Collective Weakness Is Associated With Time to Mortality in Americans.

ABSTRACT: McGrath, R, McGrath, BM, Jurivich, D, Knutson, P, Mastrud, M, Singh, B, and Tomkinson, GR. Collective weakness is associated with time to mortality in Americans. J Strength Cond Res 38(7): e398-e404, 2024-Using new weakness cutpoints individually may help estimate time to mortality, but their collective use could improve value. We sought to determine the associations of (a) each absolute and body size normalized cut point and (b) collective weakness on time to mortality in Americans. The analytic sample included 14,178 subjects aged ≥50 years from the 2006-2018 waves of the Health and Retirement Study. Date of death was confirmed from the National Death Index. Handgrip dynamometry measured handgrip strength (HGS). Men were categorized as weak if their HGS was <35.5 kg (absolute), <0.45 kg·kg -1 (body mass normalized), or <1.05 kg·kg -1 ·m -2 (body mass index [BMI] normalized). Women were classified as weak if their HGS was <20.0 kg, <0.337 kg·kg -1 , or <0.79 kg·kg -1 ·m -2 . Collective weakness categorized persons as below 1, 2, or all 3 cutpoints. Cox proportional hazard regression models were used for analyses. Subject values below each absolute and normalized cutpoint for the 3 weakness parameters had a higher hazard ratio for early all-cause mortality: 1.45 (95% confidence interval [CI]: 1.36-1.55) for absolute weakness, 1.39 (CI: 1.30-1.49) for BMI normalized weakness, and 1.33 (CI: 1.24-1.43) for body mass normalized weakness. Those below 1, 2, or all 3 weakness cut points had a 1.37 (CI: 1.26-1.50), 1.47 (CI: 1.35-1.61), and 1.69 (CI: 1.55-1.84) higher hazard for mortality, respectively. Weakness determined by a composite measure of absolute and body size adjusted strength capacity provides robust prediction of time to mortality, thus potentially informing sports medicine and health practitioner discussions about the importance of muscle strength during aging.

Increased short-term mortality among patients presenting with altered mental status to the emergency department: A cohort study.

OBJECTIVES: To evaluate the short-term mortality of adult patients presenting to the emergency department (ED) with altered mental status (AMS) as compared to other common chief complaints. METHODS: Observational cohort study of adult patients (age ≥ 40) who presented to an academic ED over a 1-year period with five pre-specified complaints at ED triage: AMS, generalized weakness, chest pain, abdominal pain, and headache. Primary outcomes included 7 and 30-day mortality. Hazard ratios (HR) were calculated with 95% confidence intervals (CI) using Cox proportional hazards models adjusted for age, acuity level, and comorbidities. RESULTS: A total of 9850 ED visits were included for analysis from which 101 (1.0%) and 295 (3.0%) died within 7 and 30 days, respectively. Among 683 AMS visits, the 7-day mortality rate was 3.2%. Mortality was lower for all other chief complaints, including generalized weakness (17/1170, 1.5%), abdominal pain (32/3609, 0.9%), chest pain (26/3548, 0.7%), and headache (4/840, 0.5%). After adjusting for key confounders, patients presenting with AMS had a significantly higher risk of death within 7 days of ED arrival than patients presenting with chest pain (HR 3.72, 95% CI 2.05 to 6.76, p < .001). Similarly, we found that patients presenting with AMS had a significantly higher risk of dying within 30 days compared to patients with chest pain (HR 3.65, 95% CI 2.49 to 5.37, p < .001), and headache (HR 2.09, 95% CI 1.09 to 4.01, p = .026). Differences were not statistically significant for comparisons with abdominal pain and generalized weakness, but confidence intervals were wide. CONCLUSION: Patients presenting with AMS have worse short-term prognosis than patients presenting to the ED with chest pain or headache. AMS may indicate an underlying brain dysfunction (delirium), which is associated with adverse outcomes and increased mortality.

Prognostic utility of dynapenia in patients with cardiovascular disease.

BACKGROUND: Dynapenia, defined as age-associated loss of skeletal muscle strength, is associated with increased mortality rate, poor activities of daily living, and reduced quality of life. Therefore, dynapenia appears to be a better independent predictor of mortality than sarcopenia in the elderly. However, the prognostic utility of dynapenia in patients with cardiovascular disease (CVD) is not clear. This study was performed to examine the prognostic utility of dynapenia defined by the criteria of Manini et al. in patients with CVD. METHODS: The findings of 4192 consecutive patients ≥30 years old (median [interquartile range (IQR)] age 69 [60-76] years, 2874 males) with CVD were reviewed. Grip strength and quadriceps isometric strength (QIS) were measured just before hospital discharge, and low grip strength (<26 kg in males and <18 kg in females), low QIS (<45.0% body mass [BM] and <35.0% BM in males and females, respectively) were considered to indicate dynapenia. The endpoint was all-cause mortality. RESULTS: A total of 507 deaths occurred during follow-up (median 2.0 years, IQR 0.8-4.4 years). The overall prevalence of dynapenia was 33.6% and increased with age (p for trend < 0.01). Females showed a significantly higher prevalence rate of dynapenia than males (43.3% vs. 29.2%, respectively; p < 0.01). Patients with dynapenia showed higher all-cause mortality rate than non-dynapenia patients (adjusted hazard ratio: 1.84; 95% confidence interval: 1.51-2.23; p < 0.01). CONCLUSIONS: Dynapenia has a high prevalence among patients with CVD and is associated with increased mortality rate.

Utility of Plasma GDF-15 for Diagnosis and Prognosis Assessment of ICU-Acquired Weakness in Mechanically Ventilated Patients: Prospective Observational Study.

OBJECTIVE: To identify the clinical correlations between plasma growth differentiation factor-15 (GDF-15), skeletal muscle function, and acute muscle wasting in ICU patients with mechanical ventilation. In addition, to investigate its diagnostic value for ICU-acquired weakness (ICU-AW) and its predictive value for 90-day survival in mechanically ventilated patients. METHODS: 95 patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2017 to January 2019. The plasma GDF-15 level was detected by ELISA, the rectus femoris cross-sectional area (RFcsa) was measured by ultrasound, and the patient's muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1, day 4, and day 7. Patients were divided into an ICU-AW group and a non-ICU-AW group according to their MRC-score on the 7th day. The differences in plasma GDF-15 level, MRC-score, and RFcsa between the two groups were compared on the 1st, 4th, and 7th day after being admitted to the ICU. Then, the correlations between plasma GDF-15 level, RFcsa loss, and MRC-score on day 7 were investigated. The receiver operating characteristic curve (ROC) was used to analyze the plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on the 7th day to the diagnosis of ICU-AW in mechanically ventilated patients. Moreover, the predictive value of GDF-15 on the 90-day survival status of patients was assessed using patient survival curves. RESULTS: Based on whether the 7th day MRC-score was <48, 50 cases were included in the ICU-AW group and 45 cases in the non-ICU-AW group. The length of mechanical ventilation, ICU length of stay, and hospital length of stay were significantly longer in the ICU-AW group than in the non-ICU-AW group (all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all. CONCLUSION: The plasma GDF-15 concentration level was significantly associated with skeletal muscle function and muscle wasting on day 7 in ICU patients with mechanical ventilation. Therefore, it can be concluded that the plasma GDF-15 level on the 7th day has a high diagnostic yield for ICU-acquired muscle weakness, and it can predict the 90-day survival status of ICU mechanically ventilated patients.

Effects of Early Enteral Nutrition on Immune Function and Prognosis of Patients With Sepsis on Mechanical Ventilation.

OBJECTIVE: To explore the therapeutic effects of early enteral nutrition (EEN) on patients with sepsis on mechanical ventilation. METHODS: Patients with sepsis on mechanical ventilation in the medical intensive care unit (ICU) from January 2013 to March 2016 were treated with enteral nutrition. Patients treated within 48 hours of initiation of mechanical ventilation were assigned to the EEN group, and the rest were assigned to the delayed enteral nutrition (DEN) group. Peripheral blood Th17 cells and Treg cells, endotoxin (ET) level, 28-day mortality, duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-acquired weakness (ICU-AW) were analyzed between the 2 groups. RESULTS: The proportion of Th17 cells and ET levels in the EEN group were significantly lower than those in the DEN group, whereas the proportion of Treg cells in the EEN group was remarkably higher than that in the DEN group (P < .05). The duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-AW were higher in the DEN group than in the EEN group (P < .05), but there was no significant difference in the 28-day mortality between the 2 groups. CONCLUSION: Patients with sepsis mainly present with an increased proportion of Th17 cells in the early stage, manifesting as enhanced immune response. Early enteral nutrition can inhibit the excessive immune response, shorten the duration of mechanical ventilation, lengths of ICU stay and hospital stay, and reduce the incidence of ICU-AW, but it has no obvious effect on 28-day mortality.

Prevalence and prognosis of respiratory muscle weakness in heart failure patients with preserved ejection fraction.

BACKGROUND: Although respiratory muscle weakness (RMW) is known to predict prognosis in patients with heart failure with reduced ejection fraction (HFrEF), RMW prevalence and its prognosis in those with preserved ejection fraction (HFpEF) remain unknown. We aimed to investigate whether the RMW predicted mortality in HFpEF patients. METHODS: We conducted a single-centre observational study with consecutive 1023 heart failure patients (445 in HFrEF and 578 in HFpEF). Maximal inspiratory pressure (PImax) was measured to assess respiratory muscle strength at hospital discharge, and RMW was defined as PImax <70% of predicted value. Endpoint was all-cause mortality after hospital discharge, and we examined the influence of RMW on the endpoint. RESULTS: Over a median follow-up of 1.8 years, 134 patients (13.1%) died; of these 53 (11.9%) were in HFrEF and 81 (14.0%) in HFpEF. RMW was evident in 190 (42.7%) HFrEF and 226 (39.1%) HFpEF patients and was independently associated with all-cause mortality in both HFrEF (adjusted hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.17-3.88) and HFpEF (adjusted HR: 2.85, 95% CI: 1.74-4.67) patients. Adding RMW to the multivariate logistic regression model significantly increased area under the receiver-operating characteristic curve (AUC) for all-cause mortality in HFpEF (AUC including RMW: 0.78, not including RMW: 0.74, P = 0.026) but not in HFrEF (AUC including RMW: 0.84, not including RMW: 0.82, P = 0.132). CONCLUSIONS: RMW was observed in 39% of HFpEF patients, which was independently associated with poor prognosis. The additive effect of RMW on prognosis was detected only in HFpEF but not in HFrEF.

Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts.

BACKGROUND: Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome. METHODS: Post hoc analysis of two prospective cohort studies conducted in two ICUs. In patients mechanically ventilated for at least 24 h undergoing a first spontaneous breathing trial, severe ICU-DD was defined as diaphragm twitch pressure < 7 cmH2O and ICU-AW was defined as Medical Research Council Score < 48. RESULTS: One hundred sixteen patients were assessed. Factors independently associated with severe ICU-DD were age, longer duration of MV, and exposure to sufentanil, and those factors associated with ICU-AW were longer duration of MV and exposure to norepinephrine. Severe ICU-DD (OR 3.56, p = 0.008), but not ICU-AW, was independently associated with weaning failure (59%). ICU-AW (OR 4.30, p = 0.033), but not severe ICU-DD, was associated with ICU mortality. Weaning failure and mortality rate were higher in patients with both severe ICU-DD and ICU-AW (86% and 39%, respectively) than in patients with either severe ICU-DD (64% and 0%) or ICU-AW (63% and 13%). CONCLUSION: Severe ICU-DD and ICU-AW have different risk factors and different impacts on weaning failure and mortality. The impact of the combination of ICU-DD and ICU-AW is more pronounced than their individual impact.

The prognosis of functional limb weakness: a 14-year case-control study.

Reliable data on the prognosis of functional motor disorder are scarce, as existing studies of the prognosis of functional motor disorder are nearly all retrospective, small and uncontrolled. In this study we used a prospectively recruited, controlled cohort design to assess misdiagnosis, mortality and symptomatic and health outcome in patients with functional limb weakness compared to neurological disease and healthy control subjects. We also carried out an exploratory analysis for baseline factors predicting outcome. One hundred and seven patients with functional limb weakness, 46 neurological and 38 healthy control subjects from our previously studied prospective cohort were traced for follow-up after an average of 14 years. Misdiagnosis was determined in a consensus meeting using information from records, patients and their GPs. Numbers and causes of death were collected via death certificates. Outcome of limb weakness, physical and psychiatric symptoms, disability/quality of life and illness perception were recorded with self-rated questionnaires. Outcome measures were compared within and between groups. Seventy-six patients (71%) with functional limb weakness, 31 (67%) neurological and 23 (61%) healthy controls were included in follow-up. Misdiagnosis was found in one patient in the functional limb weakness group (1%) and in one neurological control (2%). Eleven patients with functional limb weakness, eight neurological control subjects and one healthy control subject had died. Weakness had completely remitted in 20% of patients in the functional limb weakness group and in 18% of the neurological controls (P = 0.785) and improved in a larger proportion of functional limb weakness patients (P = 0.011). Outcomes were comparable between patient groups, and worse than the healthy control group. No baseline factors were independent predictors of outcome, although somatization disorder, general health, pain and total symptoms at baseline were univariably correlated to outcome. This study is the largest and longest follow-up study of functional limb weakness. Misdiagnosis in functional limb weakness is rare after long-term follow-up. The disorder is associated with a higher mortality rate than expected, and symptoms are persistent and disabling. It appears difficult to predict outcome based on common baseline variables. These data should help inform clinicians to provide a more realistic outlook of the outcome and emphasize the importance of active and targeted therapy.

Do Nationally Representative Cutpoints for Clinical Muscle Weakness Predict Mortality? Results From 9 Years of Follow-up in the Health and Retirement Study.

BACKGROUND: Muscle weakness, as measured by handgrip strength, is associated with cardiovascular and all-cause mortality; however, there are wide inconsistencies in the magnitude of these effects due to divergent definitions used to define muscle weakness across studies. Therefore, the objective of this study was to examine the relationship between previously defined sex- and race-specific cutpoints of clinical muscle weakness and early mortality. METHODS: Data come from the 2006-2014 Health and Retirement Study. Time-varying clinical muscle weakness, as defined by handgrip strength cutpoints, was the primary exposure. Time to death, ascertained from the National Death Index, was the outcome of interest. The association between time-varying clinical muscle weakness and early mortality across a 9-year observation period was determined using Kaplan-Meier methods and extended Cox regression. RESULTS: Out of the 8,326 individuals in the study, 1,799 deaths (21%) occurred during the observation period. Median follow-up time was 8.3 years (SD ±1.9 years). Weak individuals had a steeper decline in their survival trajectory, compared to non-weak individuals (Log-Rank test, p < .001). After adjusting for sociodemographic factors and time-varying smoking history, weak individuals were over 50% more likely to die earlier than non-weak individuals (hazard ratio [HR] = 1.52, 95% confidence interval [CI] = 1.15, 1.47). CONCLUSIONS: This is the first study to use muscle weakness cutpoints derived in a nationally representative sample to identify those individuals who may be at greatest risk for premature mortality. Results underscore the importance of muscle weakness, as defined by handgrip strength, as a key risk factor for premature mortality in older Americans.

Loss of paraspinal muscle mass is a gender-specific consequence of cirrhosis that predicts complications and death.

BACKGROUND: Loss of skeletal muscle mass is a recognised complication with a prognostic impact in patients with cirrhosis. AIM: To explore in a retrospective analysis which muscle compartment most reliably predicts the occurrence of cirrhosis-associated complications and if there are gender-related differences. METHODS: 795 patients with cirrhosis listed for liver transplantation between 2001 and 2014 met the inclusion and exclusion criteria including an abdominal CT scan (±200). Controls were 109 patients who underwent a CT scan after polytrauma. The paraspinal muscles index (PSMI), the abdominal wall muscles index (AWMI) and its combination skeletal muscle index (SMI) were assessed at L3/L4, normalised to the height (cm2 /m2 ). RESULTS: 62.0% of patients with cirrhosis had alcoholic liver disease, and 70.6% were male. As compared to controls, a reduction in PSMI and SMI but not AWMI was associated with high model of end-stage liver disease (MELD) score, high Child-Pugh class, and the presence or history of cirrhosis-associated complications in males but not females. PSMI independently predicted the occurrence of bacterial infections (HR 0.932), spontaneous bacterial peritonitis (HR 0.901), hepatic encephalopathy (HR 0.961), and hepatorenal syndrome (HR 0.946) by multivariate Cox regression analysis in a gender-independent manner. Post-transplant survival was not associated with the PSMI; neither AWMI nor SMI predicted any clinical endpoints. CONCLUSIONS: This study links muscle wasting in patients with cirrhosis predominantly to males. However, the presence of a low PSMI mass is a gender-independent predictor of developing cirrhosis-associated complications and death. Scores combining the MELD with muscle parameters should be re-validated by utilizing the PSMI.

[Current status for animal models of intensive care unit acquired muscle weakness].

Intensive care unit acquired muscle weakness (ICU-AW) is a neuromuscular complication secondary to severe illness. The essence for this disease is skeletal muscle dysfunction. With the development of medical technology, the survival rate for severe patients has been significantly improved. The long term complications for the severe patients with ICU-AW are getting more and more common, and they seriously affect the quality of life and prognosis of patients. However, the current treatment is ineffective. Establishment of ICU-AW animal model is an important way to study the pathogenesis and intervention targets for this disease. There are many risk factors for this disease, and the principles for ICU-AW animal models are not the same at home and abroad, and the methods of preparation are different. The choice of a reasonable animal model is important for the reliability of the results.

Combined Contribution of Reduced Functional Mobility, Muscle Weakness, and Low Serum Albumin in Prediction of All-Cause Mortality in Hemodialysis Patients: A Retrospective Cohort Study.

OBJECTIVES: The combined effects of reduced functional mobility, muscle weakness, and low serum albumin on mortality in hemodialysis patients have not been clarified. Here, we examined the associations of reduced functional mobility, muscle weakness, and low serum albumin-both alone and in combination-with all-cause mortality in hemodialysis patients. METHODS: A total of 490 patients treated between July 2010 and October 2016 were enrolled retrospectively in this study. The independent prognostic effect of the combination of reduced functional mobility, muscle weakness, and low serum albumin on survival was estimated by Cox proportional hazard regression analysis. We calculated the increases in predictive capacity by combining the associations of reduced functional mobility, muscle weakness, and low serum albumin in comparison to each component alone based on the receiver-operating characteristic curves, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The final study population consisted of 314 hemodialysis patients, and 56 patients died during the 6.5-year follow-up period. The high Combined score group showed a significantly lower cumulative survival rate than the low Combined score group (hazard ratio, 3.30; 95% confidence interval, 1.59-6.87; P = .001). Both NRI and IDI suggested that the addition of Combined score to patient characteristics improved discrimination of patients at high risk of mortality (NRI, 0.038 95% CI: 0.096 - 0.064, P < .001 IDI, 0.029 95% CI: 0.004 - 0.055, P = .025). CONCLUSIONS: The combined assessment of reduced functional mobility, muscle weakness, and low serum albumin was associated with poorer prognosis in patients on hemodialysis. The results presented here indicated that the combination of reduced functional mobility, muscle weakness, and low serum albumin is useful for accurate prediction of prognosis in hemodialysis patients.

Muscle Weakness and 5-Year Survival in Acute Respiratory Distress Syndrome Survivors.

OBJECTIVES: To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival. DESIGN: Longitudinal prospective cohort study over 5 years of follow-up. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: One hundred fifty-six acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Strength was evaluated with standardized manual muscle testing using the Medical Research Council sum score (range, 0-60; higher is better), with post-ICU weakness defined as sum score less than 48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after acute respiratory distress syndrome. At discharge, 38% of patients had muscle weakness. Every one point increase in sum score at discharge was associated with improved survival (hazard ratio [95% CI], 0.96 [0.94-0.98]), with similar findings longitudinally (0.95 [0.93-0.98]). Having weakness at discharge was associated with worse 5-year survival (1.75 [1.01-3.03]), but the association was attenuated (1.54 [0.82-2.89]) when evaluated longitudinally over follow-up. Persisting and resolving trajectories of muscle weakness, occurring in 50% of patients during follow-up, were associated with worse survival (3.01 [1.12-8.04]; and 3.14 [1.40-7.03], respectively) compared to a trajectory of maintaining no muscle weakness. CONCLUSIONS: At hospital discharge, greater than one third of acute respiratory distress syndrome survivors had muscle weakness. Greater strength at discharge and throughout follow-up was associated with improved 5-year survival. In patients with post-ICU weakness, both persisting and resolving trajectories were commonly experienced and associated with worse survival during follow-up.

Association of Muscle Weakness With Post-Fracture Mortality in Older Men and Women: A 25-Year Prospective Study.

Osteoporotic fracture increases the risk of premature mortality. Muscle weakness is associated with both increased fracture risk and low bone mineral density (BMD). However, the role of muscle strength in post-fracture mortality is not well understood. This study examines the change of muscle strength measured at quadriceps (QS) before and after fracture and defines the relationship between muscle strength and post-fracture mortality. The study involved 889 women and 295 men (who were participating in the Dubbo Osteoporosis Study) who had at least one low-trauma fracture (ascertained from X-ray reports) after the age of 50 years. Median follow-up time was 11 years (range 1 to 24). To determine the change in muscle strength before and after a fracture, we selected a subset of 344 women and 99 men who had had at least two muscle strength measurements before the fracture event and a subset of 407 women and 105 men who had had at least two measurements after the fracture. During the follow-up period, 366 (41.2%) women and 150 (50.9%) men died. The annual rate of decrease in height-adjusted muscle strength before fracture was 0.27 kg/m (1.85%) in women and 0.40 kg/m (1.79%) in men. Strength loss after fracture was not significantly different from that before fracture. In women, after adjusting for baseline age and BMD, each SD (5 kg/m) lower height-adjusted pre- and post-fracture quadriceps strength was associated with a 27% (hazard ratio [HR] = 1.27; 95% confidence interval [CI] 1.07, 1.50) and 18% (HR = 1.18; 95% CI 1.01, 1.38) increase in post-fracture mortality risk, respectively. Similarly, in men, each SD (5 kg/m) lower height-adjusted pre- and post-fracture QS was associated with increased mortality before fracture (HR = 1.33; 95% CI 1.09, 1.63) and after fracture (HR = 1.43; 95% CI 1.16, 1.78). Muscle weakness accounted for 15% (95% CI 0.05, 0.24) of premature deaths after fracture in women and 23% (95% CI 0.11, 0.35) in men. These results indicate that in the older individuals, lower muscle strength is an independent risk factor for post-fracture mortality. © 2017 American Society for Bone and Mineral Research.

Validation of the FNIH sarcopenia criteria and SOF frailty index as predictors of long-term mortality in ambulatory older men.

OBJECTIVE: we aimed to evaluate the Foundation for the National Institutes of Health (FNIH) criteria for weakness and low muscle mass and the Study of Osteoporotic Fractures (SOF) frailty index for prediction of long-term, all-cause mortality. DESIGN: community-based cohort study. SETTING: semi-rural community of Merelbeke (Belgium). SUBJECTS: ambulatory men aged 74 and more (n = 191). METHODS: weakness was defined on previously established criteria as low grip strength (<26 kg) or low grip strength-to-body mass index (BMI) ratio (<1.00). Low muscle mass (dual-energy x-ray absorptiometry) was categorised as low appendicular lean mass (ALM; predefined <19.75 kg) or low ALM-to-BMI ratio (predefined <0.789). Frailty status was assessed using the components of weight loss, inability to rise from a chair and poor energy (SOF index). Survival time was calculated as the number of months from assessment in 2000 until death or up to 15 years of follow-up. RESULTS: mean age of the participants was 78.4 ± 3.5 years. Combined weakness and low muscle mass was present in 3-8% of men, depending on the criteria applied. Pre-frailty and frailty were present in 30 and 7% of men, respectively. After 15 years of follow-up, 165 men (86%) died. Both the presence of combined weakness and low ALM-to-BMI ratio (age-adjusted HR = 2.50, 95% CI = 1.30-4.79) and the presence of SOF frailty (age-adjusted HR = 2.64, 95% CI = 1.44-4.86) were associated with mortality. CONCLUSIONS: our findings confirm the predictive value for mortality of the non-distribution-based FNIH criteria and SOF index in older community-dwelling Belgian men.

Association of Frailty based on self-reported physical function with directly measured kidney function and mortality.

BACKGROUND: Use of serum creatinine to estimate GFR may lead to underestimation of the association between self-reported frailty and kidney function. Our objectives were to evaluate the association of measured GFR (mGFR) with self-reported frailty among patients with CKD and to determine whether self-reported frailty was associated with death after adjusting for mGFR. METHODS: Participants in the Modification of Diet in Renal Disease study (1989-1993) had GFR measured using iothalamate clearance (mGFR), and GFR was estimated based on the CKD-EPI creatinine (eGFRcr) and cystatin C (eGFRcys) equations. We defined self-reported frailty as three or more of: exhaustion, poor physical function, low physical activity, and low body weight. Death was ascertained through 2007 using the National Death Index and the United States Renal Data System. RESULTS: Eight hundred twelve MDRD participants (97 %) had complete data on self-reported frailty (16 % prevalence, N = 130) and mGFR (mean (SD) 33.1 ± 11.7 ml/min/1.73 m(2)). Higher GFR was associated with lower odds of self-reported frailty based on mGFR, (OR 0.71, 95 % CI 0.60-0.86 per 10 ml/min/1.73 m(2)), eGFRcr (OR 0.80, 95 % CI 0.67-0.94 per 10 ml/min/1.73 m(2)), and eGFRcys (OR 0.75, 95 % CI 0.62-0.90 per 10 ml/min/1.73 m(2)). Median follow-up was 17 (IQR 11-18) years, with 371 deaths. Self-reported frailty was associated with a higher risk of death (HR 1.71, 95 % CI 1.26-2.30), which was attenuated to a similar degree when mGFR (HR 1.48, 95 % CI 1.08-2.00), eGFRcr (HR 1.57, 95 % CI 1.15-2.10), or eGFRcys (HR 1.51, 95 % CI 1.10-2.10) was included as an indicator of kidney function. CONCLUSIONS: We found an inverse association between kidney function and self-reported frailty that was similar for mGFR, eGFR and eGFRcys. In this relatively healthy cohort of clinical trial participants with CKD, using serum creatinine to estimate GFR did not substantially alter the association of GFR with self-reported frailty or of self-reported frailty with death.

Chronic critical illness: the price of survival.

BACKGROUND: The evolution of the techniques used in the intensive care setting over the past decades has led on one side to better survival rates in patients with acute conditions and severely impaired vital functions. On the other side, it has resulted in a growing number of patients who survive an acute event, but who then become dependent on one or more life support techniques. Such patients are called chronically critically ill patients. MATERIALS & METHODS: No absolute definition of the disease is currently available, although most patients are characterized by the need for prolonged mechanical ventilation. Mortality rates are still high even after dismissal from intensive care unit (ICU) and transfer to specialized rehabilitation care settings. RESULTS: In recent years, some studies have tried to clarify the pathophysiological characteristics underlying chronic critical illness (CCI), a disease that is also characterized by severe endocrine and inflammatory impairments, partly accounting for the almost constant set of symptoms. DISCUSSION: Currently, no specific treatment is available. However, a strategic early therapeutic approach on ICU admission might try to prevent the progress of the acute disease towards chronic critical illness.

Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU.

PURPOSE: Muscle weakness in long-stay ICU patients contributes to 1-year mortality. Whether electrophysiological screening is an alternative diagnostic tool in unconscious/uncooperative patients remains unknown. We aimed to determine the diagnostic properties of abnormal compound muscle action potential (CMAP), sensory nerve action potential (SNAP), and spontaneous electrical activity (SEA) for Medical Research Council (MRC)-defined weakness and their predictive value for 1-year mortality. METHODS: Data were prospectively collected during the EPaNIC trial (ClinicalTrials.gov: NCT00512122). First, sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of abnormal CMAP, SNAP, and SEA for weakness were determined. Subsequently, association between 1-year mortality and abnormal findings on electrophysiological screening was assessed by univariate and multivariate analyses correcting for weakness and other risk factors and the prediction model involved only a development phase. RESULTS: A total of 730 patients were electrophysiologically screened of whom 432 were tested for weakness. On day 8, normal CMAP excluded weakness with a high NPV (80.5 %). By day 15, abnormal SNAP and the presence of SEA had a high PPV (91.7 and 80.0 %, respectively). Only a reduced CMAP on day 8 was associated with higher 1-year mortality [35.6 vs 15.2 % (p < 0.001)]. This association remained significant after correction for weakness and other risk factors [OR 2.463 (95 % CI 1.113-5.452), p = 0.026]. Also among conscious/cooperative patients without weakness, reduced CMAP was independently associated with a higher likelihood of death occurring during 1 year [HR 2.818 (95 % CI 1.074-7.391), p = 0.035]. CONCLUSIONS: The diagnostic properties of electrophysiological screening vary over time. Abnormal CMAP documented early during critical illness carries information about longer-term outcome, which should be further investigated mechanistically.

Impact of ICU-acquired weakness on post-ICU physical functioning: a follow-up study.

INTRODUCTION: ICU-acquired weakness is thought to mediate physical impairments in survivors of critical illness, but few studies have investigated this thoroughly. The purpose was to investigate differences in post-ICU mortality and physical functioning between patients with and without ICU-acquired weakness at 6 months after ICU discharge. METHOD: ICU patients, mechanically ventilated ≥ 2 days, were included in a single-center prospective observational cohort study. ICU-acquired weakness was diagnosed when the average Medical Research Council score was <4 in awake and attentive patients. Post-ICU mortality was recorded until 6 months after ICU discharge; in surviving patients, physical functioning was assessed using the Short-Form Health Survey physical functioning domain. The independent effect of ICU-acquired weakness on post-ICU mortality was analyzed using a multivariable Cox proportional hazards model. The independent effect of ICU-acquired weakness on the physical functioning domain score was analyzed using a multivariable linear regression model. RESULTS: Of the 156 patients included, 80 had ICU-acquired weakness. Twenty-three patients died in the ICU (20 with ICU-acquired weakness); during 6 months follow-up after ICU discharge another 25 patients died (17 with ICU-acquired weakness). Physical functioning domain scores were available for 96 survivors (39 patients with ICU-acquired weakness). ICU-acquired weakness was independently associated with an increase in post-ICU mortality (hazard ratio 3.6, 95% confidence interval, 1.3 to 9.8; P = 0.01) and with a decrease in physical functioning (ß: -16.7 points; 95% confidence interval, -30.2 to -3.1; P = 0.02). CONCLUSION: ICU-acquired weakness is independently associated with higher post-ICU mortality and with clinically relevant lower physical functioning in survivors at 6 months after ICU discharge.

Muscle weakness and nutrition therapy in ICU.

PURPOSE OF REVIEW: Muscle wasting is common in severe critical illness. ICU-acquired weakness (ICU-AW) contributes to acute and long-term morbidity and mortality. The question remains whether nutrition therapy in ICU can prevent or attenuate these complications. This review aims at integrating the most recent clinical data in order to answer this important clinical and research question. Clinical evidence was obtained from randomized controlled trials (RCTs). Results from animal experiments and observational studies are referred to when - respectively - providing possible explanatory mechanisms or new hypotheses. RECENT FINDINGS: Although muscle wasting has been reproducibly quantified early in ICU, its relationship with ICU-AW has not yet been convincingly established. All recent RCTs evaluating increased energy/protein intake during ICU week 1 failed to demonstrate a protective effect against ICU-AW or physical function limitations. In one RCT, early parenteral nutrition increased the incidence of ICU-AW. The latter finding might be explained by suppressed autophagy. SUMMARY: Current evidence does not support improved physical function with increased energy/protein provision in the first ICU week. Future RCTs aimed at reducing the burden of ICU-AW and improving long-term function should particularly focus on nutrition beyond the acute phase of critical illness and on non-nutritional interventions such as early mobilization.