Gastrointestinal side effects of somatostatin analogs in neuroendocrine tumors: a focused review.

Neuroendocrine tumors (NETs) are a group of well-differentiated heterogeneous neoplasms characterized by slow progression and distinct clinical and biological behavior. In the majority of patients with NET, first-line treatment is represented by somatostatin analogs (SSAs) that, despite being drugs with high tolerability (even at high doses) and providing to carcinoid symptoms control and anti-proliferative effects, may present some side effects, with potential impact on quality of life and nutritional status. The most frequent side effects are represented by gastrointestinal events in particular alterations in bowel habits (diarrhea and constipation), abdominal pain, exocrine pancreatic insufficiency, and cholelithiasis. Considering the relative rarity of NETs, literature about frequency and standard clinical management of adverse events SSA-related is still lacking and heterogeneous. The aim of this review is to arm gastroenterologists and other physicians treating NET patients with essential knowledge on the side effects of SSAs. By identifying and managing these adverse events early, healthcare professionals can offer optimal care, avert foreseeable complications, and ensure the best outcomes for patients. Without such early recognition, there is a risk of diminishing the patient's quality of life and their ability to sustain treatment over time.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Altered insulin sensitivity and immune function in patients with colorectal cancer.

BACKGROUND & AIMS: Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls. METHODS: Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups. RESULTS: Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1ß (patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1ß production, within circulating immune cells. CONCLUSION: Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1ß and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.

Senescence: A new kid in the block of the metabolic response to surgical trauma.

Tumor growth is associated to chronic metabolic changes which inform the clinical phenotype and the outcome of patients with cancer. Surgery further triggers a cascade of acute neuro-immune responses leading to hypermetabolic and catabolic state. The metabolic mechanisms associated to surgical stress are well described. Preventive and therapeutic strategies have been developed, yet they appear not to benefit all surgical patients with cancer, even in the presence of a similar tumor type as well surgical procedures. Recent studies show that aging is associated with enrichment of senescent cells in different organs and tissues. Senescent cells are characterized by a specific senescence-associated secretory phenotype (SASP), which limits the potential for resilience of tissues and organs. Enhancement of the metabolic and functional recovery of patients with cancer undergoing surgery may therefore require additional therapies addressing SASP and senescent cells. Preliminary results obtained in experimental models recommend to further explore the role of senescence in mediating the metabolic changes and tissue resistance to efficient recovery.

Nutrition care is an integral part of patient-centred medical care: a European consensus.

While healthcare is becoming more patient-centred, evidence-based nutrition interventions are still not accessible to all patients with cancer. As nutrition interventions directly improve clinical and socioeconomic outcomes, patient-centred care is not complete without nutrition care. While awareness of the negative impact of malnutrition on clinical outcomes, quality of life, and functional and emotional wellbeing in cancer is growing, there is relatively poor awareness amongst patients, clinicians, policymakers, and payers that nutrition interventions -particularly those begun in the early stages of the disease course- are an effective method for improving such outcomes. The European Beating Cancer Plan recognises the need for a holistic approach to cancer but lacks actionable recommendations to implement integrated nutrition cancer care at member state level. When considering nutrition care as a human right, the impact on quality of life and functional status must be prioritized, as these may be equally as important to patients, especially in advanced cancer where improvements in clinical outcomes such as survival or tumour burden may not be attainable. We formulate actions needed at the regional and the European level to ensure integrated nutrition care for all patients with cancer. The 4 main Take Home Messages are as follows: 1. The goals of Europe's Beating Cancer Plan cannot be achieved without integrating nutrition across the cancer care continuum. 2. Malnutrition negatively impacts clinical outcomes and has socioeconomic consequences for patients and healthcare systems. 3. Championing integrating nutrition care into cancer care is therefore the duty and ethical responsibility of clinicians (Hippocratic Oath-primum non nocere) and 4. Nutrition care is a cost effective, evidence-based therapy.

Sarcopenia, biological age and treatment eligibility in patients with cancer.

PURPOSE OF REVIEW: Cancer incidence will dramatically increase, especially among older adults, during the next few decades. This may lead to bankruptcy of the healthcare systems worldwide if the current approach to treatment eligibility is not improved. In fact, current treatment personalization is mostly focusing on the genetic and molecular characteristics of cancer cells, whereas clinical characterization of patients is still dependent on gross variables (i.e. chronological age, BMI, comorbidities, Performance Status and so on). This could have contributed to the poor performance of many anticancer drugs in the real-world setting when compared with the results obtained in prospective, randomized clinical trials. RECENT FINDINGS: The role of chronological age in identifying patients with increased likelihood to respond to therapies has been challenged, pointing to biological age (i.e. accumulated damage to biological systems over the life course, leading to loss of reserve and capacity to respond to challenges) as a robust predictor of outcome encompassing genetic, phenotypic and clinical factors. Sarcopenia has been proposed as a reliable clinical index of biological age, but the complexity of body composition changes occurring during tumour growth appears to preclude its routine use when assessing eligibility in cancer patients. SUMMARY: Integration of sarcopenia measures within scores of allostatic load may further increase the clinical relevance of changes of body composition, highlight its sensitivity to early nutritional intervention leading to mitigation of accelerated ageing, and contribute to wide delivery of precision oncology.

Effects of oral immunonutrition on histological changes of inflammatory infiltration of the tumor microenvironment among patients with a new diagnosis of gastric cancer.

OBJECTIVES: We assessed the effects of oral immunonutrition (OI) on the inflammatory infiltration of the tumor microenvironment (TME) of patients undergoing surgery for gastric cancer. METHODS: We analyzed patients at the time of their first gastric cancer diagnosis. We collected surgical tissue specimens (stomach), and performed an immunohistochemical analysis to evaluate the inflammatory infiltration of the TME. Patients receiving OI were compared with patients receiving standard oral nutritional supplements and no nutritional support. RESULTS: We enrolled 12 patients with gastric cancer in the study. The median body weight loss was 5.6%. Four patients received OI, five patients received standard nutritional supplement, and three patients received no nutritional supplementation. No difference in age, body mass index (BMI), and body weight loss was observed between the three groups. The OI group showed a tendency of increased number of T-lymphocyte cluster of differentiation (CD) 8+ compared with the other groups, as well as the number of CD83+ and CD68+. The absence of F4/80+ cells was documented only in the TME of the OI group, where a linear positive correlation was present between lymphocytes CD4+ and CD8+ (R = 0.48), and between CD4+ and CD83+ (R = 0.89), although not statistically significant. In the OI group, we observed a positive correlation (not significant) between the number of lymphocytes CD8+ and macrophages CD68+ (R = 0.70; P = 0.30). A strong significant correlation was documented between CD68+ and CD40+ (R = 0.99; P = 0.01), but this correlation did not reach the significance among the patients of the other two groups (R = 0.60; P = 0.116). CONCLUSIONS: The administration of OI in patients with gastric cancer might determine changes in inflammatory patterns of the TME.

A Multi-Site, International Audit of Malnutrition Risk and Energy and Protein Intakes in Patients Undergoing Treatment for Head Neck and Esophageal Cancer: Results from INFORM.

Patients with foregut tumors are at high risk of malnutrition. Nutrition care focuses on identifying individuals at risk of malnutrition and optimizing nutrient intake to promote the maintenance of body weight and lean body mass. This multi-center prospective, longitudinal study audited nutrition care practices related to screening for risk of malnutrition (Patient-Generated Subjective Global Assessment Short Form; PG-SGA SF), and nutrition interventions prescribed (route; adequacy of energy and protein intakes). Audits occurred at four time periods: baseline (before treatment) and at 2, 4, and 6 months after starting cancer treatment; 170 patients (esophageal (ESO; n = 51); head and neck (HN; n = 119)) were enrolled. Nutrition risk (PG-SGA SF score ≥ 4) was prevalent at every time period: HN (baseline: 60%; 6 months 66%) and ESO (77%; 72%). Both groups had significant (p < 0.001) weight losses over the 6 month audit period (HN = 13.2% ESO = 11.4%). Enteral nutrition (EN) was most likely to be prescribed at 2 months for HN and at 4 and 6 months for ESO. Target prescribed energy and protein intakes were not met with any nutrition intervention; although adequacy was highest for those receiving EN. Nutrition care practices differed for HN and ESO cancers and there may be time points when additional nutrition support is needed.

Dietary choices after a cancer diagnosis: A narrative review.

Individuals with cancer may be motivated to make lifestyle changes and informed dietary choices, but are exposed to conflicting and erroneous nutrition information, particularly from online and social media sources. Changes to dietary choices that stem from a diagnosis of cancer are not fully understood. Thus, we conducted a narrative review to summarize the literature focused on dietary choices after a cancer diagnosis, and highlighted influential factors. Postdiagnosis dietary changes have been studied primarily in female patients with breast cancer in European countries. Reported changes typically included decreased red and processed meat intake and increased consumption of fruits and vegetables. These changes align with the recommendations for cancer prevention but were implemented after diagnosis, and may not meet nutrition guidelines for patients with cancer. Age and time since diagnosis were among the influential factors that affected these postdiagnosis changes. Data on dietary changes implemented after a diagnosis of varying cancer types in the North American population are lacking, and would provide practitioners with an enhanced understanding of patient information needs and reasons for dietary choices.

High protein diet in digestive cancers.

PURPOSE OF REVIEW: Recent advances in the nutritional management of patients with digestive cancers suggest that modulation of protein intake may significantly contribute to achieve nutritional and clinical benefits. By reviewing the available evidence, a quantitatively and qualitatively optimal protein intake could be derived. RECENT FINDINGS: High protein diets (i.e., 1-1.5 g/kg body weight/day) appear key to maintain the adequate nutritional status, and may also contribute to achieve clinical benefits. This target appears particularly relevant in patients with digestive cancers at risk or already malnourished, or in older patients. During active cancer treatments, protein intake should be closer to the upper limit of the recommended intake. Also, high protein intake should be maintained beyond the periods of catabolic crisis associated with active treatments. In contrast with general reasoning, animal proteins should represent the majority of the recommended intake. Based on the available evidence, the intake of no specific amino acid can be strongly recommended to enhance anabolic potentials or the immune modulating effects of high protein diets. SUMMARY: High protein intake, mostly based on animal proteins, should be recommended to patients with digestive cancers. However, this target should be translated into clinical prescription after considering the clinical and metabolic needs of the patients. The quest for the optimal protein intake of patients with cancer at different time points of their clinical journey is still open.

Clinical and economic value of oral nutrition supplements in patients with cancer: a position paper from the Survivorship Care and Nutritional Support Working Group of Alliance Against Cancer.

Malnutrition is a common clinical and public health problem that can frequently affect patients in hospital and community settings. In particular, cancer-related malnutrition results from a combination of metabolic dysregulation and anorexia, caused both by the tumor itself and by its treatment. Patients with head-neck cancer, or with gastroesophageal, pancreatic, lung, and colorectal cancer, are particularly at risk of developing malnutrition, with a prevalence varying between 30 and 50% depending on tumor location and anti-cancer treatment complications. Prevention and adequate management of malnutrition is now considered an essential key point of therapeutic pathways of patients with cancer, with the aim to enhance their quality of life, reduce complications, and improve clinical outcomes. Oral nutritional supplements (ONS) are part of the nutritional therapy and represent an effective tool to address cancer-related malnutrition, as supported by growing literature data. However, patients' access to ONS - which is regulated by different national and regional policies in terms of reimbursement - is quite heterogeneous. This narrative review aims to summarize the current knowledge about the role of ONS in terms of cost-effectiveness in the management of actively treated patients with cancer, following surgery and/or radiotherapy/chemotherapy treatment and to present the position on this issue of the Alliance Against Cancer, the Italian National Oncology Network, coming up from a focused virtual roundtable of the Survivorship Care and Nutritional Support Working Group.

Mapping ongoing nutrition intervention trials in muscle, sarcopenia, and cachexia: a scoping review of future research.

Muscle loss alone, or in the context of sarcopenia or cachexia, is a prevalent condition and a predictor of negative outcomes in aging and disease. As adequate nutrition is essential for muscle maintenance, a growing number of studies has been conducted to explore the role of specific nutrients on muscle mass or function. Nonetheless, more research is needed to guide evidence-based recommendations. This scoping review aimed to compile and document ongoing clinical trials investigating nutrition interventions as a strategy to prevent or treat low muscle mass or function (strength and physical performance), sarcopenia, or cachexia. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched up to 21 April 2021 for planned and ongoing trials. Randomized controlled trials with ≥20 participants per arm were included based on intent to explore the effects of nutrition interventions on muscle-related outcomes (i.e. muscle mass or strength, physical performance, or muscle synthesis rate) in both clinical and non-clinical conditions (i.e. aging). Two reviewers independently screened records for eligibility, and a descriptive synthesis of trials characteristics was conducted. A total of 113 trials were included in the review. Most trials (69.0%) enroll adults with clinical conditions, such as cancer (19.5%), obesity and metabolic diseases (16.8%), and musculoskeletal diseases (10.7%). The effects of nutrition interventions on age-related muscle loss are explored in 31% of trials. Although nutrition interventions of varied types were identified, food supplements alone (48.7%) or combined with dietary advice (11.5%) are most frequently reported. Protein (17.7%), amino acids (10.6%), and ß-hydroxy-ß-methylbutyrate (HMB, 6.2%) are the top three food supplements' nutrients under investigation. Primary outcome of most trials (54.9%) consists of measures of muscle mass alone or in combination with muscle strength and/or performance (as either primary or secondary outcomes). Muscle strength and physical performance are primary outcomes of 38% and 31.9% of the trials, respectively. These measurements were obtained using a variety of techniques. Only a few trials evaluate muscle synthesis rate either as a primary or secondary outcome (5.3%). Several nutrition studies focusing on muscle, sarcopenia, and cachexia are underway and can inform future research in this area. Although many trials have similar type of interventions, methodological heterogeneity may challenge study comparisons, and future meta-analyses aiming to provide evidence-based recommendations. Upcoming research in this area may benefit from guidelines for the assessment of therapeutic effects of nutrition interventions.

Current Screening Methods for the Risk or Presence of Malnutrition in Cancer Patients.

Malnutrition is highly common among cancer patients and is associated with a poor quality of life, increased treatment toxicities and decreased survival. The screening of malnutrition should be performed in an early stage of cancer disease and should be rapid, not expensive and highly sensitive to identify the risk of developing malnutrition. Importantly, international clinical guidelines suggest to perform screening for malnutrition in all cancer patients and if the risk is present, they recommend to perform a full nutritional assessment. During the screening phase, different nutritional parameters are considered including the loss of appetite, low food intake, body weight loss and burden of the disease. These items are present in several screening tools, such as the Nutrition Risk Screening (NRS)-2002, the Malnutrition Universal Screening Tool (MUST) and the Mini Nutritional Assessment (MNA) which represent the most widely used tools to screen for an altered nutritional status in cancer patients. Recently, the Global Leadership Initiative on Malnutrition (GLIM) developed an assessment tool for the diagnosis of malnutrition taking into account the presence of i) involuntary body weight loss, ii) body mass index, iii) low muscle mass, iv) low food intake and disease burden/inflammation; in particular, body weight loss, decreased body mass index (BMI), and low muscle mass are considered as phenotypic criteria, whereas reduced food intake, disease burden and inflammation are defined as etiologic criteria. To perform the diagnosis of malnutrition, GLIM consensus considered the presence of at least one phenotypic and one etiologic criterion. The above-mentioned screening tools were validated in different clinical settings and suggesting the use of one tool vs another is challenging considering, among others, different factors including the type and stage of cancer and the setting (i.e., inpatient or outpatient care). Recent data obtained among large cohorts of cancer patients indicate that personalized nutritional therapy reduced mortality risk and ameliorated quality of life and functionality among cancer patients with high nutritional risk, supporting the urgent need for implementing screening and diagnosis of malnutrition in this context.

Absence of risk of sarcopenia protects cancer patients from fatigue.

BACKGROUND: Cancer and its treatments often lead to sarcopenia and fatigue. However, whether these factors are associated remains unproven. OBJECTIVE: To evaluate whether the risk of sarcopenia predicts the presence of fatigue. METHODS: A cross-sectional study was completed and included 198 cancer patients of both sexes, undergoing in- and outpatient treatment. The Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and the Functional Assessment of Cancer Therapy Fatigue (FACT-F) were used to assess the risk of sarcopenia and the presence of fatigue, respectively. The cut-off values used to identify the risk of sarcopenia and the severity of fatigue scale were SARC-F ≥ 4 and Fatigue <34, respectively. Logistic regression analysis was performed to evaluate the association between SARC-F and the FACT-F. RESULTS: Out of 198 patients, 35% were at risk of sarcopenia and of these 87% had fatigue. Patients at risk of sarcopenia had lower scores in the FACT-F subscales, lower handgrip strength, lower performance status, were mostly hospitalized and were sedentary. Logistic regression analysis revealed that patients with SARC-F < 4 had a lower risk of fatigue in both models, crude (OR: 0.83; CI 95% [0.79-0.88], p < 0.0001) as well as adjusted for age, gender, BMI, physical activity, current use of alcoholic beverages, smoking, performance status, cancer type, clinical setting and use of supplements (OR: 0.87; CI 95% [0.81-0.92], p < 0.0001). CONCLUSION: In patients with cancer, 35% presented risk of sarcopenia and of these 87% had fatigue. In addition, the absence of sarcopenia was considered protective against fatigue.

Examining guidelines and new evidence in oncology nutrition: a position paper on gaps and opportunities in multimodal approaches to improve patient care.

Malnutrition, muscle loss, and cachexia are prevalent in cancer and remain key challenges in oncology today. These conditions are frequently underrecognized and undertreated and have devastating consequences for patients. Early nutrition screening/assessment and intervention are associated with improved patient outcomes. As a multifaceted disease, cancer requires multimodal care that integrates supportive interventions, specifically nutrition and exercise, to improve nutrient intake, muscle mass, physical functioning, quality of life, and treatment outcomes. An integrated team of healthcare providers that incorporates societies' recommendations into clinical practice can help achieve the best possible outcomes. A multidisciplinary panel of experts in oncology, nutrition, exercise, and medicine participated in a 2-day virtual roundtable in October 2020 to discuss gaps and opportunities in oncology nutrition, alone and in combination with exercise, relative to current evidence and international societies' recommendations. The panel recommended five principles to optimize clinical oncology practice: (1) position oncology nutrition at the center of multidisciplinary care; (2) partner with colleagues and administrators to integrate a nutrition care process into the multidisciplinary cancer care approach; (3) screen all patients for malnutrition risk at diagnosis and regularly throughout treatment; (4) combine exercise and nutrition interventions before (e.g., prehabilitation), during, and after treatment as oncology standard of care to optimize nutrition status and muscle mass; and (5) incorporate a patient-centered approach into multidisciplinary care.

The importance of protein sources to support muscle anabolism in cancer: An expert group opinion.

This opinion paper presents a short review of the potential impact of protein on muscle anabolism in cancer, which is associated with better patient outcomes. Protein source is a topic of interest for patients and clinicians, partly due to recent emphasis on the supposed non-beneficial effect of proteins; therefore, misconceptions involving animal-based (e.g., meat, fish, dairy) and plant-based (e.g., legumes) proteins in cancer are acknowledged and addressed. Although the optimal dietary amino acid composition to support muscle health in cancer is yet to be established, animal-based proteins have a composition that offers superior anabolic potential, compared to plant-derived proteins. Thus, animal-based foods should represent the majority (i.e., ≥65%) of protein intake during active cancer treatment. A diet rich in plant-derived proteins may support muscle anabolism in cancer, albeit requiring a larger quantity of protein to fulfill the optimal amino acid intake. We caution that translating dietary recommendations for cancer prevention to cancer treatment may be inadequate to support the pro-inflammatory and catabolic nature of the disease. We further caution against initiating an exclusively plant-based (i.e., vegan) diet upon a diagnosis of cancer, given the presence of elevated protein requirements and risk of inadequate protein intake to support muscle anabolism. Amino acid combination and the long-term sustainability of a dietary pattern void of animal-based foods requires careful and laborious management of protein intake for patients with cancer. Ultimately, a dietary amino acid composition that promotes muscle anabolism is optimally obtained through combination of animal- and plant-based protein sources.

Current guidelines for nutrition therapy in cancer: The arrival of a long journey or the starting point?

Large epidemiological data reveal that cancer is progressively becoming a chronic and disabling disease. Implementation in daily practice of early therapies aiming at addressing patients' needs is imperative. Nutrition is a major determinant of patients' quality of life, yet it is frequently neglected. Hopefully, reverting this skeptical clinical approach to nutrition, clinical practice guidelines of nutrition care in patients with cancer have been developed and published by international oncology and nutrition societies. By analyzing the more recent guidelines, it appears that a number of issues may contribute to their insufficient implementation in daily practice. Among them are heterogeneity of recommendations across different guidelines and insufficient robustness of evidence, as well as questionable generalization of recommendations. Future guidelines should aim at providing tumor-specific recommendations for the whole clinical journey of patients with cancer. Also, new, interesting areas should be covered, including fasting metabolism and circadian rhythmicity.

Case presentation and panel discussion: Nutrition issues in cancer.

Advances in treatment of malignancy including novel pharmacologic therapies and surgical interventions has led to significant improvement in survival. As cancer becomes a chronic disease, nutrition interventions play an increasingly important role in short- and long-term outcomes. The current manuscript presents a case of a 66-year-old male with new diagnosis of pancreatic cancer diagnosed incidentally in the setting of COVID-19. Expert panelists in the field of nutrition discuss optimal strategies for diagnosis of malnutrition along with preoperative, perioperative, and postoperative optimization of nutrition. This discussion focuses on the use of probiotics, immune-modulating nutrition, fish oil, specialized proresolving mediators, and use of enteral and parenteral nutrition support.