Outcomes in clinical trials on sarcopenia: a systematic review and meta-analysis.

Systemic Lupus, Metabolic Syndrome, Cardiac Disease, and Peripheral Artery Disease

<b>Background:</b> The Short Physical Performance Battery (SPPB) is commonly used in patients with chronic obstructive pulmonary disease (COPD) to assess mobility and balance. However, information about the response to pulmonary rehabilitation (PR) and minimal clinical important differences (MCIDs) of SPPB subtests and summary score in these patients is limited. <b>Aim:</b> To determine the response to PR and MCIDs for the SPPB subtests and SPPB summary score in patients with COPD. <b>Methods:</b> Retrospective analysis of 632 patients with COPD (age: 65±8 years, 50% male, FEV1: 43 (27-47)% predicted) following a PR program was performed. The SPPB consisted of three balance standing tests, 4-meter gait speed (4MGS) test and 5-repetition sit-to-stand (5STS) test. MCIDs were estimated with anchor-based (anchors: COPD Assessment Test and 6-minute walk test) and distribution-based methods. <b>Results:</b> 5STS (∆=1.14 (-4.20- -0.93) sec) and SPPB summary score (∆=1 (0-2) points) improved significantly after PR. Anchor-based method could not determine MCIDs as there were no significant correlations between the anchors and SPPB scores. Based on distribution-based calculations, the MCID estimates range between 0.51-0.67 sec for balance side-by-side, 0.64-0.78 sec for semi-tandem, 1.80-2.03 sec for tandem, 0.05-0.31 m/s for 4MGS, 2.19-6.33 sec for 5STS and 0.81-0.96 points for SPPB summary score. <b>Conclusions:</b> The 5STS and SPPB summary score are both responsive to PR in patients with COPD. Based on distribution-based calculations, a MCID estimate of 1 point for the SPPB summary score is recommended in these patients. Future research is needed to confirm MCID estimates for the SPPB subtests in different centres.

The Short Physical Performance Battery (SPPB) test is a well-established tool to assess physical performance, and to identify frail patients. Assessment of the SPPB in a specific population of elder patients in cardiac rehabilitation phase after a cardiac event is missing. The aim of this study was to correlate SPPB and the cardiac rehabilitation outcome in a group of elder patients after a cardiac event and to identify the Minimal Clinically Important Difference (MCID) of the SPPB. Consecutive (n = 392) patients aged ≥75 years, in the rehabilitation phase after cardiac surgery (70.1%), congestive heart failure (7.4%), or acute coronary syndrome (22.5%), were enrolled. SPPB was performed twice: on admission and discharge. The MCID was assessed with the 'anchor method', and the Patient Global Impression of Change was employed as the anchor. On admission, SPPB classified 56, 117, 116, and 94 patients as severe, moderate, mild, or minimal/no limitations, respectively. Patients with the lower SPPB had the longer length of stay, and the higher complications rate. At receiver operating characteristic analysis, an SPPB improvement >1 was identified as the MCID (area-under-curve 0.77, 95% CI 0.67-0.85). Overall, 285 patients (74.2%) had a 'clinically significant' improvement in SPPB, with a rate of improvement higher in patients with severe/moderate limitations (83.0%) and lower in those with mild (78.9%) or minimal/no limitations (53.6%). A lower SPPB score is associated with a higher complications rate in the post-acute phase. An improvement >1 point of SPPB was identified as the MCID; this reference value could serve as the goal for rehabilitation interventions.

BackgroundDespite the known association between chronic inflammation and reduced muscle mass, there is a gap in research regarding the association between the systemic immune-inflammation index (SII) and sarcopenic obesity (SO). This study aims to assess the relationship between SII and SO in middle-aged and elderly adults and the mediating role of triglyceride-glucose index (TyG).MethodsThis cross-sectional study involved 2,719 participants aged 45–90 years who underwent health check-ups. SO was evaluated by combining sarcopenia [assessed by handgrip strength and appendicular skeletal muscle index (ASMI)] with obesity (determined by body fat percentage). Association between SII and SO, sarcopenia, and obesity in middle-aged and elderly individuals was examined using multivariable logistic regression, restricted cubic spline analysis, and subgroup analysis. Bidirectional mediation analysis was conducted to determine the direct and indirect effects through SII and TyG.ResultsThe study included 2,719 participants, of which 228 had SO (8.4%). SO prevalence increased as the SII quartiles rose (Pfor trend <0.001). SII (per SD increase) had a significantly positive association with SO in both middle-aged individuals (OR = 1.69, 95% CI: 1.43 ~ 1.99) and older adults (OR = 2.52, 95% CI: 1.68 ~ 3.77). The relationship between SII and SO was found to be non-linear (Pnonlinear<0.05). In addition, SII showed a strong negative relationship with both handgrip strength and ASMI across all participants. In subgroup analysis, SII was still shown to significantly increase the risk of SO in all subgroups by gender, body mass index, waist circumference, smoking, drinking, hypertension, diabetes, dyslipidemia. TyG was found to mediate 21.36%, 11.78%, and 9.94% of the associations between SII and SO, sarcopenia, and obesity, respectively. SII had no mediation effect on the association between TyG and SO, sarcopenia, and obesity (P>0.05).ConclusionsElevated levels of SII were associated with an increased risk of SO in middle-aged and elderly adults, especially in the elderly population, and elevated TyG levels played a role in this relationship.

Rationale. Sarcopenic obesity is a combined state of low muscle mass and high adiposity associated with amplified morbidity and mortality in diverse populations. The study of body composition in interstitial lung disease (ILD), however, is nascent. We hypothesized that sarcopenic obesity would be associated with frailty, reduced exercise capacity, and reduced forced vital capacity (FVC) in adults with advanced ILD. Methods. In a cross-sectional analysis of two multicenter cohort studies of lung transplant candidates, participants with ILD were categorized by bioelectrical impedance into non-sarcopenic/non-obese; non-sarcopenic/obese; sarcopenic/non-obese; and sarcopenic obese. Two definitions of sarcopenia were considered by appendicular skeletal muscle index: lowest quartile (LQ) and European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Frailty was assessed by Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP), exercise capacity by six-minute walk distance (6MWD), and FVC by spirometry. We evaluated the association between body composition categories and clinically relevant outcomes using multivariable linear and logistic regression adjusted for age, race, and gender. We further adjusted by FVC to assess the effect of body composition on 6MWD (Table footer defines body composition and frailty thresholds). Results. Among 376 participants, 167 (44%) had idiopathic pulmonary fibrosis while 35 (9.3%) and 17 (4.5%) were sarcopenic obese by LQ and EWGSOP2 definitions, respectively. The median body mass index (BMI) of sarcopenic obese participants by LQ was 26.1 kg/m2[IQR: 4.5]. Sarcopenic obesity was associated with a 3.0-6.5-fold higher odds of frailty by SPPB compared to the non-sarcopenic/non-obese group (LQ: Odds Ratio [OR] 2.6, 95%CI: 1.1 to 5.9; EWGSOP2: OR 6.6, 95%CI: 2.0 to 22.3) and strong trends towards associations with frailty by FFP (Table). Sarcopenic obesity was associated with worse 6MWD (LQ: -57.2 meters, 95%CI: -103.9 to -10.5; EWGSOP2: -132.4 meters, 95%CI: -193.1 to -71.7). Sarcopenic obesity was also associated with lower FVC (LQ: -0.5 liters, 95%CI -0.8 to -0.3; EWGSOP2: -0.6 liters, 95%CI -0.9 to -0.3). Notably, phenotypes by BMI were not associated with either frailty or 6MWD, though BMI-defined obesity was associated with a greater FVC. Conclusions. Sarcopenic obesity is associated with increased risk of frailty, worse exercise capacity, and reduced FVC in advanced ILD. In contrast, this risk is occult when evaluating BMI-based metrics of underweight and obese. If replicated in a general ILD population, our findings suggest that advanced measures of body composition could identify novel explanatory factors for poor outcomes in ILD, and identify those for targeted intervention.

The effect of Tai Chi in elderly individuals with sarcopenia and frailty: A systematic review and meta-analysis of randomized controlled trials.

Cisplatin-based chemotherapy and radical cystectomy are standard treatments for muscle-invasive bladder cancer (MIBC), but their impact on neuromuscular integrity and functional capacity remains elusive. We investigated plasma biomarkers of neuromuscular junction degradation (c-terminal agrin-fragment-22; CAF22) and neuronal injury (Neurofilament light-chain; NfL) in relation to physical capacity in MIBC patients. In this prospective study, 42 MIBC patients undergoing neoadjuvant cisplatin-gemcitabine chemotherapy and radical cystectomy were assessed before (T1) and after (T2) chemotherapy, and 4-6weeks post-surgery (T3). Age- and BMI-matched controls (n = 46) were evaluated once. Plasma CAF22 and NfL were measured alongside handgrip strength (HGS), gait speed (GS), appendicular skeletal muscle index (ASMI), and short physical performance battery (SPPB). Plasma CAF22 and NfL were significantly elevated in patients versus controls at all time points. NfL showed more modest increases in post-treatment. HGS declined from 22.3 ± 3.9kg at T1 to 17.2 ± 3.3kg at T3 (p < 0.05), along with reductions in ASMI and GS. Cumulative SPPB scores dropped from 9.02 ± 1.02 to 8.24 ± 1.32. Sarcopenia prevalence rose from 28.5% at T1 to 52.4% at T3. CAF22 was significantly associated with lower HGS and SPPB at T1 (β = - 0.58 and - 0.42, p < 0.001). CAF22 changes correlated with HGS (r = - 0.80) and SPPB (r = - 0.75), while NfL showed weaker but significant correlations. Lab results indicated declines in hemoglobin, albumin, and renal function markers consistent with treatment effects. CAF22 showed strong associations with treatment-related decline in skeletal muscle, suggesting its potential as an early biomarker of sarcopenia that warrants validation in larger cohorts.

Purpose: The Short Physical Performance Battery (SPPB) is a test used to assess physical function; however, the minimal clinically important difference (MCID) in patients after cardiac surgery is unknown. The aim of this study was to determine the MCID of the SPPB after cardiac surgery. Methods: Seventy-two participants performed the SPPB at 4 weeks and 3 months postoperatively. The Short Form-36 version 2 was used to assess physical function and the Global Rating of Change (GRC) scale was used to assess patients' perceived change. Distribution-based methods were used to determine the MCID. Results: The mean (95% confidence intervals [CIs]) change of the SPPB between testing time points was +1.04 (0.67–1.42) points. Ninety-eight percent of patients rated their function as “changed” on the GRC scale. The MCID calculated using distribution-based methods ranged from 0.44 points (95% CI [0.191, 0.613]) for the effect size-based estimate to 1.35 points for the standard error of measurement–based estimate. No participants scored 0/12; however, 45% and 69% of participants scored 12/12 at 4 weeks and 3 months postoperatively, respectively. Conclusion: The MCID for SPPB is estimated to be between 0.44 and 1.35 points out of 12 for patients in the early postoperative period. Nearly half of the participants scored the maximum score at 4 weeks, increasing to two-thirds at 3 months meaning that the SPPB may be too easy as time from surgery increases and patients recover. Further research is required to confirm the MCID in patients closer to surgery where the ceiling effect is likely to be lower.

The minimal important difference (MID) is vital to consider when interpreting the clinical importance of observed changes from surgical interventions assessed by patient-reported outcome measures (PROMs). There is no accepted standard for how to calculate MIDs, and uptake in the plastic surgery literature is unknown, leading to methodologic and interpretation issues. Medline and Embase were searched to identify all plastic surgery randomized controlled trials (RCTs) using PROMs as outcomes and MID estimation studies for PROMs used by RCTs. Included studies were assessed for uptake and application of MIDs, and MID estimation methodology and values were categorized. A total of 554 RCTs using PROMs as outcomes were identified. Of these, 419 RCTs had the possibility of incorporating a previously published MID. The uptake rate of MIDs was 11.5% ( n = 48 of 419). The most common ways MIDs were applied were to calculate sample size (37.5%) or to determine whether results were clinically important (35.4%). A total of 99 studies estimating MID values for the most common PROMs in plastic surgery, based on our review, were analyzed. The most common estimation methodologies were receiver operating characteristic curve analysis (49%), change difference (31%), and SD (25%). This review highlights limited uptake and application of MIDs in plastic surgery. The authors propose 4 major barriers: (1) no repository of published MIDs for PROMs used in plastic surgery exists; (2) available MIDs are not specific to plastic surgery populations; (3) high heterogeneity in MID estimation methodology was present; and (4) there are wide ranges in MID values, with no superior choice identified.

Sarcopenic Obesity Phenotypes in Patients With HIV: Implications for Cardiovascular Prevention and Rehabilitation

PurposeExercise is the primary choice for managing age-related sarcopenia. However, many exercise intervention subtypes are currently used to manage age-related sarcopenia with little published evidence comparing their efficacy, meaning the optimal exercise intervention subtype for sarcopenia remains unclear. We performed a Bayesian network meta-analysis addressing these uncertainties.MethodsWe searched eight databases for literature through to 5 June 2023 to identify randomized controlled trials (RCTs) of exercise interventions for age-related sarcopenia. Skeletal muscle mass index (SMI), handgrip strength (HGS), knee extension strength (KES), gait speed (GS), chair rise test (CST) and time up and go test (TUGT) were used as outcomes. Effect estimates were expressed as standardized mean differences with 95% confidence intervals. We performed a Bayesian network meta-analysis using a random effects model and the R package gemtc to compare the relative efficacy of various exercise intervention subtypes. We also used surface under the cumulative ranking curve (SUCRA) to estimate relative treatment rankings. This systematic review is registered in PROSPERO, CRD42023474627.ResultsWe included 37 RCTs with a total of 2322 subjects and 10 unique exercise intervention subtypes. Most RCTs (72.9%) displayed unclear risk of bias. According to the value of SUCRA, whole-body vibration high frequency (WBVH) ranked first in SMI (99.8%), HGS (96.5%) and GS (76.5%), suggesting it is the most comprehensive and effective exercise intervention subtype for managing age-related sarcopenia. Combined training (CT) ranked first in CST (76.5%) and TUGT (75.2%), suggesting it is the most effective exercise intervention subtype for improving muscle function. Resistance training (RT) ranked first in KES (99.3%) and also performed well on TUGT and HGS.ConclusionOur network meta-analysis revealed that certain exercise intervention subtypes are more effective for specific muscle-related outcomes. WBHV, CT and RT are the most promising exercise intervention subtypes for managing sarcopenia, with WBHV providing the most comprehensive improvement in sarcopenia, CT the best improvement in muscle function, and RT the most common exercise intervention subtype for sarcopenia, which remains quite effective in enhancing muscle strength and function. Our meta-analysis provides a valuable reference and guidance for clinicians, researchers and policy makers, but it is limited by the heterogeneity and quality of the included RCTs.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12877-025-06529-w.

Ascites in cirrhotic patients interfere with accurate assessment of skeletal muscle when diagnosing sarcopenia. We hypothesized measurement of appendicular skeletal muscle index (ASMI) with dual-energy x-ray absorptiometry (DXA) improves the diagnosis of sarcopenia in cirrhotic patients as ASMI does not include the fluid-filled abdominal compartment. To evaluate if ASMI is influenced by ascites, lower limb edema (LLE) and predicts mortality alone or combined with handgrip strength (HGS) in cirrhotic patients. ASMI, HGS, and 36-month mortality were obtained in 144 men with cirrhosis. ASMI was compared before and after paracentesis in 20 men with ascites and to results from 20 matched controls. The prognostic value of ASMI alone and with HGS was tested in a survival. Survival probabilities were obtained for sarcopenia diagnosed by standard ASMI and HGS European Working Group on Sarcopenia in Older People (EWGSOP) cutoffs and a new cutoff calculated from our ASMI + HGS tertiles. ASMI did not change after paracentesis, was lower in patients than in controls (P < .001), and was not influenced by LLE (D = 0.30 kg/m2, P = .068; R2 = 2.40%). Mortality was influenced by ASMI and HGS (Pinteraction = 0.028). Sarcopenia diagnosed by EWGSOP was also diagnosed by our new cutoff; both predicted mortality with the latter more sensitive for mortality risk prediction (P = .011). DXA-measured ASMI is not influenced by ascites or LLE in cirrhotic patients; can diagnose low skeletal muscle/sarcopenia; and predicts mortality, particularly when combined with HGS.

Background: The results of clinical trials are routinely presented in terms of statistical significance, which may or may not indicate clinical significance. Analysis of the minimal clinically important difference (MCID) of cognitive scales has received little attention to date. Objectives: By reviewing the key methodological features (sample size, duration, statistical and clinical significance) of clinical trials examining the efficacy of tacrine in the treatment of Alzheimer’s disease (AD), we assessed their ability to detect clinically important changes in cognition. Design: The value for the MCID of the Mini-Mental State Examination (MMSE) was determined by surveying specialists in neurology and geriatric medicine. This value was then used to interpret the clinical significance of the results of published randomized controlled trials (RCTs) assessing the efficacy of tacrine in the treatment of AD and to retrospectively determine their optimal sample size and trial duration. Results: The mean survey MCID for the MMSE was 3.72 (95% confidence interval 3.50–3.95) points. Only 2 of 12 tacrine RCTs using the MMSE found a statistically significant difference in MMSE scores for patients taking tacrine compared with those taking placebo. These improvements were not clinically significant when compared with the survey MMSE MCID. For parallel trials of tacrine in AD, the smallest sample size and minimum trial duration required to demonstrate a clinically significant difference were calculated to be 53 subjects and 1 year, respectively. Five of the 7 parallel trials met the required sample size; however, none of them met the criteria for trial duration. Conclusions: When using the MMSE as an outcome measure, no tacrine trial reported results that were clinically significant as perceived by clinicians working with dementia patients. Application of a range of plausible MCIDs to the parallel design RCTs also demonstrated that 2 of 7 of these trials did not have sufficient sample size, and none had sufficient duration of treatment to reliably detect clinically meaningful changes in cognition. Future clinical trials in this area will need to incorporate the evolving knowledge of MCIDs in order to increase their chance of detecting clinically relevant results.

Inter-muscular adipose tissue is associated with adipose tissue inflammation and poorer functional performance in central adiposity

This randomized controlled trial aimed to evaluate the efficacy of electroacupuncture combined with nutritional intervention for cancer-related sarcopenia compared to nutritional intervention alone. Muscle thickness and elasticity were assessed using ultrasonography to calculate relevant parameters. By integrating these objective measures with conventional indicators and scales, this study aimed to provide a more comprehensive and intuitive evaluation of changes in muscle function, thereby offering a basis for the clinical application of electroacupuncture combined with nutritional intervention in the treatment of cancer-related sarcopenia. Seventy participants were randomly assigned to either a control group receiving nutritional intervention alone or an experimental group receiving electroacupuncture combined with nutritional intervention for 12weeks. Primary outcome measures included the appendicular skeletal muscle index (ASMI), dominant handgrip strength, 6-m walk time, and multiparameter ultrasound indices. Secondary outcomes included the Mini Nutritional Assessment (MNA), Short Physical Performance Battery (SPPB), body mass index (BMI), and body fat percentage. All measurements were taken at baseline and after the intervention. The study cohort predominantly consisted of patients diagnosed with gastrointestinal cancers. Following the intervention, participants in the control group demonstrated significant improvements in appendicular skeletal muscle index (ASMI), dominant handgrip strength, body mass index (BMI), ultrasound-derived muscle thickness, and Mini Nutritional Assessment (MNA) scores. However, no statistically significant changes were observed in the 6-m walking speed, body fat percentage, a-Ratio, or short physical performance battery (SPPB) scores. In contrast, the experimental group exhibited statistically significant enhancements across all measured outcomes, including ASMI, handgrip strength, 6-m walking speed, BMI, body fat percentage, muscle thickness by ultrasound, a-Ratio, MNA scores, and SPPB scores. Moreover, the magnitude of improvement in the experimental group surpassed that observed in the control group. This study demonstrates that electroacupuncture combined with nutritional intervention effectively improves muscle mass, dominant handgrip strength, physical performance, nutritional status, and body composition in patients with gastrointestinal cancer-related sarcopenia, with no significant safety concerns. This approach is worthy of clinical promotion to enhance the quality of life and prognosis of these patients.