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1.
The Future of Uterine Fibroid Management: a More Preventive and Personalized Paradigm.
El Sabeh, M, Borahay, MA
Reproductive sciences (Thousand Oaks, Calif.). 2021;(11):3285-3288
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Abstract
Uterine fibroids are the most common tumors of the female reproductive tract, affecting up to 80% of women. Despite their heavy burden and high prevalence, available medical treatment options are limited and are offered to patients assuming equal responsiveness. These benign tumors are complex, originating from potentially diverse pathobiologic processes, yet they are all managed in a rather standardized symptom-oriented approach that does not take into account the underlying processes. With our increasing understanding of the interplay between genes, epigenetics, individual's lifestyle, and the environment in disease development, uterine fibroid management should be geared towards individualized preventive and treatment options. For example, it seems that some subsets of patients with fibroids also suffer from vitamin D deficiency, hypertension, metabolic syndrome, or other conditions. It is possible that these subsets may have different underlying processes and different responsiveness to different treatment options. Herein, we call for a futuristic paradigm shift of research to develop a new model to manage uterine fibroids with the treatment approach varying depending on the patient's perceived underlying processes as assessed by medical, social, family history, and relevant investigations. This is only possible through the collaboration of scientists, physicians, and funding agencies and with the help of our patients.
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2.
Genetically Guided Mediterranean Diet for the Personalized Nutritional Management of Type 2 Diabetes Mellitus.
Gkouskou, K, Lazou, E, Skoufas, E, Eliopoulos, AG
Nutrients. 2021;(2)
Abstract
The current consensus for the prevention and management of type 2 diabetes mellitus (T2DM) is that high-quality diets and adherence to a healthy lifestyle provide significant health benefits. Remarkably, however, there is little agreement on the proportions of macronutrients in the diet that should be recommended to people suffering from pre-diabetes or T2DM. We herein discuss emerging evidence that underscores the importance of gene-diet interactions in the improvement of glycemic biomarkers in T2DM. We propose that we can achieve better glycemic control in T2DM patients by coupling Mediterranean diets to genetic information as a predictor for optimal diet macronutrient composition in a personalized manner. We provide evidence to support this concept by presenting a case study of a T2DM patient who achieved rapid glycemic control when adhered to a personalized, genetically-guided Mediterranean Diet.
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3.
Asthma in the Precision Medicine Era: Biologics and Probiotics.
Chiu, CJ, Huang, MT
International journal of molecular sciences. 2021;(9)
Abstract
Asthma is a major global health issue. Over 300 million people worldwide suffer from this chronic inflammatory airway disease. Typical clinical symptoms of asthma are characterized by a recurrent wheezy cough, chest tightness, and shortness of breath. The main goals of asthma management are to alleviate asthma symptoms, reduce the risk of asthma exacerbations, and minimize long-term medicinal adverse effects. However, currently available type 2 T helper cells (Th2)-directed treatments are often ineffective due to the heterogeneity of the asthma subgroups, which manifests clinically with variable and poor treatment responses. Personalized precision therapy of asthma according to individualized clinical characteristics (phenotype) and laboratory biomarkers (endotype) is the future prospect. This mini review discusses the molecular mechanisms underlying asthma pathogenesis, including the hot sought-after topic of microbiota, add-on therapies and the potential application of probiotics in the management of asthma.
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4.
Metabolic consequences of obesity and type 2 diabetes: Balancing genes and environment for personalized care.
Pillon, NJ, Loos, RJF, Marshall, SM, Zierath, JR
Cell. 2021;(6):1530-1544
Abstract
The prevalence of type 2 diabetes and obesity has risen dramatically for decades and is expected to rise further, secondary to the growing aging, sedentary population. The strain on global health care is projected to be colossal. This review explores the latest work and emerging ideas related to genetic and environmental factors influencing metabolism. Translational research and clinical applications, including the impact of the COVID-19 pandemic, are highlighted. Looking forward, strategies to personalize all aspects of prevention, management and care are necessary to improve health outcomes and reduce the impact of these metabolic diseases.
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5.
Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers.
Norwitz, NG, Saif, N, Ariza, IE, Isaacson, RS
Nutrients. 2021;(4)
Abstract
The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer's disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer's disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood-brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer's risk reduction.
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6.
Machine learning and network medicine: a novel approach for precision medicine and personalized therapy in cardiomyopathies.
Infante, T, Francone, M, De Rimini, ML, Cavaliere, C, Canonico, R, Catalano, C, Napoli, C
Journal of cardiovascular medicine (Hagerstown, Md.). 2021;(6):429-440
Abstract
The early identification of pathogenic mechanisms is essential to predict the incidence and progression of cardiomyopathies and to plan appropriate preventive interventions. Noninvasive cardiac imaging such as cardiac computed tomography, cardiac magnetic resonance, and nuclear imaging plays an important role in diagnosis and management of cardiomyopathies and provides useful prognostic information. Most molecular factors exert their functions by interacting with other cellular components, thus many diseases reflect perturbations of intracellular networks. Indeed, complex diseases and traits such as cardiomyopathies are caused by perturbations of biological networks. The network medicine approach, by integrating systems biology, aims to identify pathological interacting genes and proteins, revolutionizing the way to know cardiomyopathies and shifting the understanding of their pathogenic phenomena from a reductionist to a holistic approach. In addition, artificial intelligence tools, applied to morphological and functional imaging, could allow imaging scans to be automatically analyzed to extract new parameters and features for cardiomyopathy evaluation. The aim of this review is to discuss the tools of network medicine in cardiomyopathies that could reveal new candidate genes and artificial intelligence imaging-based features with the aim to translate into clinical practice as diagnostic, prognostic, and predictive biomarkers and shed new light on the clinical setting of cardiomyopathies. The integration and elaboration of clinical habits, molecular big data, and imaging into machine learning models could provide better disease phenotyping, outcome prediction, and novel drug targets, thus opening a new scenario for the implementation of precision medicine for cardiomyopathies.
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7.
Pasireotide in the Personalized Treatment of Acromegaly.
Puig-Domingo, M, Bernabéu, I, Picó, A, Biagetti, B, Gil, J, Alvarez-Escolá, C, Jordà, M, Marques-Pamies, M, Soldevila, B, Gálvez, MA, et al
Frontiers in endocrinology. 2021;:648411
Abstract
The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.
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8.
Personalized medicine in lipid-modifying therapy.
Tomlinson, B, Lin, CH, Chan, P, Lam, CW
Personalized medicine. 2021;(2):185-203
Abstract
The choice of lipid-modifying treatment is largely based on the absolute level of cardiovascular risk and baseline lipid profile. Statins are the first-line treatment for most patients requiring reduction of low-density-lipoprotein cholesterol (LDL-C) and ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors can be added to reach LDL-C targets. Statins have some adverse effects that are somewhat predictable based on phenotypic and genetic factors. Fibrates or omega-3 fatty acids can be added if triglyceride levels remain elevated. The RNA-targeted therapeutics in development offer the possibility of selective liver targeting for specific lipoproteins such as lipoprotein(a) and long-term reduction of LDL-C with infrequent administration of a small-interfering RNA may help to overcome the problem of adherence to therapy.
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9.
The 2019 ESPEN Arvid Wretlind lecture perioperative nutritional and metabolic care: Patient-tailored or organ-specific approach?
Gianotti, L, Sandini, M
Clinical nutrition (Edinburgh, Scotland). 2020;(8):2347-2357
Abstract
BACKGROUND & AIM: The perioperative severe changes in the nutritional and metabolic homeostasis are, by some means, proportional to the extent of tissue injury and magnitude of operative trauma. An adequate qualitative and quantitative replacement of nutritional substrates are of utmost importance to facilitate proper tissue healing and recovery and maintenance of organ function after surgery. METHODS The present manuscript has been planned to put the most recent research of the Milano-Bicocca University surgical working group in the context of a more personalized nutritional therapy and metabolic care for surgical patients. Particular prominence has been given to major pancreatic resections because these surgeries are among the most complex and challenging operations for the degree of parenchyma resection and tissue dissection, the consequent overall injury, and the fairly high rate of major complications resulting in a catabolic response. RESULTS Anthropometric parameters and particularly sarcopenia, visceral obesity - and their relative proportion -, are strongly associated with poor outcome after pancreatic surgery. Adequate perioperative nutritional therapy is of utmost importance in affecting morbidity. Long-term nutritional and metabolic sequelae, caused by exocrine pancreatic insufficiency, need to be promptly recognized and treated with an adequate enzyme supplementation. CONCLUSIONS There is strong evidence sustaining the necessity of proper perioperative metabolic and nutritional care into the management of patients undergoing major pancreatic surgery.
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10.
Small molecules under development for psoriasis: on the road to the individualized therapies.
Claudia, CD, María-Elena, VH, Josué, VE, María-Carmen, BC, Alain-Raimundo, RO, Martha-Estrella, GP
Archives of dermatological research. 2020;(9):611-627
Abstract
Psoriasis is an incurable cutaneous illness characterized by the presence of well-delimited reddish plaques and silvery-white dry scales. So far, there is a limited understanding of its pathogenesis, though recent discoveries on the immunological, genetic and molecular aspects of this disease have significantly contributed to the identification of new targets and the development of novel drugs. Despite these advances, many patients are still dissatisfied, so to improve patient satisfaction, reliability, and clinical outcomes, the individualization of the treatments for this disease becomes a necessity. This review summarizes recent findings related to psoriasis pathogenesis and describes new small molecules and targets recently identified as promising for treatments. Additionally, the current status, challenges and the future directions for achieving individualized therapy for this disease and the need for more collaborative studies are discussed. The individualization of treatments for psoriasis, rather than a goal, is analyzed as a process where a dynamic integration between the needs and characteristics of the patients, the pharmacological progress, and the clinical decisions takes place.