicted decreased donor lung use without affecting lung graft survival. A randomized clinical trial is needed to inform optimal ventilator management strategies in DBDs.

AIMS: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors.METHODS: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated.RESULTS: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden 0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (p = 0.03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA CONCLUSIONS: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a three-year period.

Background Increasing incidence rates of cutaneous melanoma (CM) observed during the last five decades in white populations are largely attributed to increased exposure to solar ultraviolet radiation (UVR), often expressed as population attributable fraction (PAF). Thus, many CMs could be prevented by reducing UVR exposure. The aim of this study was to estimate the PAF of CM attributable to UVR exposure and demographic changes in Denmark and Saarland/Germany for the period 1943 to 2036. Material and methods CM incidence data (ICD-10, C43) for Denmark (1943–2016) and the German Federal State of Saarland (1972–2016) were retrieved from the NORDCAN database and from the Saarland Cancer Registry. The number of CMs attributable to UVR exposure was calculated by comparing contemporary or predicted CM incidence rates with CM rates in Denmark during the years 1943–1946. Results In Denmark, the proportion of CM cases attributable to UVR exposure increased from around 20% in 1947–1951 to 96% in 2012–2016; in the Federal State of Saarland, it increased from 50% in 1972–1976 to 90% in 2012–2016. Until 2032–2036, the PAF is expected to rise in Denmark to 97% and in the Saarland to 92%. The demographic influence, on the other hand, is rather small. Conclusions More than 90% of all CM in Germany and Denmark are attributable to UVR exposure, and in principle, preventable. These findings underline the need for primary prevention strategies, aiming to increase the awareness of melanoma and its risk factors and to promote behavioural changes that decrease sun exposure.

BACKGROUND AND METHODS: Treatment strategies for pancreatic cancer patients are made by a multidisciplinary team (MDT) board. We aimed to assess intra-observer variance at MDT boards. Participating units staged, assessed resectability, and made treatment allocations for the same patients as they did two years earlier. We disseminated clinical information and CT images of pancreatic cancer patients judged by one MDT board to have nonmetastatic pancreatic cancer to the participating units. All units were asked to re-assess the TNM stage, resectability, and treatment allocation for each patient. To assess intra-observer variance, we computed %-agreements for each participating unit, defined as low (75%) agreement.RESULTS: Eighteen patients were re-assessed by six MDT boards. The overall agreement was moderate for TNM-stage (ranging from 50%-70%) and resectability assessment (53%) but low for treatment allocation (46%). Agreement on resectability assessments was low to moderate. Findings were similar but more pronounced for treatment allocation. We observed a shift in treatment strategy towards increasing use of neoadjuvant chemotherapy, particularly in patients with borderline resectable and locally advanced tumors.CONCLUSIONS: We found substantial intra-observer agreement variations across six different MDT boards of 18 pancreatic cancer patients with two years between the first and second assessment.

A highly efficient air-filled multiband antenna is presented for unobtrusive integration into smart surfaces. By introducing a capacitive loading ridge in the cavity formed by two coupled eighth-mode resonators, the higher order modes are judiciously manipulated. A supplementary slot-mode resonance is provided by a resonant U-slot in the first resonator. These measures yield dual-band impedance matching, covering the SRD860 (863-870 MHz), 2.4 GHz ISM (2.4-2.4835 GHz), and LTE-7 (2.5-2.69 GHz) standards. The antenna, fully realized in low-cost FR-4 substrate layers, complies with standard printed circuit board manufacturing. Measurements on a prototype reveal an impedance bandwidth of 51.8 MHz (6.1%) and 428.6 MHz (17.0%) in the lower and upper frequency band, respectively. Furthermore, a total efficiency and peak gain of 86.1% and 3.8 dBi at 866 MHz, 75.2% and 9.0 dBi at 2.45 GHz, and 70.1% and 8.1 dBi at 2.6 GHz were obtained in standalone conditions. At 2.4 GHz, a measured total efficiency and gain of 73.9% and 8.9 dBi are reported for the antenna covered by a cork superstrate, and 73.6% and 6.6 dBi for the antenna inside a drywall construction.

AimsTo examine the temporal trends and factors associated with national cardiac rehabilitation (CR) referral and compare the risk of hospital readmission and mortality in those referred for CR versus no referral.Methods and resultsThis cohort study includes all adult patients alive 120 days from incident heart failure (HF) identified by the Danish Heart Failure Registry (n = 33 257) between 2010 and 2018. Multivariable logistic regression models were used to assess the association between CR referral and patient factors and acute all-cause hospital readmission and mortality at 1 year following HF admission. Overall, 46.7% of HF patients were referred to CR, increasing from 31.7% in 2010 to 52.2% in 2018. Several factors were associated with lower odds of CR referral: male sex [odds ratio (OR): 0.85; 95% confidence interval: 0.80–0.89], older age, unemployment, retirement, living alone, non-Danish ethnic origin, low educational level, New York Heart Association (NYHA) class IV vs. I (OR: 0.75; 0.60–0.95), left ventricular ejection fraction >40%, and comorbidity (stroke, chronic kidney disease, atrial fibrillation/flutter, and diabetes). Myocardial infarction, arthritis, coronary artery bypass grafting, percutaneous coronary intervention, valvular surgery, NYHA class II, and use of angiotensin-converting enzyme inhibitors were associated with higher odds of CR referral. CR referral was associated with lower risk of acute all-cause readmission (OR: 0.92; 0.87–0.97) and all-cause mortality (OR: 0.65; 0.58–0.72).ConclusionAlthough increased over time, only one in two HF patients in Denmark were referred to CR in 2018. Strategies are needed to reduce referral disparities, focusing on subgroups of patients at highest risk of non-referral.

BackgroundLittle is known about variations in the provision of chronic care services in primary care.AimTo describe the frequency of chronic care services provided by GPs and analyse the extent of non-random variation in service provision.Design and settingNationwide cohort study undertaken in Denmark using data from 2016.MethodInformation on chronic care services was obtained from national health registers, including annual chronic care consultations, chronic care procedures, outreach home visits, and talk therapy. The associations between services provided, patient morbidity, and socioeconomic factors were estimated. Service variations were analysed, and excess variation related to practice-specific factors was estimated while accounting for random variation.ResultsChronic care provision was associated with increasing patient age, increasing number of long-term conditions, and indicators of low socioeconomic status. Variation across practices ranged from 1.4 to 128 times more than expected after adjusting for differences in patient population and random variation. Variation related to practice-specific factors was present for all the chronic care services that were investigated. Older patients with lower socioeconomic status and multimorbidity were clustered in practices with low propensity to provide certain chronic care services.ConclusionChronic care was provided to patients typically in need of health care, that is, older adults, those with multimorbidity, and those with low socioeconomic status, but service provision varied more than expected across practices. GPs provided slightly fewer chronic care services than expected in practices where many patients with multimorbidity and low socioeconomic status were clustered, suggesting inverse care law mechanisms.

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0–3 lymph nodes in a high-volume community hospital. Methods: Patients with non-metastatic HR+/HER2– EBC and 0–3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated. Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR+/HER– EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR+/HER2– breast cancer with 0–3 positive lymph nodes and RS

BACKGROUND A causal treatment effect of complete mesocolic excision for right-sided colon cancer on the risk of recurrence has been shown, but it is still unclear whether this is caused solely by a risk reduction of local recurrence. OBJECTIVE To assess to what extent complete mesocolic excision attributes to the risk of local recurrence. DESIGN Post-hoc analyses of data from a population-based cohort. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. SETTING Data from the four public colorectal cancer centers in the Capital Region of Denmark. PATIENTS Patients undergoing elective colon resections for right-sided colon cancer without distant metastases during the period 2010-2013. One center performed complete mesocolic excision, the remainder conventional resections. MAIN OUTCOME MEASURES The primary outcome was the cumulative incidence of solely local recurrence 5.2 years after surgery. Secondary outcomes were solely distant recurrence and both local and distant recurrence diagnosed within 180 days. RESULTS A total of 807 patients were included with 186 undergoing complete mesocolic excision and 621 conventional resections. The 5.2-year cumulative incidence of a solely local recurrence was 3.7% (95% CI: 0.5-6.1) after complete mesocolic excision compared with 7.0% (5.0-8.9) in the control group, and the absolute risk reduction of complete mesocolic excision was 3.7% (2.5-7.1; p=0.035). The absolute risk reduction on local and distant recurrence was 3.4% (1.3-5.6; p=0.0019) and on solely distant recurrence 3.1% (0.0-6.2; p=0.0516). LIMITATIONS The recurrence risk after conventional resection might under estimated by the use of inappropriate modalities to diagnose local recurrence for some patients and the shorter duration in this group. CONCLUSION This study shows a causal treatment effect of complete mesocolic excision on the risk of a solely local recurrence and of distant recurrence with or without local recurrence. See Video Abstract at http://links.lww.com/DCR/B832 .

Objective To investigate and compare clinical features and US signs of inflammation in joints and entheses in patients with psoriasis with and without musculoskeletal pain, and the additional value of US in classification of PsA. Furthermore, to explore the association between such findings and patient-reported outcomes (PROs) and the performance of screening-questionnaires for identifying patients with PsA. Methods Patients with psoriasis (n = 126) recruited from a nationwide survey were evaluated at one of four rheumatology departments. The evaluation included clinical examination, laboratory tests, radiography, greyscale and colour Doppler US of 48 joints and 12 entheses, PROs, and four screening questionnaires for PsA. Patients were classified with Classification for PsA (CASPAR), US-modified CASPAR, and US-only criteria. Results When subgroups of self-reported pain (63%), no pain (29%) and diagnosed PsA (9%) were compared, patients with pain had higher tenderness-related clinical scores (tender joints, entheses and FM points) and US greyscale sum-scores, compared with ‘no pain’ patients. PROs were negligibly moderately correlated with pain-related clinical scores (Spearman’s rho = 0.11–0.59, all patients), and negligibly weakly with US sum-scores (rho = 0.01–0.34). More patients could be classified as PsA when US synovitis/enthesitis was included as an entry criterion (US-modified CASPAR, 66% of all patients) compared with conventional CASPAR (35%) or US-only criteria (52%). Sensitivities of screening questionnaires were low for fulfilment of CASPAR (0.23–0.66), US-modified CASPAR (0.17–0.57), and US-only (0.20–0.57) criteria. Conclusion Self-reported pain in psoriasis is related to US inflammation. US-modified CASPAR criteria identified almost twice as many patients as conventional CASPAR criteria. Screening questionnaires showed limited value.

Oocyte morphology assessment is easy to implement in any laboratory with possible quality grading prior to fertilization. At present, comprehensive oocyte morphology scoring is not performed as a routine procedure. However, it may augment chances for successful treatment outcomes if a correlation with certain dysmorphisms can be proven. In order to determine a correlation between oocyte morphology and treatment outcome, we performed a systematic search in PubMed and Cochrane Controlled Trials Register following PRISMA guidelines. A total of 52 articles out of 6,755 search results met the inclusion criteria. Dark colour of the cytoplasm (observed with an incidence rate of 7%), homogeneous granularity of the cytoplasm (19%) and ovoid shape of oocytes (7%) appeared to have no influence on treatment outcome. Abnormalities such as refractile bodies (10%), fragmented first polar body (37%), dark zona pellucida (9%), enlarged perivitelline space (18%) and debris in it (21%) are likely to affect the treatment outcome to some extent. Finally, cytoplasmic vacuoles (4%), centrally located cytoplasmic granularity (12%) and clusters of smooth endoplasmic reticulum (4%) negatively impact infertility treatment outcomes. Nonetheless, morphological assessment is informative rather than predictive. Adding oocyte morphology to the artificial intelligence (AI)-driven selection process may improve the precision of the algorithms. Oocyte morphology assessment can be especially useful in oocyte donation cycles, during oocyte freezing for fertility preservation and finally, objective oocyte scoring can be important in cases of very poor treatment outcome as a tool for explanation of results to the patient.

Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) is an established method to enhance the Graft-versus-Leukemia (GvL) effect. However, alterations of cellular subsets in the peripheral blood of DLI recipients have not been studied. We investigated the changes in lymphocyte subpopulations in 16 patients receiving DLI after successful alloSCT. Up to three DLIs were applied in escalating doses, prophylactically for relapse prevention in high-risk disease (n = 5), preemptively for mixed chimerism and/or a molecular relapse/persistence (n = 8), or as part of treatment for hematological relapse (n = 3). We used immunophenotyping to measure the absolute numbers of CD4+, CD8+, NK, and CD56+ T cells and their respective subsets in patients’ peripheral blood one day before DLI (d-1) and compared the results at day + 1 and + 7 post DLI to the values before DLI. After the administration of 1 × 106 CD3+ cells/kg body weight, we observed an overall increase in the CD8+ and CD56+ T cell counts. We determined significant changes between day − 1 compared to day + 1 and day + 7 in memory and activated CD8+ subsets and CD56+ T cells. Applying a higher dose of DLI (5 × 106 CD3+ cells/kg) led to a significant increase in the overall counts and subsets of CD8+, CD4+, and NK cells. In conclusion, serial immune phenotyping in the peripheral blood of DLI recipients revealed significant changes in immune effector cells, in particular for various CD8+ T cell subtypes, indicating proliferation and differentiation.

Background Fluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of stroke symptom onset. Evolution of signal intensities in FLAIR is associated with time since stroke onset with continuous linear increases. Aims Estimating symptom onset during night-sleep in patients from the WAKE-UP trial based on relative signal intensities FLAIR (FLAIR-rSI) from acute stroke lesions an independent dataset (PRE-FLAIR study). Methods FLAIR-rSI was quantified in stroke lesions in PRE-FLAIR and WAKE-UP. The PRE-FLAIR study was a multicenter observational trial establishing FLAIR as a surrogate parameter for time since stroke onset. WAKE-UP was a randomized controlled trial that revealed a benefit for alteplase in patients selected based on a DWI-FLAIR mismatch. Stroke onset times were recorded in PRE-FLAIR and used to fit a linear regression model with FLAIR-rSI, adjusted for patient age and lesion volume. The model was applied to FLAIR-rSI of stroke lesions to estimate onset times in those patients enrolled in WAKE-UP who had symptom onset during night-sleep. Results FLAIR-rSI was quantified in 399 patients from PRE-FLAIR. Linear regression indicated a significant association of age ( p = 0.001), lesion volume ( p = 0.005) and FLAIR-rSI ( p 2 = 0.179). In 813 patients from WAKE-UP, distribution of times of last seen well, symptom recognition and MRI examination were recorded. Median times of last seen well were 1 h before midnight (IQR 2.4 h) and symptom recognition 7 h after midnight (IRQ 2.2 h). Based on the FLAIR-rSI profiles, we estimated median stroke onset 6.1 h after midnight (IQR 2.7 h). Conclusion Nocturnal strokes during night-sleep may predominantly occur during the early morning hours. Our results are in line with evidence of characteristic diurnal patterns of cardiovascular events.