Growth differentiation factor 15 (GDF15) levels are associated with malnutrition in acutely admitted older adults.

BACKGROUND AND AIMS: The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults. METHODS: Plasma GDF15 levels were measured using immunoassays in 302 older adults (≥65 years) admitted to the emergency department (ED). Nutritional status was evaluated with the Mini Nutritional Assessment Short-Form (MNA®-SF), appetite was evaluated with the Simplified Nutritional Appetite Questionnaire (SNAQ), and physical function was evaluated with handgrip strength (HGS), 30-s chair stand test (30s-RSS), and gait speed (GS). Associations between GDF15 and each outcome was determined by logistic regression adjusted for age, sex, and C-reactive protein (CRP). RESULTS: Each doubling in plasma GDF15 level was associated with an adjusted odds ratio (OR) (95% confidence interval) of 1.59 (1.10-2.29, P = 0.01) for risk of malnutrition compared to normal nutrition and 1.19 (0.85-1.69, P = 0.3)) for malnutrition compared to risk of malnutrition. Each doubling in GDF15 was associated with an adjusted OR of 1.63 (1.21-2.23)) for having poor appetite, 1.46 (1.07-1.99) for having low HGS, 1.74 (1.23-2.51) for having low 30s-RSS, and 1.99 (1.39-2.94) for having low GS. CONCLUSION: Among older adults admitted to the ED, higher GDF15 levels were significantly associated with malnutrition, poor appetite, and low physical function independent of age, sex, and CRP.

Effectiveness of a multidisciplinary and transitional nutritional intervention compared with standard care on health-related quality of life among acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition: A randomized controlled trial.

BACKGROUND & AIM: Malnutrition, risk of malnutrition, and risk factors for malnutrition are prevalent among acutely admitted medical patients aged ≥65 years and have significant health-related consequences. Consequently, we aimed to investigate the effectiveness of a multidisciplinary and transitional nutritional intervention on health-related quality of life compared with standard care. METHODS: The study was a block randomized, observer-blinded clinical trial with two parallel arms. The Intervention Group was offered a multidisciplinary transitional nutritional intervention consisting of dietary counselling and six sub-interventions targeting individually assessed risk factors for malnutrition, while the Control Group received standard care. The inclusion criteria were a Mini Nutritional Assessment Short-Form score ≤11, age ≥65 years, and an acute admittance to the Emergency Department. Outcomes were assessed on admission and 8 and 16 weeks after hospital discharge. The primary outcome was the difference between groups in change in health-related quality of life (assessed by the EuroQol-5D-5L) from baseline to 16 weeks after discharge. The secondary outcomes were difference in intake of energy and protein, well-being, muscle strength, and body weight at all timepoints. RESULTS: From October 2018 to April 2021, 130 participants were included. Sixteen weeks after discharge, 29% in the Intervention Group and 19% in the Control Group were lost to follow-up. Compliance varied between the sub-interventions targeting nutritional risk factors and was generally low after discharge, ranging from 0 to 61%. No difference was found between groups on change in health-related quality of life or on well-being, muscle strength, and body weight at any timepoint, neither using the intention-to-treat analysis nor the per-protocol analysis. The protein intake was higher in the Intervention Group during hospitalization (1.1 (Standard Deviation (SD) 0.4) vs 0.8 (SD 0.5) g/kg/day, p = 0.0092) and 8 weeks after discharge (1.2 (SD 0.5) vs 0.9 (0.4) g/kg/day, p = 0.0025). The percentual intake of calculated protein requirements (82% (SD 24) vs 61% (SD 32), p = 0.0021), but not of calculated energy requirements (89% (SD 23) vs 80% (SD 37), p = 0.2), was higher in the Intervention Group than in the Control Group during hospitalization. Additionally, the Intervention Group had a significantly higher percentual intake of calculated protein requirements (94% (SD 41) vs 74% (SD 30), p = 0.015) and calculated energy requirements (115% (SD 37) vs 94% (SD 31), p = 0.0070) 8 weeks after discharge. The intake of energy and protein was comparable between the groups 16 weeks after discharge. CONCLUSION: We found no effect of a multidisciplinary and transitional nutritional intervention for acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition on our primary outcome, health-related quality of life 16 weeks after discharge. Nor did the intervention affect the secondary outcomes, well-being, muscle strength, and body weight from admission to 8 or 16 weeks after discharge. However, the intervention improved energy and protein intake during hospitalization and 8 weeks after discharge. Low compliance with the intervention after discharge may have compromised the effect of the intervention. The study is registered at ClinicalTrials.gov (identifier: NCT03741283).

Severity of Inflammation Is Associated with Food Intake in Hospitalized Geriatric Patients-A Merged Data Analysis.

The extent to which inflammation impacts food intake remains unclear, serving as a key risk factor for malnutrition as defined by the Global Leadership Initiative on Malnutrition (GLIM). To address this, we analyzed a large, merged dataset of geriatric hospitalized patients across Europe. The study included 1650 consecutive patients aged ≥65 year from Germany, Italy, Finland, Denmark, and Poland. Nutritional intake was assessed using the first item of the Mini Nutritional Assessment Short Form; C-reactive protein (CRP) levels were measured using standard procedures. In total (age 79.6 ± 7.4 year, 1047 females), 23% exhibited moderate to severe inflammation, and 12% showed severe inflammation; 35% showed moderate reductions in food intake, and 28% were considered malnourished. Median CRP levels differed significantly between patients with severe, moderate, and no decrease in food intake. Among patients with a CRP level of 3.0-4.99 mg/dL, 19% experienced a severe decrease in food intake, while 66% experienced moderate to severe decreases. Regression analysis revealed that inflammation was the most prominent risk factor for low food intake and malnutrition, surpassing other factors such as age, gender, infection, and comorbidity. A CRP level of ≥3.0 mg/dL is associated with reduced food intake during last 3 months in two thirds of hospitalized geriatric patients and therefore indicative for a high risk of malnutrition.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.

Estimated glomerular filtration rate based on creatinine, cystatin C, ß-trace protein and ß2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

AIMS: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, ß-trace protein (BTP) and ß2 microglobulin (B2M) among patients undergoing major amputation. METHODS: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. RESULTS: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. CONCLUSION: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Evaluation of Multi-Frequency Bioelectrical Impedance Analysis against Dual-Energy X-ray Absorptiometry for Estimation of Low Muscle Mass in Older Hospitalized Patients.

The accuracy of multi-frequency (MF) bioelectrical impedance analysis (BIA) to estimate low muscle mass in older hospitalized patients remains unclear. This study aimed to describe the ability of MF-BIA to identify low muscle mass as proposed by The Global Leadership Initiative on Malnutrition (GLIM) and The European Working Group on Sarcopenia in Older People (EWGSOP-2) and examine the association between muscle mass, dehydration, malnutrition, and poor appetite in older hospitalized patients. In this prospective exploratory cohort study, low muscle mass was estimated with MF-BIA against dual-energy X-ray absorptiometry (DXA) in 42 older hospitalized adults (≥65 years). The primary variable for muscle mass was appendicular skeletal muscle mass (ASM), and secondary variables were appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI). Cut-off values for low muscle mass were based on recommendations by GLIM and EWGSOP-2. MF-BIA was evaluated against DXA on the ability to estimate absolute values of muscle mass by mean bias, limits of agreement (LOA), and accuracy (5% and 10% levels). Agreement between MF-BIA and DXA to identify low muscle mass was evaluated with sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The association between muscle mass, dehydration, malnutrition, and poor appetite was visually examined with boxplots. MF-BIA overestimated absolute values of ASM with a mean bias of 0.63 kg (CI: -0.20:1.46, LOA: -4.61:5.87). Agreement between MF-BIA and DXA measures of ASM showed a sensitivity of 86%, specificity of 94%, PPV of 75% and NPV of 97%. Boxplots indicate that ASM is lower in patients with malnutrition. This was not observed in patients with poor appetite. We observed a tendency toward higher ASM in patients with dehydration. Estimation of absolute ASM values with MF-BIA should be interpreted with caution, but MF-BIA might identify low muscle mass in older hospitalized patients.

Mild Cognitive Impairment Is Associated with Poorer Nutritional Status on Hospital Admission and after Discharge in Acutely Hospitalized Older Patients.

In acutely hospitalized older patients (≥65 years), the association between mild cognitive impairment (MCI) and malnutrition is poorly described. We hypothesized that (1) MCI is associated with nutritional status on admission and after discharge; (2) MCI is associated with a change in nutritional status; and (3) a potential association is partly explained by frailty, comorbidity, medication use, and age. We combined data from a randomized controlled trial (control group data) and a prospective cohort study (ClinicalTrials.gov: NCT01964482 and NCT03052192). Nutritional status was assessed on admission and follow-up using the Mini Nutritional Assessment-Short Form. MCI or intact cognition (noMCI) was classified by three cognitive performance tests at follow-up. Data on frailty, comorbidity, medication use, and age were drawn from patient journals. MCI (n = 42) compared to noMCI (n = 47) was associated with poorer nutritional status with an average difference of -1.29 points (CI: -2.30; -0.28) on admission and -1.64 points (CI: -2.57; -0.70) at 4-week follow-up. Only age influenced the estimates of -0.85 (CI: -1.86; 0.17) and -1.29 (CI: -2.25; -0.34), respectively. In acutely hospitalized older patients, there is an association between MCI and poorer nutritional status upon admission and four weeks after discharge. The association is partly explained by higher age.

Optimization of Nutrition And Medication (OptiNAM) for acutely admitted older patients: protocol for a randomized single-blinded controlled trial.

BACKGROUND: Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on 99mTechnetium-diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED. METHODS: The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge. DISCUSSION: The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED. TRAIL REGISTRATION: ClinicalTrials.gov NTC03741283 . Retrospectively registered on 14 November 2018.

Risk of Malnutrition upon Admission and after Discharge in Acutely Admitted Older Medical Patients: A Prospective Observational Study.

There is a lack of knowledge about malnutrition and risk of malnutrition upon admission and after discharge in older medical patients. This study aimed to describe prevalence, risk factors, and screening tools for malnutrition in older medical patients. In a prospective observational study, malnutrition was evaluated in 128 older medical patients (≥65 years) using the Nutritional Risk Screening 2002 (NRS-2002), the Mini Nutritional Assessment-Short Form (MNA-SF) and the Eating Validation Scheme (EVS). The European Society of Clinical Nutrition (ESPEN) diagnostic criteria from 2015 were applied for diagnosis. Agreement between the screening tools was evaluated by kappa statistics. Risk factors for malnutrition included polypharmacy, dysphagia, depression, low functional capacity, eating-related problems and lowered cognitive function. Malnutrition or risk of malnutrition were prevalent at baseline (59-98%) and follow-up (30-88%). The baseline, follow-up and transitional agreements ranged from slight to moderate. NRS-2002 and MNA-SF yielded the highest agreement (kappa: 0.31 (95% Confidence Interval (CI) 0.18-0.44) to 0.57 (95%CI 0.42-0.72)). Prevalence of risk factors ranged from 17-68%. Applying ESPEN 2015 diagnostic criteria, 15% had malnutrition at baseline and 13% at follow-up. In conclusion, malnutrition, risk of malnutrition and risk factors hereof are prevalent in older medical patients. MNA-SF and NRS-2002 showed the highest agreement at baseline, follow-up, and transitionally.

Dysphagia Prevalence, Time Course, and Association with Probable Sarcopenia, Inactivity, Malnutrition, and Disease Status in Older Patients Admitted to an Emergency Department: A Secondary Analysis of Cohort Study Data.

There is evolving evidence for an association between dysphagia and sarcopenia in older adults. For optimizing the acute health care initiative across health care settings, this study investigated prevalence and time-course of dysphagia in older patients admitted to an emergency department (ED) as well as its association with parameters for probable sarcopenia, inactivity, malnutrition, disease status, and systemic inflammation. A secondary analysis of data from the FAM-CPH cohort study on acutely admitted older medical patients (n = 125). Data were collected upon ED admission as well as four and 56 weeks after discharge. Using the Eating Assessment Tool cut-off score ≥ 2, signs of dysphagia were present in 34% of the patients at ED admission and persisted in 25% of the patients 56 weeks after discharge. Signs of dysphagia at 56-week follow-up were significantly (p < 0.05) associated with probable sarcopenia (low handgrip strength (OR = 3.79), low leg muscle strength (OR = 8.14), and low physical performance (OR = 5.68)) and with baseline swallowing inactivity (OR = 5.61), malnutrition (OR = 4.35), and systemic inflammation (OR = 1.33). Signs of dysphagia in older patients admitted to an ED was prevalent, persisted 56 weeks after discharge, and was associated with probable sarcopenia and related conditions; all modifiable targets for management of dysphagia in older patients.

Association of GDF15 With Inflammation and Physical Function During Aging and Recovery After Acute Hospitalization: A Longitudinal Study of Older Patients and Age-Matched Controls.

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine. Its plasma levels increase during aging and acute illness. In older Patients and age-matched Controls, we evaluated whether GDF15 levels (i) were associated with recovery after acute illness, and (ii) reflected different trajectories of aging and longitudinal changes in health measures. Fifty-two older Patients (≥65 years) were included upon admission to the emergency department (ED). At 30 days after discharge (time of matching), Patients were matched 1:1 on age and sex with Controls who had not been hospitalized within 2 years of inclusion. Both groups were followed up after 1 year. We assessed plasma levels of GDF15 and inflammatory biomarkers, frailty, nutritional status (mini nutritional assessment short-form), physical and cognitive function, and metabolic biomarkers. In Patients, elevated GDF15 levels at ED admission were associated with poorer resolution of inflammation (soluble urokinase plasminogen activator receptor [suPAR]), slowing of gait speed, and declining nutritional status between admission and 30-day follow-up. At time of matching, Patients were frailer and overall less healthy than age-matched Controls. GDF15 levels were significantly associated with participant group, on average Patients had almost 60% higher GDF15 than age-matched Controls, and this difference was partly mediated by reduced physical function. Increases in GDF15 levels between time of matching and 1-year follow-up were associated with increases in levels of interleukin-6 in Patients, and tumor necrosis factor-α and suPAR in age-matched Controls. In older adults, elevated GDF15 levels were associated with signs of accelerated aging and with poorer recovery after acute illness.

A Collaborative Medication Review Including Deprescribing for Older Patients in an Emergency Department: A Longitudinal Feasibility Study.

Medication review for older patients with polypharmacy in the emergency department (ED) is crucial to prevent inappropriate prescribing. Our objective was to assess the feasibility of a collaborative medication review in older medical patients (≥65 years) using polypharmacy (≥5 long-term medications). A pharmacist performed the medication review using the tools: Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria, a drug-drug interaction database (SFINX), and Renbase® (renal dosing database). A geriatrician received the medication review and decided which recommendations should be implemented. The outcomes were: differences in Medication Appropriateness Index (MAI) and Assessment of Underutilization Index (AOU) scores between admission and 30 days after discharge and the percentage of patients for which the intervention was completed before discharge. Sixty patients were included from the ED, the intervention was completed before discharge for 50 patients (83%), and 39 (61.5% male; median age 80 years) completed the follow-up 30 days after discharge. The median MAI score decreased from 14 (IQR 8-20) at admission to 8 (IQR 2-13) 30 days after discharge (p < 0.001). The number of patients with an AOU score ≥1 was reduced from 36% to 10% (p < 0.001). Thirty days after discharge, 83% of the changes were sustained and for 28 patients (72%), 1≥ medication had been deprescribed. In conclusion, a collaborative medication review and deprescribing intervention is feasible to perform in the ED.

Alterations of monocyte NF-κB p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults.

BACKGROUND: Altered monocyte NF-κB signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-κB signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults. METHODS: We used data from: 52 older (≥65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- and sex-matched Older Controls without recent hospitalization; and 60 healthy Young Controls (20-35 years). Using flow cytometry, we assessed basal NF-κB phosphorylation (pNF-κB p65/RelA; Ser529) and induction of pNF-κB following stimulation with LPS or TNF-α in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-α, and soluble urokinase plasminogen activator receptor. RESULTS: Patients at follow-up were frailer, had higher levels of inflammatory markers and decreased physical and cognitive function than Older Controls. Patients at follow-up had higher basal pNF-κB levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105-153 vs. MFI: 80, IQR: 71-90, p < 0.0001), and reduced pNF-κB induction in response to LPS (mean pNF-κB MFI fold change calculated as the log10 ratio of LPS-stimulation to the PBS-control: 0.10, 95% CI: 0.08 to 0.12 vs. 0.13, 95% CI: 0.10 to 0.15, p = 0.05) and TNF-α stimulation (0.02, 95% CI: - 0.00 to 0.05 vs. 0.10, 95% CI: 0.08 to 0.12, p < 0.0001). Older Controls had higher levels of inflammatory markers than Young Controls, but basal pNF-κB MFI did not differ between Older and Young Controls (MFI: 81, IQR: 70-86; p = 0.72). Older Controls had reduced pNF-κB induction in response to LPS and TNF-α compared to Young Controls (LPS: 0.40, 95% CI: 0.35 to 0.44, p < 0.0001; and TNF-α: 0.33, 95% CI: 0.27 to 0.40, p < 0.0001). In Older Controls, basal pNF-κB MFI was associated with FI-OutRef (p = 0.02). CONCLUSIONS: Increased basal pNF-κB activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-κB activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS.

Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR), interleukin-6, C-reactive protein (CRP), and albumin were measured at admission, discharge, and 4 and 13 weeks after discharge. The Intervention group had an earlier decrease in suPAR levels than the Control group: -15.4% vs. +14.5%, P=.007 during hospitalization, and -2.4% vs. -28.6%, P=.007 between discharge and 4 weeks. There were no significant effects of the intervention on the other biomarkers. All biomarkers improved significantly between admission and 13 weeks, although with different kinetics (suPAR: -22%, interleukin-6: -86%, CRP: -89%, albumin: +11%). Nutritional support during hospitalization was associated with an accelerated decrease in suPAR levels, whereas the combined nutrition and resistance training intervention after discharge did not appear to affect the inflammatory state. Our results indicate that improved nutritional care during hospitalization may accelerate recovery in acutely ill elderly medical patients.

The effect of protein intake and resistance training on muscle mass in acutely ill old medical patients - A randomized controlled trial.

BACKGROUND & AIM: Stress metabolism is associated with accelerated loss of muscle that has large consequences for the old medical patient. The aim of this study was to investigate if an intervention combining protein and resistance training was more effective in counteracting loss of muscle than standard care. Secondary outcomes were changes in muscle strength, functional ability and body weight. METHODS: 29 acutely admitted old (>65 years) patients were randomly assigned to the intervention (n = 14) or to standard care (n = 15). The Intervention Group received 1.7 g protein/kg/day during admission and a daily protein supplement (18.8 g protein) and resistance training 3 times per week the 12 weeks following discharge. Muscle mass was assessed by Dual-energy X-ray Absorptiometry. Muscle strength was assessed by Hand Grip Strength and Chair Stand Test. Functional ability was assessed by the de Morton Mobility Index, the Functional Recovery Score and the New Mobility Score. Changes in outcomes from time of admission to three-months after discharge were analysed by linear regression analysis. RESULTS: The intention-to-treat analysis showed no significant effect of the intervention on lean mass (unadjusted: ß-coefficient = -1.28 P = 0.32, adjusted for gender: ß-coefficient = -0.02 P = 0.99, adjusted for baseline lean mass: ß-coefficient = -0.31 P = 0.80). The de Morton Mobility Index significantly increased in the Control Group (ß-coefficient = -11.43 CI: 0.72-22.13, P = 0.04). No other differences were found. CONCLUSION: No significant effect on muscle mass was observed in this group of acutely ill old medical patients. High compliance was achieved with the dietary intervention, but resistance training was challenging. Clinical trials identifier NCT02077491.