11,706 results
Search Results
2. Oral phytate supplementation on the progression of mild cognitive impairment, brain iron deposition and diabetic retinopathy in patients with type 2 diabetes: a concept paper for a randomized double blind placebo controlled trial (the PHYND trial).
- Author
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Pujol A, Sanchis P, Tamayo MI, Nicolau J, Grases F, Espino A, Estremera A, Rigo E, Amengual GJ, Rodríguez M, Ribes JL, Gomila I, Simó-Servat O, and Masmiquel L
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- Adult, Aged, Female, Humans, Male, Middle Aged, Administration, Oral, Double-Blind Method, Randomized Controlled Trials as Topic, Brain metabolism, Brain drug effects, Cognitive Dysfunction metabolism, Cognitive Dysfunction etiology, Cognitive Dysfunction prevention & control, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 complications, Diabetic Retinopathy metabolism, Diabetic Retinopathy drug therapy, Dietary Supplements, Disease Progression, Iron metabolism, Iron administration & dosage, Phytic Acid administration & dosage
- Abstract
Type 2 diabetes mellitus has a worldwide prevalence of 10.5% in the adult population (20-79 years), and by 2045, the prevalence is expected to keep rising to one in eight adults living with diabetes. Mild cognitive impairment has a global prevalence of 19.7% in adults aged 50 years. Both conditions have shown a concerning increase in prevalence rates over the past 10 years, highlighting a growing public health challenge. Future forecasts indicate that the prevalence of dementia (no estimations done for individuals with mild cognitive impairment) is expected to nearly triple by 2050. Type 2 diabetes mellitus is a risk factor for the development of cognitive impairment, and such impairment increase the likelihood of poor glycemic/metabolic control. High phytate intake has been shown to be a protective factor against the development of cognitive impairment in observational studies. Diary phytate intake might reduce the micro- and macrovascular complications of patients with type 2 diabetes mellitus through different mechanisms. We describe the protocol of the first trial (the PHYND trial) that evaluate the effect of daily phytate supplementation over 56 weeks with a two-arm double-blind placebo-controlled study on the progression of mild cognitive impairment, cerebral iron deposition, and retinal involvement in patients with type 2 diabetes mellitus. Our hypothesis proposes that phytate, by inhibiting advanced glycation end product formation and chelating transition metals, will improve cognitive function and attenuate the progression from Mild Cognitive Impairment to dementia in individuals with type 2 diabetes mellitus and mild cognitive impairment. Additionally, we predict that phytate will reduce iron accumulation in the central nervous system, mitigate neurodegenerative changes in both the central nervous system and retina, and induce alterations in biochemical markers associated with neurodegeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pujol, Sanchis, Tamayo, Nicolau, Grases, Espino, Estremera, Rigo, Amengual, Rodríguez, Ribes, Gomila, Simó-Servat and Masmiquel.)
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- 2024
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3. Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART
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Ehrenberg, Alexander J, Kelberman, Michael A, Liu, Kathy Y, Dahl, Martin J, Weinshenker, David, Falgàs, Neus, Dutt, Shubir, Mather, Mara, Ludwig, Mareike, Betts, Matthew J, Winer, Joseph R, Teipel, Stefan, Weigand, Alexandra J, Eschenko, Oxana, Hämmerer, Dorothea, Leiman, Marina, Counts, Scott E, Shine, James M, Robertson, Ian H, Levey, Allan I, Lancini, Elisa, Son, Gowoon, Schneider, Christoph, Van Egroo, Maxime, Liguori, Claudio, Wang, Qin, Vazey, Elena M, Rodriguez‐Porcel, Federico, Haag, Lena, Bondi, Mark W, Vanneste, Sven, Freeze, Whitney M, Yi, Yeo‐Jin, Maldinov, Mihovil, Gatchel, Jennifer, Satpati, Abhijit, Babiloni, Claudio, Kremen, William S, Howard, Robert, Jacobs, Heidi IL, and Grinberg, Lea T
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Neurosciences ,Dementia ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Humans ,Alzheimer Disease ,Brain ,Biomarkers ,Disease Progression ,Clinical Sciences ,Geriatrics - Abstract
The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.
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- 2023
4. Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.
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Perucca, Emilio, French, Jacqueline A., Aljandeel, Ghaieb, Balestrini, Simona, Braga, Patricia, Burneo, Jorge G., Felli, Augustina Charway, Cross, J. Helen, Galanopoulou, Aristea S., Jain, Satish, Jiang, Yuwu, Kälviäinen, Reetta, Lim, Shih Hui, Meador, Kimford J., Mogal, Zarine, Nabbout, Rima, Sofia, Francesca, Somerville, Ernest, Sperling, Michael R., and Triki, Chahnez
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SEIZURES (Medicine) , *DRUGS , *DIRECT action , *MEDICAL care , *DISEASE progression - Abstract
A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English‐language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease‐modifying" effects. A more‐refined terminology to describe precisely these actions needs to be developed. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Critically appraised paper: In adolescents with moderate-grade idiopathic scoliosis, nighttime bracing with self-mediated physical activity prevented Cobb angle progression [synopsis].
- Author
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Milne, Nikki
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HOSPITAL night care ,SCOLIOSIS ,EXERCISE therapy ,ORTHOPEDIC apparatus ,DISEASE progression ,PHYSICAL activity ,ADOLESCENCE - Abstract
The article explores how nighttime bracing combined with self-mediated physical activity can effectively prevent the progression of the Cobb angle in adolescents with moderate-grade idiopathic scoliosis. Topics discussed include the mechanisms of nighttime bracing in scoliosis management, the role of self-directed physical activities in supporting spinal health, and the overall outcomes in slowing disease progression with this combined approach.
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- 2024
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6. Tracking amyotrophic lateral sclerosis disease progression using passively collected smartphone sensor data.
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Karas M, Olsen J, Straczkiewicz M, Johnson SA, Burke KM, Iwasaki S, Lahav A, Scheier ZA, Clark AP, Iyer AS, Huang E, Berry JD, and Onnela JP
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- Humans, Male, Female, Middle Aged, Aged, Mobile Applications, Walking physiology, Exercise physiology, Amyotrophic Lateral Sclerosis physiopathology, Amyotrophic Lateral Sclerosis diagnosis, Smartphone, Disease Progression, Accelerometry instrumentation
- Abstract
Background: Passively collected smartphone sensor data provide an opportunity to study physical activity and mobility unobtrusively over long periods of time and may enable disease monitoring in people with amyotrophic lateral sclerosis (PALS)., Methods: We enrolled 63 PALS who used Beiwe mobile application that collected their smartphone accelerometer and GPS data and administered the self-entry ALS Functional Rating Scale-Revised (ALSFRS-RSE) survey. We identified individual steps from accelerometer data and used the Activity Index to summarize activity at the minute level. Walking, Activity Index, and GPS outcomes were then aggregated into day-level measures. We used linear mixed effect models (LMMs) to estimate baseline and monthly change for ALSFRS-RSE scores (total score, subscores Q1-3, Q4-6, Q7-9, Q10-12) and smartphone sensor data measures, as well as the associations between them., Findings: The analytic sample (N = 45) was 64.4% male with a mean age of 60.1 years. The mean observation period was 292.3 days. The ALSFRS-RSE total score baseline mean was 35.8 and had a monthly rate of decline of -0.48 (p-value <0.001). We observed statistically significant change over time and association with ALSFRS-RSE total score for four smartphone sensor data-derived measures: walking cadence from top 1 min and log-transformed step count, step count from top 1 min, and Activity Index from top 1 min., Interpretation: Smartphone sensors can unobtrusively track physical changes in PALS, potentially aiding disease monitoring and future research., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
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- 2024
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7. Nature of the evidence base and approaches to guide nutrition interventions for individuals: a position paper from the Academy of Nutrition Sciences.
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Hickson, Mary, Papoutsakis, Constantina, Madden, Angela M, Smith, Mary Anne, and Whelan, Kevin
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DIETETICS ,MEDICAL protocols ,PROFESSIONAL practice ,NATURAL foods ,PROFESSIONAL associations ,FOOD security ,NUTRITIONAL requirements ,MISINFORMATION ,INFORMATION resources ,NON-communicable diseases ,DIETETICS research ,NUTRITION services ,EVIDENCE-based medicine ,DIET ,DISEASE progression ,NUTRITION education - Abstract
This Position Paper from the Academy of Nutrition Sciences is the third in a series which describe the nature of the scientific evidence and frameworks that underpin nutrition recommendations for health. This paper focuses on evidence which guides the application of dietary recommendations for individuals. In some situations, modified nutrient intake becomes essential to prevent deficiency, optimise development and health, or manage symptoms and disease progression. Disease and its treatment can also affect taste, appetite and ability to access and prepare foods, with associated financial impacts. Therefore, the practice of nutrition and dietetics must integrate and apply the sciences of food, nutrition, biology, physiology, behaviour, management, communication and society to achieve and maintain human health. Thus, there is huge complexity in delivering evidence-based nutrition interventions to individuals. This paper examines available frameworks for appraising the quality and certainty of nutrition research evidence, the development nutrition practice guidelines to support evidence implementation in practice and the influence of other sources of nutrition information and misinformation. The paper also considers major challenges in applying research evidence to an individual and suggests consensus recommendations to begin to address these challenges in the future. Our recommendations target three groups; those who deliver nutrition interventions to individuals, those funding, commissioning or undertaking research aimed at delivering evidence-based nutrition practice, and those disseminating nutritional information to individuals. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).
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Duseja, Ajay, Singh, S.P., De, Arka, Madan, Kaushal, Rao, Padaki Nagaraja, Shukla, Akash, Choudhuri, Gourdas, Saigal, Sanjiv, Shalimar, Arora, Anil, Anand, Anil C., Das, Ashim, Kumar, Ashish, Eapen, Chundamannil E., Devadas, Krishnadas, Shenoy, Kotacherry T., Panigrahi, Manas, Wadhawan, Manav, Rathi, Manish, and Kumar, Manoj
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NON-alcoholic fatty liver disease , *TYPE 2 diabetes , *DISEASE progression , *LIVER diseases , *FATTY liver - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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9. mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.
- Author
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Ravizza T, Scheper M, Di Sapia R, Gorter J, Aronica E, and Vezzani A
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- Humans, Animals, Signal Transduction physiology, Brain metabolism, Brain pathology, Anticonvulsants therapeutic use, Anticonvulsants pharmacology, Epilepsy drug therapy, TOR Serine-Threonine Kinases metabolism, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases metabolism, Disease Progression
- Abstract
Epilepsy remains a major health concern as anti-seizure medications frequently fail, and there is currently no treatment to stop or prevent epileptogenesis, the process underlying the onset and progression of epilepsy. The identification of the pathological processes underlying epileptogenesis is instrumental to the development of drugs that may prevent the generation of seizures or control pharmaco-resistant seizures, which affect about 30% of patients. mTOR signalling and neuroinflammation have been recognized as critical pathways that are activated in brain cells in epilepsy. They represent a potential node of biological convergence in structural epilepsies with either a genetic or an acquired aetiology. Interventional studies in animal models and clinical studies give strong support to the involvement of each pathway in epilepsy. In this Review, we focus on available knowledge about the pathophysiological features of mTOR signalling and the neuroinflammatory brain response, and their interactions, in epilepsy. We discuss mitigation strategies for each pathway that display therapeutic effects in experimental and clinical epilepsy. A deeper understanding of these interconnected molecular cascades could enhance our strategies for managing epilepsy. This could pave the way for new treatments to fill the gaps in the development of preventative or disease-modifying drugs, thus overcoming the limitations of current symptomatic medications., (© 2024. Springer Nature Limited.)
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- 2024
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10. Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG)
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Helen Jenkinson, Francis L. Munier, Philippe Maeder, Christina Stathopoulos, Livia Lumbroso-Le Rouic, François Doz, Maja Beck Popovic, Guillermo L. Chantada, Annette C. Moll, Manoj Parulekar, Ophthalmology, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Quality of Care, CCA - Cancer Treatment and quality of life, CCA - Imaging and biomarkers, and Amsterdam Reproduction & Development (AR&D)
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Cancer Research ,medicine.medical_specialty ,Conservative management ,Enucleation ,Guidelines ,survival ,retinoblastoma ,intra-arterial chemotherapy ,External beam irradiation ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,metastasis ,Intensive care medicine ,RC254-282 ,Biologic marker ,intravenous chemotherapy ,business.industry ,Retinoblastoma ,Disease progression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,eye diseases ,Oncology ,030220 oncology & carcinogenesis ,030221 ophthalmology & optometry ,Position paper ,secondary enucleation ,external beam irradiation ,business ,Disease persistence - Abstract
Simple Summary Although secondary enucleation (SE) is the treatment of choice for retinoblastoma eyes that did not respond favorably to conservative therapies, clear criteria for its indication are, however, currently missing. In this position paper on behalf of the European Retinoblastoma Group (EURbG), we discuss the available literature on SE, including its influence on metastases rate and survival, and propose guidelines to assist decision-making to interrupt eye-preserving therapies depending on the availabilities of advanced diagnostic and therapeutic modalities. Absolute indications to SE may be restricted to eyes with refractory tumor activity resisting all salvage treatments or eyes under apparent tumor control but no visual potential and irreducible complications. In contrast, eyes with an obscured optic nerve head and/or ocular complications amenable to specific surgical or medical management can be considered relative indications, provided that appropriate follow-up can be implemented and that parents are fully aware of a residual risk. Abstract Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.
- Published
- 2021
11. Multilayer three-dimensional filter paper constructs for the culture and analysis of aortic valvular interstitial cells.
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Sapp, Matthew C., Fares, Hannelle J., Estrada, Ana C., and Grande-Allen, K. Jane
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FILTER paper ,INTERSTITIAL cells ,CELL culture ,COLLAGEN ,AORTIC valve diseases ,DISEASE progression - Abstract
Culturing aortic valvular interstitial cells in an environment that models the aortic valve is an essential step towards understanding the progression of calcific aortic valve disease. Here the adaption of a three-dimensional (3-D) stacked paper-based culture system is presented for analyzing valve cells in a thick collagen gel matrix. Filter paper layers, modeled after a 96-well plate design, were printed with a wax well-plate template and then seeded with valve cell and collagen mixtures that quickly gelled into 3-D cultures. Stacking these layers permitted extensive customization of culture thickness and cell density profiles to model the full thickness of native valve tissue. Aortic valvular interstitial cells seeded into the paper-based constructs consistently demonstrated high survival up to 14 days of culture with significant increases in cell number through the first 3 days of culture. After 4 days following seeding, valve cells in single layer cultures showed reduced smooth muscle α-actin expression with a stabilized cell density, suggesting a transition from an activated phenotype to a more quiescent state. Valve cells in multilayer cultures demonstrated the ability to migrate from layer to layer and had the highest smooth muscle α-actin expression in areas with predicted low oxygen tensions. These results establish the filter-paper-based method as a viable culture system for analyzing valve cells in an in vitro 3-D model of the aortic valve. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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12. Paper-based Transwell assays: an inexpensive alternative to study cellular invasion
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Adam Loeser, Nathan A. Whitman, Matthew R. Lockett, and Rachael M. Kenney
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Paper ,02 engineering and technology ,01 natural sciences ,Biochemistry ,Article ,Analytical Chemistry ,Extracellular matrix ,Cell Movement ,Cell Line, Tumor ,Electrochemistry ,Animals ,Humans ,Environmental Chemistry ,Neoplasm Invasiveness ,Spectroscopy ,Chemistry ,010401 analytical chemistry ,Exogenous factor ,Disease progression ,Reproducibility of Results ,Cell movement ,Paper based ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Cell biology ,Cell culture ,Biological Assay ,Cattle ,0210 nano-technology - Abstract
Cellular movement is essential in the formation and maintenance of healthy tissues as well as in disease progression such as tumor metastasis. In this work, we describe a paper-based Transwell assay capable of quantifying cellular invasion through an extracellular matrix. The paper-based Transwell assays generate similar datasets, with equivalent reproducibility, to commercially available Transwell assays. With different culture configurations, we quantify invasion: upon addition of an exogenous factor or in the presence of medium obtained from other cell types, in an indirect or direct co-culture format whose medium composition is dynamically changing, and in a single-zone or parallel (96-zone) format.
- Published
- 2019
13. The different risk of new-onset, chronic, worsening, and advanced heart failure: A systematic review and meta-regression analysis.
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Shakoor A, Abou Kamar S, Malgie J, Kardys I, Schaap J, de Boer RA, van Mieghem NM, van der Boon RMA, and Brugts JJ
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- Humans, Prognosis, Hospitalization statistics & numerical data, Chronic Disease, Risk Assessment methods, Cause of Death trends, Risk Factors, Global Health, Heart Failure epidemiology, Disease Progression
- Abstract
Aims: Heart failure (HF) is a chronic and progressive syndrome associated with a poor prognosis. While it may seem intuitive that the risk of adverse outcomes varies across the different stages of HF, an overview of these risks is lacking. This study aims to determine the risk of all-cause mortality and HF hospitalizations associated with new-onset HF, chronic HF (CHF), worsening HF (WHF), and advanced HF., Methods and Results: We performed a systematic review of observational studies from 2012 to 2022 using five different databases. The primary outcomes were 30-day and 1-year all-cause mortality, as well as 1-year HF hospitalization. Studies were pooled using random effects meta-analysis, and mixed-effects meta-regression was used to compare the different HF groups. Among the 15 759 studies screened, 66 were included representing 862 046 HF patients. Pooled 30-day mortality rates did not reveal a significant distinction between hospital-admitted patients, with rates of 10.13% for new-onset HF and 8.11% for WHF (p = 0.10). However, the 1-year mortality risk differed and increased stepwise from CHF to advanced HF, with a rate of 8.47% (95% confidence interval [CI] 7.24-9.89) for CHF, 21.15% (95% CI 17.78-24.95) for new-onset HF, 26.84% (95% CI 23.74-30.19) for WHF, and 29.74% (95% CI 24.15-36.10) for advanced HF. Readmission rates for HF at 1 year followed a similar trend., Conclusions: Our meta-analysis of observational studies confirms the different risk for adverse outcomes across the distinct HF stages. Moreover, it emphasizes the negative prognostic value of WHF as the first progressive stage from CHF towards advanced HF., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Published
- 2024
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14. Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline.
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Bayas, Antonios, Berthele, Achim, Blank, Norbert, Dreger, Peter, Faissner, Simon, Friese, Manuel A., Gerdes, Lisa-Ann, Grauer, Oliver Martin, Häussler, Vivien, Heesen, Christoph, Janson, Dietlinde, Korporal-Kuhnke, Mirjam, Kowarik, Markus, Kröger, Nikolaus, Lünemann, Jan D., Martin, Roland, Meier, Uwe, Meuth, Sven, Muraro, Paolo, and Platten, Michael
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STEM cells ,MULTIPLE sclerosis ,DISEASE progression ,MAGNETIC resonance imaging - Abstract
Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS. Objective: To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project. Methods: An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings. Results: We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM). Conclusion: Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages. Plain language summary: Autologous haematopoietic stem cell transplantation for multiple sclerosis Substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS) during the last 20 years. However, in a relevant percentage of patients, the disease cannot completely be contained. Autologous haematopoietic stem cell transplantation (AHSCT) enables rebuilding of a new and healthy immune system and to potentially stop the autoimmune disease process for a long time. A number of studies documenting 4000 cases cumulatively over the past 20 years reported high efficacy of AHSCT in controlling MS inflammatory disease activity. These data and improved safety profiles of the treatment procedures spurred interest in using AHSCT as a treatment option for MS. An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of video calls to develop recommendations and outline a registry study project. We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS. Current data indicate that patients are most likely to benefit from AHSCT if they are young, ambulatory, with high disease activity, that is, relapses or new magnetic resonance imaging (MRI) lesions. Treatment data with AHSCT will be collected within the German REgistry Cohort of autoLogous haematopoietic stem cell transplantation MS (RECLAIM). Further clinical trials including registry-based analyses and systematic follow-up are urgently needed to better define the optimal patient characteristics as well as the efficacy and safety profile of AHSCT compared with other high-efficacy therapies. These will help to position AHSCT as a treatment option in different MS disease stages. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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15. Rapid Diagnosis of Prostate Cancer Disease Progression Using Paper Spray Ionization Mass Spectrometry
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Iqbal Mahmud, Vanessa Y. Rubio, Bongyong Lee, Timothy J. Garrett, Ranjan J. Perera, Christian P. Pavlovich, and Frederico Garcia Pinto
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Male ,Oncology ,medicine.medical_specialty ,Urine ,010402 general chemistry ,01 natural sciences ,Mass Spectrometry ,Analytical Chemistry ,Prostate cancer ,Metabolomics ,Prostate ,Internal medicine ,medicine ,Humans ,Rapid diagnostic test ,Chemistry ,010401 analytical chemistry ,Prostatic Neoplasms ,Cancer ,Prostate-Specific Antigen ,medicine.disease ,0104 chemical sciences ,Prostate-specific antigen ,medicine.anatomical_structure ,Disease Progression ,Neoplasm Grading ,Progressive disease - Abstract
The limitation of prostate specific antigen (PSA) for prostate cancer (PC) diagnosis is well-recognized. The Gleason score (GS) has been the most widely used grading system for prostate tumor differentiation and represents the best-established prognostic indicator for prostate cancer progression. However, a rapid and sensitive noninvasive diagnostic marker that differentiates GS-based prostate cancer disease progression is needed. As PC is becoming a leading cause of cancer related death for men in the U.S. and worldwide, an immediate need exists for an improved, sensitive, noninvasive, and rapid diagnostic test for PC screening. Here, we employed paper spray ionization-mass spectrometry (PSI MS)-based global metabolomics of urine liquid biopsies to distinguish between healthy (negative for any prostate specific health problems) and progressive PC states (low grade PC such as GS6 and high-grade PC such as GS7, GS8, and GS9). For PSI-MS-based direct untargeted metabolic investigation, a raw urine sample was directly pipetted onto a triangular paper substrate, without any additional sample preparation. Multivariate statistical analysis revealed distinct GS-specific metabolic signatures compared to a healthy control. Variable importance in projection from partial least-squares-discriminant analysis showed distinct metabolic patterns that were correlatively elevated with progressive disease and could serve as biomarkers for diagnosis of prostate cancer risk categorization.
- Published
- 2021
16. Recommendations for advance care planning in adults with congenital heart disease: a position paper from the ESC Working Group of Adult Congenital Heart Disease, the Association of Cardiovascular Nursing and Allied Professions (ACNAP), the European Association for Palliative Care (EAPC), and the International Society for Adult Congenital Heart Disease (ISACHD)
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Adrienne H. Kovacs, Corina Thomet, Markus Schwerzmann, Jolien W. Roos-Hesselink, Piotr Z Sobanski, Philip Moons, Matthias Greutmann, Daniel Tobler, Eva Goossens, Pastora Gallego, L. Swan, Harald Gabriel, Noémi de Stoutz, University of Zurich, Schwerzmann, Markus, and Cardiology
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Advance care planning ,Adult ,Cardiovascular Nursing ,Heart Defects, Congenital ,medicine.medical_specialty ,Palliative care ,Heart disease ,Population ,610 Medicine & health ,030204 cardiovascular system & hematology ,2705 Cardiology and Cardiovascular Medicine ,03 medical and health sciences ,Advance Care Planning ,0302 clinical medicine ,Medicine ,Humans ,Adult congenital heart disease ,030212 general & internal medicine ,Association (psychology) ,education ,Cardiovascular nursing ,education.field_of_study ,business.industry ,Communication ,Disease progression ,Palliative Care ,medicine.disease ,Family medicine ,10209 Clinic for Cardiology ,Position paper ,Human medicine ,Cardiology and Cardiovascular Medicine ,business - Abstract
Survival prospects in adults with congenital heart disease (CHD), although improved in recent decades, still remain below expectations for the general population. Patients and their loved ones benefit from preparation for both unexpected and predictable deaths, sometimes preceded by a prolonged period of declining health. Hence, advance care planning (ACP) is an integral part of comprehensive care for adults with CHD. This position paper summarizes evidence regarding benefits of and patients' preferences for ACP and provides practical advice regarding the implementation of ACP processes within clinical adult CHD practice. We suggest that ACP be delivered as a structured process across different stages, with content dependent upon the anticipated disease progression. We acknowledge potential barriers to initiate ACP discussions and emphasize the importance of a sensitive and situation-specific communication style. Conclusions presented in this article reflect agreed expert opinions and include both patient and provider perspectives. ispartof: EUROPEAN HEART JOURNAL vol:41 issue:43 pages:4200-4210 ispartof: location:England status: published
- Published
- 2020
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17. Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic Research
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Joshua M. Campbell, Sharif M. Rahman, Joseph B. Balhoff, Manibarathi Vaithiyanathan, Adam T. Melvin, and Grant M. Landwehr
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0301 basic medicine ,Disease detection ,Computer science ,Point-of-Care Systems ,Microfluidics ,Early detection ,single cell analysis ,Nanotechnology ,Review ,high-throughput screening ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,PDMS ,Lab-On-A-Chip Devices ,Humans ,polydimethylsiloxane ,Dimethylpolysiloxanes ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,microfluidic devices ,Spectroscopy ,Drug discovery ,Capture antibody ,lateral flow strip assays ,Organic Chemistry ,Disease progression ,µPADs ,General Medicine ,Paper based ,Equipment Design ,Microfluidic Analytical Techniques ,point of care ,3. Good health ,Computer Science Applications ,030104 developmental biology ,Drug development ,lcsh:Biology (General) ,lcsh:QD1-999 ,Single-Cell Analysis ,LFSAs - Abstract
Recent developments in microfluidic devices, nanoparticle chemistry, fluorescent microscopy, and biochemical techniques such as genetic identification and antibody capture have provided easier and more sensitive platforms for detecting and diagnosing diseases as well as providing new fundamental insight into disease progression. These advancements have led to the development of new technology and assays capable of easy and early detection of pathogenicity as well as the enhancement of the drug discovery and development pipeline. While some studies have focused on treatment, many of these technologies have found initial success in laboratories as a precursor for clinical applications. This review highlights the current and future progress of microfluidic techniques geared toward the timely and inexpensive diagnosis of disease including technologies aimed at high-throughput single cell analysis for drug development. It also summarizes novel microfluidic approaches to characterize fundamental cellular behavior and heterogeneity.
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- 2018
18. Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19
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Dominic Dellweg, Michael Westhoff, Stefan Kluge, Santiago Ewig, Bernd Schönhofer, Philipp M. Lepper, Torsten T. Bauer, Winfried Randerath, Thomas Voshaar, Wolfram Windisch, J. Geiseler, and Michael Pfeifer
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,ARDS ,medicine.medical_treatment ,Pneumonia, Viral ,Guidelines ,Acute respiratory failure ,Hypoxemia ,law.invention ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,law ,Germany ,Oxygen therapy ,Humans ,Medicine ,Intubation ,030212 general & internal medicine ,Continuous positive airway pressure ,Hypoxia ,Pandemics ,Oxygen saturation (medicine) ,Respiratory Distress Syndrome ,SARS-CoV-2 ,business.industry ,Respiratory support ,Patient Acuity ,COVID-19 ,Respiration Disorders ,medicine.disease ,Respiration, Artificial ,Intensive care unit ,030228 respiratory system ,Acute Disease ,Emergency medicine ,Disease Progression ,Breathing ,medicine.symptom ,Coronavirus Infections ,Respiratory Insufficiency ,business - Abstract
Against the background of the pandemic caused by infection with the SARS-CoV-2 virus, the German Respiratory Society has appointed experts to develop therapy strategies for COVID-19 patients with acute respiratory failure (ARF). Here we present key position statements including observations about the pathophysiology of (ARF). In terms of the pathophysiology of pulmonary infection with SARS-CoV-2, COVID-19 can be divided into 3 phases. Pulmonary damage in advanced COVID-19 often differs from the known changes in acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in the respiratory support of ARF. The assessment of the extent of ARF should be based on arterial or capillary blood gas analysis under room air conditions, and it needs to include the calculation of oxygen supply (measured from the variables of oxygen saturation, hemoglobin level, the corrected values of Hüfner’s factor, and cardiac output). Aerosols can cause transmission of infectious, virus-laden particles. Open systems or vented systems can increase the release of respirable particles. Procedures in which the invasive ventilation system must be opened and endotracheal intubation carried out are associated with an increased risk of infection. Personal protective equipment (PPE) should have top priority because fear of contagion should not be a primary reason for intubation. Based on the current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. A significant proportion of patients with ARF present with relevant hypoxemia, which often cannot be fully corrected, even with a high inspired oxygen fraction (FiO2) under NHF. In this situation, the oxygen therapy can be escalated to CPAP or NIV when the criteria for endotracheal intubation are not met. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring and readiness for intubation are to be ensured at all times. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a “do not intubate” order.
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- 2020
19. Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium
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E. Palacio, Koos de Wit, Daniela Campion, Salvatore Piano, Elisa Pose, T. Lanzillotti, Carlos Jiménez, Sara Montagnese, Patrick S. Kamath, Rajeshwar P. Mookerjee, Miquel Gómez i Serra, Ruben Hernaez, M. Aban, Marta Carol, G. Nicolao, Claire Francoz, Giacomo Zaccherini, Hugh Watson, Isabel Graupera, M.T. Chiappa, Jonel Trebicka, Macarena Simón-Talero, Frank Erhard Uschner, Cristina Solé, Alejandro Forner, Ulrich Beuers, F. Durand, Paolo Caraceni, Victor Vargas, Marta Cervera, Carlo Alessandria, Adrià Juanola, V. Esnault, Jeltje Helder, Marko Korenjak, Olivier Roux, Laura Napoleone, Ferran Torres, S. Graf-Dirmeier, Judit Pich, Ann T. Ma, Maria Martha Bernardi, M. Pérez-Guasch, Núria Fabrellas, Pere Ginès, Maricela Quintana López, Elsa Solà, Emma Avitabile, Aleksander Krag, Juan G. Abraldes, Gastroenterology and Hepatology, Graduate School, Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Elsa Solà, Elisa Pose, Daniela Campion, Salvatore Piano, Olivier Roux, Macarena Simon-Talero, Frank Uschner, Koos de Wit, Giacomo Zaccherini, Carlo Alessandria, Ulrich Beuers, Paolo Caraceni, Claire Francoz, Rajeshwar P. Mookerjee, Jonel Trebicka, Victor Vargas, Miquel Serra, Ferran Torres, Sara Montagnese, Aleksander Krag, Ruben Hernaez, Marko Korenjak, Hugh Watson, Juan G. Abraldes, Patrick S. Kamath, Pere Ginès, LiverHope Consortium Investigators, Institut Català de la Salut, [Solà E, Pose E] Liver Unit, Hospital Clínic De Barcelona, Barcelona, School of Medicine and Health Sciences University of Barcelona, Spain. Institut d´Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain. [Campion D] Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy. [Piano S] Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy. [Roux O] Hepatology and Liver Intensive Care Unit, Hospital Beaujon, APHP, Clichy, France. [Simon-Talero M] Unitat del Fetge, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Liver Cirrhosis ,0301 basic medicine ,Cirrhosis ,administración de los servicios de salud::gestión de la atención al paciente::tratamiento de las enfermedades [ATENCIÓN DE SALUD] ,enfermedades del sistema digestivo::enfermedades hepáticas::cirrosis hepática [ENFERMEDADES] ,Digestive System Diseases::Liver Diseases::Liver Cirrhosis [DISEASES] ,Trasplantament hepàtic ,Disease ,Severity of Illness Index ,0302 clinical medicine ,Clinical trials ,Quality of life ,ACLF ,Ascites ,Secondary Prevention ,Liver transplant ,Otros calificadores::/terapia [Otros calificadores] ,Hepatic encephalopathy ,Clinical Trials as Topic ,education.field_of_study ,Disease Management ,3. Good health ,Clinical trial ,Europe ,Natural history ,Hepatic cirrhosis ,Research Design ,Qualitat de vida ,Ascite ,Disease Progression ,030211 gastroenterology & hepatology ,AKI ,ascites ,cirrhosis ,clinical trials ,endpoints ,hepatic encephalopathy ,hyponatremia ,infections ,liver transplant ,quality of life ,medicine.symptom ,Infection ,Hyponatremia ,técnicas de investigación::métodos::diseño de la investigación [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,medicine.medical_specialty ,Consensus ,Cirrosi hepàtica ,Endpoint Determination ,Population ,Infections ,03 medical and health sciences ,Investigative Techniques::Methods::Research Design [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Hypertension, Portal ,medicine ,Humans ,Intensive care medicine ,education ,Health Services Administration::Patient Care Management::Disease Management [HEALTH CARE] ,Cirrosi hepàtica - Tractament ,Cirrhosi ,Hepatology ,business.industry ,Other subheadings::/therapy [Other subheadings] ,Endpoint ,medicine.disease ,Assaigs clínics - Disseny ,030104 developmental biology ,Etiology ,Endpoints ,business ,Hepatic transplantation - Abstract
Clinical trials; Liver transplant; Quality of life Ensayos clínicos; Trasplante de hígado; Calidad de vida Assaigs clínics; Trasplantament de fetge; Qualitat de vida Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
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- 2021
20. Management of hepatitis C positive patients undergoing active treatment for malignancies: A position paper from the Associazione Italiana di Oncologia Medica (AIOM) and the Società Italiana di Malattie Infettive e Tropicali (SIMIT)
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Paolo Pedrazzoli, Gloria Taliani, Giovanni Battista Gaeta, Saverio Cinieri, Fausto Baldanti, Massimo Puoti, Anna Pagani, Valentina Zuccaro, Carmine Pinto, Raffaele Bruno, Bruno, R, Zuccaro, V, Pinto, C, Puoti, M, Gaeta, G, Pagani, A, Taliani, G, Baldanti, F, Cinieri, S, and Pedrazzoli, P
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medicine.medical_specialty ,Exacerbation ,Genotype ,Hepatitis C virus ,Anticancer treatment ,Hepatitis C ,Reactivation ,Antiviral Agents ,Disease Management ,Disease Progression ,Humans ,Italy ,Neoplasms ,Practice Guidelines as Topic ,Risk Assessment ,Risk Factors ,Virus Activation ,Hepacivirus ,Hematology ,Oncology ,medicine.disease_cause ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,medicine ,business.industry ,Evidence-based medicine ,Hepatology ,medicine.disease ,Surgery ,Regimen ,030220 oncology & carcinogenesis ,Position paper ,030211 gastroenterology & hepatology ,Liver function ,Active treatment ,business - Abstract
Purpose To develop, on behalf of Associazione Italiana di Oncologia Medica and Societa Italiana di Malattie Infettive e Tropicali, evidence-based and practical recommendations for the management of cancer patients who are Hepatitis C virus (HCV)-positive and are undergoing antitumor treatment. Methods Recommendations were generated by panel of experts selected by the boards of the Societies Associazione Italiana di Oncologia Medica and Societa Italiana di Malattie Infettive e Tropicali (4 oncologists and 6 infectious disease and hepatology specialist). The level of evidence and grade or recommendation was assessed according to the Grading of Recommendations Assessment, Development and Evaluation for practice guidelines [5] : A (high), B (moderate), and C (low), together with 2 recommendation levels: 1 (strong), and 2 (weak). Experts provided additional information, which helped greatly in clarifying some issues in the absence of clear-cut information from the literature. The final draft was then submitted to the evaluation of experts and the text modified according to their suggestion and comments. Results HCV screening rates are low in patients with malignancies. The risk of reactivation or exacerbation of hepatitis C is higher in patients receiving immunosuppressive agents. It may be difficult to discriminate naturally occurring cancer-related complications from true reactivation or exacerbation of hepatitis C and hepatotoxicity due to cancer treatment. No conclusive data are available concerning the appropriate monitoring of liver function and when an antiviral regimen should be proposed. Conclusions Patients at risk of any flare of HCV-related liver disease during active therapy for cancer should be managed with a multidisciplinary approach where all relevant diagnostic techniques and therapeutic resources are available. Prospective studies are needed to identify optimal strategies for the management of HCV infected cancer patients.
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- 2017
21. Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry
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Sze Hway Lim, Drupad Trivedi, Depanjan Sarkar, Joy Milne, Monty Silverdale, Perdita E. Barran, Caitlin Walton-Doyle, Kaneez Jafri, and Eleanor Sinclair
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Chromatography ,Training set ,Parkinson's disease ,Ion-mobility spectrometry ,Chemistry ,Matched control ,Disease progression ,medicine ,Treatment options ,Sample preparation ,Tandem mass spectrometry ,medicine.disease - Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.
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- 2020
22. Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology
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Elias Gialafos, Marco Metra, Johannes Backs, Davor Milicic, Gordana Krljanac, Andrew J.S. Coats, Johann Bauersachs, Jelena Celutkiene, Alexander R. Lyon, Ali Oto, Loreena Hill, Giuseppe Limongelli, Eloisa Arbustini, Stephan B. Felix, Tiny Jaarsma, Brenda Moura, Öztekin Oto, Christian Mueller, Marija Polovina, Arsen D. Ristić, Yuri Lopatin, Petar M. Seferovic, Hubert Seggewiss, Rudolf A. de Boer, Ovidiu Chioncel, Sinisa U. Pavlovic, Vladimir Kanjuh, Ivan Milinković, Carsten Tschöpe, Michael Arad, Dimitrios Farmakis, Massimo F Piepoli, Gerasimos Filippatos, Stefan D. Anker, Claudio Rapezzi, Jelena P. Seferovic, Ružica Maksimović, Lars Lund, Giuseppe M.C. Rosano, Alida L.P. Caforio, Aleš Linhart, Michel Noutsias, Frank Ruschitzka, Tuvia Ben Gal, Milika Asanin, Maurizio Volterrani, Wilfried Mullens, Seferovic, P. M., Polovina, M., Bauersachs, J., Arad, M., Gal, T. B., Lund, L. H., Felix, S. B., Arbustini, E., Caforio, A. L. P., Farmakis, D., Filippatos, G. S., Gialafos, E., Kanjuh, V., Krljanac, G., Limongelli, G., Linhart, A., Lyon, A. R., Maksimovic, R., Milicic, D., Milinkovic, I., Noutsias, M., Oto, A., Oto, O., Pavlovic, S. U., Piepoli, M. F., Ristic, A. D., Rosano, G. M. C., Seggewiss, H., Asanin, M., Seferovic, J. P., Ruschitzka, F., Celutkiene, J., Jaarsma, T., Mueller, C., Moura, B., Hill, L., Volterrani, M., Lopatin, Y., Metra, M., Backs, J., Mullens, W., Chioncel, O., de Boer, R. A., Anker, S., Rapezzi, C., Coats, A. J. S., Tschope, C., and Cardiovascular Centre (CVC)
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Male ,Cardiac & Cardiovascular Systems ,Peripartum cardiomyopathy ,Epidemiology ,medicine.medical_treatment ,Dilated cardiomyopathy ,030204 cardiovascular system & hematology ,0302 clinical medicine ,Restrictive cardiomyopathy ,Pregnancy ,Dilated cardiomyopathy, Epidemiology, Heart failure, Hypertrophic cardiomyopathy, Management, Natural history, Pathophysiology, Peripartum cardiomyopathy, Restrictive cardiomyopathy ,HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY ,1102 Cardiorespiratory Medicine and Haematology ,Cause of death ,Heart transplantation ,Cardiomyopathy, Restrictive ,Ejection fraction ,Hypertrophic cardiomyopathy ,Disease Management ,SURGICAL SEPTAL MYECTOMY ,3. Good health ,Management ,CARDIOVASCULAR MAGNETIC-RESONANCE ,Disease Progression ,Cardiology ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,Human ,Cardiomyopathy, Dilated ,medicine.medical_specialty ,OUTFLOW TRACT OBSTRUCTION ,LIGHT-CHAIN AMYLOIDOSIS ,Pregnancy Complications, Cardiovascular ,Natural history ,Heart failure ,Pathophysiology ,NO ,03 medical and health sciences ,VENTRICULAR SYSTOLIC FUNCTION ,Internal medicine ,medicine ,Humans ,PRIMARY DIAGNOSTIC INDICATIONS ,Puerperal Disorder ,Cardiomyopathie ,Science & Technology ,FUNCTIONAL MITRAL REGURGITATION ,SUBSEQUENT IMMUNOGLOBULIN SUBSTITUTION ,business.industry ,Stroke Volume ,Puerperal Disorders ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,Heart Transplantation ,business - Abstract
Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and similar to 10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.
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- 2019
23. Study of Flare Assessment in Systemic Lupus Erythematosus Based on Paper Patients
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Anca Askanase, Dafna D. Gladman, J. Romero-Diaz, Munther A. Khamashta, Asad Zoma, Diane L. Kamen, Susan Manzi, R. van Vollenhoven, Caroline Gordon, Murray B. Urowitz, Kristjan Steinsson, Jill P. Buyon, Ricard Cervera, Murat Inanc, Mary Anne Dooley, Jorge Sanchez-Guerrero, J. Sturgess, Christine A. Peschken, Guillermo Ruiz-Irastorza, Ellen M. Ginzler, Gunnar Sturfelt, J G Hanly, Ola Nived, Ann E. Clarke, David A. Isenberg, Joan T. Merrill, Anisur Rahman, Cynthia Aranow, Rosalind Ramsey-Goldman, Kenneth C. Kalunian, Daniel J. Wallace, B. Sang-Cheol, S. Sam Lim, Paul R. Fortin, Ian N. Bruce, Elizabeth Allen, Sasha Bernatsky, Søren Jacobsen, M. Petri, AII - Inflammatory diseases, Clinical Immunology and Rheumatology, Amsterdam Movement Sciences, Amsterdam institute for Infection and Immunity, Rheumatology, and CCA - Cancer immunology
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0301 basic medicine ,medicine.medical_specialty ,Consensus ,Severity of Illness Index ,Systemic Lupus Erythematosus ,Medical Records ,law.invention ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Case mix index ,Rheumatology ,law ,Predictive Value of Tests ,Internal medicine ,Surveys and Questionnaires ,Severity of illness ,medicine ,Journal Article ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,030203 arthritis & rheumatology ,Observer Variation ,Systemic lupus erythematosus ,Lupus erythematosus ,business.industry ,Medical record ,Reproducibility of Results ,medicine.disease ,Surgery ,030104 developmental biology ,Predictive value of tests ,Disease Progression ,Original Article ,Clinical Competence ,business ,Kappa ,Flare - Abstract
Objective: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. Methods: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. Results: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. Conclusion: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.
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- 2018
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24. Cross-sectional observation study to investigate the impact of risk-based stratification on care pathways for patients with chronic kidney disease: protocol paper
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Paul Cockwell, Anuradhaa Subramanian, Harjeet Kaur Bhachu, Melanie Calvert, Krishnarajah Nirantharakumar, and Derek Kyte
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Male ,Nephrology ,medicine.medical_treatment ,030232 urology & nephrology ,Nice ,0302 clinical medicine ,Risk Factors ,Protocol ,030212 general & internal medicine ,computer.programming_language ,education.field_of_study ,Renal Medicine ,General Medicine ,Middle Aged ,Prognosis ,Creatinine ,Population Surveillance ,Disease Progression ,Medicine ,Female ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,Referral ,Population ,end stage renal failure ,Risk Assessment ,Secondary Care ,Young Adult ,03 medical and health sciences ,chronic renal failure ,Internal medicine ,medicine ,Humans ,Renal replacement therapy ,Renal Insufficiency, Chronic ,education ,Intensive care medicine ,Aged ,Retrospective Studies ,business.industry ,Guideline ,medicine.disease ,United Kingdom ,Cross-Sectional Studies ,Observational study ,Morbidity ,business ,computer ,Biomarkers ,Follow-Up Studies ,Kidney disease - Abstract
IntroductionChronic kidney disease (CKD) management in the UK is usually primary care based, with National Institute for Health and Care Excellence (NICE) guidelines defining criteria for referral to secondary care nephrology services. Estimated glomerular filtration rate (eGFR) is commonly used to guide timing of referrals and preparation of patients approaching renal replacement therapy. However, eGFR lacks sensitivity for progression to end-stage renal failure; as a consequence, the international guideline group, Kidney Disease: Improving Global Outcomes has recommended the use of a risk calculator. The validated Kidney Failure Risk Equation may enable increased precision for the management of patients with CKD; however, there is little evidence to date for the implication of its use in routine clinical practice. This study will aim to determine the impact of the Kidney Failure Risk Equation on the redesignation of patients with CKD in the UK for referral to secondary care, compared with NICE CKD guidance.Method and analysisThis is a cross-sectional population-based observational study using The Health Improvement Network database to identify the impact of risk-based designation for referral into secondary care for patients with CKD in the UK. Adult patients registered in primary care and active in the database within the period 1 January 2016 to 31 March 2017 with confirmed CKD will be analysed. The proportion of patients who meet defined risk thresholds will be cross-referenced with the current NICE guideline recommendations for referral into secondary care along with an evaluation of urinary albumin–creatinine ratio monitoring.Ethics and disseminationApproval was granted by The Health Improvement Network Scientific Review Committee (Reference number: 18THIN061). Study outcomes will inform national and international guidelines including the next version of the NICE CKD guideline. Dissemination of findings will also be through publication in a peer-reviewed journal, presentation at conferences and inclusion in the core resources of the Think Kidneys programme.
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- 2019
25. A scoping review of mathematical models covering Alzheimer's disease progression.
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Moravveji, Seyedadel, Doyon, Nicolas, Mashreghi, Javad, and Duchesne, Simon
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ALZHEIMER'S disease ,MATHEMATICAL models ,DISEASE progression ,TAU proteins ,PARTIAL differential equations - Abstract
Alzheimer's disease is a complex, multi-factorial, and multi-parametric neurodegenerative etiology. Mathematical models can help understand such a complex problem by providing a way to explore and conceptualize principles, merging biological knowledge with experimental data into a model amenable to simulation and external validation, all without the need for extensive clinical trials. We performed a scoping review of mathematical models describing the onset and evolution of Alzheimer's disease as a result of biophysical factors following the PRISMA standard. Our search strategy applied to the PubMed database yielded 846 entries. After using our exclusion criteria, only 17 studies remained from which we extracted data, which focused on three aspects of mathematical modeling: how authors addressed continuous time (since even when the measurements are punctual, the biological processes underlying Alzheimer's disease evolve continuously), howmodels were solved, and how the high dimensionality and non-linearity of models were managed. Most articles modeled Alzheimer's disease at the cellular level, operating on a short time scale (e.g., minutes or hours), i.e., the micro view (12/17); the rest considered regional or brain-level processes with longer timescales (e.g., years or decades) (the macro view). Most papers were concerned primarily with amyloid beta (n = 8), few described both amyloid beta and tau proteins (n = 3), while some considered more than these two factors (n = 6). Models used partial differential equations (n = 3), ordinary differential equations (n = 7), and both partial differential equations and ordinary differential equations (n = 3). Some did not specify their mathematical formalism (n = 4). Sensitivity analyses were performed in only a small number of papers (4/17). Overall, we found that only two studies could be considered valid in terms of parameters and conclusions, and two more were partially valid. This puts the majority (n = 13) as being either invalid or with insufficient information to ascertain their status. This was themain finding of our paper, in that serious shortcomings make their results invalid or non-reproducible. These shortcomings come from insufficient methodological description, poor calibration, or the impossibility of experimentally validating or calibrating the model. Those shortcomings should be addressed by future authors to unlock the usefulness of mathematicalmodels in Alzheimer's disease. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Mild Alzheimer's disease: a 'position paper'
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Fati Nourhashemi, Mathieu Ceccaldi, Olivier Moreaud, J. F. Dartigues, P.J. Ousset, C. Mekies, Stéphane Lehéricy, Bruno Vellas, F. Puisieux, Thierry Voisin, Florence Pasquier, Serge Belliard, P. Robert, Bruno Dubois, Joël Belmin, François Blanchard, Sandrine Andrieu, Lionel Naccache, Jacques Touchon, J. Delrieu, Pierre Payoux, and B. Defontaines
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Pathology ,medicine.medical_specialty ,Medicine (miscellaneous) ,Disease ,Severity of Illness Index ,Cognition ,Alzheimer Disease ,Epidemiology ,medicine ,Dementia ,Humans ,Mass Screening ,Geriatric Assessment ,Mass screening ,Neuroradiology ,Aged ,Geriatrics ,Nutrition and Dietetics ,business.industry ,Mental Disorders ,medicine.disease ,Family medicine ,Disease Progression ,Position paper ,Geriatrics and Gerontology ,Alzheimer's disease ,business ,Biomarkers - Abstract
Under the auspices of the Societe Francaise de Geriatrie et Gerontologie, a multi-disciplinary group of specialists in geriatrics, neurology, epidemiology, psychiatry, neuroradiology and nuclear medicine met with the aim of drawing up references on the methods for diagnosing and treating mild Alzheimer's disease. The critical analysis of international literature, conducted by Professor Bruno Vellas for the scientific committee, has served to support study of the latest knowledge in 2008. The multi-disciplinary group met on 14 and 15 May 2008 in order to set out the questions that this study must answer and to allocate draft studies. Thus, it has been possible to conduct a study focused on mild Alzheimer's disease, giving particular attention to diagnostic procedure, specific methods of treatment and the benefits of making a diagnosis.
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- 2009
27. Critically appraised paper: A home-based standing frame program may improve motor function in people with progressive multiple sclerosis [synopsis].
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Plummer, Prudence
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COST effectiveness ,HOME care services ,MOTOR ability ,MULTIPLE sclerosis ,PHYSICAL therapy ,TREATMENT effectiveness ,DISEASE progression ,EVALUATION of human services programs - Abstract
The article inform people with progressive multiple sclerosis and expanded disability status scale scores are at the risk of physical inactivity, face barriers to adequate physical inactivity and require ongoing intervention to sustain the benefits of increased physical activity. Topic include comparison between standing frame intervention and other interventions for people with Expanded Disability Status Scale scores of 6.5 is warranted to assess the feasibility and cost-effectiveness.
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- 2021
- Full Text
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28. Use of paper selectively absorbing long wavelengths to reduce the impact of educational near work on human refractive development
- Author
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Stefanie Binder and Ronald H.H Kröger
- Subjects
Adult ,Paper ,Refractive error ,genetic structures ,Light ,Writing ,Color temperature ,Eye ,Refraction, Ocular ,Cellular and Molecular Neuroscience ,Near vision ,Optics ,Risk Factors ,Chromatic aberration ,medicine ,Myopia ,Focal length ,Near work ,Humans ,business.industry ,Accommodation, Ocular ,medicine.disease ,Original articles - Clinical science ,Sensory Systems ,Ophthalmology ,Wavelength ,Reading ,Disease Progression ,Optometry ,business ,Accommodation - Abstract
BACKGROUND/AIMS Educational near work has been identified as a major risk factor for the development of juvenile progressive myopia. A study was undertaken to determine whether differences in focal length resulting from longitudinal chromatic aberration of the eye can be exploited to reduce the impact of near work on refractive development. METHODS Infrared photorefraction was used to determine refractive states in young adult volunteers performing a task similar to reading and writing under various spectral environments. The potential benefits of the observed differences in accommodation demand were studied with a computational model of emmetropisation and myopia progression. RESULTS The refractive state was largely independent of the colour temperature of the illumination light (white paper) and the colour of commercially available papers (white illumination). Selective elimination of long wavelengths, however, significantly reduced the accommodation stimulus by about 0.5 dioptres. CONCLUSION Results from model calculations suggest that the use of paper which selectively absorbs long wavelengths may significantly reduce the myopiagenic effects of educational near work.
- Published
- 2000
29. Human papillomavirus vaccines: WHO position paper, May 2017
- Subjects
Male ,Time Factors ,Adolescent ,Drug Storage ,Papillomavirus Infections ,Uterine Cervical Neoplasms ,World Health Organization ,Immunocompromised Host ,Immunogenicity, Vaccine ,Sex Factors ,Seroconversion ,Disease Progression ,Humans ,Female ,Papillomavirus Vaccines ,Child ,Immunization Schedule - Published
- 2017
30. Magnetic resonance imaging T1- and T2-mapping to assess renal structure and function : a systematic review and statement paper
- Author
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Marcos Wolf, Gere Sunder-Plassmann, Anna Caroli, Peter Boor, Anneloes de Boer, Ewald Moser, Neil P. Jerome, Tim Leiner, and Kanishka Sharma
- Subjects
medicine.medical_specialty ,Relaxometry ,kidney ,relaxometry ,030232 urology & nephrology ,Urology ,Autosomal dominant polycystic kidney disease ,Renal function ,Reviews ,Kidney Volume ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,magnetic resonance imaging ,mapping ,Acute tubular necrosis ,Transplantation ,Kidney ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,Nephrology ,Practice Guidelines as Topic ,Disease Progression ,Kidney Diseases ,business ,Biomarkers ,chronic kidney disease ,Kidney disease - Abstract
This systematic review, initiated by the European Cooperation in Science and Technology Action Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease (PARENCHIMA), focuses on potential clinical applications of magnetic resonance imaging in renal non-tumour disease using magnetic resonance relaxometry (MRR), specifically, the measurement of the independent quantitative magnetic resonance relaxation times T1 and T2 at 1.5 and 3Tesla (T), respectively. Healthy subjects show a distinguishable cortico-medullary differentiation (CMD) in T1 and a slight CMD in T2. Increased cortical T1 values, that is, reduced T1 CMD, were reported in acute allograft rejection (AAR) and diminished T1 CMD in chronic allograft rejection. However, ambiguous findings were reported and AAR could not be sufficiently differentiated from acute tubular necrosis and cyclosporine nephrotoxicity. Despite this, one recent quantitative study showed in renal transplants a direct correlation between fibrosis and T1 CMD. Additionally, various renal diseases, including renal transplants, showed a moderate to strong correlation between T1 CMD and renal function. Recent T2 studies observed increased values in renal transplants compared with healthy subjects and in early-stage autosomal dominant polycystic kidney disease (ADPKD), which could improve diagnosis and progression assessment compared with total kidney volume alone in early-stage ADPKD. Renal MRR is suggested to be sensitive to renal perfusion, ischaemia/oxygenation, oedema, fibrosis, hydration and comorbidities, which reduce specificity. Due to the lack of standardization in patient preparation, acquisition protocols and adequate patient selection, no widely accepted reference values are currently available. Therefore this review encourages efforts to optimize and standardize (multi-parametric) protocols to increase specificity and to tap the full potential of renal MRR in future research. Copyright © 2018, Oxford University Press. Open Access. This article is available under the Creative Commons CC-BY-NC license and permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
- Published
- 2018
31. Additive quantile mixed effects modelling with application to longitudinal CD4 count data.
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Yirga AA, Melesse SF, Mwambi HG, and Ayele DG
- Subjects
- Adolescent, Adult, Aged, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Female, Follow-Up Studies, HIV Infections epidemiology, HIV Infections virology, Humans, Linear Models, Longitudinal Studies, Middle Aged, Prognosis, Risk Factors, South Africa epidemiology, Treatment Outcome, Viral Load, Young Adult, Anti-HIV Agents therapeutic use, Disease Progression, HIV, HIV Infections drug therapy, HIV Infections immunology
- Abstract
Quantile regression offers an invaluable tool to discern effects that would be missed by other conventional regression models, which are solely based on modeling conditional mean. Quantile regression for mixed-effects models has become practical for longitudinal data analysis due to the recent computational advances and the ready availability of efficient linear programming algorithms. Recently, quantile regression has also been extended to additive mixed-effects models, providing an efficient and flexible framework for nonparametric as well as parametric longitudinal forms of data analysis focused on features of the outcome beyond its central tendency. This study applies the additive quantile mixed model to analyze the longitudinal CD4 count of HIV-infected patients enrolled in a follow-up study at the Centre of the AIDS Programme of Research in South Africa. The objective of the study is to justify how the procedure developed can obtain robust nonlinear and linear effects at different conditional distribution locations. With respect to time and baseline BMI effect, the study shows a significant nonlinear effect on CD4 count across all fitted quantiles. Furthermore, across all fitted quantiles, the effect of the parametric covariates of baseline viral load, place of residence, and the number of sexual partners was found to be major significant factors on the progression of patients' CD4 count who had been initiated on the Highly Active Antiretroviral Therapy study., (© 2021. The Author(s).)
- Published
- 2021
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32. TOP CITED PAPERS IN INTERNATIONAL PSYCHOGERIATRICS: 6c. TRACKING COGNITIVE DECLINE IN ALZHEIMER'S DISEASE USING THE MINI-MENTAL STATE EXAMINATION: A META-ANALYSIS ('MINI' IS NOT NECESSARILY TRIVIAL!)
- Author
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Ling Han
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Psychometrics ,media_common.quotation_subject ,Applied psychology ,MEDLINE ,Developmental psychology ,Meta-Analysis as Topic ,Alzheimer Disease ,Gratitude ,medicine ,Humans ,Cognitive decline ,Aged ,media_common ,Aged, 80 and over ,Mini–Mental State Examination ,medicine.diagnostic_test ,Psychiatry and Mental health ,Clinical Psychology ,Expression (architecture) ,Disease Progression ,Tracking (education) ,Geriatrics and Gerontology ,Unavailability ,Cognition Disorders ,Mental Status Schedule ,Psychology ,Gerontology - Abstract
It was well beyond my expectations when I heard from Professor Ames that our meta-analysis paper (Han et al., 2000) was among the top-cited papers in International Psychogeriatrics. As an expression of my gratitude to the editor for the invitation and to the audience of this paper, I would like to offer this informal discussion on the background of the paper and extend a few ideas that were not conveyed fully at the time, due either to insufficient knowledge or unavailability of relevant data or methodologies.
- Published
- 2009
33. Transcriptomic analysis of castration, chemo-resistant and metastatic prostate cancer elucidates complex genetic crosstalk leading to disease progression.
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Mukherjee S and Sudandiradoss C
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- Gene Expression Profiling, Gene Regulatory Networks, Humans, Male, MicroRNAs genetics, Castration, Disease Progression, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Neoplastic, Neoplasm Metastasis genetics, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Transcriptome genetics
- Abstract
Prostate adenocarcinoma, with its rising numbers and high fatality rate, is a daunting healthcare challenge to clinicians and researchers alike. The mainstay of our meta-analysis was to decipher differentially expressed genes (DEGs), their corresponding transcription factors (TFs), miRNAs (microRNA) and interacting pathways underlying the progression of prostate cancer (PCa). We have chosen multiple datasets from primary, castration-resistant, chemo-resistant and metastatic prostate cancer stages for investigation. From our tissue-specific and disease-specific co-expression networks, fifteen hub genes such as ACTB, ACTN1, CDH1, CDKN1A, DDX21, ELF3, FLNA, FLNC, IKZF1, ILK, KRT13, KRT18, KRT19, SVIL and TRIM29 were identified and validated by molecular complex detection analysis as well as survival analysis. In our attempt to highlight hub gene-associated mutations and drug interactions, FLNC was found to be most commonly mutated and CDKN1A gene was found to have highest druggability. Moreover, from DAVID and gene set enrichment analysis, the focal adhesion and oestrogen signalling pathways were found enriched which indicates the involvement of hub genes in tumour invasiveness and metastasis. Finally by Enrichr tool and miRNet, we identified transcriptional factors SNAI2, TP63, CEBPB and KLF11 and microRNAs, namely hsa-mir-1-3p, hsa-mir-145-5p, hsa-mir-124-3p and hsa-mir-218-5p significantly controlling the hub gene expressions. In a nutshell, our report will help to gain a deeper insight into complex molecular intricacies and thereby unveil the probable biomarkers and therapeutic targets involved with PCa progression., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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34. Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper
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Paul Emery, Jean-François Nicolas, Mona Ståhle, Matthieu Allez, Lluís Puig, Carle Paul, P.C.M. van de Kerkhof, James G. Krueger, Cem Griffiths, Frank O. Nestle, Giampiero Girolomoni, and Jörg C. Prinz
- Subjects
medicine.medical_specialty ,Dermatology ,Disease ,Comorbidities ,early intervention ,management ,pathophysiology ,psoriasis ,Arthritis, Rheumatoid ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,Crohn Disease ,Psoriasis ,Intervention (counseling) ,Humans ,Medicine ,Dosing ,Intensive care medicine ,030304 developmental biology ,0303 health sciences ,business.industry ,medicine.disease ,Pathophysiology ,3. Good health ,Rheumatoid arthritis ,Disease Progression ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Physical therapy ,Immune-mediated inflammatory diseases ,business - Abstract
Contains fulltext : 155098.pdf (Publisher’s version ) (Open Access) Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely clear lesions. Treatment with systemic agents including biologics is often undertaken only when topical agents have proved unsuitable, even in patients with moderate to severe disease. However, there is evidence that in other IMIDs (rheumatoid arthritis and Crohn's disease), targeted systemic treatment given early in the treatment pathway may improve long-term patient outcomes. We hypothesize that a patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway ("early intervention") with the goal of complete clearance, may improve control of cutaneous symptoms and may also modify disease course and burden. Critical points to address when designing an early intervention study would include: the definition of psoriasis disease activity; patient selection; intervention selection; and dosing strategies.
- Published
- 2015
35. Recommendations for advance care planning in adults with congenital heart disease: a position paper from the ESC Working Group of Adult Congenital Heart Disease, the Association of Cardiovascular Nursing and Allied Professions (ACNAP), the European Association for Palliative Care (EAPC), and the International Society for Adult Congenital Heart Disease (ISACHD)
- Author
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Schwerzmann, Markus, Goossens, Eva, Gallego, Pastora, Kovacs, Adrienne H, Moons, Philip, Swan, Lorna, Tobler, Daniel, Stoutz, Noémi de, Gabriel, Harald, Greutmann, Matthias, Roos-Hesselink, Jolien W, Sobanski, Piotr Z, and Thomet, Corina
- Subjects
CONGENITAL heart disease ,NURSING ,DISEASE progression ,DEATH ,COMMUNICATION - Abstract
Survival prospects in adults with congenital heart disease (CHD), although improved in recent decades, still remain below expectations for the general population. Patients and their loved ones benefit from preparation for both unexpected and predictable deaths, sometimes preceded by a prolonged period of declining health. Hence, advance care planning (ACP) is an integral part of comprehensive care for adults with CHD. This position paper summarizes evidence regarding benefits of and patients' preferences for ACP and provides practical advice regarding the implementation of ACP processes within clinical adult CHD practice. We suggest that ACP be delivered as a structured process across different stages, with content dependent upon the anticipated disease progression. We acknowledge potential barriers to initiate ACP discussions and emphasize the importance of a sensitive and situation-specific communication style. Conclusions presented in this article reflect agreed expert opinions and include both patient and provider perspectives. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]
- Published
- 2020
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36. Lone Atrial Fibrillation: Does It Exist? A 'White Paper' of the Journal of the American College of Cardiology
- Author
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Wyse, D. George, Van Gelder, Isabelle C., Ellinor, Patrick T., Go, Alan S., Kalman, Jonathan M., Narayan, Sanjiv M., Nattel, Stanley, Schotten, Ulrich, and Rienstra, Michiel
- Subjects
Cardiac Resynchronization Therapy ,Heart Diseases ,Heart Conduction System ,Risk Factors ,Incidence ,Atrial Fibrillation ,Age Factors ,Disease Progression ,Humans ,Global Health ,Article - Abstract
The historical origin of the term "lone atrial fibrillation" (AF) predates by 60 years our current understanding of the pathophysiology of AF, the multitude of known etiologies for AF, and our ability to image and diagnose heart disease. The term was meant to indicate AF in patients for whom subsequent investigations could not demonstrate heart disease, but for many practitioners has become synonymous with "idiopathic AF." As the list of heart diseases has expanded and diagnostic techniques have improved, the prevalence of lone AF has fallen. The legacy of the intervening years is that definitions of lone AF in the literature are inconsistent so that studies of lone AF are not comparable. Guidelines provide a vague definition of lone AF but do not provide direction about how much or what kind of imaging and other testing are necessary to exclude heart disease. There has been an explosion in the understanding of the pathophysiology of AF in the last 20 years in particular. Nevertheless, there are no apparently unique mechanisms for AF in patients categorized as having lone AF. In addition, the term "lone AF" is not invariably useful in making treatment decisions, and other tools for doing so have been more thoroughly and carefully validated. It is, therefore, recommended that use of the term "lone AF" be avoided.
- Published
- 2014
37. Progression of Subclinical Vascular Damage in People Living With HIV Is Not Predicted by Current Cardiovascular Risk Scores: A Prospective 3-Year Study.
- Author
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Kapelios CJ, Argyris AA, Protogerou AD, Katsarolis I, Arida A, Papadopoulou M, Ntaroutsou E, Kitas G, Sfikakis PP, and Psichogiou M
- Subjects
- Anti-HIV Agents therapeutic use, Atherosclerosis, Biomarkers, Cardiovascular Diseases chemically induced, Carotid Artery Diseases epidemiology, Female, Greece, HIV Infections drug therapy, Humans, Male, Plaque, Atherosclerotic complications, Prospective Studies, Risk Assessment, Risk Factors, Anti-HIV Agents adverse effects, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Disease Progression, HIV Infections complications
- Abstract
Background: People living with HIV (PLWH) are at high cardiovascular disease (CVD) risk. Traditional CVD risk scores do not accurately reflect their CVD risk. Noninvasive subclinical vascular damage (SVD) biomarkers are valid surrogates of CVD and able to stratify CVD risk., Setting: We tested whether 4 widely applied CVD risk scores [Framingham (FRS), Atherosclerotic CVD, Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D), and Greek-specific European Society of Cardiology (ESC) risk scores] are associated with or detect the presence, incidence, and progression of arteriosclerosis, atheromatosis, and arterial hypertrophy in PLWH and uninfected individuals., Methods: We prospectively examined (at baseline and 3-year follow-up) 10 different arterial sites applying 5 different noninvasive vascular biomarkers and measured all 4 CVD risk scores at baseline., Results: In both PLWH (n = 138) and uninfected (n = 664) individuals, the CVD risk scores (except the ESC) performed differently but reasonably well in identifying the presence of SVD, but all scores failed to predict the incidence/progression of overall SVD. The most clinically useful biomarkers (carotid plaque/atheromatosis) revealed that in PLWH, only the FRS was able to stratify the progression (11% of the low-risk, 33.3% of the medium-risk, and 0% of the high-risk group)., Conclusions: This extensive vascular phenotyping study demonstrated the clear need to incorporate vascular imaging in CVD risk stratification, in addition to designing more accurate HIV-specific CVD risk models. The use of FRS would further enable treatment optimization and CVD prevention strategies in PLWH at medium CVD risk because one-third of carotid atheromatosis progresses within 3 years.
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- 2020
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38. Diagnosis of nonalcoholic fatty liver disease inchildren and adolescents: position paper of the ESPGHAN Hepatology Committee
- Author
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Ulrich Baumann, S. Lenta, F. Lacaille, Ozlem Durmaz, Anil Dhawan, Valerio Nobili, Valérie Anne Mclin, Patrick J. McKiernan, Piotr Socha, and Pietro Vajro
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Overweight ,Chronic liver disease ,Gastroenterology ,Liver Cirrhosis/complications/diagnosis/physiopathology ,Liver disease ,Liver Function Tests ,Non-alcoholic Fatty Liver Disease ,Fatty Liver/complications/diagnosis/epidemiology ,Risk Factors ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Prevalence ,Humans ,Genetic Predisposition to Disease ,Obesity ,Child ,ddc:618 ,medicine.diagnostic_test ,business.industry ,Fatty liver ,children ,histology ,imaging ,liver biopsy ,nonalcoholic fatty liver disease ,nonalcoholic steatohepatitis ,noninvasive biomarkers ,obesity-related liver disease ,adolescent ,child ,disease progression ,fatty liver ,female ,gastroenterology ,genetic predisposition to disease ,humans ,liver ,liver cirrhosis ,liver function tests ,male ,non-alcoholic fatty liver disease ,obesity ,prevalence ,risk factors ,united states ,pediatrics, perinatology and child health ,Hepatology ,medicine.disease ,United States/epidemiology ,United States ,Fatty Liver ,Liver ,Liver biopsy ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Obesity/complications/diagnosis/epidemiology ,Female ,medicine.symptom ,Liver/pathology ,Liver function tests ,business - Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents in the United States, and most probably also in the rest of the industrialized world.As the prevalence of NAFLD in childhood increases with the worldwide obesity epidemic, there is an urgent need for diagnostic standards that can be commonly used by pediatricians and hepatologists. To this end, we performed a PubMed search of the adult and pediatric literature on NAFLD diagnosis through May 2011 using Topics and/or relevant Authors as search words. According to the present literature, NAFLD is suspected based on the association of fatty liver combined with risk factors (mainly obesity), after the exclusion of other causes of liver disease. The reference but imperfect standard for confirming NAFLD is liver histology. The following surrogate markers are presently used to estimate degree of steatosis and liver fibrosis and risk of progression to end-stage liver disease: imaging by ultrasonography or magnetic resonance imaging, liver function tests, and serum markers of liver fibrosis.NAFLD should be suspected in all of the overweight or obese children and adolescents older than 3 years with increased waist circumference especially if there is a NAFLD history in relatives. The typical presentation, however, is in children ages 10 years and older. The first diagnostic step in these children should be abdominal ultrasound and liver function tests, followed by exclusion of other liver diseases. Overweight/obese children with normal ultrasonographic imaging and normal liver function tests should still be monitored due to the poor sensitivity of these tests at a single assessment.Indications for liver biopsy include the following: to rule out other treatable diseases, in cases of clinically suspected advanced liver disease, before pharmacological/surgical treatment, and as part of a structured intervention protocol or clinical research trial.
- Published
- 2012
39. Rapid cognitive decline in Alzheimer's disease. Consensus paper
- Author
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Soto, M. E., Andrieu, S., Arbus, C., Ceccaldi, Mathieu, Couratier, Philippe, Dantoine, Thierry, Dartigues, Jean-François, Gillette-Guyonnet, S., Nourashemi, Fati, Ousset, P.-J., Poncet, M., Portet, F., Touchon, J., Vellas, B., Service de médecine gériatrique, CHU Toulouse [Toulouse], Département d'épidémiologie et santé publique, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Epidémiologie et Analyses en Santé Publique : risques, maladies chroniques et handicap (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Service de psychatrie adulte, Service de neurologie, CHU Marseille, Service de Neurologie [CHU Limoges], CHU Limoges, Service de Médecine Gériatrique [CHU Limoges], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Département de neurologie [Montpellier], and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
- Subjects
Time Factors ,MESH: Humans ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,MESH: Time Factors ,MESH: Algorithms ,MESH: Cognition ,Cognition ,Alzheimer Disease ,Disease Progression ,Humans ,MESH: Disease Progression ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Algorithms ,MESH: Alzheimer Disease - Abstract
International audience; The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different "a priori" definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.
- Published
- 2008
40. Study of Flare Assessment in Systemic Lupus Erythematosus Based on Paper Patients.
- Author
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Isenberg, D., Sturgess, J., Allen, E., Aranow, C., Askanase, A., Sang-Cheol, B., Bernatsky, S., Bruce, I., Buyon, J., Cervera, R., Clarke, A., Dooley, Mary Anne, Fortin, P., Ginzler, E., Gladman, D., Hanly, J., Inanc, M., Jacobsen, S., Kamen, D., and Khamashta, M.
- Subjects
SYSTEMIC lupus erythematosus diagnosis ,CLINICAL competence ,COMPARATIVE studies ,CONSENSUS (Social sciences) ,DECISION making ,RESEARCH methodology ,MEDICAL cooperation ,MEDICAL records ,RESEARCH ,RESEARCH evaluation ,EVALUATION research ,PREDICTIVE tests ,RESEARCH bias ,SEVERITY of illness index ,DISEASE progression - Abstract
Objective: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus.Methods: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity.Results: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features.Conclusion: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved. [ABSTRACT FROM AUTHOR]- Published
- 2018
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41. Gene Dysregulations Driven by Somatic Copy Number Aberrations-Biological and Clinical Implications in Colon Tumors: A Paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology
- Author
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Bacolod, Manny D. and Barany, Francis
- Subjects
Chromosome Aberrations ,Colonic Neoplasms ,Disease Progression ,Gene Dosage ,Reviews ,Humans - Abstract
The majority of colorectal cancer (CRC) cases have chromosomal instability, in which the tumor genome is characterized by gross chromosomal aberrations such as gains in 20q, 13q, 8q, and 7, and losses in 4, 8p, 18q, and 17p. These somatic copy number changes (gains, losses, and somatic uniparental disomies) are crucial to CRC progression as they drive genes toward cancer-promoting (oncogenic or tumor suppressive) states. Numerous studies have shown that the loss of 18q or 8p is associated with poorer clinical outcome in CRCs. Either chromosomal arm may contain a tumor suppressor gene (or genes), whose deactivation by copy loss (loss of wild-type allele, decreased expression) can be crucial to the later stages of cancer progression. Our own integrated genomic analysis (single nucleotide polymorphism array, expression array) of more than 200 CRC tumor and normal samples indicates that the overall down-regulation of genes within the 8p or 18q arm is associated with lower survival rate. Among the often down-regulated, poor prognosis-associated 8p genes is MTUS1, whose gene product (a mitotic spindle-associated protein) was recently demonstrated to have a tumor suppressive property. Within 18q is ATP5A1, which codes for the catalytic a component of mitochondrial H(+)-ATP synthase. Like SMAD4 (also in 18q), the decreased expression of ATP5A1 appears to be a marker of unfavorable clinical outcome in CRCs.
- Published
- 2010
42. For which glaucoma suspects is it appropriate to initiate treatment? Article Type: AAO Meeting Paper Section/Category
- Subjects
Aged, 80 and over ,Family Health ,Consensus ,Delphi Technique ,Optic Disk ,Age Factors ,Glaucoma ,Middle Aged ,Sensitivity and Specificity ,Article ,Cornea ,Life Expectancy ,Risk Factors ,Optic Nerve Diseases ,Disease Progression ,Humans ,Ocular Hypertension ,Intraocular Pressure ,Aged ,Quality of Health Care - Abstract
Because uncertainty exists about which glaucoma suspects should be treated, this study sought to identify the glaucoma suspects who an expert panel could agree would be appropriate or inappropriate to treat.The RAND/UCLA appropriateness method, a well-established procedure to synthesize the scientific literature with expert opinion to resolve uncertainty on a health topic.Eleven-member panel composed of recognized international leaders in the field of glaucoma.Based on a systematic review of the literature on potentially important factors to consider when deciding to initiate treatment, more than 1000 scenarios of glaucoma suspects initially were created. The panel formally rated the appropriateness of initiating treatment for glaucoma suspects through a 2-round modified Delphi method, a technique that preserves the confidentiality of individual panelists'ratings but allows panelists to compare their own ratings with those of the entire panel.Final ratings for scenarios were categorized as appropriate, uncertain, or inappropriate to treat according to typical prespecified statistical criteria previously used in projects using the RAND/UCLA appropriateness method. Tools were developed to help clinicians to approximate the panel ratings of glaucoma suspects.The panel chose age, life expectancy, intraocular pressure (IOP), central corneal thickness, cup-to-disc ratio, disc size, and family history as the variables to consider when deciding whether to treat glaucoma suspects. Permutations of these variables created 1800 unique scenarios. The panel rated 587 (33%) scenarios as appropriate, 585 (33%) as uncertain, and 628 (35%) as inappropriate for treatment initiation. Analysis of variance determined that IOP had greater impact than any other variable on panel ratings. A point system was created with 96% sensitivity and 93% specificity for predicting panel ratings of appropriateness for a glaucoma suspect.An expert panel can reach agreement on the appropriateness and inappropriateness of treatment for glaucoma suspects.
- Published
- 2009
43. New Insights in Prebiotic Utilization: A Systematic Review.
- Author
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Arapović, Martina, Puljić, Leona, Kajić, Nikolina, Kartalović, Brankica, Habschied, Kristina, and Mastanjević, Krešimir
- Subjects
PREBIOTICS ,GUT microbiome ,FUNCTIONAL foods ,FOOD production ,PROBIOTICS ,DISEASE progression - Abstract
The hectic pace of modern life often leads to quick solutions, both in lifestyle and the choice of food we consume. The importance of the gut microbiome and its balance is being increasingly researched, with the prebiotic concept itself becoming a topic of scientific investigation. The aim of this paper is to analyze scientific studies on the understanding of prebiotics conducted between 2019 and 2024 in order to see what new knowledge, new sources, new ways of use, and newly established effects on certain disease states have been discovered during this period. The question that the authors are trying to answer is how specific prebiotics affect the growth and activity of selected probiotic strains in the human gut (have impact on gut microbiome) and what the implications of these interactions are. Four databases were searched: Pubmed/MEDLINE, Springerlink, Google Scholar, and Scopus. The keywords used were prebiotics, functional food, probiotics, gut microbiome, and trends. A systematic review of 30 scientific studies on the topic of prebiotics revealed significant advances in understanding and application. Research particularly indicates how prebiotics stimulate the growth of beneficial probiotic strains, such as Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, and Bifidobacterium. In addition, innovative approaches in food production, including pasta rich in prebiotic fibers, chocolate with inulin and stevia, and the use of fruit by-products, show promising results in creating "healthier" food options. Although the papers had differing objectives and research methodologies, certain similarities were found. All papers emphasized the importance of using prebiotics, although it depended on the type they come from and their impact on the gut microbiome, i.e., the stimulation of probiotic action within the gut microbiome, which consequently has benefits on health. This review serves as a springboard for further research in this exciting field, with the ultimate goal of harnessing the power of prebiotics to improve health outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. How does early chronic kidney disease progress? A background paper prepared for the UK Consensus Conference on early chronic kidney disease
- Author
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Wendy Metcalfe
- Subjects
Transplantation ,medicine.medical_specialty ,Pathology ,business.industry ,Life style ,medicine.medical_treatment ,Disease progression ,Consensus conference ,MEDLINE ,Renal function ,medicine.disease ,Nephrology ,Risk Factors ,Disease Progression ,Medicine ,Humans ,Kidney Failure, Chronic ,Hemodialysis ,business ,Intensive care medicine ,Life Style ,Kidney disease ,Glomerular Filtration Rate - Published
- 2007
45. Main editor’s comment to the paper: the response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. Stanislaw R. Burzynski, Tomasz J. Janicki, Gregory S. Burzynski, Ania Marszalek
- Author
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Concezio Di Rocco
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Male ,Oncology ,medicine.medical_specialty ,Pathology ,Adolescent ,Glutamine ,General problem ,Treatment outcome ,Benzeneacetamides ,Neoplasm Recurrence ,Pons ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Brainstem glioma ,Brain Stem Neoplasms ,Humans ,Medicine ,In patient ,Child ,Infusions, Intravenous ,Piperidones ,Phenylacetates ,business.industry ,Antineoplaston ,Disease progression ,Glioma ,General Medicine ,medicine.disease ,Survival Rate ,Drug Combinations ,Treatment Outcome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Female ,Neurology (clinical) ,Neoplasm Recurrence, Local ,business - Published
- 2014
46. Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling
- Author
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J N, Cohn, R, Ferrari, and N, Sharpe
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Heart Failure ,Cardiotonic Agents ,Ventricular Remodeling ,Heart Ventricles ,Adrenergic beta-Antagonists ,Angiotensin-Converting Enzyme Inhibitors ,Apoptosis ,Stroke Volume ,Treatment Outcome ,Echocardiography ,Disease Progression ,Humans ,Radionuclide Ventriculography ,Cell Division - Abstract
Cardiac remodeling is generally accepted as a determinant of the clinical course of heart failure (HF). Defined as genome expression resulting in molecular, cellular and interstitial changes and manifested clinically as changes in size, shape and function of the heart resulting from cardiac load or injury, cardiac remodeling is influenced by hemodynamic load, neurohormonal activation and other factors still under investigation. Although patients with major remodeling demonstrate progressive worsening of cardiac function, slowing or reversing remodeling has only recently become a goal of HF therapy. Mechanisms other than remodeling can also influence the course of heart disease, and disease progression may occur in other ways in the absence of cardiac remodeling. Left ventricular end-diastolic and end-systolic volume and ejection fraction data provide support for the beneficial effects of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents on the remodeling process. These agents also provide benefits in terms of morbidity and mortality. Although measurement of ejection fraction can reliably guide initiation of treatment in HF, opinions differ regarding the value of ejection fraction data in guiding ongoing therapy. The role of echocardiography or radionuclide imaging in the management and monitoring of HF is as yet unclear. To fully appreciate the potential benefits of HF therapies, clinicians should understand the relationship between remodeling and HF progression. Their patients may then, in turn, acquire an improved understanding of their disease and the treatments they are given.
- Published
- 2000
47. Diagnostic criteria for primary progressive multiple sclerosis: A position paper
- Author
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A J, Thompson, X, Montalban, F, Barkhof, B, Brochet, M, Filippi, D H, Miller, C H, Polman, V L, Stevenson, W I, McDonald, Thompson, Aj, Montalban, X, Barkhof, F, Brochet, B, Filippi, Massimo, Miller, Dh, Polman, Ch, Stevenson, Vl, and Mcdonald, Wi
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Diagnosis, Differential ,Disease Progression ,Evoked Potentials, Visual ,Humans ,Documentation ,Multiple Sclerosis, Chronic Progressive ,Evoked Potentials ,Magnetic Resonance Imaging - Abstract
The unique clinical characteristics of primary progressive multiple sclerosis (PPMS) pose particular diagnostic difficulties, both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS, which is not adequately addressed by current diagnostic criteria. This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS. (We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made.) Three levels of diagnostic certainty have been defined-definite, probable, and possible--based on clinical findings, abnormal cerebrospinal fluid, abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord, and evoked potentials. In definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required: (1) nine brain lesions, (2) two spinal cord lesions, or (3) four to eight brain lesions and one spinal cord lesion. Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS: 64% fulfilled the criteria for definite PPMS, 35% for probable PPMS, and only 1% for possible PPMS. These criteria now require prospective validation in a cohort of newly diagnosed patients and by postmortem examination.
- Published
- 2000
48. An Approach to Identify Individual Functional Single Nucleotide Polymorphisms and Isoform MicroRNAs.
- Author
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Wang, Ying, Ru, Jidong, Jin, Tao, Sun, Ming, Jia, Lizhu, and Sun, Guijiang
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BIOMARKERS ,COMPUTER software ,DISEASE susceptibility ,GENE expression ,GENES ,GENETIC polymorphisms ,HUMAN genome ,PAPER chromatography ,RISK assessment ,PHENOTYPES ,DISEASE progression ,INDIVIDUALIZED medicine ,MICRORNA ,SEQUENCE analysis - Abstract
MicroRNAs (miRNAs) and single nucleotide polymorphisms (SNPs) play important roles in disease risk and development, especially cancer. Importantly, when SNPs are located in pre-miRNAs, they affect their splicing mechanism and change the function of miRNAs. To improve disease risk assessment, we propose an approach and developed a software tool, IsomiR_Find, to identify disease/phenotype-related SNPs and isomiRs in individuals. Our approach is based on the individual's samples, with SNP information extracted from the 1000 Genomes Project. SNPs were mapped to pre-miRNAs based on whole-genome coordinates and then SNP-pre-miRNA sequences were constructed. Moreover, we developed matpred2, a software tool to identify the four splicing sites of mature miRNAs. Using matpred2, we identified isomiRs and then verified them by searching within individual miRNA sequencing data. Our approach yielded biomarkers for biological experiments, mined functions of miRNAs and SNPs, improved disease risk assessment, and provided a way to achieve individualized precision medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
49. Optimizing a Deep Residual Neural Network with Genetic Algorithm for Acute Lymphoblastic Leukemia Classification
- Author
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Larissa Ferreira Rodrigues, André Ricardo Backes, Bruno Augusto Nassif Travençolo, and Gina Maira Barbosa de Oliveira
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Original Paper ,Radiological and Ultrasound Technology ,Disease Progression ,Image Processing, Computer-Assisted ,Humans ,Bayes Theorem ,Radiology, Nuclear Medicine and imaging ,Neural Networks, Computer ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Child ,Computer Science Applications - Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide, and it is characterized by the production of immature malignant cells in the bone marrow. Computer vision techniques provide automated analysis that can help specialists diagnose this disease. Microscopy image analysis is the most economical method for the initial screening of patients with ALL, but this task is subjective and time-consuming. In this study, we propose a hybrid model using a genetic algorithm (GA) and a residual convolutional neural network (CNN), ResNet-50V2, to predict ALL using microscopy images available in ALL-IDB dataset. However, accurate prediction requires suitable hyperparameters setup, and tuning these values manually still poses challenges. Hence, this paper uses GA to find the best hyperparameters that lead to the highest accuracy rate in the models. Also, we compare the performance of GA hyperparameter optimization with Random Search and Bayesian optimization methods. The results show that GA optimization improves the accuracy of the classifier, obtaining 98.46% in terms of accuracy. Additionally, our approach sheds new perspectives on identifying leukemia based on computer vision strategies, which could be an alternative for applications in a real-world scenario.
- Published
- 2022
50. Neurophotonics: a comprehensive review, current challenges and future trends.
- Author
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Barros, Beatriz Jacinto and Cunha, João P. S.
- Subjects
TECHNOLOGICAL innovations ,NEURAL circuitry ,SYSTEMS design ,DISEASE progression ,DATA management ,OPTOGENETICS ,BRAIN-computer interfaces - Abstract
The human brain, with its vast network of billions of neurons and trillions of synapses (connections) between diverse cell types, remains one of the greatest mysteries in science and medicine. Despite extensive research, an understanding of the underlying mechanisms that drive normal behaviors and response to disease states is still limited. Advancement in the Neuroscience field and development of therapeutics for related pathologies requires innovative technologies that can provide a dynamic and systematic understanding of the interactions between neurons and neural circuits. In this work, we provide an up-to-date overview of the evolution of neurophotonic approaches in the last 10 years through a multi-source, literature analysis. From an initial corpus of 243 papers retrieved from Scopus, PubMed and WoS databases, we have followed the PRISMA approach to select 56 papers in the area. Following a full-text evaluation of these 56 scientific articles, six main areas of applied research were identified and discussed: (1) Advanced optogenetics, (2) Multimodal neural interfaces, (3) Innovative therapeutics, (4) Imaging devices and probes, (5) Remote operations, and (6) Microfluidic platforms. For each area, the main technologies selected are discussed according to the photonic principles applied, the neuroscience application evaluated and the more indicative results of efficiency and scientific potential. This detailed analysis is followed by an outlook of the main challenges tackled over the last 10 years in the Neurophotonics field, as well as the main technological advances regarding specificity, light delivery, multimodality, imaging, materials and system designs. We conclude with a discussion of considerable challenges for future innovation and translation in Neurophotonics, from light delivery within the brain to physical constraints and data management strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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