Mediterranean diet in the targeted prevention and personalized treatment of chronic diseases: evidence, potential mechanisms, and prospects.

The prevalence of chronic diseases is currently a major public health issue worldwide and is exploding with the population growth and aging. Dietary patterns are well known to play a important role in our overall health and well-being, and therefore, poor diet and malnutrition are among the most critical risk factors for chronic disease. Thus, dietary recommendation and nutritional supplementation have significant clinical implications for the targeted treatment of some of these diseases. Multiple dietary patterns have been proposed to prevent chronic disease incidence, like Dietary Approaches to Stop Hypertension (DASH) and Diabetes Risk Reduction Diet (DRRD). Among them, the MedDiet, which is one of the most well-known and studied dietary patterns in the world, has been related to a wide extent of health benefits. Substantial evidence has supported an important reverse association between higher compliance to MedDiet and the risk of chronic disease. Innovative strategies within the healthcare framework of predictive, preventive, and personalized medicine (PPPM/3PM) view personalized dietary customization as a predictive medical approach, cost-effective preventive measures, and the optimal dietary treatment tailored to the characteristics of patients with chronic diseases in primary and secondary care. Through a comprehensive collection and review of available evidence, this review summarizes health benefits of MedDiet in the context of PPPM/3PM for chronic diseases, including cardiovascular disease, hypertension, type 2 diabetes, obesity, metabolic syndrome, osteoporosis, and cancer, thereby a working hypothesis that MedDiet can personalize the prevention and treatment of chronic diseases was derived.

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.

Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease). The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches. Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles-all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00357-5.

Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations.

Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles-all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.

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.

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.

XEN® 45 en el manejo quirúrgico del glaucoma en fases tempranas: estudio nacional de consenso según metodología Delphi / XEN-45 in the management of Early Glaucoma Surgery: A National Delphi Consensus Study

Antecedentes y objetivo: Las recomendaciones sobre el manejo general del glaucoma y el uso de cirugías mínimamente-invasivas y microincisionales en fases tempranas son limitadas. El objetivo de este estudio fue establecer un consenso sobre el manejo del glaucoma, centrándose en el implante XEN 45 (AbbVie Inc., North Chicago, IL, EE. UU.). Métodos: Se utilizó un método Delphi. El comité científico dirigió el estudio, identificó el panel de expertos y participó en la elaboración del cuestionario. Se invitó a 51 expertos a completar, en una escala Likert de 9 puntos, un cuestionario de 89 ítems que cubría 3 bloques temáticos. Se realizaron 2 rondas Delphi. Se logró consenso si≥66,6% de los expertos llegaron a un acuerdo o desacuerdo. Resultados: Los panelistas acordaron 84 ítems relacionados con la calidad de vida, el algoritmo terapéutico y el perfil del paciente, y el manejo quirúrgico pre y postoperatorio. Los panelistas consideraron el implante XEN idóneo para tratar el glaucoma en diferentes etapas y para diferentes perfiles de pacientes: pacientes jóvenes/ancianos/con comorbilidades-significativas, glaucoma-miópico, pacientes con fracaso quirúrgico previo y con postoperatorio complejo. El implante XEN se consideró un paso terapéutico previo a la cirugía filtrante clásica y una posible primera opción quirúrgica en pacientes ancianos con comorbilidades y presión intraocular descontrolada. El implante XEN permite al paciente retomar sus actividades diarias más rápidamente que las cirugías filtrantes convencionales y reducir y/o eliminar los tratamientos tópicos. Conclusiones: Este consenso según la metodología Delphi proporcionó una serie de recomendaciones generales para el tratamiento del glaucoma, incluidas aquellas relacionadas con la calidad de vida del paciente, el algoritmo terapéutico y el perfil del paciente, y específicas con respecto al uso del implante XEN.(AU)

Background and objective: Recommendations on general glaucoma management and the use of early minimally invasive and microincisional surgeries are limited. This study aimed to establish consensus regarding glaucoma management, focusing on the XEN-45 gel stent implant. Methods: A Delphi consensus-driven process was used. The scientific committee led the study, identified the expert panel, and participated in elaborating the questionnaire. Fifty-one panelists were invited to complete, on a nine-point Likert scale, an 89-item questionnaire covering three topic blocks. Two Delphi rounds were performed. Consensus was achieved if ≥66.6% of panelists reached agreement or disagreement. Results: Panelists agreed on 84 items related to the patients’ quality of life, the therapeutic algorithm and patient profile, and surgical and pre- and post-operative management. Panelists agreed on the suitability of XEN stent implants to treat glaucoma at different stages and for different patient profiles: young patients, elderly or with significant comorbidities, and with myopic glaucoma, patients who failed previous surgeries, and with previous poor post-operative experience. XEN surgery was considered a therapeutic step prior to classic filtering surgery and a possible first surgical option in elderly patients with comorbidities and uncontrolled intraocular pressure. XEN surgery allows the patient to return to routine daily activities faster than conventional filtering surgeries and to reduce and/or eliminate topical treatments. Conclusions: This Delphi-driven consensus resulted in a series of general recommendations for glaucoma management, including those related to patient quality of life, therapeutic algorithm, and patient profile, and specific ones regarding the use of XEN stent gel surgery.(AU)

Personalized Drug Therapy: Innovative Concept Guided With Proteoformics.

Personalized medicine can reduce adverse effects, enhance drug efficacy, and optimize treatment outcomes, which represents the essence of personalized medicine in the pharmacy field. Protein drugs are crucial in the field of personalized drug therapy and are currently the mainstay, which possess higher target specificity and biological activity than small-molecule chemical drugs, making them efficient in regulating disease-related biological processes, and have significant potential in the development of personalized drugs. Currently, protein drugs are designed and developed for specific protein targets based on patient-specific protein data. However, due to the rapid development of two-dimensional gel electrophoresis and mass spectrometry, it is now widely recognized that a canonical protein actually includes multiple proteoforms, and the differences between these proteoforms will result in varying responses to drugs. The variation in the effects of different proteoforms can be significant and the impact can even alter the intended benefit of a drug, potentially making it harmful instead of lifesaving. As a result, we propose that protein drugs should shift from being targeted through the lens of protein (proteomics) to being targeted through the lens of proteoform (proteoformics). This will enable the development of personalized protein drugs that are better equipped to meet patients' specific needs and disease characteristics. With further development in the field of proteoformics, individualized drug therapy, especially personalized protein drugs aimed at proteoforms as a drug target, will improve the understanding of disease mechanisms, discovery of new drug targets and signaling pathways, provide a theoretical basis for the development of new drugs, aid doctors in conducting health risk assessments and making more cost-effective targeted prevention strategies conducted by artificial intelligence/machine learning, promote technological innovation, and provide more convenient treatment tailored to individualized patient profile, which will benefit the affected individuals and society at large.

XEN-45 in the management of early glaucoma surgery: A national Delphi consensus study.

BACKGROUND AND OBJECTIVE: Recommendations on general glaucoma management and the use of early minimally invasive and microincisional surgeries are limited. This study aimed to establish consensus regarding glaucoma management, focusing on the XEN-45 gel stent implant. METHODS: A Delphi consensus-driven process was used. The scientific committee led the study, identified the expert panel, and participated in elaborating the questionnaire. Fifty-one panelists were invited to complete, on a nine-point Likert scale, an 89-item questionnaire covering three topic blocks. Two Delphi rounds were performed. Consensus was achieved if ≥66.6% of panelists reached agreement or disagreement. RESULTS: Panelists agreed on 84 items related to the patients' quality of life, the therapeutic algorithm and patient profile, and surgical and pre- and post-operative management. Panelists agreed on the suitability of XEN stent implants to treat glaucoma at different stages and for different patient profiles: young patients, elderly or with significant comorbidities, and with myopic glaucoma, patients who failed previous surgeries, and with previous poor post-operative experience. XEN surgery was considered a therapeutic step prior to classic filtering surgery and a possible first surgical option in elderly patients with comorbidities and uncontrolled intraocular pressure. XEN surgery allows the patient to return to routine daily activities faster than conventional filtering surgeries and to reduce and/or eliminate topical treatments. CONCLUSIONS: This Delphi-driven consensus resulted in a series of general recommendations for glaucoma management, including those related to patient quality of life, therapeutic algorithm, and patient profile, and specific ones regarding the use of XEN stent gel surgery.

Nitroproteomics is instrumental for stratification and targeted treatments of astrocytoma patients: expert recommendations for advanced 3PM approach with improved individual outcomes.

Protein tyrosine nitration is a selectively and reversible important post-translational modification, which is closely related to oxidative stress. Astrocytoma is the most common neuroepithelial tumor with heterogeneity and complexity. In the past, the diagnosis of astrocytoma was based on the histological and clinical features, and the treatment methods were nothing more than surgery-assisted radiotherapy and chemotherapy. Obviously, traditional methods short falls an effective treatment for astrocytoma. In late 2021, the World Health Organization (WHO) adopted molecular biomarkers in the comprehensive diagnosis of astrocytoma, such as IDH-mutant and DNA methylation, which enabled the risk stratification, classification, and clinical prognosis prediction of astrocytoma to be more correct. Protein tyrosine nitration is closely related to the pathogenesis of astrocytoma. We hypothesize that nitroproteome is significantly different in astrocytoma relative to controls, which leads to establishment of nitroprotein biomarkers for patient stratification, diagnostics, and prediction of disease stages and severity grade, targeted prevention in secondary care, treatment algorithms tailored to individualized patient profile in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Nitroproteomics based on gel electrophoresis and tandem mass spectrometry is an effective tool to identify the nitroproteins and effective biomarkers in human astrocytomas, clarifying the biological roles of oxidative/nitrative stress in the pathophysiology of astrocytomas, functional characteristics of nitroproteins in astrocytomas, nitration-mediated signal pathway network, and early diagnosis and treatment of astrocytomas. The results finds that these nitroproteins are enriched in mitotic cell components, which are related to transcription regulation, signal transduction, controlling subcellular organelle events, cell perception, maintaining cell homeostasis, and immune activity. Eleven statistically significant signal pathways are identified in astrocytoma, including remodeling of epithelial adherens junctions, germ cell-sertoli cell junction signaling, 14-3-3-mediated signaling, phagosome maturation, gap junction signaling, axonal guidance signaling, assembly of RNA polymerase III complex, and TREM1 signaling. Furthermore, protein tyrosine nitration is closely associated with the therapeutic effects of protein drugs, and molecular mechanism and drug targets of cancer. It provides valuable data for studying the protein nitration biomarkers, molecular mechanisms, and therapeutic targets of astrocytoma towards PPPM (3P medicine) practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00348-y.

A holistic profile for cancer-related fatigue for women with breast cancer - a qualitative study.

Objective: Cancer- related fatigue (CRF) is one of the most reported long-term effects after breast cancer and severely impacts quality of life. To come towards optimal treatment of multidimensional CRF, the first step is to use a holistic approach to develop a holistic patient profile including the patient's experience and impact of CRF on their life. Methods and measures: Four semi- structured focus groups with twenty- seven breast cancer patients and fourteen interviews with healthcare professionals (HCPs) were held. Reflexive thematic analysis was used to define (sub)themes for the holistic patient profile. The themes of the interviews and focus groups were compared for validity. Results: Breast cancer patients and HCPs described the same five major themes, consisting of experience of CRF, impact and consequences, coping, personality, and CRF treatment. Experience of CRF consists of cognitive, emotional, and physical aspects. Impact and consequences include work, family, partner relation, social contact and hobbies, body, and misunderstanding. Coping consists of twelve (mal)adaptive strategies. Personality and CRF treatment were summarised as themes. Conclusions: A first holistic patient profile was introduced for CRF for breast cancer. This profile can be conceptualized into a questionnaire to collect information for personalized treatment recommendations and monitoring of CRF over time.

Evolución del diagnóstico y tratamiento de la nefritis lúpica en España / Evolution of diagnosis and treatment for lupus nephritis in Spain

La nefritis lúpica (NL) es una manifestación grave del lupus eritematoso sistémico que puede llevar a una enfermedad renal terminal. La mayor parte de los datos clínicos y pronósticos que manejamos, y sobre los que tomamos decisiones terapéuticas, proceden de cohortes internacionales con importantes diferencias étnicas y relativas al pronóstico renal. Para conocer los datos clínicos y pronósticos de los pacientes con NL en España se realizó una búsqueda bibliográfica de artículos relacionados con la NL publicados por autores españoles en revistas nacionales e internacionales entre 2005 y 2022. Las referencias seleccionadas mostraron que la biopsia no solo es clave en el diagnóstico de la NL, sino que su repetición puede ser útil en el seguimiento. En cuanto al tratamiento el abordaje estándar de la NL consiste en una fase de inducción y una fase de mantenimiento. Sin embargo, la aparición de nuevos fármacos ha motivado que se postule un nuevo paradigma de tratamiento en una sola fase continuada y personalizada (AU)

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. Many clinical and prognostic data on which our therapeutic decisions are based come from international cohorts, which have important ethnic and prognostic differences. To identify clinical and prognostic data from patients with LN in Spain, we undertook a bibliographic search of LN-related papers by Spanish authors and published in national and international journals between 2005 and 2022. According to the selected references, renal biopsy is not only essential for LN diagnosis but its repetition can be useful for the follow-up. Regarding LN treatment, standard strategy consists of an induction phase and a maintenance phase. However, as new drugs have been released, a new paradigm of treatment in a single, continuing and personalized phase has been proposed (AU)

Machine learning-couched treatment algorithms tailored to individualized profile of patients with primary anterior chamber angle closure predisposed to the glaucomatous optic neuropathy.

Background: Primary angle closure glaucoma (PACG) is still one of the leading causes of irreversible blindness, with a trend towards an increase in the number of patients to 32.04 million by 2040, an increase of 58.4% compared with 2013. Health risk assessment based on multi-level diagnostics and machine learning-couched treatment algorithms tailored to individualized profile of patients with primary anterior chamber angle closure are considered essential tools to reverse the trend and protect vulnerable subpopulations against health-to-disease progression. Aim: To develop a methodology for personalized choice of an effective method of primary angle closure (PAC) treatment based on comparing the prognosis of intraocular pressure (IOP) changes due to laser peripheral iridotomy (LPI) or lens extraction (LE). Methods: The multi-parametric data analysis was used to develop models predicting individual outcomes of the primary angle closure (PAC) treatment with LPI and LE. For doing this, we suggested a positive dynamics in the intraocular pressure (IOP) after treatment, as the objective measure of a successful treatment. Thirty-seven anatomical parameters have been considered by applying artificial intelligence to the prospective study on 30 (LE) + 30 (LPI) patients with PAC. Results and data interpretation in the framework of 3P medicine: Based on the anatomical and topographic features of the patients with PAC, mathematical models have been developed that provide a personalized choice of LE or LPI in the treatment. Multi-level diagnostics is the key tool in the overall advanced approach. To this end, for the future application of AI in the area, it is strongly recommended to consider the following:Clinically relevant phenotyping applicable to advanced population screeningSystemic effects causing suboptimal health conditions considered in order to cost-effectively protect affected individuals against health-to-disease transitionClinically relevant health risk assessment utilizing health/disease-specific molecular patterns detectable in body fluids with high predictive power such as a comprehensive tear fluid analysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00337-1.

Profile and quality of life of the adult population in good health according to the level of vitality: European NHWS cross sectional analysis.

BACKGROUND: The World Health Organization's definition of health highlights the importance of mental and physical wellbeing and not only disease state. However, lack of awareness on the burden of impaired vitality and its impact on the quality of life of the general healthy population prevents healthcare providers from delivering appropriate solutions and advice. This study aims to better characterize this population in Europe and identify the profile and the health reported outcomes associated with impaired vitality. METHODS: This retrospective observational study included National Health and Wellness Survey (NHWS) data collected in healthy participants aged 18-65 years from five European Union countries in 2018. Socio-demographic and lifestyle characteristics, comorbidities, attitudes towards healthcare systems, Patient Activation Measure, health-related quality of life outcomes (EQ-5D), and work productivity and activity impairment were analysed according to SF-12 vitality score subgroups (≥ 60, 50- < 60, 40- < 50, < 40). RESULTS: A total of 24,295 participants were enrolled in the main analysis. Being a female, younger, having a lower income and being obese or having sleep and mental disorders was associated with an increased risk of impaired vitality. This was associated with a higher consumption of healthcare resources along with having a weak patient-physician relationship. Participants who were disengaged in the self-management of their health were 2.6 times more likely to have a low level of vitality. For participants in the lowest vitality group, odds of mobility problems increased by 3.4, impairment of usual activity by 5.8, increased of pain and discomfort by 5.6 and depression and anxiety by 10.3, compared with participants in the highest vitality group. Also, odds of presenteeism increased by 3.7, overall work impairment by 3.4 and daily activity losses by 7.1. CONCLUSION: Evidence-based trends facilitate the identification of a healthy population with impaired vitality in real-world practice. This study highlights the actual burden of low vitality on daily life activities, particularly on mental health and reduced work productivity. Additionally, our results underline the importance of self-engagement in the management of vitality impairment and highlights the need to implement strategies to address this public health concern in the affected population (HCP-patient communication, supplements, meditation).

Real-World Experience on the Use of Mepolizumab from the Severe Asthma Registry of the German Asthma Net (MepoGAN-Study).

Purpose: The German Asthma Net (GAN) operates a Severe Asthma Registry that provides an overview of the clinical presentation and management of patients with severe asthma. Based upon data from the GAN registry, the MepoGAN study aimed to describe clinical profiles and treatment outcomes of patients who were treated with the anti-IL-5 monoclonal antibody mepolizumab (NucalaTM) in routine practice in Germany. Patients and Methods: The MepoGAN study is a descriptive retrospective non-interventional cohort study. Mepolizumab patients enrolled in the GAN registry were evaluated with results being described in two different data sets: Cohort 1 (n=131) started on mepolizumab when the patients entered the registry. Results were reported after 4 months of therapy. Patients in Cohort 2 (n=220) were on treatment with mepolizumab at the time of enrollment and follow-up data were collected after a further year of treatment. Outcome measures included asthma control, lung function, disease symptoms, OCS use, and exacerbations. Results: Patients enrolled in the registry who started on mepolizumab in Cohort 1 had a mean age of 55 years, were former smokers in 51% of the cases, had a mean blood eosinophil count of 500 cells/µL, and frequently had maintenance OCS use (55%). In this real-world setting, mepolizumab therapy was associated with a clinically relevant reduction in blood eosinophils (-445.7 cells/µL), OCS use (-30%), and improvement in asthma control. Fifty-five percent (vs 10% at baseline) of the patients reported controlled or partially controlled asthma 4 months after starting therapy. In patients who were already treated with mepolizumab at registry enrollment (Cohort 2), asthma control and lung function remained stable after a further year of observation. Conclusion: The GAN registry data confirm the effectiveness of mepolizumab in a real-world setting. Treatment benefits are maintained over time. While the asthma of patients treated in routine practice was more severe, the results observed with mepolizumab are broadly consistent with RCTs.

AO Spine Adult Spinal Deformity Patient Profile: A Paradigm Shift in Comprehensive Patient Evaluation in Order to Optimize Treatment and Improve Patient Care.

STUDY DESIGN: Modified Delphi study. OBJECTIVE: Adult spinal deformity (ASD) is an increasingly recognized condition, comprising a spectrum of pathologies considerably impacting patients' health and functional status. Patients present with a combination of pain, disability, comorbidities and radiological deformity. The study aims to propose a systematic approach of gathering information on the factors that drive decision-making by developing a patient profile. METHODS: The present study comprises of 3 parts. Part 1: Development of prototype of patient profile: The data from the Core Outcome Study on SCOlisis (COSSCO) by Scoliosis Research Society (SRS) was categorized into a conceptual framework. Part 2: Modified Delphi study: Items reaching >70% agreement were included in a 4 round iterative process with 51 panellists across the globe. Part 3: Pilot testing-feasibility: Content validity and usability were evaluated quantitatively. RESULTS: The profile consisted of 4 domains. 1. General health with demographics and comorbidities, 2.Spine-specific health with spine related health and neurological status, 3. Imaging with radiographic and MRI parameters and 4. Deformity type. Each domain consisted of 1 or 2 components with various factors and their measuring instruments. Profile was found to have an excellent content validity (I-CVIr 0.78-1.00; Ave-CVI 0.92) appropriateness, relevance and usefulness. CONCLUSIONS: The present study, is first to provide a universally applicable multimodal ASD patient profile to methodically describe patients. Physicians are encouraged to assess ASD patients holistically using this profile and not just based on radiographic findings.

Plasma proteomics identify potential severity biomarkers from COVID-19 associated network.

PURPOSE: Coronavirus disease 2019 (COVID-19) continues to threaten public health globally. Severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection-dependent alterations in the host cell signaling network may unveil potential target proteins and pathways for therapeutic strategies. In this study, we aim to define early severity biomarkers and monitor altered pathways in the course of SARS-CoV-2 infection. EXPERIMENTAL DESIGN: We systematically analyzed plasma proteomes of COVID-19 patients from Turkey by using mass spectrometry. Different severity grades (moderate, severe, and critical) and periods of disease (early, inflammatory, and recovery) are monitored. Significant alterations in protein expressions are used to reconstruct the COVID-19 associated network that was further extended to connect viral and host proteins. RESULTS: Across all COVID-19 patients, 111 differentially expressed proteins were found, of which 28 proteins were unique to our study mainly enriching in immunoglobulin production. By monitoring different severity grades and periods of disease, CLEC3B, MST1, and ITIH2 were identified as potential early predictors of COVID-19 severity. Most importantly, we extended the COVID-19 associated network with viral proteins and showed the connectedness of viral proteins with human proteins. The most connected viral protein ORF8, which has a role in immune evasion, targets many host proteins tightly connected to the deregulated human plasma proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma proteomes from critical patients are intrinsically clustered in a distinct group than severe and moderate patients. Importantly, we did not recover any grouping based on the infection period, suggesting their distinct proteome even in the recovery phase. The new potential early severity markers can be further studied for their value in the clinics to monitor COVID-19 prognosis. Beyond the list of plasma proteins, our disease-associated network unravels altered pathways, and the possible therapeutic targets in SARS-CoV-2 infection by connecting human and viral proteins. Follow-up studies on the disease associated network that we propose here will be useful to determine molecular details of viral perturbation and to address how the infection affects human physiology.

Homecare interventions as a Service model for Obstructive sleep Apnea: Delivering personalised phone call using patient profiling and adherence predictions.

BACKGROUND AND OBJECTIVE: Obstructive Sleep Apnea (OSA) is a sleep disorder that leads to different pathologies like depression and cardiovascular problems. The first-line medical treatment for OSA is Continuous Positive Airway Pressure (CPAP) therapy. However, this therapy has the lowest adherence level when compared to other homecare therapies. Consequently, the main objective of this paper is to increase this adherence level with methods that can be replicated in a large number of patients. METHODS: The Homecare Intervention as a Service model can build, verify, and deliver per-sonalised home care interventions. With the Homecare Intervention as a Service model, we build and provide on-demand personalised interventions according to the patient's needs. The 2 core components of this model are patient clustering and CPAP adherence predictions. To define the patient profiles and predict the adherence level, we apply the K-means and the Logistic Regression algorithm respectively. To support these algorithms, we use the CPAP monitoring data and qualitative data on the patients. RESULTS: We demonstrate that there are 3 patient profiles (non-adherent, attempter, and adherent). We draw a comparison with multiple machine learning algorithms to predict CPAP adherence at 30, 60 and 90 days. In this case, the Logistic Regression gives the best results with a f1-score of 0.84 for30 days, 0.79 for 60 days and 0.76 for 90 days. These newly build profiles were to be used to deliver personalised phone call interventions. The phone call intervention shows an increase in adherence by 1.02 h/night for non-adherent patients and 0.69 h/night for attempter patients. CONCLUSIONS: This is the first study in CPAP therapy that formalises the process of transforming raw data into effective home care interventions that can be delivered directly to the patients. In fact,it is the first time that both patient characterisation and predictions based on data are used to provide personalised patient management for CPAP therapy. Our model is flexible to be extended to new types of interventions and other homecare therapies.

Evolution of diagnosis and treatment for lupus nephritis in Spain.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. Many clinical and prognostic data on which our therapeutic decisions are based come from international cohorts, which have important ethnic and prognostic differences. To identify clinical and prognostic data from patients with LN in Spain, we undertook a bibliographic search of NL-related papers by Spanish authors and published in national and international journals between 2005 and 2022. According to the selected references, renal biopsy is not only essential for LN diagnosis but its repetition can be useful for the follow-up. Regarding LN treatment, standard strategy consists of an induction phase and a maintenance phase. However, as new drugs have been released, a new paradigm of treatment in a single, continuing and personalized phase has been proposed.

Study of Health in Primary Care of the Amazonas Population: Protocol for an Observational Study on Diabetes Management in Brazil.

BACKGROUND: Changes in the profiles of patients have significant impacts on the health care system. Diabetes mellitus type 2 (T2DM) prevention and management should be studied in different contexts. OBJECTIVE: The Study of Health in Primary Care for the Amazonas Population (SAPPA) primarily aims to describe T2DM prevention and management actions offered by primary health care settings in Brazil and whether the care delivered is consistent with the chronic care model (CCM). Second, the study aims to examine the impact of T2DM management actions on health and lifestyle, and third, to understand how sociodemographic characteristics, health, and subjective outcomes impact diabetes management. METHODS: As part of this observational study, managers and health professionals complete a questionnaire containing information about T2DM prevention and management actions and CCM dimensions. During in-home visits, patients are asked about their health, lifestyle, sociodemographics, diabetes care, and subjective variables. RESULTS: A total of 34 managers, 1560 professional health workers, and 955 patients will be recruited. The data collection will be completed in October 2022. CONCLUSIONS: The SAPPA is an observational study that intends to understand the T2DM management process in primary health care, including planning, execution, reach, and impact on patient motivation and adherence. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37572.

Axial Disease in Psoriatic Arthritis: how can we Define it, and does it have an Impact on Treatment?

The Spondyloarthritis (SpA) represents a group of rheumatic inflammatory entities that share clinical, laboratory and imaging features, including Psoriatic Arthritis (PsA). Axial involvement may occur in up to 50% of patients with PsA (axPsA), causing inflammatory back pain, stiffness and changes on imaging. Whether axial SpA (axSpA) with psoriasis represents a distinct entity than axPsA is a matter of debate, since similarities and differences have been reported in terms of clinical expression and imaging. Patients with radiographically axPsA show lower prevalence of inflammatory b ack pain, lumbar and buttock pain in comparison with axSpA. In addition, imaging features differ between axPsA and axSpA, with less sacroiliitis in axPsA and more asymmetrical, chunky syndesmophytes which are predominant at the cervical spine location. Data on treatment efficacy and management recommendations are extrapolated from studies on axSpA, and only one published randomized clinical trial is dedicated specifically to axPsA to date.

Antithrombotic and antiplatelet effects of plant-derived compounds: a great utility potential for primary, secondary, and tertiary care in the framework of 3P medicine.

Thromboembolism is the third leading vascular disease, with a high annual incidence of 1 to 2 cases per 1000 individuals within the general population. The broader term venous thromboembolism generally refers to deep vein thrombosis, pulmonary embolism, and/or a combination of both. Therefore, thromboembolism can affect both - the central and peripheral veins. Arterial thromboembolism causes systemic ischemia by disturbing blood flow and oxygen supply to organs, tissues, and cells causing, therefore, apoptosis and/or necrosis in the affected tissues. Currently applied antithrombotic drugs used, e.g. to protect affected individuals against ischemic stroke, demonstrate significant limitations. For example, platelet inhibitors possess only moderate efficacy. On the other hand, thrombolytics and anticoagulants significantly increase hemorrhage. Contextually, new approaches are extensively under consideration to develop next-generation antithrombotics with improved efficacy and more personalized and targeted application. To this end, phytochemicals show potent antithrombotic efficacy demonstrated in numerous in vitro, ex vivo, and in vivo models as well as in clinical evaluations conducted on healthy individuals and persons at high risk of thrombotic events, such as pregnant women (primary care), cancer, and COVID-19-affected patients (secondary and tertiary care). Here, we hypothesized that specific antithrombotic and antiplatelet effects of plant-derived compounds might be of great clinical utility in primary, secondary, and tertiary care. To increase the efficacy, precise patient stratification based on predictive diagnostics is essential for targeted protection and treatments tailored to the person in the framework of 3P medicine. Contextually, this paper aims at critical review toward the involvement of specific classes of phytochemicals in antiplatelet and anticoagulation adapted to clinical needs. The paper exemplifies selected plant-derived drugs, plant extracts, and whole plant foods/herbs demonstrating their specific antithrombotic, antiplatelet, and fibrinolytic activities relevant for primary, secondary, and tertiary care. One of the examples considered is antithrombotic and antiplatelet protection specifically relevant for COVID-19-affected patient groups.