Surrogate Marker For Sarcopenia Research Articles

Association between macro- and microvascular damage and sarcopenia index in individuals with type 2 diabetes mellitus.

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L])×100. The subjects were divided into three groups according to SI tertiles: T1 (41.27-81.37), T2 (81.38- 99.55), and T3 (99.56-192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend <0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252-3.090) in T2, 2.195 (1.278-3.769) in T1, for MAU was 1.805 (1.149-2.837) in T2, 2.537 (1.490-4.320) in T1, for DPN was 2.244 (1.485-3.391) in T2, 3.172 (1.884-5.341) in T1, and for LEAD was 2.017 (1.002-4.057) in T2, 2.405 (1.107-5.225) in T1 (all P<0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia.

NIMG-34. TEMPORAL MUSCLE THICKNESS AS A PROGNOSTIC MARKER IN A REAL-LIFE COHORT OF NEWLY DIAGNOSED MGMT PROMOTER METHYLATED GLIOBLASTOMA PATIENTS: A MULTICENTRIC IMAGING ANALYSIS

Abstract BACKGROUND In cranial MRI assessed temporal muscle thickness (TMT) correlates with lumbar skeletal muscle mass, which serves as surrogate marker of sarcopenia. Prior research has identified TMT as a prognostic marker in glioblastoma. However, incorporation into clinical practice is challenging due to the heterogeneity of previous studies and the absence of established cutoff values. To address this, we conducted a multicenter analysis to validate recently proposed sex-specific cutoff values in a homogeneous real-life cohort of newly diagnosed MGMT promoter-methylated glioblastoma patients uniformly treated with combined CCNU/temozolomide. We implemented a balanced control cohort for comparison. METHODS TMT was measured at baseline using preoperative or early postoperative MRI and in the disease course using the first MRI after completion of radiotherapy. Patients were TMT-based divided into “at risk of sarcopenia” or “normal muscle status”. Kaplan-Meier statistics and multivariable Cox regression analysis were used for correlation with survival. RESULTS In total, n = 126 patients were analyzed (n = 66 received CCNU/temozolomide; n = 60 received temozolomide). Patients with normal muscle mass at baseline (&amp;gt; 6,3 mm for men; &amp;gt; 5,2 mm for women) had significantly prolonged mOS (44.3 versus 16.7 months for CCNU/temozolomide; 29.5 versus 17.4 months for temozolomide) compared to those at risk of sarcopenia. In a multivariable Cox regression analysis, normal muscle mass (HR: 0.39, 95% CI: 0.23-0.66; p = 0.0003) and age at diagnosis of &amp;lt; 50 years (HR: 0.42, 95% CI: 0.22-0.79; p = 0.0067) were significant prognostic markers. Longitudinally, survival was best in patients with lack of TMT decline. CONCLUSIONS This analysis suggests TMT to serve as a prognostic marker in glioblastoma patients treated with CCNU/temozolomide or with temozolomide. However, for TMT assessment to be implemented in a generalizable manner, such as for patient selection for therapeutic measures, further validation in prospective controlled trials is necessary.

Low Alanine-Aminotransferase Blood Activity Is Associated with Increased Mortality in Chronic Lymphocytic Leukemia Patients: A Retrospective Cohort Study of 716 Patients.

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies, especially among elderlies. Several prognostic scores are available that utilize the characteristics of patients' blood counts and cytogenetic anomalies-all are features of the disease rather than of the patient. Addressing the route of personalized rather than precise medicine, we refer to the assessment of patients' status of sarcopenia and frailty. Low alanine aminotransferase (ALT) was already shown to function as a surrogate marker for sarcopenia and frailty. We decided to find a possible correlation between low ALT values and poor prognosis of CLL patients. This is a retrospective cohort study of CLL patients treated in a large, tertiary medical center, as outpatients or inpatients. Their frailty status was evaluated in a retrospective manner. We defined patients with ALT below 12 IU/L as frail and divided our cohort into two groups including a low ALT level group (ALT < 12) and a normal ALT level group (ALT ≥ 12). Overall, our final analysis included 716 CLL patients, of which 161 (22.5%) had ALT levels lower than 12 IU/L. There was no significant difference in patients' age between the two groups. Patients with the low ALT had a lower hemoglobin concentration (median 10.8 g/dL [IQR = 2.7] vs. 12.2 [IQR = 3.1]; p < 0.001) and a higher proportion of patients were classified as Binet C score [48.4% vs. 31.1%]; p < 0.001). Frail CLL patients' survival was significantly shorter when compared to non-frail patients, in both the univariate [HR = 1.6 [95% confidence interval, CI 1.23, 2.0]; p < 0.01] and multivariate analyses [HR = 1.3 [95% CI 1.0, 1.7]; p = 0.03]. Sarcopenia and frailty assessment, based on blood ALT measurements, could potentially point out differences in CLL patients' prognoses. Such assessment could serve the purpose of treatment personalization of CLL patients.

P11.65.B TEMPORAL MUSCLE THICKNESS AS A PROGNOSTIC MARKER IN A REAL-LIFE COHORT OF NEWLY DIAGNOSEDMGMT PROMOTER METHYLATED GLIOBLASTOMA PATIENTS: A MULTICENTRIC IMAGING ANALYSIS

Abstract BACKGROUND In cranial magnetic resonance imaging (MRI) assessed temporal muscle thickness (TMT) correlates with lumbar skeletal muscle mass, which serves as a surrogate marker of sarcopenia. Prior research has identified TMT as a prognostic marker in glioblastoma. However, incorporation into clinical practice is challenging due to the heterogeneity of previous studies and the absence of established cutoff values. To address this, we conducted a multicenter analysis to validate recently proposed sex-specific cutoff values in a homogeneous cohort of newly diagnosed MGMT promoter-methylated glioblastoma patients uniformly treated under real-life conditions with combined CCNU/temozolomide. We also included a balanced control cohort for comparison. MATERIAL AND METHODS TMT was measured at baseline using initial preoperative and postoperative MRI and during the course of the disease using the first MRI after completion of radiotherapy in the first therapy-line. Using TMT and previously reported cutoff values from the literature, patients were classified into "at risk of sarcopenia" or "normal muscle status" cohorts. To correlate TMT with survival, we conducted Kaplan-Meier and multivariable Cox regression analyses. RESULTS A total of 126 patients were analyzed, with 66 patients treated with combined CCNU/temozolomide and 60 patients treated with temozolomide single-drug treatment. In both cohorts, patients with normal muscle mass at baseline had significantly longer survival. Specifically, in the CCNU/temozolomide cohort median progression-free survival (mPFS) was 16.7 months in the normal muscle mass group versus 6.8 months in the at-risk group (p=0.0008); median overall survival (mOS) was 44.2 months in the normal muscle mass group versus 16.7 months in the at-risk group (p=0.0046). In the temozolomide single-drug cohort, mPFS was 12.4 months in the normal muscle mass group versus 7.7 months in the at-risk group, and mOS was 29.5 months in the normal muscle mass group versus 17.4 months in the at-risk group (p=0.0006). Using multivariable Cox regression analysis, we found normal muscle mass (HR: 0.39, 95% CI: 0.23-0.66; p=0.0003) and initial age at diagnosis of less than 50 years (HR: 0.42, 95% CI: 0.22-0.79; p=0.0067) were statistically significant prognostic markers. Longitudinally, patients with lacking TMT decline during the course of the disease had the best survival outcomes. CONCLUSION This analysis suggests TMT to serve as a prognostic marker in glioblastoma patients treated with CCNU/temozolomide or single-drug treatment with temozolomide. However, for TMT assessment to be implemented in a generalizable manner, such as for patient selection for therapeutic measures, further validation in prospective controlled trials is necessary.

Do low levels of alanine aminotransferase, a baseline marker of sarcopenia and frailty, associate with worse clinical outcomes among hospitalized COVID-19 patients? A Retrospective Cohort Study.

COVID-19 geoperdize lives. Not all the risk factors for negative outcomes are known. Sarcopenia and frailty are common, negatively affecting clinical outcomes. Studies have shown that sarcopenia and frailty are associated with worse outcomes. Our objective was to examine whether low ALT (Alanine-aminotranferase), a surrogate marker for sarcopenia, is associated with worse clinical outcomes among hospitalized COVID-19 patients. We reviewed cases of COVID-19 in a tertiary hospital, during three COVID-19 waves and examined correlations between ALT and mortality using crude, univariate and multivariate analysis for age, gender, hypertension, Chronic obstructive pulmonary disease and Congestive heart failure. 357 patients were included in this analysis. Median age was 69, 54% were males. Median ALT was 19 IU/L. During follow-up, 73 (20%) died. Patients with low ALT were more likely to die (HR 1.82, 95% CI 1.06-3.09, P=0.028). Other predictors for mortality were low albumin, background COPD, dyslipidemia, dementia, and malignancy. The multivariate analysis showed that low ALT was still an independent predictor of poor prognosis (HR 1.7, 95% CI 1.0-2.9, P=0.049). In our analysis of COVID-19 patients, low ALT levels were independently associated with increased risk of mortality, both as standalone and when incorporated into a multivariate analysis.

Psoas muscle analysis as a surrogate marker of sarcopenia and frailty: A multicenter analysis of predictive capacities over short- and long-term outcomes after abdominal aortic aneurysm repair.

Several predictive models exist for estimating the postoperative risks of abdominal aortic aneurysm (AAA) repair, although no particular tool has seen widespread use. We present the results of a multicenter, historic cohort study comparing the predictive capacity of the psoas muscle area (PMA), radiodensity (PMD), and lean muscle area (LMA) as surrogate markers of sarcopenia, over short- and long-term outcomes after AAA repair, compared to the mFI-5 and American Society of Anesthesiologists (ASA) scales. Retrospective review was conducted of all consecutive AAA elective repair cases (open or endovascular) in three tertiary-care centers from 2014 to 2019. Cross-sectional PMA, PMD, and LMA at the mid-body of the L3 vertebra were measured by two independent operators in the preoperative computed tomography. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values. Bivariate analysis, logistic regression, and Cox's proportional hazards models were built to examine the relationship between baseline variables and postoperative mortality, long-term mortality, and complications. 596 patients were included (mean age 72.7 ± 8years, 95.1% male, 66.9% EVAR). Perioperative mortality was 2.3% (EVAR 1.2% vs open repair 4.6%, p = .015), and no independent predictors could be identified in the multivariate analysis. Conversely, an age over 74years old (OR 1.84 95%CI 1.25-2.70), previous heart diseases (OR 1.62 95%CI 1.13-2.32), diabetes mellitus (OR 1.61 95%CI 1.13-2.32), and a PMD value over 66 HU (OR 0.58 95%CI 0.39-0.84) acted as independent predictors of long-term mortality in the Cox's proportional hazards model. Heart diseases (congestive heart failure or coronary artery disease), serum creatinine levels over 1.05mg/dL, and an aneurysm diameter over 60mm were independent predictors of major complications. Surrogate markers of sarcopenia had a poor predictive profile for postoperative mortality after AAA repair in our sample. However, PMD stood out as an independent predictor of long-term mortality. This finding can guide future research and should be confirmed in larger datasets.

Incidence and risks of coronary heart disease and heart failure in Japanese patients with type 2 diabetes mellitus: The Fukuoka diabetes registry

AimsWe prospectively investigated the incidence of coronary heart disease (CHD) and heart failure (HF), risk factors and prognosis in Japanese patients with type 2 diabetes. MethodsA total of 4,874 outpatients with type 2 diabetes (mean age 65 years, male 57%, previous CHD 14%) were registered at multicenter diabetes clinics of a prefecture in 2008–2010 and followed for the development of CHD and HF requiring hospitalization for a median of 5.3 years (follow-up rate 98%). Risk factors were evaluated using multivariable adjusted Cox proportional models. ResultsThe incidence rates per 1,000 person-years were 12.3 for CHD (silent myocardial ischemia 5.8, angina pectoris 4.3, myocardial infarction 2.1) and 3.1 for hospitalized HF, respectively. New-onset CHD was significantly associated with higher serum adiponectin [the highest quartile vs. the lowest quartile HR 1.6 (95%CI 1.0–2.6)]. HF was significantly associated with higher serum adiponectin [the highest quartile vs. the lowest quartile HR 2.4 (95%CI 1.1–5.2)], and lower serum creatinine/cystatin C ratio, a surrogate marker for sarcopenia [lowest quartile vs. the highest quartile HR 4.6 (95%CI 1.9–11.1)]. ConclusionsThe incidence of heart disease was low and circulating adiponectin and sarcopenia may predict the development of heart disease in Japanese patients with type 2 diabetes.

Temporal Muscle Thickness Correlates with Sarcopenia in Parkinson's Disease.

Sarcopenia is characterized by a progressive loss of muscle mass, strength, and function resulting in adverse health outcomes. Current assessment strategies are bothersome and means to simplify the diagnosis are an unmet medical need in Parkinson's disease (PD). To evaluate temporal muscle thickness (TMT) obtained on routine cranial MRI as a surrogate marker of sarcopenia in PD patients. We correlated TMT from axial non-contrast-enhanced T1-weighted sequences of MRI close (±12 months) to an outpatient visit including sarcopenia (EWGSOP1, EWGSOP2, SARC-F), frailty (Fried's criteria, clinical frailty scale), and disease characteristics of Parkinson's patients (Hoehn and Yahr-scale, Movement Disorder Society-Unified Parkinson's Disease Rating Scale, quality of life with the Parkinson's Disease Questionnaire-8) assessments. Cranial MRI was available in 32 patients with a mean age of 73.56±5.14 years, mean disease duration of 11.46±5.66 years, and median Hoehn and Yahr stage of 2.5. The mean TMT was 7.49±2.76 (7.15) mm. Mean TMT was significantly associated with sarcopenia (EWGSOP2, p = 0.018; EWGSOP1, p = 0.023) and frailty status (physical phenotype; p = 0.045). Moreover, there were significant moderate to strong correlations between TMT measurement and appendicular skeletal muscle mass index (r: 0.437, p = 0.012), as well as handgrip strength (r: 0.561, p < 0.001). Reduced TMT seems to be a promising surrogate marker for sarcopenia (EWGSOP2) and muscle strength in this pilot study in PD patients.

Association of temporalis muscle thickness with functional outcomes in patients undergoing endovascular thrombectomy

IntroductionTemporalis muscle thickness (TMT) is a surrogate marker for sarcopenia. This study investigated the association of TMT with clinical outcomes in patients receiving endovascular thrombectomy (EVT) for stroke involving acute large vessel occlusion (LVO). Material and methodsWe enrolled consecutive patients who had undergone EVT between September 2014 and December 2021 at three thrombectomy-capable institutes. TMT was measured through preprocedural computerized tomography angiography. The clinical variables affecting TMT were investigated. The associations between TMT and clinical functional outcomes, defined using the modified Rankin scale, were also studied. ResultsA total of 657 patients were included (mean age: 72.0 ± 12.7 years; male: 52.1%). The mean TMT was 6.35 ± 1.84 mm. Younger age, male sex, higher body mass index, and premorbid functional independence were associated with larger TMT in both univariate and multivariate linear regression (P <.05). Ordinal logistic regression revealed that TMT was associated with better clinical outcomes at 90 days (Ptrend = 0.047); multivariate logistic regression indicated that larger TMT was an independent predictor (adjusted odds ratio: 1.14, 95% confidence interval: 1.03–1.27, P = 0.02) of favorable functional independence (modified Rankin scale score: 0–2). The effect was stronger in older patients (≥80 years) than younger patients, as revealed by interaction modeling analysis (Pinteraction = 0.06). ConclusionTMT is associated with age, sex, body mass index, and premorbid functional status. Larger TMT is associated with better outcomes after EVT. The effects of TMT are more pronounced in older adults, indicating that sarcopenia may have influence on stroke outcomes.

Abstract P2-03-01: Sarcopenia on baseline imaging is associated with toxicity-related discontinuation of endocrine therapy in women with early-stage hormone-positive breast cancer

Abstract Background Adjuvant endocrine therapy (ET) is standard of care in women with hormone receptor-positive (HR+) breast cancer (BC) with the goal to reduce recurrence. However, early discontinuation of ET occurs in 30-40% of women, largely attributable to toxicity, and leads to increased recurrence risk. There is considerable overlap in risk factors that predict toxicity from ET and chemotherapy, including age, co-morbidities, and geriatric conditions. Baseline low skeletal muscle area (SMA) on chest computed tomography (CT) is a surrogate marker for sarcopenia and predicts for significant toxicity and intolerance to chemotherapy in women with BC. No study has assessed the association of sarcopenia with toxicity-related discontinuation of ET in women with early-stage HR+ BC. Methods This single center retrospective cohort study included consecutive women with Stage 0-II HR+ BC who received ET and adjuvant radiotherapy (RT) from 01/2011-12/2017. Inclusion required a minimum of 5-year clinical follow-up after diagnosis. We used a validated deep learning pipeline to quantify SMA (cm2) at the tenth thoracic (T10) vertebral body on existing RT planning CT. The skeletal muscle index (SMI [cm2/m2] = SMA/(patient height (m))2) was calculated to adjust for patient height. Sarcopenia was defined as SMI&amp;lt; 32.3 cm2/m2, based on a previously validated independent cohort of young healthy women. The primary endpoint was toxicity-related discontinuation of ET less than 60 months after initiation of ET. Secondary endpoints included any NCI CTCAE v5.0 Grade 3-5 toxicity from ET and ipsilateral breast tumor recurrence. We assessed associations between ET discontinuation and SMI (continuous), as well as thoracic sarcopenia (dichotomous), using logistic regression adjusting for baseline characteristics. We used cox proportional hazards regression to assess disease-free survival (DFS), defined as ipsilateral breast tumor recurrence, locoregional recurrence, or distant metastasis adjusting for baseline and treatment characteristics. Results A total of 265 women (median age 67 years) met inclusion criteria. The majority of women had a comorbidity index of 0-1 (89%) and were Caucasian (89%). The median follow-up was 82 months, 5-year overall survival was 96% and 5-year DFS was 94%. Diagnoses included DCIS (12%), IDC (76%), or ILC (12%); most were T1 (69%) or T2 (18%) and N0 (85%), ER-positive (100%), PR-positive (85%), or HER2-negative (9%). Most common ET type was anastrozole (63%), letrozole (16%), and tamoxifen (17%). SMI (continuous) was not associated with older age, Charlson Comorbidity Index (CCI), race, or tumor stage. A total of 64 (24%) women experienced toxicity-related early discontinuation of ET. On multivariate analysis (MVA), lower SMI was associated with increased toxicity-related early discontinuation of ET (Odds Ratio [OR] 0.89 per 1 cm2/m2 SMI, p=0.001) independent of age, CCI, ET type, or receipt of adjuvant chemotherapy. Lower SMI was associated with higher risk of grade 3-5 toxicity from ET (OR 0.89 per 1 unit SMI, p=0.001) independent of age, CCI, ET type, or receipt of adjuvant chemotherapy. On MVA, sarcopenia was associated with higher risk of toxicity-related early discontinuation of ET (OR 2.43, p=0.019). DFS was associated with toxicity-related early discontinuation of ET (HR 8.06, p=0.005), grade 3 histology (HR 1.42, p=0.042), and multifocal disease (HR 2.55, p=0.040), but not age, histology, stage, or lymphovascular invasion (p&amp;gt;.05 for all). Conclusion Low baseline thoracic skeletal muscle is associated with toxicity-related early ET discontinuation in women with early-stage HR+ BC. Further studies should attempt to generalize this association to all HR+ BC who are candidates for ET. High-risk patients may be candidates for aggressive symptom management or alternative adjuvant therapies. Citation Format: Anurag Saraf, Ismail Tahir, Bonnie Hu, Anna-Sophia Dietrich, Paul Erik Tonnesen, Greg Sharp, Gayle Tillman, Florian Fintelmann, Rachel Jimenez. Sarcopenia on baseline imaging is associated with toxicity-related discontinuation of endocrine therapy in women with early-stage hormone-positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-01.

Influence of temporal muscle thickness on the outcome of radiosurgically treated patients with brain metastases from non-small cell lung cancer.

The purpose of this study was to assess the impact of temporal muscle thickness (TMT), a surrogate marker for sarcopenia, in radiosurgically treated patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC). For 566 patients with BMs from NSCLC in the period between June 2012 and December 2019, TMT values were retrospectively measured on the planning brain magnetic resonance imaging (MRI) studies that had been obtained before their first Gamma Knife radiosurgery treatment (GKRS1). Predefined sex-specific TMT cutoff values were used to stratify the study cohort into patients at risk for sarcopenia and patients with normal muscle status. Cox regression models adjusted for other prognostic parameters were used to evaluate sarcopenia as an independent prognostic factor. In sarcopenia patients with a TMT below the sex-specific cutoff values, the risk of death was significantly increased (HR 1.908, 95% CI 1.550-2.349, p < 0.001). In addition, sarcopenia was revealed as an independent prognostic factor even after adjusting for age groups, sex, number of BMs, presence of extracranial metastases, NSCLC subtypes, Karnofsky Performance Status groups, recursive partitioning analysis classes, and concomitant immunotherapy or targeted therapy (HR 1.680, 95% CI 1.347-2.095, p < 0.001). However, patients at risk for sarcopenia showed no significant differences in the estimated mean time until local BM progression after GKRS1, compared to patients with normal muscle status (p = 0.639). TMT obtained from planning MRI studies is an independent prognostic marker in radiosurgically treated patients with BMs from NSCLC and may aid patient stratification in future clinical trials.

Association of SARC-F Score and Rockwood Clinical Frailty Scale with CT-Derived Muscle Mass in Patients with Aortic Aneurysms.

Patients with aortic aneurysms (AA) are often co-morbid and susceptible to frailty. Low core muscle mass has been used as a surrogate marker of sarcopenia and indicator of frailty. This study aimed to assess association between core muscle mass with sarcopenia screening tool SARC-F and Clinical Frailty Scale (CFS) in patients with AA. Prospective audit of patients in pre-operative aortic clinic between 01/07/2019-31/01/2020 including frailty assessment using Rockwood CFS and sarcopenia screening using SARC-F questionnaire. Psoas and sartorius muscle area were measured on pre-operative CT scans and adjusted for height. Association was assessed using Spearman's rank correlation coefficient. Of 84 patients assessed, median age was 75 years [72,82], 84.5% were men, 65.5% were multimorbid and 63.1% had polypharmacy. Nineteen percent were identified as frail (CFS score >3) and 6.1% positively screened for sarcopenia (SARC-F score 4 or more). Median psoas area (PMA) at L3 was 5.6cm2/m2 [4.8,6.6] and L4 was 7.4cm2/m2 [6.3,8.6]. Median sartorius area (SMA) was 1.8 cm2/m2 [1.5,2.2]. CFS demonstrated weak but statistically significant negative correlation with height-adjusted PMA at L3 (r=-0.25, p=0.034) but not at L4 (r=-0.23, p=0.051) or with SMA (r=-0.22, p=0.065). No association was observed between SARC-F score and PMA or SMA (L3 PMA r=-0.015, p=0.9; L4 PMA r=-0.0014, p= 0.99; SMA r=-0.051, p=0.67). CFS showed higher association with CT-derived muscle mass than SARC-F. Comprehensive pre-operative risk-stratification tools which incorporate frailty assessment and body composition analysis may assist in decision making for surgery and allow opportunity for pre-habilitation.

Serum creatinine/cystatin C ratio is a surrogate marker for sarcopenia in patients with idiopathic pulmonary fibrosis

BackgroundThe serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a marker for sarcopenia, but has not been studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to confirm the utility of the serum Cr/CysC ratio in predicting sarcopenia and investigate its clinical relevance.MethodsThis cross-sectional pilot study prospectively enrolled patients with stable IPF. IPF was diagnosed through multidisciplinary discussions according to the 2018 international guidelines, and sarcopenia was diagnosed according to the 2019 consensus report of the Asian Working Group for Sarcopenia. Patient-reported outcomes (PROs) were evaluated using the modified Medical Research Council (mMRC) dyspnea scale, chronic obstructive pulmonary disease assessment test (CAT), and King’s Brief Interstitial Lung Disease (K-BILD) questionnaire. The associations between serum Cr/CysC ratio and the presence of sarcopenia and other clinical parameters, including PROs scores, were examined.ResultsThe study enrolled 49 Japanese patients with IPF with a mean age of 73.0 ± 7.7 years and a mean percentage of predicted forced vital capacity of 80.4 ± 15.5%. Sarcopenia was diagnosed in 18 patients (36.7%), and the serum Cr/CysC ratio was 0.86 [0.76–0.94] (median [interquartile range]). The receiver operating characteristic curve analyses for the detection of sarcopenia according to the serum Cr/CysC showed that the area under the curve, optimal cutoff value, specificity, and sensitivity were 0.85, 0.88, 0.65, and 0.94, respectively. Sarcopenia was identified in 13% of patients with a high serum Cr/CysC ratio (≥ 0.88) and 60% of patients with a low serum Cr/CysC ratio (< 0.88) (P < 0.001). Multiple linear regression analysis showed that the serum Cr/CysC ratio was an independent predictive marker of worse PROs evaluated using mMRC (P < 0.05), CAT (P < 0.05), and K-BILD (P < 0.05).ConclusionsThis study showed that the serum Cr/CysC ratio may be a surrogate marker of sarcopenia in patients with IPF. Furthermore, it is important to pay attention to the serum Cr/CysC ratio because a lower serum Cr/CysC ratio is associated with worse PROs. Further studies are required to validate these observations to determine whether the Cr/CysC ratio can be used to detect sarcopenia in patients with IPF.

Normalized Creatinine-to-Cystatin C Ratio and Risk of Diabetes in Middle-Aged and Older Adults: The China Health and Retirement Longitudinal Study.

BackgroundCreatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort.MethodsA population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed.ResultsDuring follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (Pinteraction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively.ConclusionHigh normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

A Novel Application of Serum Creatinine and Cystatin C to Predict Sarcopenia in Advanced CKD.

Sarcopenia is highly prevalent in patients with advanced chronic kidney disease (CKD), yet a reliable serum index has not been established. The product of serum creatinine and the estimated glomerular filtration rate based on cystatin C (Cr×eGFRcys) was recently proposed as a sarcopenia index (SI), approximately to 24-h filtered creatinine through the glomerulus. We aimed to evaluate the diagnostic validity of the novel SI in advanced CKD. In 297 patients with non-dialysis stage 3b-5 CKD, aged 68.8 ± 12.9 years, the total skeletal muscle mass (SMM), handgrip strength (HGS), and usual gait speed were assessed. Sarcopenia was defined based on the Asian Working Group for Sarcopenia 2019 consensus update. The prevalence of sarcopenia in this cohort was 20.2%. The SI correlated moderately with SMM (r = 0.503, P < 0.001), HGS (r = 0.508, P < 0.001), and gait speed (r = 0.381, P < 0.001); the independency of the SI with three muscle metrics was confirmed after extensive adjustment. For sarcopenia prediction, the SI had acceptable discriminative powers in males [area under the receiver operating characteristic curve (AUC) 0.646, 95% confidence interval (CI) 0.569–0.718] and females (AUC 0.754, 95% CI 0.670–0.826). In males, the best cut-off was 53.9, which provided 71.1% sensitivity, 58.0% specificity, 32.9% positive predictive value (PPV), and 87.4% negative predictive value (NPV); in females, the best cut-off was 45.8, which provided 81.8% sensitivity, 62.3% specificity, 31.0% PPV, and 94.3% NPV. In conclusion, Cr×eGFRcys could be served as a surrogate marker for sarcopenia and may be helpful for sarcopenia screening in advanced CKD. Further studies are needed to expand our investigation.

Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with gastric cancer

BackgroundSarcopenia is an age-related syndrome that may have negative impact on surgical outcomes and long-term survival of patients with gastric cancer. Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with gastric cancer. The purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and prognosis of patients with gastric cancer.MethodsWe retrospectively studied 327 patients who underwent surgery for gastric cancer from June 2009 to October 2021. The skeletal muscle mass index was calculated using computed tomography (CT). We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers. The Concordance index (C-index) was calculted to measure whether the Cr/CysC ratio can prognosis of patients with gastric cancer.ResultsSerum Cr/CysC was significantly correlated with with Skeletal Muscle Index (SMI) (r = 0.221, p < 0.001) and Skeletal Muscle Area (SMA) (r = 0.258, p < 0.001). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.644, CysC: 0.535, Cr: 0.556). Patients in the high-Cr/CysC group have longer survival time than that in low-Cr/CysC group, defined by the cutoff value 0.67. The C-index of both Cr/CysC ratio and SMI with OS was 0.63.ConclusionsSerum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with gastric cancer. Our study shows that patients with Cr/CysC below 0.67 had possibility of sarcopenia and would be poor prognosis.

Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study.

BackgroundPatients with end‐stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT).MethodsIn a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross‐sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross‐sectional area normalized for height2, reported in cm2/m2) and MD (mean attenuation of muscle cross‐sectional area, expressed in Hounsfield units). We determined age‐specific and sex‐specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival.ResultsAmong the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm2/m2 in men and 42.3 ± 7.3 cm2/m2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22–12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30–10.7, P = 0.015), and body mass index > 25 kg/m2 (aOR 2.94, 95% CI: 1.4–6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06–4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02–4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03–1.09, P = 0.0003). Low SMI was not associated with mortality.ConclusionsMyosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

Sarcopenia index as a predictor of clinical outcomes in older patients undergoing transcatheter aortic valve replacement.

Sarcopenia is a prevalent condition in elderly patients and has been associated with adverse outcomes following transcatheter aortic valve replacement (TAVR). The present study aimed to determine the predictive value of serum creatinine-cystatin C ratio, that is, "Sarcopenia Index" (SI) as a surrogate marker of sarcopenia, and investigate its association with clinical outcomes after TAVR. We conducted a retrospective observational study of patients undergoing TAVR between January, 2016 and December, 2018 at Hospital Italiano de Buenos Aires, Argentina. Patients were excluded if <65-years old, presented previous surgical aortic valve replacement, severe chronic kidney disease, or hemodialysis requirement. The SI was obtained at baseline before TAVR. All-cause mortality and/or readmissions for congestive heart failure (CHF) were defined as the primary endpoint. In total 100 patients met inclusion criteria for the purpose of the study. Sarcopenia Index was significantly correlated with Timed Up and Go (r=-0.272, p=.010) and Gait Speed (r=-0.278, p=.005). During follow-up, 5/100 patients died within 30 days and a total of 10/100 patients died at 1-year follow-up. Moreover, survival curves were significantly worse (Log-rank test=p=.02) and CHF readmissions were more prevalent in the lowest SI tertile (Log-rank test=p=.01). In multivariate Cox regression analysis, we identified low SI (cutoff ≤66) as an independent predictor of long-term adverse outcomes (HR=4.01, 95% CI=1.31-12.27, p=.015) at 1-year follow-up. Sarcopenia Index, surrogate for the degree of skeletal muscle mass (SMM), could be used as a predictor of adverse outcomes in patients undergoing TAVR.

Temporalis Muscle Thickness as an Indicator of Sarcopenia Is Associated With Long-term Motor Outcomes in Parkinson's Disease.

To investigate the relationship between temporalis muscle thickness (TMT) at baseline as a surrogate marker for sarcopenia and long-term motor outcomes in patients with Parkinson's disease (PD). We enrolled 249 patients with drug-naïve early-stage PD (119 males and 130 females, follow-up > 3 years). Baseline TMT of each patient was measured on the axial plane of T1-weighted images. The association between baseline TMT and long-term motor outcomes in PD was assessed using Cox regression models for levodopa-induced dyskinesia, wearing-off, and freezing of gait and a linear mixed model for the longitudinal increases in levodopa-equivalent dose per body weight over time. Statistical analyses were performed separately for sex if an interaction effect between TMT and sex was assumed. TMT differed substantially between the sexes, and male PD patients had higher TMT (6.69 ± 1.39 mm) than female PD patients (5.64 ± 1.34 mm, p < .001). Cox regression models demonstrated that baseline TMT was not associated with the risk of developing levodopa-induced dyskinesia, wearing-off, or freezing of gait during the follow-up period. The linear mixed model was applied separately for sex and demonstrated that higher TMT at baseline was associated with slower increases in levodopa-equivalent dose per body weight in male PD patients, but not in female PD patients. This study demonstrated that baseline TMT could be an indicator of the longitudinal requirement for dopaminergic medications in male patients with PD, suggesting that sarcopenia may have a detrimental effect on disease progression in PD in a sex-specific manner.

Possible Influence of Weight Gain and Creatinine Levels in Predicting Response to Nivolumab: A Multicenter Analysis.

Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma treated with nivolumab between 2018 and 2020. Patients were stratified by creatinine levels both at treatment initiation and at first follow-up (at three months) and by BMI for the same intervals, as recorded in the patients’ charts. Creatinine was considered a surrogate marker for sarcopenia. IBM SPSS version 20 was used for statistical analysis. A total of 57 (n = 57) patients were included in the trial. Overall response rate (ORR) for the entire population was 38.59% (p = 0.02). Patients with BMI lower than 25 had an ORR of 28.5% (p = 0.003), whereas patients with BMI higher than 25 had an ORR of 42.3% (p = 0.002). Patients who gained weight during treatment had a lower probability of having progressive disease (OR = 0.4 [95% CI; 0.4–1.2]), as did patients with creatinine higher than 0.9 (OR = 0.39 [95% CI: 0.13–1.14]). No superiority was found in progression-free survival (PFS) when patients were dichotomized for BMI = 25 or BMI = 18.5. Mean PFS in the BMI under 18.5 group was 10.2 months [95% CI: 5.8–23.1], versus 11.2 for BMI over 18.5 [95% CI: 5.3–25.3], p < 0.03. Mean PFS for the BMI under 25 was 11.2 months [95% CI: 7.2–20.1], vs. 13.3 months [95% CI: 6.4–22] for the BMI over 25, p < 0.001. There were also differences in PFS in the patients with baseline creatinine over 0.9 when compared with under 0.9 values. Mean PFS in the first group was 19.78 months [95% CI: 16.23–22.9] vs. 16.1 [95% CI: 12.2–20.3], p < 0.001. Patients treated with nivolumab who have weight gain during treatment have a better PFS than the ones who do not. Creatinine levels of over 0.9 at treatment initiation also have positive predictive value.