The Impact of Obesity and Lifestyle on the Immune System and Susceptibility to Infections Such as COVID-19

Background: COVID-19 is a global challenge to healthcare. Obesity is common in patients with COVID-19 and seems to aggravate disease prognosis. In this review we explore the link between obesity, chronic disease, life

Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen

Tamoxifen is a prodrug that is primarily metabolized into the pharmacologically active metabolite endoxifen and eventually into inactive metabolites. The herb curcumin may increase endoxifen exposure by affecting phase II metabolism. We compared endoxifen and tamoxifen exposure in breast cancer patients with or without curcumin, and with addition of the bio-enhancer piperine. Tamoxifen (20–30mg per day (q.d.)) was either given alone, or combined with curcumin (1200 mg three times daily (t.i.d.)) +/− piperine (10 mg t.i.d.). The primary endpoint of this study was the difference in geometric means for the area under the curve (AUC) of endoxifen. Genotyping was performed to determine CYP2D6 and CYP3A4 phenotypes. The endoxifen AUC0–24h decreased with 7.7% (95%CI: −15.4 to 0.7%; p = 0.07) with curcumin and 12.4% (95%CI: −21.9 to −1.9%; p = 0.02) with curcumin and piperine, compared to tamoxifen alone. Tamoxifen AUC0–24h showed similar results. For patients with an extensive CYP2D6 metabolism phenotype (EM), effects were more pronounced than for intermediate CYP2D6 metabolizers (IMs). In conclusion, the exposure to tamoxifen and endoxifen was significantly decreased by concomitant use of curcumin (+/− piperine). Therefore, co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy (potentially 20–40% of the patients), especially in EM patients

Integrating treatment cost reduction strategies and biomarker research to reduce costs and personalize expensive treatments: an example of a self-funding trial in non-small cell lung cancer

Personalization of treatment offers the opportunity to treat patients more effectively based on their dominant disease-specific features. The increasing number and types of treatment, and the high costs associated with these treatments, however, demand new approaches that improve patient selection while reducing treatment-associated costs to ensure sustainable healthcare. The DEDICATION-1 trial has been designed to investigate the non-inferiority of lower dosing regimens when compared to standard of care dosing regimens as a potential effective treatment cost reduction strategy to reduce costs of treatment with expensive immune checkpoint inhibitors in non-small cell lung cancer. If non-inferiority is confirmed, lower dosing regimens could be implemented for all therapeutic indications of pembrolizumab. The cost savings obtained within the trial are partly reinvested in biomarker research to improve the personalization of pembrolizumab treatment. The implementation of these biomarkers will potentially lead to additional cost savings by preventing ineffective pembrolizumab exposure, thereby further reducing the financial pressure on healthcare systems. The concepts discussed within this perspective can be applied both to other anticancer agents, as well as to treatments prescribed outside the oncology field

Transient atrial inflammation in a murine model of Coxsackievirus B3-induced myocarditis

Atrial dysfunction is a relatively common complication of acute myocarditis, although its pathophysiology is unclear. There is limited information on myocarditis-associated histological changes in the atria and how they develop in time. The aim of this study therefore was to investigate inflammation, fibrosis and viral genome in the atria in time after mild CVB3-induced viral myocarditis (VM) in mice. C3H mice (n = 68) were infected with 105 PFU of Coxsackievirus B3 (CVB3) and were compared with uninfected mice (n = 10). Atrial tissue was obtained at days 4, 7, 10, 21, 35 or 49 post-infection. Cellular infiltration of CD45+ lymphocytes, MAC3+ macrophages, Ly6G+ neutrophils and mast cells was quantified by (immuno)histochemical staining. The CVB3 RNA was determined by in situ hybridization, and fibrosis was evaluated by elastic van Gieson (EvG) staining. In the atria of VM mice, the numbers of lymphocytes on days 4 and 7 (p <.05) and days 10 (p <.01); macrophages on days 7 (p <.01) and 10 (p <.05); neutrophils on days 4 (p <.05); and mast cells on days 4 and 7 (p <.05) increased significantly compared with control mice and decreased thereafter to basal levels. No cardiomyocyte death was observed, and the CVB3 genome was detected in only one infected mouse on Day 4 post-infection. No significant changes in the amount of atrial fibrosis were found between VM and control mice. A temporary increase in inflammation is induced in the atria in the acute phase of CVB3-induced mild VM, which may facilitate the development of atrial arrhythmia and contractile dysfunction

A serum and platelet-rich plasma serotonin assay using liquid chromatography tandem mass spectrometry for monitoring of neuroendocrine tumor patients

Background Serotonin is used for the diagnosis and follow-up of neuroendocrine tumors (NET). We describe the analytical and clinical validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) based serotonin assay for serum and platelet-rich plasma (PRP). Methods An LC-MS/MS based method for serum and PRP serotonin was validated by determination of assay imprecision, carry-over, linearity, interference, recovery, sample stability and a matrix/method comparison of serum and PRP serotonin was made with whole blood serotonin. Furthermore, upper limits of normal were determined and serotonin concentrations of healthy individuals, 14 NET patients without evidence of disease and 51 NET patients with evidence of disease were compared. Results For serum and PRP fractions, total assay imprecision was <5%. All correlation coefficients were 0.98 and the serum and platelet-rich serotonin upper limit of normal were 5.5nmol/109 platelet and 5.1nmol/109 platelet, respectively. NET patients with confirmed evidence of disease had significantly higher serum and PRP serotonin levels when compared to NET patients without evidence of disease and healthy volunteers. Conclusions LC-MS/MS based serum and PRP serotonin assays were developed with suitable analytical characteristics. Furthermore, serum and PRP serotonin was found to be useful for monitoring NET patients

The Impact of Obesity and Lifestyle on the Immune System and Susceptibility to Infections Such as COVID-19

Background: COVID-19 is a global challenge to healthcare. Obesity is common in patients with COVID-19 and seems to aggravate disease prognosis. In this review we explore the link between obesity, chronic disease, lifestyle factors and the immune system, and propose societal interventions to enhance global immunity. Search Strategy and Selection Criteria: We performed three literature searches using the keywords (1) coronavirus AND comorbidities, (2) comorbidities AND immune system, and (3) lifestyle factors AND immune system. Results were screened for relevance by the main author and a total of 215 articles were thoroughly analyzed. Results: The relationship between obesity and unfavorable COVID-19 prognosis is discussed in light of the impact of chronic disease and lifestyle on the immune system. Several modifiable lifestyle factors render us susceptible to viral infections. In this context, we make a case for fostering a healthy lifestyle on a global scale. Conclusions: Obesity, additional chronic disease and an unhealthy lifestyle interactively impair immune function and increase the risk of severe infectious disease. In adverse metabolic and endocrine conditions, the immune system is geared toward inflammation. Collective effort is needed to ameliorate modifiable risk factors for obesity and chronic disease on a global scale and increase resistance to viruses like SARS-CoV-2

Combining digital adherence technology and therapeutic drug monitoring for personalised TB care

Tuberculosis (TB) is the world-leading cause of infectious disease related mortality, apart from COVID-19 presently [1]. Standard TB treatment for drug-susceptible (DS) TB takes 6–9 months and requires daily intake of multiple medications [1]. Notably, proper treatment adherence is essential for successful treatment outcome [1, 2]. To improve adherence, counseling and education are important. For specific patient groups, such as those with drug-resistant TB, HIV co-infection and those on intermittent treatment regiments, the World Health Organization (WHO) advises to use the Directly Observed Treatment (DOT) strategy. However, even with DOT, treatment completion is still challenging and cure rates and outcomes remain suboptimal [3]

Food-Based Dietary Guidelines - development of a conceptual framework for future food-based dietary guidelines in Europe:Report of a Federation of European Nutrition Societies Task-Force Workshop in Copenhagen, 12-13 March 2018

Identifying a need for developing a conceptual framework for the future development of Food-Based Dietary Guidelines (FBDG) in Europe, The Federation of European Nutrition Sciences established a Task Force for this purpose. A workshop was held with the specific objective to discuss the various dimensions considered as particularly relevant. Existing frameworks for FBDG were discussed, and presentations from various countries illustrated not only several commonalities but also a high degree of heterogeneity in the guidelines from different countries. Environmental aspects were considered in several countries, and dimensions like food safety, dietary habits and preparation were included in others. The workshop provided an overview of the use of FBDG - both in developing front-of-pack nutrition labels and for reformulation and innovation. The European FBDG dimensions were described with examples from the close connection between FBDG and European Union (EU) policies and activities and from the compilation of a database of national FBDG. Also, the challenges with communication of FBDG were discussed. Considering the current scientific basis and the experiences from several countries, the Task Force discussed the various dimensions of developing FBDG and concluded that environmental aspects should be included in the future conceptual framework for FBDG. A change in terminology to sustainable FDBG (SFBDG) could reflect this. The Task Force concluded that further work needs to be done exploring current practice, existing methodologies and the future prospects for incorporating other relevant dimensions into a future Federation of European Nutrition Societies conceptual framework for SFBDG in Europe and working groups were formed to address that