Showing papers by "Medical University of Graz published in 2019"
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, Medical University of South Carolina9, University of Cambridge10, University of Barcelona11, The Feinstein Institute for Medical Research12, Toronto Western Hospital13, University of California, Los Angeles14, Humboldt University of Berlin15, Copenhagen University Hospital16, University of Michigan17, University of the Basque Country18, University Health Network19, University of Crete20, University of Zagreb21, University of Paris-Sud22, University of Hong Kong23, University of Calgary24, Hospital for Special Surgery25, University of Pécs26, University of Padua27, Medical University of Graz28, National Institutes of Health29, New York University30, Université Paris-Saclay31, University Hospital Complex Of Vigo32, University of Occupational and Environmental Health Japan33, University of Porto34, Leeds Teaching Hospitals NHS Trust35, Cedars-Sinai Medical Center36, Istanbul Bilim University37, McMaster University38
TL;DR: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism and the American College of Rheumatology (ACR).
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
1,018 citations
Medical University of Vienna1, Charles University in Prague2, University of Regensburg3, Pierre-and-Marie-Curie University4, Royal Surrey County Hospital5, Autonomous University of Barcelona6, Netherlands Cancer Institute7, University of Paris8, European Association of Urology9, Medical University of Graz10, First Faculty of Medicine, Charles University in Prague11, Royal Free London NHS Foundation Trust12, University of Rennes13
TL;DR: The European Association of Urology Non-muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC.
897 citations
Carlos III Health Institute1, University of Cologne2, University of Sydney3, Paris Descartes University4, Universidade Federal de Ciências da Saúde de Porto Alegre5, Pontifícia Universidade Católica do Rio Grande do Sul6, University of California, San Diego7, Medical University of Graz8, University of Copenhagen9, Katholieke Universiteit Leuven10, University of Bologna11, University of the Witwatersrand12, RMIT University13, McGill University14, Hacettepe University15, University of Paris16, Utrecht University17, Mazandaran University of Medical Sciences18, Tel Aviv University19, Hospital General de México20, Istituto Giannina Gaslini21, Mahidol University22, Federal University of São Paulo23, King's College, Aberdeen24, Comenius University in Bratislava25, Boston Children's Hospital26, Hospital General Universitario Gregorio Marañón27, Complutense University of Madrid28, University Hospital Heidelberg29, University of California, Los Angeles30, American University of Beirut31, Innsbruck Medical University32, University of Lausanne33, Catholic University of Korea34, Goethe University Frankfurt35, National and Kapodistrian University of Athens36, Erasmus University Rotterdam37, Monash University38, Federal University of Rio de Janeiro39, Catholic University of the Sacred Heart40, University of Health Sciences Antigua41, National Institutes of Health42, Amrita Institute of Medical Sciences and Research Centre43, University of Pittsburgh44, University of Melbourne45, Peter MacCallum Cancer Centre46, P. D. Hinduja Hospital and Medical Research Centre47, University of Southern California48, Duke University49, Singapore General Hospital50, NewYork–Presbyterian Hospital51, Cardiff University52, University of Texas Health Science Center at San Antonio53, Children's Hospital of Philadelphia54, Post Graduate Institute of Medical Education and Research55
TL;DR: Management of mucormycosis depends on recognising disease patterns and on early diagnosis, and limited availability of contemporary treatments burdens patients in low and middle income settings.
Abstract: Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
842 citations
TL;DR: The potential of liquid biopsies is highlighted by studies that show they can track the evolutionary dynamics and heterogeneity of tumours and can detect very early emergence of therapy resistance, residual disease and recurrence, but their analytical validity and clinical utility must be rigorously demonstrated before this potential can be realized.
Abstract: Precision oncology seeks to leverage molecular information about cancer to improve patient outcomes. Tissue biopsy samples are widely used to characterize tumours but are limited by constraints on sampling frequency and their incomplete representation of the entire tumour bulk. Now, attention is turning to minimally invasive liquid biopsies, which enable analysis of tumour components (including circulating tumour cells and circulating tumour DNA) in bodily fluids such as blood. The potential of liquid biopsies is highlighted by studies that show they can track the evolutionary dynamics and heterogeneity of tumours and can detect very early emergence of therapy resistance, residual disease and recurrence. However, the analytical validity and clinical utility of liquid biopsies must be rigorously demonstrated before this potential can be realized.
809 citations
TL;DR: The characteristic features of these new and modified entities as well as the results of recent molecular studies with diagnostic, prognostic, and/or therapeutic significance for the different types of primary cutaneous lymphomas are reviewed.
720 citations
TL;DR: Recent findings in pathology and cellular mechanisms contributing to the onset and progression of pulmonary vascular remodelling associated with various forms of pulmonary hypertension are reviewed and ways to improve management and to support and optimise drug development are discussed.
Abstract: Clinical and translational research has played a major role in advancing our understanding of pulmonary hypertension (PH), including pulmonary arterial hypertension and other forms of PH with severe vascular remodelling (e.g. chronic thromboembolic PH and pulmonary veno-occlusive disease). However, PH remains an incurable condition with a high mortality rate, underscoring the need for a better transfer of novel scientific knowledge into healthcare interventions. Herein, we review recent findings in pathology (with the questioning of the strict morphological categorisation of various forms of PH into pre- or post-capillary involvement of pulmonary vessels) and cellular mechanisms contributing to the onset and progression of pulmonary vascular remodelling associated with various forms of PH. We also discuss ways to improve management and to support and optimise drug development in this research field.
702 citations
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
698 citations
11 Jul 2019
TL;DR: Gestational diabetes mellitus is the most common complication in pregnancy and has short-term and long-term effects in both mother and offspring, and dietary modification and increased physical activity are the primary treatments, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved.
Abstract: Hyperglycaemia that develops during pregnancy and resolves after birth has been recognized for over 50 years, but uniform worldwide consensus is lacking about threshold hyperglycaemic levels that merit a diagnosis of ‘gestational diabetes mellitus’ (GDM) and thus treatment during pregnancy. GDM is currently the most common medical complication of pregnancy, and prevalence of undiagnosed hyperglycaemia and even overt diabetes in young women is increasing. Maternal overweight and obesity, later age at childbearing, previous history of GDM, family history of type 2 diabetes mellitus and ethnicity are major GDM risk factors. Diagnosis is usually performed using an oral glucose tolerance test (OGTT), although a non-fasting, glucose challenge test (GCT) is used in some parts of the world to screen women for those requiring a full OGTT. Dietary modification and increased physical activity are the primary treatments for GDM, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved. Oral hypoglycaemic agents, principally metformin and glibenclamide (glyburide), are also used in some countries. Treatment improves immediate pregnancy outcomes, reducing excess fetal growth and adiposity and pregnancy-related hypertensive disorders. GDM increases the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease, in both the mother and infant. Optimal management of mother and infant during long-term follow-up remains challenging, with very limited implementation of preventive strategies in most parts of the world. Gestational diabetes mellitus (GDM) is the most common complication in pregnancy and has short-term and long-term effects in both mother and offspring. This Primer discusses the definitions of GDM, diagnosis and management of the disease and areas requiring further research.
643 citations
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, University of Cyprus9, Medical University of South Carolina10, University of Cambridge11, University of Barcelona12, University Health Network13, The Feinstein Institute for Medical Research14, Toronto Western Hospital15, University of California, Los Angeles16, Humboldt University of Berlin17, Copenhagen University Hospital18, University of Michigan19, Harvard University20, University of the Basque Country21, University of Crete22, University of Kiel23, University Hospital Centre Zagreb24, University of Paris-Sud25, University of Hong Kong26, University of Calgary27, Hospital for Special Surgery28, University of Pécs29, University of Padua30, Medical University of Graz31, National Institutes of Health32, New York University33, Université Paris-Saclay34, University Hospital Complex Of Vigo35, University of Occupational and Environmental Health Japan36, University of Porto37, University of Leeds38, Leeds Teaching Hospitals NHS Trust39, Cedars-Sinai Medical Center40, Istanbul Bilim University41, McMaster University42, University of Toronto43, University of Paris44
TL;DR: These new classification criteria for systemic lupus erythematosus have excellent sensitivity and specificity, and were developed using rigorous methodology with multidisciplinary and international input.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
606 citations
VU University Amsterdam1, Sahlgrenska University Hospital2, University of Gothenburg3, Umeå University4, Charles University in Prague5, University of Antwerp6, University of California, San Francisco7, Karolinska Institutet8, Uppsala University9, Aarhus University10, First Faculty of Medicine, Charles University in Prague11, Copenhagen University Hospital12, University of Oxford13, Örebro University14, Lund University15, University of Basel16, Karolinska University Hospital17, Medical University of Graz18, University of Eastern Finland19, University of Bari20, UCL Institute of Neurology21, Erasmus University Rotterdam22, University of California, San Diego23, University of Puerto Rico24, Belmont University25, University of Ferrara26, Radboud University Nijmegen27, Maastricht University28, Evotec29
TL;DR: The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC, and has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
Abstract: Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses. Results: Data were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. Conclusions and Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
419 citations
TL;DR: The fractal and particle analysis provide a relevant methodological framework to further the understanding of the spatial effects of economic pressure on forestry.
Abstract: The ever decreasing area of forests has lead to environmental and economical challenges and has brought with it a renewed interest in developing methodologies that quantify the extent of deforestation and reforestation. In this study we analyzed the deforested areas of the Apuseni Mountains, which has been under economic pressure in recent years and resulted in widespread deforestation as a means of income. Deforested surface dynamics modeling was based on images contained in the Global Forest Database, provided by the Department of Geographical Sciences at Maryland University between 2000 and 2014. The results of the image particle analysis and modelling were based on Total Area (ha), Count of patches and Average Size whereas deforested area distribution was based on the Local Connected Fractal Dimension, Fractal Fragmentation Index and Tug-of-War Lacunarity as indicators of forest fragmentation or heterogeneity. The major findings of the study indicated a reduction of the tree cover area by 3.8%, an increase in fragmentation of 17.7% and an increase in heterogeneity by 29%, while fractal connectivity decreased only by 0.1%. The fractal and particle analysis showed a clustering of forest loss areas with an average increase from 1.1 to 3.0 ha per loss site per year. In conclusion, the fractal and particle analysis provide a relevant methodological framework to further our understanding of the spatial effects of economic pressure on forestry.
TL;DR: Conditions for the long-term growth of primary kidney tubular epithelial organoids, or ‘tubuloids’, are described and tubuloids grown from human kidney tissue and urine aid the study of BK virus infection, Wilms tumors and cystic fibrosis.
Abstract: Adult stem cell-derived organoids are three-dimensional epithelial structures that recapitulate fundamental aspects of their organ of origin. We describe conditions for the long-term growth of primary kidney tubular epithelial organoids, or 'tubuloids'. The cultures are established from human and mouse kidney tissue and can be expanded for at least 20 passages (>6 months) while retaining a normal number of chromosomes. In addition, cultures can be established from human urine. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. We apply tubuloids to model infectious, malignant and hereditary kidney diseases in a personalized fashion. BK virus infection of tubuloids recapitulates in vivo phenomena. Tubuloids are established from Wilms tumors. Kidney tubuloids derived from the urine of a subject with cystic fibrosis allow ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function.
TL;DR: It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification to enhance the understanding of role of environmental factors in the etiology of ASD.
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc–copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene–environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.
The Catholic University of America1, Brown University2, Imperial College London3, Brigham and Women's Hospital4, Massachusetts Institute of Technology5, Indiana University – Purdue University Indianapolis6, Loyola University Medical Center7, University of Adelaide8, Medical University of Graz9, University of Helsinki10, Boston Children's Hospital11, University of Alberta12, Leiden University13, University of Cologne14, Agostino Gemelli University Polyclinic15, University of Amsterdam16, Hospital Universitario de Canarias17, Lithuanian University of Health Sciences18, Innsbruck Medical University19
TL;DR: This consensus project gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues.
Abstract: Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.
University of Liège1, University of Toulouse2, Heidelberg University3, University of Erlangen-Nuremberg4, University of Oxford5, University of Southampton6, King Saud University7, World Health Organization8, Vrije Universiteit Brussel9, Catholic University of the Sacred Heart10, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico11, University of Milan12, Tufts University13, University of Sheffield14, Australian Catholic University15, Ghent University Hospital16, Medical University of Graz17, Public Health Research Institute18, Geneva College19
TL;DR: An overview of different methods available and applicable in clinical settings and the use of grip strength to measure muscle strength and theUse of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice are proposed.
Abstract: It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).
TL;DR: It is suggested that skin markings should be avoided in dermoscopic images intended for analysis by a CNN by increasing the melanoma probability scores and consequently the false-positive rate.
Abstract: Importance Deep learning convolutional neural networks (CNNs) have shown a performance at the level of dermatologists in the diagnosis of melanoma. Accordingly, further exploring the potential limitations of CNN technology before broadly applying it is of special interest. Objective To investigate the association between gentian violet surgical skin markings in dermoscopic images and the diagnostic performance of a CNN approved for use as a medical device in the European market. Design and Setting A cross-sectional analysis was conducted from August 1, 2018, to November 30, 2018, using a CNN architecture trained with more than 120 000 dermoscopic images of skin neoplasms and corresponding diagnoses. The association of gentian violet skin markings in dermoscopic images with the performance of the CNN was investigated in 3 image sets of 130 melanocytic lesions each (107 benign nevi, 23 melanomas). Exposures The same lesions were sequentially imaged with and without the application of a gentian violet surgical skin marker and then evaluated by the CNN for their probability of being a melanoma. In addition, the markings were removed by manually cropping the dermoscopic images to focus on the melanocytic lesion. Main Outcomes and Measures Sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the CNN’s diagnostic classification in unmarked, marked, and cropped images. Results In all, 130 melanocytic lesions (107 benign nevi and 23 melanomas) were imaged. In unmarked lesions, the CNN achieved a sensitivity of 95.7% (95% CI, 79%-99.2%) and a specificity of 84.1% (95% CI, 76.0%-89.8%). The ROC AUC was 0.969. In marked lesions, an increase in melanoma probability scores was observed that resulted in a sensitivity of 100% (95% CI, 85.7%-100%) and a significantly reduced specificity of 45.8% (95% CI, 36.7%-55.2%,P Conclusions and Relevance This study’s findings suggest that skin markings significantly interfered with the CNN’s correct diagnosis of nevi by increasing the melanoma probability scores and consequently the false-positive rate. A predominance of skin markings in melanoma training images may have induced the CNN’s association of markings with a melanoma diagnosis. Accordingly, these findings suggest that skin markings should be avoided in dermoscopic images intended for analysis by a CNN. Trial Registration German Clinical Trial Register (DRKS) Identifier:DRKS00013570
TL;DR: It is shown that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average, and supports its safety.
TL;DR: In this article, a deep learning system was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation.
Abstract: Skin conditions affect an estimated 1.9 billion people worldwide. A shortage of dermatologists causes long wait times and leads patients to seek dermatologic care from general practitioners. However, the diagnostic accuracy of general practitioners has been reported to be only 0.24-0.70 (compared to 0.77-0.96 for dermatologists), resulting in referral errors, delays in care, and errors in diagnosis and treatment. In this paper, we developed a deep learning system (DLS) to provide a differential diagnosis of skin conditions for clinical cases (skin photographs and associated medical histories). The DLS distinguishes between 26 skin conditions that represent roughly 80% of the volume of skin conditions seen in primary care. The DLS was developed and validated using de-identified cases from a teledermatology practice serving 17 clinical sites via a temporal split: the first 14,021 cases for development and the last 3,756 cases for validation. On the validation set, where a panel of three board-certified dermatologists defined the reference standard for every case, the DLS achieved 0.71 and 0.93 top-1 and top-3 accuracies respectively. For a random subset of the validation set (n=963 cases), 18 clinicians reviewed the cases for comparison. On this subset, the DLS achieved a 0.67 top-1 accuracy, non-inferior to board-certified dermatologists (0.63, p<0.001), and higher than primary care physicians (PCPs, 0.45) and nurse practitioners (NPs, 0.41). The top-3 accuracy showed a similar trend: 0.90 DLS, 0.75 dermatologists, 0.60 PCPs, and 0.55 NPs. These results highlight the potential of the DLS to augment general practitioners to accurately diagnose skin conditions by suggesting differential diagnoses that may not have been considered. Future work will be needed to prospectively assess the clinical impact of using this tool in actual clinical workflows.
TL;DR: A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci that improve the prediction of gout in an independent cohort of 334,880 individuals, and implicates the kidney and liver as key target organs and prioritize potential causal genes.
Abstract: Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
TL;DR: Obesity management guidelines specifically tailored to GPs are provided, favouring a practical patient-centred approach, with a focus on GP communication and motivational interviewing as well as on therapeutic patient education.
Abstract: The first contact for patients with obesity for any medical treatment or other issues is generally with General Practitioners (GPs). Therefore, given the complexity of the disease, continuing GPs' education on obesity management is essential. This article aims to provide obesity management guidelines specifically tailored to GPs, favouring a practical patient-centred approach. The focus is on GP communication and motivational interviewing as well as on therapeutic patient education. The new guidelines highlight the importance of avoiding stigmatization, something frequently seen in different health care settings. In addition, managing the psychological aspects of the disease, such as improving self-esteem, body image and quality of life must not be neglected. Finally, the report considers that achieving maximum weight loss in the shortest possible time is not the key to successful treatment. It suggests that 5-10% weight loss is sufficient to obtain substantial health benefits from decreasing comorbidities. Reducing waist circumference should be considered even more important than weight loss per se, as it is linked to a decrease in visceral fat and associated cardiometabolic risks. Finally, preventing weight regain is the cornerstone of lifelong treatment, for any weight loss techniques used (behavioural or pharmaceutical treatments or bariatric surgery).
TL;DR: The current knowledge about the URT microbiome in health and disease is summarized, methodological issues are discussed, and the potential of the nasal microbiome to be used for medical diagnostics and as a target for therapy is considered.
Abstract: The human upper respiratory tract (URT) offers a variety of niches for microbial colonization. Local microbial communities are shaped by the different characteristics of the specific location within the URT, but also by the interaction with both external and intrinsic factors, such as ageing, diseases, immune responses, olfactory function, and lifestyle habits such as smoking. We summarize here the current knowledge about the URT microbiome in health and disease, discuss methodological issues, and consider the potential of the nasal microbiome to be used for medical diagnostics and as a target for therapy.
01 Mar 2019
TL;DR: Major inequalities in acute stroke treatment between and within 44 European countries are observed, which will assist decision makers implementing tailored stroke care programmes for reducing stroke-related morbidity and mortality in Europe.
Abstract: IntroductionAcute stroke unit care, intravenous thrombolysis and endovascular treatment significantly improve the outcome for patients with ischaemic stroke, but data on access and delivery through...
TL;DR: This work proposes a CNN architecture that learns to split the localization task into two simpler sub‐problems, reducing the overall need for large training datasets, and proposes a fully convolutional SpatialConfiguration‐Net (SCN), which outperforms related methods in terms of landmark localization error.
University of Colorado Denver1, University of Southern California2, University of North Carolina at Chapel Hill3, Katholieke Universiteit Leuven4, University of California, San Diego5, Ljubljana University Medical Centre6, French Institute of Health and Medical Research7, State University of New York System8, JDRF9, National Research Council10, Royal Melbourne Hospital11, University of Sheffield12, San Antonio River Authority13, Tel Aviv University14, Medical University of Graz15, University of Florida16, University of Miami17, Yale University18, Chiba University19
TL;DR: This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of S GLT inhibitors in people with type 1 diabetes.
Abstract: Sodium-glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes.
TL;DR: Nearly one-third of infants born to mothers with confirmed Zika virus (ZIKV) infection during pregnancy have developmental impairments that can be delayed in their presentation, warranting long-term monitoring of ZIKV-exposed children.
Abstract: We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015–2016 (refs. 1,2). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below –2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between −1 and −2 s.d. in any domain (scores <85–70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life. Nearly one-third of infants born to mothers with confirmed Zika virus (ZIKV) infection during pregnancy have developmental impairments that can be delayed in their presentation, warranting long-term monitoring of ZIKV-exposed children.
TL;DR: This review will focus on targeting p21 in cancer research and its potential in providing novel therapies as well as therapeutic approaches in cancer field.
Abstract: p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer, the role of p21 in phenotypic plasticity and its oncogenic/anti-apoptotic function, depending on p21 subcellular localization and p53 status, have been under scrutiny recently. Basic science and translational studies use precision gene editing to manipulate p21 itself, and proteins that interact with it; these studies have led to regulatory/functional/drug sensitivity discoveries as well as therapeutic approaches in cancer field. In this review, we will focus on targeting p21 in cancer research and its potential in providing novel therapies.
TL;DR: This chapter will provide an up to date review on ctDNA, CTCs and circulating miRNAs as new biomarkers for CRC, either for clinical management or early detection, highlighting their advantages and limitations.
Claudia L. Satizabal1, Claudia L. Satizabal2, Claudia L. Satizabal3, Hieab H.H. Adams4 +372 more•Institutions (111)
TL;DR: This paper identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank.
Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Transylvania University1, Charité2, Swiss Institute of Allergy and Asthma Research3, Wrocław Medical University4, National Institutes of Health5, Istanbul Medeniyet University6, Saga Group7, Hacettepe University8, University of Cologne9, Complutense University of Madrid10, University of Manchester11, National and Kapodistrian University of Athens12, University of Southampton13, Hospital Clínico San Carlos14, University of Messina15, University of Marburg16, University Hospital Southampton NHS Foundation Trust17, St Mary's Hospital18, University of Edinburgh19, Medical University of Graz20, University of Amsterdam21, Erasmus University Rotterdam22, University of Los Andes23
TL;DR: The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence‐based recommendations for the use of house dust mites (HDM) AIT as add‐on treatment for HDM‐driven allergic asthma.
Abstract: Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).
TL;DR: An update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues is provided.
Abstract: Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25-30 nmol/L (10-12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health.