The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

Abstract

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990–2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep–wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population—all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

“…Contextually, a precise metabolic phenotyping based on individualized patient profile is crucial to improve individual outcomes in overall lung cancer prevention and treatments. To this end, all relevant demographic, socioeconomical, clinical, non-clinical, and metabolic parameters have to be considered for individualized patient profile such as described elsewhere for other systemic disorders [ 13 ]. Specific clinically relevant phenotypes can be exemplified such as the Flammer syndrome [ 14 ].…”

Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care—clinically relevant 3PM innovation

“… The functional link between FSF, systemic ischemic lesions, energy deficits, and compromized mitochondrial health is evidence-based and detailed in the peer-reviewed scientific literature [ 11 , 523 – 528 ]. Tear fluid analysis demonstrated a significantly decreased mitophagy level compared to the reference values in the corresponding group of age (the know-how of “3PMedicon GmbH” performing internationally validated tests) [ 529 ]; the methodology is described elsewhere [ 528 ]. Self-reported anxiety and chronic fatigue symptoms correlate well with the low mitophagy levels recorded.…”

“…The functional link between FSF, systemic ischemic lesions, energy deficits, and compromized mitochondrial health is evidence-based and detailed in the peer-reviewed scientific literature [ 11 , 523 – 528 ].…”

“… The functional link between overweight, metabolic syndrome, cascading complications on one hand, and, on the other hand, compromized mitochondrial health is evidence-based and detailed in the peer-reviewed scientific literature [ 1 , 2 ]. Tear fluid analysis demonstrated a significantly increased mitophagy level compared to the reference values in the corresponding group of age (the know-how of “3PMedicon GmbH” performing internationally validated tests) [ 529 ]; the methodology is described elsewhere [ 528 ]. Mitochondria-relevant nutraceuticals are considered supportive to stabilize health condition of the patient: CoQ 10 (anti-inflammatory effects, increases ECT efficacy, mitigates oxidative stress, protects mitochondrial health under pre/diabetic medical conditions), Ketogenic diet in combination with the L-carnitine supplement (promotes ß-oxidation pathways, protects against cascading complications associated with pre/diabetes), resveratrol (strong anti-inflammatory and anticancer effects), and either curcumin or silibinin (strong anti-inflammatory and anticancer protection).…”

“…Tear fluid analysis demonstrated a significantly increased mitophagy level compared to the reference values in the corresponding group of age (the know-how of “3PMedicon GmbH” performing internationally validated tests) [ 529 ]; the methodology is described elsewhere [ 528 ].…”