Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials.

Background: Driven by reduced nutritional intakes and metabolic alterations, malnutrition in cancer patients adversely affects quality of life, treatment tolerance and survival. We examined evidence for oral nutritional interventions during chemo(radio)therapy. Design: We carried out a systematic review of randomized controlled trials (RCT) with either dietary counseling (DC), high-energy oral nutritional supplements (ONS) aiming at improving intakes or ONS enriched with protein and n-3 polyunsaturated fatty acids (PUFA) additionally aiming for modulation of cancer-related metabolic alterations. Meta-analyses were carried out on body weight (BW) response to nutritional interventions, with subgroup analyses for DC and/or high-energy ONS or high-protein n-3 PUFA-enriched ONS. Results: Eleven studies were identified. Meta-analysis showed overall benefit of interventions on BW during chemo(radio)therapy (+1.31 kg, 95% CI 0.24-2.38, P = 0.02, heterogeneity Q = 21.1, P = 0.007). Subgroup analysis showed no effect of DC and/or high-energy ONS (+0.80 kg, 95% CI -1.14 to 2.74, P = 0.32; Q = 10.5, P = 0.03), possibly due to limited compliance and intakes falling short of intake goals. A significant effect was observed for high-protein n-3 PUFA-enriched intervention compared with isocaloric controls (+1.89 kg, 95% CI 0.51-3.27, P = 0.02; Q = 3.1 P = 0.37). High-protein, n-3 PUFA-enriched ONS studies showed attenuation of lean body mass loss (N = 2 studies) and improvement of some quality of life domains (N = 3 studies). Overall, studies were limited in number, heterogeneous, and inadequately powered to show effects on treatment toxicity or survival. Conclusion: This systematic review suggests an overall positive effect of nutritional interventions during chemo(radio)therapy on BW. Subgroup analyses showed effects were driven by high-protein n-3 PUFA-enriched ONS, suggesting the benefit of targeting metabolic alterations. DC and/or high-energy ONS were less effective, likely due to cumulative caloric deficits despite interventions. We highlight the need and provide recommendations for well-designed RCT to determine the effect of nutritional interventions on clinical outcomes, with specific focus on reaching nutritional goals and providing the right nutrients, as part of an integral supportive care approach.

Malnutrition is prevalent in patients with cardiorenal syndrome and negatively influences clinical outcome.

Cardiorenal syndrome (CRS) describes the concurrent failure of cardiac and renal function, each influencing the other. Malnutrition and cachexia frequently develop in patients with heart failure or kidney failure. However, no information is currently available on the prevalence of malnutrition in CRS patients. We studied CRS patients admitted to an internal medicine ward during a 5-month period and evaluated their clinical characteristics and nutritional status. Malnutrition risk was assessed by using the validated screening tool NRS-2002 whilst body composition was assessed by bioimpedance analysis and muscle function was measured by handgrip (HG) strength. Cardiac mass was also recorded. Length of stay, hospital readmission and 6-month mortality were registered. During the study period, 22 CRS patients were studied. Twenty patients were diagnosed with either CRS type 1 or CRS type 5. In CRS patients, fat-free mass showed a trend toward representing a protective factor for 6-month mortality (OR=0.904; p=0.06). Also, fat-free mass correlated with HG strength and cardiac ejection fraction. Malnutrition risk was diagnosed in 45% of the patients, whereas 8 patients met the definition of cachexia. Even without statistical significance, CRS patients with malnutrition had lower BMI (Body Mass Index) (p=0.038) and fat-free mass (p= n.s.). However, CRS malnutrition was associated to higher 6-month mortality (p= 0.05), and appears to negatively influence the outcome in CRS (OR= 9; p= 0.06). Our results show that malnutrition is prevalent in CRS patients and influences the clinical outcome. The assessment of nutritional status, and particularly body composition, should be implemented in daily practice of patients with CRS.

Altered diurnal cardiac sympathovagal balance correlates with nutritional status indexes in systemic sclerosis patients.

Autonomic nervous system is involved in body weight regulation. Gastrointestinal manifestations of systemic sclerosis (SSc) can influence patients’ nutritional status and facilitate the development of protein–energy malnutrition. The aim of the study is to assess the nutritional status of SSc patients and to explore its possible correlation with autonomic dysfunction using heart rate variability (HRV). We enrolled 19 SSc subjects and 19 healthy subjects as controls. Body mass index (BMI) and body surface area (BSA) were collected and recorded in all patients. HRV was measured and the domains of low frequencies (LF, index of the sympathetic modulation) and high frequencies (HF, index of the parasympathetic modulation) were recorded. As assessed by the LF/HF RATIO, sympathovagal balance is altered in SSc patients because of increased sympathetic modulation and reduced parasympathetic activity. BMI positively correlates with LF (r=0.57; p less than 0.01) and LF/HF RATIO during daytime (r= 0.46; p less than 0.05). Similarly, BSA positively correlates with LF (r= 0.51; p less than 0.05), LF day time (r= 0.53; p less than 0.05) and LF/HF RATIO night time (r=-0.51; p less than 0.05). In SSc patients the autonomic dysfunction is characterized by increased sympathetic modulation. We observed a correlation between autonomic dysfunction and nutritional status in SSc patients.

Linguistic and content validation of the translated and culturally adapted patient-generated subjective global assessment (PG-SGA).

The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument to screen, assess and monitor malnutrition and risk factors, and to triage for interventions. After having translated and culturally adapted the original PG-SGA for the Italian setting, according to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles, we tested linguistic validity, i.e., perceived comprehensibility and difficulty, and content validity (relevance) of the Italian version of the PG-SGA in patients with cancer and a multidisciplinary sample of healthcare professionals (HCPs). METHODS: After the translation and cultural adaptation of the original PG-SGA for the Italian setting, the patient component (i.e., PG-SGA Short Form (SF) was tested for linguistic validity (i.e., comprehensibility ad difficulty) in 120 Italian patients with cancer and 81 Italian HCPs. The full PG-SGA, i.e., patient and professional component of the PG-SGA, was tested for content validity, i.e., relevance, in 81 Italian HCPs. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Through item and scale indices we evaluated the comprehensibility (I-CI, S-CI), difficulty (I-DI, S-DI) and content validity (I-CVI, S-CVI). Scale indices 0.80-0.89 were considered acceptable, and scale indices ≥0.90 were considered excellent. RESULTS: Patients perceived comprehensibility and difficulty of the PG-SGA SF (Boxes) as excellent (S-CI = 0.98, S-DI = 0.96). Professionals perceived comprehensibility of the professional component (Worksheets) as excellent (S-CI = 0.92), difficulty as acceptable (S-DI = 0.85), and content validity of the full PG-SGA as excellent (S-CVI = 0.92). Dietitians gave higher scores (indicating better scores) on comprehensibility, difficulty, and content validity of Worksheet 4 (physical exam) than the other professions. In Worksheet 4, four items were considered most difficult to complete and were considered below acceptable range. Relevance was perceived as excellent by professionals for both the patient component (S-CVI = 0.93) and the professional component (S-CVI = 0.90), resulting in S-CVI = 0.92 for the full PG-SGA. Slight textual modifications were implemented resulting in the final version of the Italian PG-SGA. CONCLUSIONS: Translation and cultural adaptation of the original PG-SGA resulted in the Italian version of the PG-SGA that maintained its original purpose and meaning and can be completed adequately and easily by patients and professionals. The Italian PG-SGA is considered relevant for screening, assessing and monitoring malnutrition and risk factors, as well as triaging for interventions by Italian HCPs.

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice.

Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6-7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumour-bearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (P<0.02)) and improved muscle performance (loss of max force reduced to 55-64% of TB-con (P<0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (P<0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided.

Direct effects of doxorubicin on skeletal muscle contribute to fatigue.

Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation followed in time by contraction impediment, which could be explained by DOX-induced changes in Ca(2+) responses of myotubes in vitro. The Ca(2+) responses in skeletal muscle, however, could not be explained by oxidative stress.

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia.

The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients.

[Treatment of mild malnutrition and reduction of morbidity in major abdominal surgery: randomized trial on 153 patients]. / Trattamento della malnutrizione lieve e riduzione delle compli- canze in chirurgia addominale maggiore: studio randomizzato su 153 pazienti.

OBJECTIVES: Severe malnutrition (defined as weight loss more than 10% in a period of six months) is considered an important risk factor in major abdominal surgery, because of a higher post-operative mortality and morbidity. The aim of our study is to assess the role of mild malnutrition (weight loss low than 10% in a period of six months) as a risk factor in major abdominal surgery and to evaluate the efficacy of therapy in order to improve outcomes in terms of in-hospital mortality, length of hospital stay and post-operative complications. Moreover, we evaluated serum albuminemia and lymphocyte count, important nutritional index, as predictive risk factors. MATERIALS AND METHODS: We performed a randomized prospective trial, and admitted in our institution 153 adult patients, 43 with mild malnutrition and 110 without. The malnourished patients were randomized in two groups: the first one received oral immunonutrition (Impact Oral) for 7-10 days before surgery (22 pz), the second one received no nutritional support. RESULTS: We observed a higher number of complications in the non-treated malnourished patients (57%) versus both the treated malnourished patients (13.6%) and the normal group (19%) (p<0.001). Increased morbidity was observed in patients with serum albuminemia <2.8 gr/dl (69.2%) and with lymphocyte count <1.500 mm3 (57%). CONCLUSIONS: Nutritional enriched support demonstrated his efficacy in reducing morbidity, and length of hospital stay. Pre-operative oral immunonutrition might be suggested and established in all the patients with mild malnutrition that will be operated on major abdominal surgery.

[Relationship between nutritional intervention and quality of life in cancer patients]. / Relación entre la intervención nutricional y la calidad de vida en el paciente con cáncer.

Quality of life (QOL) is a concept assessing physical, psychological and social factors which are influencing the patients' well being. Cancer and its therapy induce severe metabolic changes associated with QOL impairment. These alterations contribute to an increased energy wasting and a decreased food intake. Besides, it may lead to tumoral cachexia due to the complex interactions between pro-inflammatory cytokines and the host metabolism. On the other hand, and beyond physical impairments and metabolic effects from cancer, patients often suffer from psychological stress, such as depression. A nutritional intervention should be implemented as soon as cancer is diagnosed. It should be appropriate to the individual needs of the patient, considering the type of oncologic treatment (whether it is curative or palliative), the clinical conditions and the nutritional status. The aim is to reduce or even revert nutritional status impairment, improve the general condition, and subsequently improve quality of life. The primary focus of nutritional intervention accompanying oncologic treatment intended to cure is on the optimization of the balance between energy waste and food intake. Thus trying to achieve further specific purposes such as a decrease of rate of complications and an amelioration of the response and tolerance to the oncologic therapy. The purpose of nutritional support in palliative care is controlling the symptoms related to food intake and delaying the loss of autonomy. And by this means maintaining or improving patients' QOL. It is corraborated by a literature review, that nutritional therapy should form part of the integral oncological support since it contributes considerably to a QOL improvement. Because of the possibility to identify the patients' needs and expectations by assessing their QOL it should be generally included into their nutritional evaluation to be able to tailor the adequate nutritional support.

Nutritional status and intrarenal arterial stiffness in cardiorenal syndrome: a pilot study.

OBJECTIVE: Cardio-Renal Syndrome (CRS) is a condition, which is more frequently observed in clinical practice. The aim of this study is to explore nutritional status and intrarenal arterial stiffness in patients affected by CRS. PATIENTS AND METHODS: 14 consecutive CRS patients, screened for anthropometry, biochemistry, nutritional and metabolic status underwent renal Doppler ultrasound and whole-body bioimpedance spectroscopy (BIS). RESULTS: We found a positive correlation between phase angle (PA) and CKD-EPI and MDRD (p=0.011 and p=0.007), and between body mass index and renal resistive index (RRI) (p=0.002). Finally, we found a negative correlation between fat-free mass and RRI (p=0.024). CONCLUSIONS: Body composition assessment may improve the care of patients with chronic kidney disease (CKD). Also, BIS may help identify changes in hydration status in CKD patients resulting as a significant predictor of mortality.

ESPEN expert group recommendations for action against cancer-related malnutrition.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.

ESPEN Guidelines on Enteral Nutrition: Cardiology and pulmonology.

These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They have been discussed and accepted in a consensus conference. EN by means of oral nutritional supplements (ONS) or tube feeding (TF) enables nutritional intake to be maintained or increased when normal oral intake is inadequate. No data are yet available concerning the effects of EN on cachexia in CHF patients. However, EN is recommended to stop or reverse weight loss on the basis of physiological plausibility. In COPD patients, EN in combination with exercise and anabolic pharmacotherapy has the potential to improve nutritional status and function. Frequent small amounts of ONS are preferred in order to avoid postprandial dyspnoea and satiety as well as to improve compliance.

ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation.

Enhanced recovery of patients after surgery ("ERAS") has become an important focus of perioperative management. From a metabolic and nutritional point of view, the key aspects of perioperative care include: Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and if necessary tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in surgical patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1980. The guideline was discussed and accepted in a consensus conference. EN is indicated even in patients without obvious undernutrition, if it is anticipated that the patient will be unable to eat for more than 7 days perioperatively. It is also indicated in patients who cannot maintain oral intake above 60% of recommended intake for more than 10 days. In these situations nutritional support should be initiated without delay. Delay of surgery for preoperative EN is recommended for patients at severe nutritional risk, defined by the presence of at least one of the following criteria: weight loss >10-15% within 6 months, BMI<18.5 kg/m(2), Subjective Global Assessment Grade C, serum albumin <30 g/l (with no evidence of hepatic or renal dysfunction). Altogether, it is strongly recommended not to wait until severe undernutrition has developed, but to start EN therapy early, as soon as a nutritional risk becomes apparent.

A systematic review of the cost and cost effectiveness of using standard oral nutritional supplements in community and care home settings.

BACKGROUND & AIMS: Despite the clinical benefits of using standard (non-disease specific) oral nutritional supplements (ONS) in the community and care homes, there is uncertainty about their economic consequences. METHODS: A systematic review was undertaken according to recommended procedures to assess whether ONS can produce cost savings and cost-effective outcomes. RESULTS: 19 publications with and without a hospital component were identified: 9 full text papers, 9 abstracts, and 1 report with retrospective analyses of 6 randomised controlled trials. From these publications a total of 31 cost and 4 cost-effectiveness analyses were identified. Most were retrospective analyses based on clinical data from randomised controlled trials (RCTs). In 9 studies/economic models involving ONS use for <3 months, there were consistent cost savings compared to the control group (median cost saving 9.2%; P < 0.01). When used for ≥3 months, the median cost saving was 5% (P > 0.05; 5 studies). In RCTs, ONS accounted for less than 5% of the total costs and the investment in the community produced a cost saving in hospital. Meta-analysis indicated that ONS reduced hospitalisation significantly (16.5%; P < 0.001; 9 comparisons) and mortality non-significantly (Relative risk 0.86 (95% CI, 0.61, 1.22); 8 comparisons). Many clinically relevant outcomes favouring ONS were reported: improved quality of life, reduced infections, reduced minor post-operative complications, reduced falls, and functional limitations. Of the cost-effectiveness analyses involving quality adjusted life years or functional limitations, most favoured the ONS group. The care home studies (4 cost analyses; 2 cost-effectiveness analyses) had differing aims, designs and conclusions. CONCLUSIONS: Overall, the reviewed studies, mostly based on retrospective cost analyses, indicate that ONS use in the community produce an overall cost advantage or near neutral balance, often in association with clinically relevant outcomes, suggesting cost effectiveness. There is a need for prospective studies designed to examine primary economic outcomes.

A systematic review of the cost and cost effectiveness of using standard oral nutritional supplements in the hospital setting.

BACKGROUND & AIMS: There is limited information about the economic impact of nutritional support despite its known clinical benefits. This systematic review examined the cost and cost effectiveness of using standard (non-disease specific) oral nutritional supplements (ONS) administered in the hospital setting only. METHODS: A systematic literature search of multiple databases, data synthesis and analysis were undertaken according to recommended procedures. RESULTS: Nine publications comprising four full text papers, two abstracts and three reports, one of which contained 11 cost analyses of controlled cohort studies, were identified. Most of these were based on retrospective analyses of randomised controlled trials designed to assess clinically relevant outcomes. The sample sizes of patients with surgical, orthopaedic and medical problems and combinations of these varied from 40 to 1.16 million. Of 14 cost analyses comparing ONS with no ONS (or routine care), 12 favoured the ONS group, and among those with quantitative data (12 studies) the mean cost saving was 12.2%. In a meta-analysis of five abdominal surgical studies in the UK, the mean net cost saving was £746 per patient (se £338; P = 0.027). Cost savings were typically associated with significantly improved outcomes, demonstrated through the following meta-analyses: reduced mortality (Risk ratio 0.650, P < 0.05; N = 5 studies), reduced complications (by 35% of the total; P < 0.001, N = 7 studies) and reduced length of hospital stay (by ∼2 days, P < 0.05; N = 5 surgical studies) corresponding to ∼13.0% reduction in hospital stay. Two studies also found ONS to be cost effective, one by avoiding development of pressure ulcers and releasing hospital beds, and the other by gaining quality adjusted life years. CONCLUSION: This review suggests that standard ONS in the hospital setting produce a cost saving and are cost effective. The evidence base could be further strengthened by prospective studies in which the primary outcome measures are economic.