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Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?
Kooman, JP, Usvyat, LA, Dekker, MJE, Maddux, DW, Raimann, JG, van der Sande, FM, Ye, X, Wang, Y, Kotanko, P
Blood purification. 2019;(1-3):171-184
Abstract
Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.
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Innovations in personalised diabetes care and risk management.
Nijpels, G, Beulens, JW, van der Heijden, AA, Elders, PJ
European journal of preventive cardiology. 2019;(2_suppl):125-132
Abstract
Type 2 diabetes is associated with an increased risk of developing macro and microvascular complications. Nevertheless, there is substantial heterogeneity between people with type 2 diabetes in their risk of developing such complications. Personalised medicine for people with type 2 diabetes may aid in efficient and tailored diabetes care for those at increased risk of developing such complications. Recently, progress has been made in the development of personalised diabetes care in several areas. Particularly for the risk prediction of cardiovascular disease, retinopathy and nephropathy, innovative methods have been developed for prediction and tailored monitoring or treatment to prevent such complications. For other complications or subpopulations of people with type 2 diabetes, such as the frail elderly, efforts are currently ongoing to develop such methods. In this review, we discuss the recent developments in innovations of personalised diabetes care for different complications and subpopulations of people with type 2 diabetes, their performance and modes of application in clinical practice.
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Review article: biological mechanisms for symptom causation by individual FODMAP subgroups - the case for a more personalised approach to dietary restriction.
Wang, XJ, Camilleri, M, Vanner, S, Tuck, C
Alimentary pharmacology & therapeutics. 2019;(5):517-529
Abstract
BACKGROUND Due to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates-fructans, galacto-oligosaccharides, lactose, excess fructose and polyols-are thought to trigger gastrointestinal symptoms and are referred to collectively as "FODMAPs". AIMS To examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustment METHODS Recent literature was analysed via search databases including Medline, PubMed and Scopus. RESULTS Lactose, fructans and galacto-oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation. CONCLUSIONS While some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised "bottom-up" approach to the low-FODMAP diet, such as dietary restriction relevant to the patients' ethnicity, symptom profile and usual dietary intake.
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The Importance of School-based Healthy Living Initiatives: Introducing the Health and Wellness Academy Concept.
Strieter, L, Laddu, DR, Sainsbury, J, Arena, R
Progress in cardiovascular diseases. 2019;(1):68-73
Abstract
Over the last 15 years, the number of school and community based health-intervention programs in the United States has grown. Many of these programs aim to prevent non-communicable chronic disease diagnoses (e.g., obesity, cardiovascular disease and type-2 diabetes). The Department of Physical Therapy in the College of Applied Health Sciences (CAHS) at the University of Illinois at Chicago (UIC) created a school-based wellness program (SBWP) that focuses on nutrition and physical activity, providing tailored experiences that motivate adolescents to make healthier lifestyle choices. The SBWP began as a camp for children in the surrounding neighborhoods and implemented healthy living practices utilizing students from Departments in the CAHS. From this camp, the Health and Wellness Academy (HWA) evolved. This paper provides a review of school-based initiatives and introduces the UIC HWA, an innovative and reproducible approach that can bring positive environmental change by improving health outcomes for children and their families.
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5.
[Development of Stratified and Personalized Medicine Based on Pharmacogenomic and Pharmacokinetic Analyses].
Hirai, K
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2019;(10):1253-1258
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Abstract
To administer optimal and safe pharmacotherapy, development of stratified and personalized therapy is imperative. Pharmacogenomics (PGx) is useful in elucidating factors causing individual differences in drug efficacy and the emergence of adverse effects. It also helps design accurate drug administration methods by evaluating the effects of patient-related factors, such as genetic factors, that influence pharmacokinetics (PK) and pharmacodynamics (PD). In addition, selection of appropriate therapeutic agents requires the implementation of precision medicine allowing accurate disease diagnosis. To establish precision medicine, it is necessary to uncover the association of pathophysiological factors, which are represented as endotype or genotype, with the pathology of several phenotypes. This review describes two aspects related to realization of individualized medicine, namely the effectiveness of PK/PD/PGx studies and the stratification of pathological conditions. First, we conducted a PK/PD/PGx study with the aim to individualize warfarin treatment. In this study, we elucidated the effect of CYP4F2 polymorphisms associated with vitamin K metabolism by measuring the blood concentrations of warfarin and vitamin K. Then, to develop precision medicine for asthma and chronic obstructive pulmonary disease (COPD), we analyzed not only clinical symptoms but also pathological biomarkers and genes associated with inflammation. The findings may contribute toward better understanding of the pathological conditions of asthma, COPD, and asthma-COPD overlap.
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DERIVING PRIMARY CANCER CELL CULTURES FOR PERSONALIZED THERAPY.
Esparza-López, J, Martínez-Aguilar, JF, Ibarra-Sánchez, MJ
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2019;(6):369-380
Abstract
Cancer is the second-leading cause of death in the world, accounting for one out of six deaths. Consequently, there is an urgent need for new and more effective therapeutic options as well as drug screening methods. Immortal, "stable" cancer cell lines have been employed since the past century to assess drug response but face several disadvantages. They often accumulate new genetic aberrations due to long-term culture and lack the indisputable heterogeneity of solid tumors, therefore, compromising the recapitulation of molecular features from parental tumors. Primary cancer cells have emerged as an attractive alternative to commercial cell lines since they can preserve such properties more closely. Here, we provide an overview of the basic concepts underlying generation and characterization of primary cell cultures from tumor samples. We emphasize the advantages and disadvantages of using these types of cancer cell cultures, and we make a comparison with other types of cultures used for personalized therapy. Finally, we consider the use of primary cancer cell cultures in personalized therapy as a means to improve drug response prediction and therapeutic outcomes.
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The Role of the Gut Microbiome in Predicting Response to Diet and the Development of Precision Nutrition Models. Part II: Results.
Hughes, RL, Kable, ME, Marco, M, Keim, NL
Advances in nutrition (Bethesda, Md.). 2019;(6):979-998
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Abstract
The gut microbiota is increasingly implicated in the health and metabolism of its human host. The host's diet is a major component influencing the composition and function of the gut microbiota, and mounting evidence suggests that the composition and function of the gut microbiota influence the host's metabolic response to diet. This effect of the gut microbiota on personalized dietary response is a growing focus of precision nutrition research and may inform the effort to tailor dietary advice to the individual. Because the gut microbiota has been shown to be malleable to some extent, it may also allow for therapeutic alterations of the gut microbiota in order to alter response to certain dietary components. This article is the second in a 2-part review of the current research in the field of precision nutrition incorporating the gut microbiota into studies investigating interindividual variability in response to diet. Part I reviews the methods used by researchers to design and carry out such studies as well as analyze the results subsequently obtained. Part II reviews the findings of these studies and discusses the gaps in our current knowledge and directions for future research. The studies reviewed provide the current understanding in this field of research and a foundation from which we may build, utilizing and expanding upon the methods and results they present to inform future studies.
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Malnutrition-Wasting Conditions in Older Dialysis Patients: An Individualized Approach.
Hanafusa, N, Tsuchiya, K, Nitta, K
Contributions to nephrology. 2019;:12-20
Abstract
BACKGROUND The dialysis population is growing and aging worldwide. The aging dialysis population exhibits specific conditions, including sarcopenia, protein-energy wasting, and frailty, that are associated with worse outcomes. Thus, strategies to address these conditions are indispensable to improving prognosis, quality of life, and ability to perform activities of daily living in older patients. SUMMARY Several strategies have been employed to manage these conditions. The two major approaches are nutritional therapy and exercise training. These correlate strongly with each other and each is necessary to maintain the health of patients. Ensuring adequate protein and energy intake is the mainstay of nutritional therapy. However, older dialysis patients often have reduced appetite, and appropriate nutritional therapy can enhance appetite. Conversely, nutritional therapy without an appropriate exercise training system will fail to enhance physical function. Thus, the focus of attention has been on exercise training both during dialysis treatment and while at home. The Japanese Society of Renal Rehabilitation has issued a guideline for exercise training in patients with kidney disease. It encourages using the time during dialysis treatment for performing both nutritional intake measures and exercise training. Nutritional care in dialysis patients has previously focused on restriction of dietary intake. However, patients with these malnutrition-wasting conditions should be encouraged to improve their dietary intake and physical activity. Older dialysis patients have heterogenic characteristics in terms of frailty, so their nutritional and exercise plans should be individualized. Key Messages: Individualized management should be used in the heterogeneous older dialysis population, with special considerations for malnutrition-wasting conditions.
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Precision in Promoting Physical Activity and Exercise With the Overarching Goal of Moving More.
Ozemek, C, Arena, R
Progress in cardiovascular diseases. 2019;(1):3-8
Abstract
Physical inactivity is strongly associated with an unfavorable health profile, increasing an individual's risk for developing cardiovascular disease. Initiating a regular exercise routine contributes to improvements in cardiorespiratory fitness, body composition, resting blood pressure, blood glucose, and circulating lipoproteins. However, the extent to which positive changes occur come with significant inter-individual variability within intervention groups; non-responders and responders have been commonly identified across populations, highlighting that not all exercise regimens are universally effective in all individuals and should therefore not be treated as a "one-size fits all" prescription. Recent studies have therefore emphasized reporting the quantity of participants favorably and meaningfully "responding" to varying amounts and intensities of exercise, thereby presenting the opportunity to view exercise prescription in the context of precision medicine. This review will address the impact of varying amounts and intensities of physical activity and exercise, highlighting their impact on key health metrics.
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Individualized Hemodialysis Treatment: A Perspective on Residual Kidney Function and Precision Medicine in Nephrology.
Hur, I, Lee, YK, Kalantar-Zadeh, K, Obi, Y
Cardiorenal medicine. 2019;(2):69-82
Abstract
BACKGROUND Residual kidney function (RKF) is often expected to inevitably and rapidly decline among hemodialysis patients and, hence, has been inadvertently ignored in clinical practice. The importance of RKF has been revisited in some recent studies. Given that patients with end-stage renal disease now tend to initiate maintenance hemodialysis therapy with higher RKF levels, there seem to be important opportunities for incremental hemo-dialysis by individualizing the dose and frequency according to their RKF levels. This approach is realigned with precision medicine and patient-centeredness. SUMMARY In this article, we first review the available methods to estimate RKF among hemodialysis patients. We then discuss the importance of maintaining and monitoring RKF levels based on a variety of clinical aspects, including volume overload, blood pressure control, mineral and bone metabolism, nutrition, and patient survival. We also review several potential measures to protect RKF: the use of high-flux and biocompatible membranes, the use of ultrapure dialysate, the incorporation of hemodiafiltration, incremental hemodialysis, and a low-protein diet, as well as general care such as avoiding nephrotoxic events, maintaining appropriate blood pressure, and better control of mineral and bone disorder parameters. Key Message: Individualized hemodialysis regimens may maintain RKF, lead to a better quality of life without compromising long-term survival, and ensure precision medicine and patient-centeredness in nephrology practice.