In 2010, the definition of cachexia was jointly developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) "Cachexia-anorexia in chronic wasting diseases" and "Nutrition in geriatrics". Cachexia was considered as a synonym of disease-related malnutrition (DRM) with inflammation by the ESPEN guidelines on definitions and terminology of clinical nutrition. Starting from these concepts and taking into account the available evidence the SIG "Cachexia-anorexia in chronic wasting diseases" conducted several meetings throughout 2020-2022 to discuss the similarities and differences between cachexia and DRM, the role of inflammation in DRM, and how it can be assessed. Moreover, in line with the Global Leadership Initiative on Malnutrition (GLIM) framework, in the future the SIG proposes to develop a prediction score to quantify the individual and combined effect(s) of multiple muscle and fat catabolic mechanisms, reduced food intake or assimilation and inflammation, which variably contribute to the cachectic/malnourished phenotype. This DRM/cachexia risk prediction score could consider the factors related to the direct mechanisms of muscle catabolism separately from those related to the reduction of nutrient intake and assimilation. Novel perspectives in the field of DRM with inflammation and cachexia were identified and described in the report.
DOCUMENT
Background and aims: Observational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge.Methods: In this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload.Results: Administration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected.Conclusion: This study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.Keywords: biomarkers; diet; glucoraphanin; hormesis; inflammation; nutrients; phenotypic flexibility; sulforaphane.
DOCUMENT
BACKGROUND: Preventing metabolic syndrome (MetS) and frailty in older adults is crucial for healthy aging. The association between MetS and physical frailty is well-documented, with low-grade inflammation as potential explanation. However, the association between MetS and frailty as a multidimensional concept, and the association of low-grade inflammation with presence of MetS and frailty, is yet unclear. Therefore, we examined these associations low-grade inflammation in a large cohort of community-dwelling older adults.METHODS: This cross-sectional study was performed among adults aged ≥ 65 years enrolled in the Dutch Lifelines population cohort. MetS was defined according to the Joint Interim Statement of 2009. Frailty was measured by the Groningen Frailty Indicator (GFI), which consists of 15 self-reported items on both physical and psychosocial functioning, with a score ≥ 4 indicating presence of frailty. The association between MetS and its five components and frailty was assessed using logistic regression models. Low-grade inflammation was represented by high-sensitivity C-reactive protein (hsCRP) level. The association of hsCRP level with presence of MetS and frailty was assessed using multinomial logistic regression in a sub-cohort with available hsCRP measurements.RESULTS: Of 11,552 adults (52.1% women) included, the prevalences of MetS and frailty were 28% and 15%, respectively. MetS was positively associated with frailty after adjusting for relevant covariates (OR: 1.37; 95% CI: 1.22-1.53). MetS components elevated blood pressure was most strongly associated with frailty. In the sub-cohort of 3896 participants, high hsCRP was associated with presence of MetS and frailty (OR: 1.31; 95% CI: 1.15-1.51), and MetS alone (OR: 1.44; 95% CI: 1.33-1.56), but not to frailty alone. A higher hsCRP level was associated with a higher score on the physical domain of frailty (b: 0.06; 95% CI: 0.03-0.08).CONCLUSIONS: Presence of MetS is associated with presence of frailty indicated by a multidimensional index in a large group of Dutch older adults. Low-grade inflammation, indicated by plasma hsCRP level, was found to be associated with both presence of MetS and frailty and presence of MetS alone. Increased hsCRP levels were associated with the physical component of frailty, but not with frailty as a multidimensional concept.
DOCUMENT
Background & aims: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. Methods: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. Results: The final round of review was highly favorable with 99 % overall “agree” or “strongly agree” responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. Conclusion: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.
DOCUMENT
Background: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. Methods: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. Results: The final round of review was highly favorable, with 99% overall “agree” or “strongly agree” responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. Conclusion: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.
DOCUMENT
Purpose: Exercise therapy with a focus on muscle strengthening has proven to be effective for the management of knee osteoarthritis (OA). Yet it is not known whether high-intensity resistance training (RT) is more effective in improving upper leg muscle strength and physical performance than low-intensity RT. Still, there is some controversy regarding the effectiveness of high-intensity RT and whether or not it is harmful, for instance by accelerating cartilage degeneration, osteophyte formation, or increasing synovitis. Any catabolic or anabolic response of musculoskeletal tissue to RT might first be visible on a biochemical level before changes in clinical symptoms are measurable. Serum biomarkers can objectively measure early biochemical changes and assess whether RT leads to a more anabolic or catabolic response. The aim of this study is to assess (i) whether high-intensity RT elicits a different response (e.g. catabolic) on systemic inflammation and musculoskeletal tissues in and surrounding the joint, including bone, cartilage, muscle, and synovial tissue compared to low-intensity RT; and (ii) whether there is an association between changes in serum levels of inflammatory and musculoskeletal tissue-derived biomarkers and improvements in clinical outcomes (performance-based tests and self-reported outcomes on pain and activity limitations).Methods: In a randomized controlled trial, 177 participants with knee OA conducted a high-intensity (70%-80% of the Repetition Maximum (1RM)) or low-intensity (40%-50% 1RM) RT program 3 times a week for 12 weeks. Measures of clinical outcomes and serum samples were collected at the start of RT (pre-intervention), after 3 months at the end of RT (post-intervention), and 6 months after RT (follow-up). As a reflection of systemic inflammation (CRP), synovitis (CRPM, C3M), bone turnover (OC, CTX-I), cartilage turnover (PRO-C2, C2M, huARGS), muscle turnover (PRO-C3, PRO-C6), and cell behaviour (col10neo) a total of eleven serum biomarkers were analysed. With the exception of CRP, which was determined with an immunoturbidimetric assay, ELISA assays were used to quantify serum levels of the other 10 serum biomarkers. The primary outcome measures are the changes in serum biomarker levels. Other outcome measures include upper leg muscle strength, performance-based tests, and self-reported outcomes on pain and activity limitations.Results: High-intensity RT resulted in greater improvements in muscle strength compared to low-intensity RT when measured by the estimated 1RM. No significant differences between groups were found for upper leg muscle strength (Nm/kg) when measured with an isokinetic dynamometer. Both groups showed similar improvements in pain and physical functioning. Although there is no difference between groups in clinical outcomes, except for the estimated 1RM, we expect that participants in the high-intensity RT group are more likely to have enhanced serum levels of catabolic biomarkers than participants in the low-intensity RT group. Since both the high-intensity RT group and low-intensity RT group improved over time, we expect that changes in serum biomarker levels are associated with overall improvements in clinical outcomes. Almost all participants had normal CRP values (<10 mg/L) at baseline. No significant differences between the intensity RT groups in CRP levels at baseline, at 3 months, and 6 months were found. In both groups, there was no evidence that RT influenced CRP serum levels.Conclusions: The work to date on CRP serum levels suggests that RT did not influence CRP levels. This result may be explained by the high percentage of participants with normal CRP levels (<10 mg/L). We are currently in the process of analyzing the remaining 10 neo-epitope biomarkers. We expect that our remaining 10 assays have the potential to measure changes in serum biomarker levels in response to RT. This will be the first study to investigate the effects of high-intensity versus low-intensity RT on musculoskeletal tissue turnover in individuals with knee OA. With this, we aim to determine whether high-intensity RT can improve upper leg muscle strength and physical performance without worsening systemic inflammation or causing adverse effects on musculoskeletal knee OA-related tissues.
DOCUMENT
The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NMon ILCs and other components of the serosal immune systemare scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NMmay lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NMon the serosal immune system.
DOCUMENT
Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers. Methods: For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results: Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some proinflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Conclusion: Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
DOCUMENT
Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
DOCUMENT
