Association of tryptophan pathway metabolites with mortality and effectiveness of nutritional support among patients at nutritional risk: secondary analysis of a randomized clinical trial.

Tryptophan is an essential amino acid and is the precursor of many important metabolites and neurotransmitters. In malnutrition, the availability of tryptophan is reduced, potentially putting patients at increased risks. Herein, we investigated the prognostic implications of the tryptophan metabolism in a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized, controlled trial comparing individualized nutritional support to usual care in patients at risk for malnutrition. Among 238 patients with available measurements, low plasma levels of metabolites were independently associated with 30-day mortality with adjusted hazard ratios (HR) of 1.77 [95% CI 1.05-2.99, p 0.034] for tryptophan, 3.49 [95% CI 1.81-6.74, p < 0.001] for kynurenine and 2.51 [95% CI 1.37-4.63, p 0.003] for serotonin. Nutritional support had more beneficial effects on mortality in patients with high tryptophan compared to patients with low tryptophan levels (adjusted HR 0.61 [95% CI 0.29-1.29] vs. HR 1.72 [95% CI 0.79-3.70], p for interaction 0.047). These results suggest that sufficient circulating levels of tryptophan might be a metabolic prerequisite for the beneficial effect of nutritional interventions in this highly vulnerable patient population.

Prognostic implications of the arginine metabolism in patients at nutritional risk: A secondary analysis of the randomized EFFORT trial.

BACKGROUND: Arginine, a conditionally essential amino acid, is key component in metabolic pathways including immune regulation and protein synthesis. Depletion of arginine contributes to worse outcomes in severely ill and surgical patient populations. We assessed prognostic implications of arginine levels and its metabolites and ratios in polymorbid medical inpatients at nutritional risk regarding clinical outcomes and treatment response. METHODS: Within this secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), we investigated the association of arginine, its metabolites and ratios (i.e., ADMA and SDMA, ratios of arginine/ADMA, arginine/ornithine, and global arginine bioavailability ratio) measured on hospital admission with short-term and long-term mortality by means of regression analysis. RESULTS: Among the 231 patients with available measurements, low arginine levels ≤90.05 µmol/l (n = 86; 37 %) were associated with higher all-cause mortality at 30 days (primary endpoint, adjusted HR 3.27, 95 % CI 1.86 to 5.75, p < 0.001) and at 5 years (adjusted HR 1.50, 95 % CI 1.07 to 2.12, p = 0.020). Arginine metabolites and ratios were also associated with adverse outcome, but had lower prognostic value. There was, however, no evidence that treatment response was influenced by admission arginine levels. CONCLUSION: This secondary analysis focusing on medical inpatients at nutritional risk confirms a strong association of low plasma arginine levels and worse clinical courses. The potential effects of arginine-enriched nutritional supplements should be investigated in this population of patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov as NCT02517476 (registered 7 August 2015).

Red blood cell distribution width (RDW) - A new nutritional biomarker to assess nutritional risk and response to nutritional therapy?

BACKGROUND & AIMS: Red cell distribution width (RDW) has been proposed as a surrogate marker for acute and chronic diseases and may be influenced by nutritional deficits. We assessed the prognostic value of RDW regarding clinical outcomes and nutritional treatment response among medical inpatients at nutritional risk. METHODS: This is a secondary analysis of EFFORT, a randomized, controlled, prospective, multicenter trial investigating the effects of nutritional support in patients at nutritional risk in eight Swiss hospitals. We examined the association between RDW and mortality in regression analysis. RESULTS: Among 1,244 included patients (median age 75 years, 46.6 % female), high RDW (≥15 %) levels were found in 38 % of patients (n = 473) with a significant association of higher malnutrition risk [OR 1.48 (95%CI 1.1 to 1.98); p = 0.009]. Patients with high RDW had a more than doubling in short-term (30 days) mortality risk [adjusted HR 2.12 (95%CI 1.44 to 3.12); p < 0.001] and a signficant increase in long-term (5 years) mortality risk [adjusted HR 1.73 (95%CI 1.49 to 2.01); p < 0.001]. Among patients with high RDW, nutritional support reduced morality within 30 days [adjusted OR 0.56 (95%CI 0.33 to 0.96); p = 0.035], while the effect of the nutritional intervention in patients with low RDW was markedly smaller. CONCLUSIONS: Among medical patients at nutritional risk, RDW correlated with several nutritional parameters and was a strong prognostic marker for adverse clinical outcomes at short- and long-term, respectively. Patients with high baseline RDW levels also showed a strong benefit from the nutritional intervention. Further research is needed to understand whether monitoring of RDW over time severs as a nutritional biomarker to assess effectiveness of nutritional treatment in the long run. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Adaptation of nutritional risk screening tools may better predict response to nutritional treatment: a secondary analysis of the randomized controlled trial Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT).

BACKGROUND: Nutritional screening tools have proven valuable for predicting clinical outcomes but have failed to determine which patients would be most likely to benefit from nourishment interventions. The Nutritional Risk Screening 2002 (NRS) and the Mini Nutritional Assessment (MNA) are 2 of these tools, which are based on both nutritional parameters and parameters reflecting disease severity. OBJECTIVES: We hypothesized that the adaptation of nutritional risk scores, by removing parameters reflecting disease severity, would improve their predictive value regarding response to a nutritional intervention while providing similar prognostic information regarding mortality at short and long terms. METHODS: We reanalyzed data of 2028 patients included in the Swiss-wide multicenter, randomized controlled trial EFFORT (Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial) comparing individualized nutritional support with usual care nutrition in medical inpatients. The primary endpoint was 30-d all-cause mortality. RESULTS: Although stratifying patients by high compared with low NRS score showed no difference in response to nutritional support, patients with high adapted NRS showed substantial benefit, whereas patients with low adapted NRS showed no survival benefit [adjusted hazard ratio: 0.55 [95% confidence interval (CI): 0.37, 0.80]] compared with 1.17 (95% CI: 0.70, 1.93), a finding that was significant in an interaction analysis [coefficient: 0.48 (95% CI: 0.25, 0.94), P = 0.031]. A similar effect regarding treatment response was found when stratifying patients on the basis of MNA compared with the adapted MNA. Regarding the prognostic performance, both original scores were slightly superior in predicting mortality than the adapted scores. CONCLUSIONS: Adapting the NRS and MNA by including nutritional parameters only improves their ability to predict response to a nutrition intervention, but slightly reduces their overall prognostic performance. Scores dependent on disease severity may best be considered prognostic scores, whereas nutritional risk scores not including parameters reflecting disease severity may indeed improve a more personalized treatment approach for nourishment interventions. The trial was registered at clinicaltrials.gov as NCT02517476.

Association of Glutamine and Glutamate Metabolism with Mortality among Patients at Nutritional Risk-A Secondary Analysis of the Randomized Clinical Trial EFFORT.

Glutamine and its metabolite glutamate serve as the main energy substrates for immune cells, and their plasma levels drop during severe illness. Therefore, glutamine supplementation in the critical care setting has been advocated. However, little is known about glutamine metabolism in severely but not critically ill medical patients. We investigated the prognostic impact of glutamine metabolism in a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care in patients at nutritional risk. Among 234 patients with available measurements, low plasma levels of glutamate were independently associated with 30-day mortality (adjusted HR 2.35 [95% CI 1.18-4.67, p = 0.015]). The impact on mortality remained consistent long-term for up to 5 years. No significant association was found for circulating glutamine levels and short- or long-term mortality. There was no association of glutamate nor glutamine with malnutrition parameters or with the effectiveness of nutritional support. This secondary analysis found glutamate to be independently prognostic among medical inpatients at nutritional risk but poorly associated with the effectiveness of nutritional support. In contrast to ICU studies, we found no association between glutamine and clinical outcome.

Association of admission cortisol levels with outcomes and treatment response in patients at nutritional risk : A secondary analysis of a randomized clinical trial.

INTRODUCTION: Cortisol is a metabolically active stress hormone that may play a role in the pathogenesis of malnutrition. We studied the association between admission cortisol levels and nutritional parameters, disease severity, and response to nutritional support among medical inpatients at nutritional risk. METHODS: Admission cortisol was measured in a subset of 764 patients participating in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicentre, randomized-controlled trial that compared individualized nutritional support with usual nutritional care. RESULTS: Overall, mean cortisol levels were 570 (± 293) nmol/L and significantly higher in patients with high nutritional risk (NRS ≥ 5) and in patients reporting loss of appetite. Cortisol levels in the highest quartile (> 723 nmol/l) were associated with adverse outcomes including mortality at 30 days and 5 years (adjusted HR 2.31, [95%CI 1.47 to 3.62], p = 0.001 and 1.51, [95%CI 1.23 to 1.87], p < 0.001). Nutritional treatment tended to be more effective regarding mortality reduction in patients with high vs. low cortisol levels (adjusted OR of nutritional support 0.54, [95%CI 0.24 to 1.24] vs. OR 1.11, [95%CI 0.6 to 2.04], p for interaction = 0.134). This effect was most pronounced in the subgroup of patients with severe malnutrition (NRS 2002 ≥ 5, p for interaction = 0.047). CONCLUSION: This secondary analysis of a randomized nutritional trial suggests that cortisol levels are linked to nutritional and clinical outcome among multimorbid medical patients at nutritional risk and may help to improve risk assessment, as well as response to nutritional treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Changes in serum albumin concentrations over 7 days in medical inpatients with and without nutritional support. A secondary post-hoc analysis of a randomized clinical trial.

BACKGROUND: Serum albumin concentrations are frequently used to monitor nutritional therapy in the hospital setting but supporting studies are largely lacking. Within this secondary analysis of a randomized nutritional trial (EFFORT), we assessed whether nutritional support affects short-term changes in serum albumin concentrations and whether an increase in albumin concentration has prognostic implications regarding clinical outcome and response to treatment. METHODS: We analyzed patients with available serum albumin concentrations at baseline and day 7 included in EFFORT, a Swiss-wide multicenter randomized clinical trial that compared individualized nutritional therapy with usual hospital food (control group). RESULTS: Albumin concentrations increased in 320 of 763 (41.9%) included patients (mean age 73.3 years (SD ± 12.9), 53.6% males) with no difference between patients receiving nutritional support and controls. Compared with patients that showed a decrease in albumin concentrations over 7 days, those with an increase had a lower 180-day mortality [74/320 (23.1%) vs. 158/443 (35.7%); adjusted odds ratio 0.63, 95% CI 0.44 to 0.90; p = 0.012] and a shorter length of hospital stay [11.2 ± 7.3 vs. 8.8 ± 5.6 days, adjusted difference -2.2 days (95%CI -3.1 to -1.2)]. Patients with and without a decrease over 7 days had a similar response to nutritional support. CONCLUSION: Results from this secondary analysis indicate that nutritional support did not increase short-term concentrations of albumin over 7 days, and changes in albumin did not correlate with response to nutritional interventions. However, an increase in albumin concentrations possibly mirroring resolution of inflammation was associated with better clinical outcomes. Repeated in-hospital albumin measurements in the short-term is, thus, not indicated for monitoring of patients receiving nutritional support but provides prognostic information. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

[Malnutrition in internal medicine : Screening, assessment and importance]. / Mangelernährung in der Inneren Medizin : Screening, Assessment und Bedeutung.

Disease-related malnutrition has a strong influence on the further course of the disease and mortality, especially in chronically ill patients. In recent years it could be shown in large randomized studies that an individual nutrition therapy could significantly and relevantly improve the clinical outcome of patients in internal medicine with a risk of malnutrition, both in hospital and in aftercare. Therefore, due to the increasing proportion of multimorbid patients the significance of malnutrition and its treatment is becoming increasingly more important in the practice and in research. Nutritional medicine should nowadays be considered as an effective and integral component of a holistic treatment in internal medicine; however, further research is necessary in order to investigate new nutritional biomarkers and for a better integration of an evidence-based personalized nutritional medicine into routine clinical practice.

Association between prealbumin, all-cause mortality, and response to nutrition treatment in patients at nutrition risk: Secondary analysis of a randomized controlled trial.

BACKGROUND: Because of the shorter half-life as compared with albumin, serum prealbumin concentrations have been proposed to be useful nutrition biomarkers for the assessment of patients at nutrition risk. In a post hoc analysis of patients at nutrition risk from a randomized controlled nutrition trial, we tested the hypothesis that (1) prealbumin is associated with higher all-cause 180-day mortality rates and that (2) individualized nutrition support compared with usual-care nutrition more effectively improves survival at 30 days in patients with low prealbumin levels compared with patients with normal prealbumin levels. METHODS: We performed a prespecified cohort study in patients included in the pragmatic, Swiss, multicenter randomized controlled EFFORT trial comparing the effects of individualized nutrition support with usual care. We studied low prealbumin concentrations (<0.17 g/L) in a subgroup of 517 patients from one participating center. RESULTS: A total of 306 (59.2%) patients (mean age 71.9 years, 53.6% men) had low admission prealbumin levels (<0.17 g/L). There was a significant association between low prealbumin levels and mortality at 180 days (115/306 [37.6%] vs 47/211 [22.3%], fully adjusted hazard ratio [HR]=1.59, 95% CI 1.11-2.28; P = 0.011). Prealbumin levels significantly improved the prognostic value of the Nutritional Risk Screening total score regarding mortality prediction at short- and long-term. The difference in mortality between patients receiving individualized nutrition support and usual-care nutrition was similar for patients with low prealbumin levels compared with patients with normal prealbumin levels (HR=0.90 [95% CI=0.51-1.59] vs HR=0.88 [95% CI=0.35-2.23]) with no evidence for interaction (P = 0.823). CONCLUSION: Among medical inpatients at nutrition risk, low admission prealbumin levels correlated with different nutrition markers and higher mortality risk, but patients with low or high prealbumin levels had a similar benefit from nutrition support. Further studies should identify nutrition markers that help further personalize nutrition interventions.

Association of CT-based diagnosis of sarcopenia with prognosis and treatment response in patients at risk of malnutrition - A secondary analysis of the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial.

BACKGROUND & AIM: CT-derived measures of muscle mass may help to identify patients with sarcopenia. We investigated the prognostic significance of CT-derived sarcopenia and muscle attenuation with nutritional markers, clinical outcomes and response to nutritional support in medical in-patients at nutritional risk. METHOD: Within this secondary analysis of the randomized-controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) comparing individualized nutritional support with usual care nutrition in medical inpatients, we investigated associations of CT-based sarcopenia and muscle attenuation at the level L3 with different nutritional and clinical outcomes, and the response to the nutritional intervention. The primary composite endpoint was adverse clinical outcome within 30 days of hospital admission. RESULTS: We included 573 of 2028 EFFORT patients with available CT scans, of which 68.4% met the CT-based definition of sarcopenia and 72.9% had low muscle attenuation. In multivariate analysis, low skeletal muscle index was associated with higher nutritional risk (coefficient per NRS class -0.94 (95%CI -1.87 to -0.01) p = 0.049) and higher risk for adverse clinical outcomes (adjusted odds ratio 1.59 (95% CI 1.06 to 2.38), p = 0.024). Low muscle attenuation was also associated with adverse clinical outcome (adjusted odds ratio 1.67 (95%CI 1.08 to 2.58), p = 0.02). Nutritional support tended to be more effective in reducing mortality in non-sarcopenic patients compared to patients with CT-based sarcopenia (p for interaction 0.058). CONCLUSIONS: Within a population of medical patients at nutritional risk, CT-based sarcopenia and muscle attenuation were associated with several nutritional parameters and predicted adverse clinical outcomes. Information from CT scans, thus may help to better characterize these patients, and may be helpful in guiding therapeutic interventions.

Low T3 Syndrome on Admission and Response to Nutritional Support in Malnourished Medical Inpatients.

CONTEXT: During illness, deiodination of thyroxine (T4) to triiodothyronine (T3) is downregulated. This is called "low T3 syndrome", an adaptive metabolic mechanism to reduce energy expenditure and prevent catabolism. OBJECTIVE: We aimed to investigate the prognostic role of low T3 syndrome in patients at nutritional risk regarding mortality, clinical outcomes, and response to nutritional support. METHODS: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled, Swiss, multicenter trial comparing effects of individualized nutritional support with usual care in adult medical inpatients at nutritional risk. The primary endpoint was all-cause mortality over 30, 180 days, and 5 years. RESULTS: We had complete data including fT3 concentration of 801/2028 (39.5%) patients from the initial trial. Of these 492 (61.4%) had low T3 syndrome (fT3 < 3.2 pmol/L). Low T3 syndrome was associated with higher mortality over 30 days (adjusted hazard ratio 1.97, 95% CI 1.17-3.31, P = .011) and other adverse clinical outcomes. Nutritional support only lowered mortality in the group of patients with low T3 syndrome but not in those without low T3 syndrome (adjusted odds ratio of nutritional support of 0.82 [95% CI 0.47-1.41] vs 1.47 [95% CI 0.55-3.94]). This finding, however, was not significant in interaction analysis (P for interaction = .401). CONCLUSION: Our secondary analysis of a randomized trial suggests that medical inpatients at nutritional risk with low T3 syndrome have a substantial increase in mortality and may show a more pronounced beneficial response to nutritional support interventions.

Nutrition issues in the general medical ward patient: From general screening to specific diagnosis and individualized treatment.

Disease-related malnutrition in patients in the general medical ward remains a complex syndrome, which contributes to high morbidity and mortality, and seriously interferes with recovery from acute illness. Recently, there have been important advances in the development of consensus diagnostic criteria for malnutrition, and through the recent completion of large-scale trials, the understanding of pathophysiological pathways and evidence-based treatment algorithms to provide nutrition care to patients at risk for malnutrition in the hospital setting has advanced. There is need to identify more specific clinical parameters and blood biomarkers, which allow a more personalized approach to the malnourished patients, because not all patients show the same response to nutrition interventions. Recent studies have suggested that some nutrition biomarkers of inflammation, kidney function and muscle health, among others, predict treatment response to nutrition interventions and may help to personalize treatments. In addition to advancing the science, there is need for more education of students and treating teams in the hospital to improve the screening of patients at hospital admission regarding nutrition risk with the start of individualized nutrition support interventions, thereby bringing optimal nutrition care to the bedside.

Prospective validation of five malnutrition screening and assessment instruments among medical inpatients: Secondary analysis of a randomized clinical trial.

BACKGROUND & AIMS: Screening for malnutrition upon hospital admission is the first crucial step for proper nutritional assessment and treatment. While several nutritional screening and assessment instruments exist, there is a lack of head-to-head validation of these instruments. We studied the ability of five different nutrition screening and assessment instruments to predict 1-year mortality and response to nutritional treatment in participants of the EFFORT randomized trial. METHODS: In this secondary analysis of a Swiss-wide multicenter, randomized clinical trial comparing individualized nutritional support with usual care nutrition in medical inpatients, we prospectively classified patients as low, intermediate, and high nutritional risk based on five nutritional screening and assessment instruments (NRS 2002, SGA, SNAQ, MNA and MUST). RESULTS: Overall mortality at 1-year in the 1866 included patients was 30.4%. There were significant correlations and a significant concordance between all instruments with r-values ranging from 0.23 to 0.55 and kappa values ranging from 0.10 to 0.36. While high nutritional risk was associated with higher mortality in all instruments, SGA and MNA showed the strongest association with adjusted odds ratios of 3.17 (95%CI, 2.18 to 4.61, p < 0.001) and 3.45 (95%CI, 2.28 to 5.22, p < 0.001). When comparing mortality in intervention group patients to control group patients stratified by severity of malnutrition, there was overall no clear trend towards more benefit in patients with more severe malnutrition, with NRS 2002 and SGA showing the most pronounced relationship between the severity of malnutrition and reduction in mortality as a response to nutritional support. CONCLUSION: Among all five screening and assessment instruments, higher nutritional risk was associated with higher risk for mortality and adverse clinical outcome, but not with more or less treatment response from nutritional support with differences among scores. Adding more specific parameters to these instruments is important when using them to decide for or against nutritional support interventions in an individual patient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02517476.

Handgrip Strength Values Depend on Tumor Entity and Predict 180-Day Mortality in Malnourished Cancer Patients.

BACKGROUND: Cancer-related malnutrition is a prevalent condition associated with a loss of muscle mass and impaired functional status, leading to immunodeficiency, impaired quality of life and adverse clinical outcomes. Handgrip strength (HGS) is a practical measure to assess muscle strength in individual patients during clinical practice. However, HGS reference values refer to populations of healthy people, and population-specific values, such as those in the population of cancer patients, still need to be defined. METHODS: Within a secondary analysis of a previous randomized controlled nutritional trial focusing on hospitalized cancer patients at risk for malnutrition, we investigated sex-specific HGS values stratified by age and tumor entity. Additionally, we examined the association between HGS and 180-day all-cause mortality. RESULTS: We included data from 628 cancer patients, which were collected from eight hospitals in Switzerland. Depending on the age of patients, HGS varied among female patients from 7 kg to 26 kg and among male patients from 20.5 kg to 44 kg. An incremental decrease in handgrip strength by 10 kg resulted in a 50% increase in 180-day all-cause mortality (odds ratio 1.52 (95%CI 1.19 to 1.94), p = 0.001). CONCLUSION: Our data provide evidence of the prognostic implications of HGS measurement in cancer patients and validate the prognostic value of handgrip strength in regard to long-term mortality. In addition, our results provide expected HGS values in the population of hospitalized malnourished cancer patients, which may allow better interpretation of values in individual patients.

Validation of modified GLIM criteria to predict adverse clinical outcome and response to nutritional treatment: A secondary analysis of a randomized clinical trial.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) recently suggested specific criteria to standardize the diagnosis of malnutrition. There is need for validation of these criteria regarding response to nutrition treatment. Our aim was to validate modified GLIM (mGLIM) criteria among medical inpatients at risk of disease related malnutrition for prediction of outcome and response to nutritional therapy. METHODS: This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicenter randomized controlled trial conducted between April 2014 and February 2018. Adult medical inpatients at nutritional risk (Nutrition Risk Score 2002 ≥ 3 points) were randomly assigned to receive nutritional therapy according to an algorithm based on individualized nutritional requirements (intervention group) or standard hospital food (control group). We included all participants with available information regarding mGLIM criteria. The primary outcome was adverse clinical outcome, which was a composite of 30-day all-cause mortality, ICU-admission, rehospitalization rate, major complications and decline in functional status. RESULTS: Of 1917 eligible participants at nutritional risk, 1181 (61.6%) met the diagnosis of malnutrition based on mGLIM criteria. The incidence of adverse clinical outcome was significantly higher in mGLIM-positive participants compared with mGLIM-negative participants [330/1181 (27.9%) versus 140/736 (19.0%); multivariable adjusted odds ratio [OR] 1.53; 95% CI 1.22-1.93; p < 0.001]. Regarding the effect of nutritional therapy, the reduction in adverse clinical outcomes was higher in mGLIM-positive participants [180/581 (31.0%) vs. 150/600 (25.0%), OR 0.69; 95% CI 0.53-0.9, p = 0.007], compared with mGLIM-negative participants [75/379 (19.8%) versus 65/357 (18.2%), OR 0.95; 95% CI 0.65-1.40, p = 0.797], a finding that was, however, not significant in interaction analysis (p for interaction = 0.217). CONCLUSION: Data from this secondary analysis of a multicenter randomized trial involving medical inpatients at nutritional risk validate the strong prognostic value of mGLIM criteria regarding adverse clinical outcomes and other long-term outcomes. However, further research is needed to improve the ability of GLIM criteria to predict therapeutic response to nutritional interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Admission serum albumin concentrations and response to nutritional therapy in hospitalised patients at malnutrition risk: Secondary analysis of a randomised clinical trial.

BACKGROUND: Historically, admission serum albumin concentrations have been considered useful biochemical markers for nutrition assessment. However, there is a lack of randomised trial data investigating whether low albumin concentrations are helpful for identifying patients benefitting from nutritional support. METHODS: This study was a secondary analysis of the EFFORT trial, a Swiss-wide multicentre, randomised controlled trial comparing individualised nutritional support with usual care nutrition in medical inpatients from April 1, 2014, to February 1, 2018. 1389 of 2028 patients at nutritional risk with available albumin concentrations on admission were included. The primary endpoint was all-cause mortality within 30 and 180 days. Patients were stratified into groups of low or normal albumin based on the albumin cut-off of 30 g/L. ClinicalTrials.gov number, NCT02517476. FINDINGS: 1389 patients (mean age, 73.1 (SD 3.5) years; 747 (53.8%) men) were included and 676 (48.7%) had low serum albumin concentrations at admission (<30 g/L). Mortality at 180 days was significantly increased in the low albumin group compared with patients with normal albumin concentrations (219/676 (32.4%) vs. 162/713 (22.7%), fully adjusted HR 1.4, 95%CI 1.11 to 1.77, p = 0.005]. Effects of nutritional support on 30-day mortality were similar for patients with low compared to patients with normal albumin concentrations (HR 0.68, 95%CI 0.44 to 1.05 vs. HR 0.70, 95%CI 0.41 to 1.20), with no evidence for a subgroup effect (p for interaction=0.97). INTERPRETATION: Based on this secondary analysis of a randomised trial, low admission serum albumin concentrations in hospitalised, non-critically ill, medical patients at nutritional risk had prognostic implications and indicated higher mortality risk but were not helpful in selecting patients for nutritional interventions. FUNDING: The Swiss National Science Foundation (SNSF) (PP00P3_150531) and the Research Council of the Kantonsspital Aarau (1410.000.058 and 1410.000.044) provided funding for the EFFORT trial.

Effect of micronutrient supplementation in addition to nutritional therapy on clinical outcomes of medical inpatients: results of an updated systematic review and meta-analysis.

BACKGROUND: There is increasing evidence from randomized controlled trials showing that different types of nutritional support interventions improve clinical outcomes in malnourished medical inpatients. Whether trials using micronutrient supplementation in addition to nutritional therapy are superior to trials without micronutrient supplementation remains unclear. METHODS: This is a secondary analysis of a systematic search and meta-analysis. We searched Cochrane Library, MEDLINE, and EMBASE electronic database from inception to December 15, 2020, for randomized controlled trials comparing the nutritional support interventions vs. usual care on all-cause mortality (primary endpoint) of medical inpatients with nutritional risk. We stratified trials based on whether or not micronutrient supplementation was used as part of the nutritional strategy. RESULTS: We included 23 randomized controlled trials (5 trials with and 18 trials without micronutrient supplementation) with a total of 6745 patients. Overall, mortality was significantly lower in patients receiving nutritional support compared to control group patients with an odds ratio of 0.74 (95% CI 0.59-0.94, p = 0.01). There was no difference between trials with and without micronutrient supplementation on mortality (odds ratio 0.70 (95% CI 0.46-1.08) vs. 0.77 (95% CI 0.57-1.04), I2 = 0%, p for subgroup difference = 0.73). Similarly, no differences in effect were found regarding non-elective readmissions and length of hospital stay. CONCLUSIONS: While nutritional support reduces mortality and improves other clinical outcomes, we did not find evidence that trials using micronutrient supplementation in addition to nutritional therapy were superior to trials with no supplementation. The role of micronutrient supplementation in addition to nutritional support needs further research.

Nutritional trials using high protein strategies and long duration of support show strongest clinical effects on mortality.: Results of an updated systematic review and meta-analysis.

BACKGROUND: There is increasing evidence from randomized-controlled trials demonstrating that nutritional support improves clinical outcomes in the population of malnourished medical inpatients. We investigated associations of trial characteristics including clinical setting, duration of intervention, individualization of nutritional support and amount of energy and protein, and effects on clinical outcomes in an updated meta-analysis. METHODS: We searched Cochrane Library, MEDLINE and EMBASE, from inception to December 15, 2020. Randomized-controlled trials investigating the effect of oral and enteral nutritional support interventions, when compared to usual care, on clinical outcomes of malnourished non-critically ill medical inpatients were included. Two reviewers independently extracted data and assessed risk of bias. The primary endpoint was all cause-mortality within 12-months. RESULTS: We included 29 randomized-controlled trials with a total of 7,166 patients. Heterogeneity across RCTs was high, with overall moderate study quality and mostly moderate or unclear risk of bias. Overall, there was an almost 30%-reduction in mortality in patients receiving nutritional support compared to patients not receiving nutritional support (253/2960 [8.5%] vs. 336/2976 [11.3%]) with an odds ratio of 0.72 (95% CI 0.57 to 0.91, p = 0.006). The most important predictors for the effect of nutritional trials on mortality were high protein strategies (odds ratio 0.57 vs. 0.93, I2 = 86.3%, p for heterogenity = 0.007) and long-term nutritional interventions (odds ratio 0.53 vs. 0.85, I2 = 76.2%, p for heterogenity = 0.040). Nutritional support also reduced unplanned hospital readmissions and length of hospital stay. CONCLUSIONS: There is increasing evidence from randomized trials showing that nutritional support significantly reduces mortality, unplanned hospital readmissions and length of stay in medical inpatients at nutritional risk, despite heterogeneity and varying methodological quality among trials. Trials with high-protein strategies and long-lasting nutritional support interventions were most effective.

The impact of nutritional support on malnourished inpatients with aging-related vulnerability.

OBJECTIVES: Malnutrition is highly prevalent in patients with aging-related vulnerability defined by very old age (≥80 y), physical frailty or cognitive impairment, and increases the risks for morbidity and mortality. The effects of individualized nutritional support for patients with aging-related vulnerability in the acute hospital setting on mortality and other clinical outcomes remains understudied. METHODS: For this secondary analysis of the randomized-controlled Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), we analyzed data of patients at a nutritional risk (Nutritional Risk Screening 2002 score ≥3 points) with aging-related vulnerability, randomized to receive protocol-guided individualized nutritional support to reach specific protein and energy goals (intervention group) or routine hospital food (control group). The primary endpoint was all-cause 30-d mortality. RESULTS: Of the 881 patients with aging-related vulnerability, 23.4% presented with a frailty syndrome, 81.8% were age ≥80 y and 15.3% showed cognitive impairment. Patients with aging-related vulnerability receiving individualized nutritional support compared with routine hospital food showed a >50% reduction in the risk of 30-day mortality (60 of 442 [13.6%] versus 31 of 439 [7.1%]; odds ratio: 0.48; 95% confidence interval, 0.31-0.76; P = 0.002). Significant improvements were also found for long-term mortality at 180 days, as well as functional outcomes and quality of life measures. CONCLUSIONS: Malnourished patients with aging-related vulnerability show a significant and clinically relevant reduction in the risk of mortality and other adverse clinical outcomes after individualized in-hospital nutritional support compared to routine hospital nutrition. These data support the early screening of patients with aging-related vulnerability for nutritional risk, followed by a nutritional assessment and implementation of individualized nutritional interventions.

Individualized Nutritional Support for Hospitalized Patients With Chronic Heart Failure.

BACKGROUND: Deterioration of nutritional status during hospitalization in patients with chronic heart failure increases mortality. Whether nutritional support during hospitalization reduces these risks, or on the contrary, may be harmful due to an increase in salt and fluid intake, remains unclear. OBJECTIVES: The purpose of this trial was to study the effect of nutritional support on mortality in patients hospitalized with chronic heart failure who are at nutritional risk. METHODS: A total of 645 patients with chronic heart failure (36% [n = 234] with acute decompensation) participated in the investigator-initiated, open-label EFFORT (Effect of early nutritional support on Frailty, Functional Outcomes and Recovery of malnourished medical inpatients) trial. Patients were randomized to protocol-guided individualized nutritional support to reach energy, protein, and micronutrient goals (intervention group) or standard hospital food (control group). The primary endpoint was all-cause mortality at 30 days. RESULTS: Mortality over 180 days increased with higher severity of malnutrition (odds ratio per 1-point increase in Nutritional Risk Screening 2002 score: 1.65; 95% confidence interval [CI]: 1.21 to 2.24; p = 0.001). By 30 days, 27 of 321 intervention group patients (8.4%) died, compared with 48 of 324 (14.8%) control group patients (odds ratio: 0.44; 95% CI: 0.26 to 0.75; p = 0.002). Patients at high nutritional risk showed the most benefit from nutritional support. Mortality effects remained significant at 180-day follow-up. Intervention group patients also had a lower risk for major cardiovascular events at 30 days (17.4% vs. 26.9%; odds ratio: 0.50; 95% CI: 0.34 to 0.75; p = 0.001). CONCLUSIONS: Among hospitalized patients with chronic heart failure at high nutritional risk, individualized nutritional support reduced the risk for mortality and major cardiovascular events compared with standard hospital food. These data support malnutrition screening upon hospital admission followed by an individualized nutritional support strategy in this vulnerable patient population. (Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial [EFFORT]; NCT02517476).