The accuracy of screening instruments for sarcopenia: a diagnostic systematic review and meta-analysis.

OBJECTIVE: This review aimed to summarise the diagnostic accuracy of screening tools for sarcopenia. METHODS: We conducted a systematic review along with a critical appraisal of published studies on screening tools for sarcopenia. We assessed the measurement properties of screening instruments using the consensus-based standards for selecting health measurement instruments (COSMIN) checklist. We evaluated the risk bias of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The diagnostic test accuracy of instruments for sarcopenia was reported using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR). RESULTS: We screened 7,120 titles and abstracts; 42 studies including five screening tools for sarcopenia were included. The overall study quality assessed by the QUADAS-2 tool was moderate to good. Of the five screening tools, three instruments had specificities ≥85%: 92% [95% confidence interval (CI): 63-99%] for the SARC-F modified version, 87% (95% CI: 82-90%) for the SARC-F and 85% (95% CI: 77-90%) for the Ishii score. Three tools had sensitivity ≥75%, namely, MSRA 82% (95% CI: 69-90%), Ishii score 79% (95% CI: 62-89%) and U-TEST 76%. PLR higher than 5.0 were present for the Ishii score and SARC-F modified versions; the Ishii score also had the best NLR of 0.25 of all scales. CONCLUSION: The MSRA and Ishii score had excellent sensitivity for sarcopenia screening at an early stage; SARC-F modified versions and Ishii score had superior specificity for sarcopenia diagnosis.

Prevalence and prognostic value of preexisting sarcopenia in patients with mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia is defined as age-related loss of muscle mass, strength, and/or function in the context of aging. Mechanical ventilation (MV) is one of the most frequently used critical care technologies in critically ill patients. The prevalence of preexisting sarcopenia and the clinical impact of its prognostic value on patients with MV are unclear. This review sought to identify the prevalence and prognostic value of preexisting sarcopenia on MV patient health outcomes. METHODS: Relevant studies were identified by searching MEDLINE, Embase, and the Cochrane library and were searched for all articles published as of December 2021. The prevalence of sarcopenia was determined using the authors' definitions from the original studies. Comparisons were made between patients who did and did not have sarcopenia for prognostic outcomes, including mortality, the number of days of MV, the length of intensive care unit stay, and the length of hospital stay. Odds ratios (ORs) and weighted mean differences with 95% confidence intervals (CIs) were used for pooled analyses of the relationships between sarcopenia and prognostic outcomes. RESULTS: The initial search identified 1333 studies, 17 of which met the eligibility criteria for the quantitative analysis, including 3582 patients. The pooled prevalence was 43.0% (95% CI 34.0-51.0%; I2 = 96.7%). The pooled analyses showed that sarcopenia was related to increased mortality (OR 2.13; 95% CI 1.70, 2.67; I2 = 45.0%), longer duration of MV (MD = 1.22; 95% CI 0.39, 2.05; I2 = 97.0%), longer days of ICU stay (MD = 1.31; 95% CI 0.43, 2.19; I2 = 97.0%), and hospital stay (MD 2.73; 95% CI 0.58, 4.88; I2 = 98.0%) in patients with MV. CONCLUSION: The prevalence of sarcopenia is relatively high in patients with MV, and it will have a negative impact on the prognosis of patients. However, further, large-scale, high-quality prospective cohort studies are required.

Neutrophil-lymphocyte ratio as a predictor of delirium in older internal medicine patients: a prospective cohort study.

BACKGROUNDS: Delirium is a common neuropsychiatric syndrome in older hospitalized patients. Previous studies have suggested that inflammation and oxidative stress contribute to the pathophysiology of delirium. However, it remains unclear whether neutrophil-lymphocyte ratio (NLR), an indicator of systematic inflammation, is associated with delirium. This study aimed to investigate the value of NLR as an independent risk factor for delirium among older hospitalized patients. METHODS: We conducted a prospective study of 740 hospitalized patients aged ≥ 70 years in the geriatric ward of West China Hospital of Sichuan University. Neutrophil and lymphocyte counts were collected within 24 h after hospital admission. Delirium was assessed on admission and every 48 h thereafter. We used the receiver operating characteristic analysis to assess the ability of the NLR for predicting delirium. The optimal cut-point value of the NLR was determined based on the highest Youden index (sensitivity + specificity - 1). Patients were categorized according to the cut-point value and quartiles of NLR, respectively. We then used logistic regression to identify the unadjusted and adjusted associations between NLR as a categorical variable and delirium. RESULTS: The optimal cut-point value of NLR for predicting delirium was 3.626 (sensitivity: 75.2 %; specificity: 63.4 %; Youden index: 0.386). The incidence of delirium was significantly higher in patients with NLR > 3.626 than NLR ≤ 3.626 (24.5 % vs. 5.8 %; P < 0.001). Significantly fewer patients in the first quartile of NLR experienced delirium than in the third (4.3 % vs. 20.0 %; P < 0.001) and fourth quartiles of NLR (4.3 % vs. 24.9 %; P < 0.001). Results from the multivariable logistic regression models showed that NLR was independently associated with delirium. CONCLUSIONS: NLR is a simple and practical marker that can predict the development of delirium in older internal medicine patients.

[Research of relationship between frailty and gut microbiota on middle-aged and the aged patients with diabetes].

Gut microbiota plays an important role in development of diabetes with frailty. Therefore, it is of great significance to study the structural and functional characteristics of gut microbiota in Chinese with frailty. Totally 30 middle-aged and the aged participants in communities with diabetes were enrolled in this study, and their feces were collected. At the same time, we developed a metagenome analysis to explore the different of the structural and functional characteristics between diabetes with frailty and diabetes without frailty. The results showed the alpha diversity of intestinal microbiota in diabetes with frailty was lower. Collinsella and Butyricimonas were more abundant in diabetes with frailty. The functional characteristics showed that histidine metabolism, Epstein-Barr virus infection, sulfur metabolism, and biosynthesis of type Ⅱ polyketide products were upregulated in diabetes with frailty. Otherwise, butanoate metabolism and phenylalanine metabolism were down-regulated in diabetes with frailty. This research provides theoretical basic for exploring the mechanism of the gut microbiota on the occurrence and development of diabetes with frailty, and provides a basic for prevention and intervention of it.

Sulfate radical induced degradation of Methyl Violet azo dye with CuFe layered doubled hydroxide as heterogeneous photoactivator of persulfate.

Persulfate (PS)-based advanced oxidation processes have aroused considerable attentions due to their higher efficiency and wider adaptability to the degradation of bio-recalcitrant organic contaminants. In this study, Cu-Fe layered doubled hydroxide (CuFe-LDH) was employed to degrade Methyl Violet (MV) through heterogeneous photo-activation of PS under visible-light irradiation. The reaction kinetics, degradation mechanism, catalyst stability were investigated in detail. Under the conditions of CuFe-LDH (3:1) dosage 0.2 g/L, PS concentration 0.2 g/L and without initial pH adjustment, 20 mg/L MV was almost completely degraded within 18 min. Electron Spin Resonance (ESR) test and radical quenching experiment indicated that sulfate radicals (SO4-) were the dominant reactive oxidants for the MV decolorization, while hydroxyl radicals (OH) were also involved. The CuFe-LDH/PS/Vis system was applicable at wide range of pH level (3-9). However, extreme pH level would lead to the reduction or transformation of SO4-. The catalyst CuFe-LDH exhibited excellent stability and maintained relatively high catalytic activity to PS even after four recycles. Mechanism study revealed that the redox cycle of Fe3+/Fe2+ and Cu2+/Cu3+ assisted by visible-light irradiation accounted for the enhanced generation of radicals in CuFe-LDH/PS/Vis system, resulting in the improved degradation of organic contaminants. Overall, the CuFe-LDH/PS/Vis process could be a promising approach for the removal of refractory organic pollutants in wastewater.

Association of handgrip strength asymmetry and weakness with depression among middle-aged and older population in China: A cohort study.

BACKGROUND: Handgrip strength (HGS) weakness and asymmetry were recently reported to be associated with age-related health conditions. However, little is known about their combined effects on depression. We aimed to explore the joint association of HGS asymmetry and weakness with depressive symptoms in Chinese middle and older aged population. METHODS: 8700 participants aged ≥45 years were enrolled from China Health and Retirement Longitudinal Study (2015-2018). HGS weakness was determined as maximal HGS < 28 kg in males and <18 kg in females. HGS asymmetry was measured by HGS ratio and was defined using two different rules. Specifically, HGS ratio < 0.90 or >1.10 (10 % rule) and <0.80 or >1.20 (20 % rule) were considered as asymmetry. Participants were classified into four groups: normal and symmetric HGS, asymmetry only, weakness only, and both weakness and asymmetry. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale, with scores ≥12 defined as depression. The logistic regression and multiple linear regression models were conducted to estimate the associations between HGS status and depressive symptoms. RESULTS: The three-year incidence of depression was 19.2 %. After adjusting for covariates, compared to normal and symmetric HGS, participants with both HGS asymmetry and weakness showed the greatest risk of incident depression (10 % rule: OR 1.55, 95 % CI 1.19-2.02; 20 % rule: OR 1.71, 95 % CI 1.16-2.50). The coexistence of asymmetry and weakness was related to a significant increase in depression score (10 % rule: ß 0.96, 95 % CI 0.38-1.54; 20 % rule: ß 0.94, 95 % CI 0.08-1.81). The complete case analysis supported the results, and the associations were not modified by age, sex, and hand dominance. LIMITATIONS: Depressive assessment was based on self-reported screening instrument. CONCLUSIONS: The presence of both HGS asymmetry and weakness was associated with a higher risk of depression. Examining HGS asymmetry along with weakness may aid in identifying individuals at risk of depression to enable early interventions.

Association of handgrip strength asymmetry and weakness with functional disability among middle-aged and older adults in China.

Background: Little is known about the association of handgrip strength (HGS) asymmetry with functional disability in China. We aimed to examine the individual and combined association of HGS asymmetry and weakness with functional disability among middle-aged and older Chinese adults. Methods: We included participants aged ≥45 years from two waves of the China Health and Retirement Longitudinal Study (2011 and 2015). HGS weakness was defined as the maximal HGS<28 kg for men and <18 kg for women. HGS asymmetry was measured by dividing the maximal nondominant HGS (kg) by the maximal dominant HGS (kg), with the value <0.90 or >1.10 considered as asymmetry. Functional disability was assessed by activities of daily living (ADL) and instrumental activities of daily living (IADL) and was defined as encountering difficulty in completing one or more ADL/IADL tasks. The logistic regression models were used to explore the association between HGS measures and functional disability. Results: 11 950 (mean age 59.2 ± 9.6 years, 47.9% males) and 7540 (mean age 57.5 ± 8.6 years, 50.1% males) participants were included in the cross-sectional and prospective study, respectively. HGS asymmetry and weakness, individually or simultaneously, were associated with an increased prevalence of functional disability. During the four-year follow-up, 1822 (24.2%) participants had incident functional disability. The separate exposure to HGS asymmetry (odds ratio (OR) = 1.18; 95% confidence interval (CI) = 1.05-1.32) or weakness (OR = 1.59; 95% CI = 1.30-1.95) was independently associated with functional disability. For combined associations, those with both weakness and asymmetry showed the greatest risk of new-onset functional disability (OR = 1.91; 95% CI = 1.45-2.52). Conclusions: HGS asymmetry and weakness were associated with a higher risk of functional disability. Assessing HGS asymmetry together with weakness may help to better identify those at risk of functional disability to enable early interventions.

Sarcopenia in systemic sclerosis: prevalence and impact-a systematic review and meta-analysis.

OBJECTIVE: This review aims to provide an estimate of sarcopenia prevalence and its impact on clinical characteristics in patients with systemic sclerosis (SSc). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, Web of Science and the Cochrane Central Register of Controlled Trials were systemically searched from inception to 24 May 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included observational studies that reported the prevalence of sarcopenia in patients with SSc. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed study selection and data extraction using standardised methods. Risk of bias was assessed using the Agency for Healthcare Research and Quality Scale and the Newcastle-Ottawa Scale. Meta-analysis was conducted using random effects models. RESULTS: A total of 4583 articles were screened and 9 studies with data from 815 patients were included in the analysis (8 cross-sectional studies and 1 retrospective cohort study). The overall prevalence of sarcopenia in patients with SSc was 22% (95% CI 17% to 28%). Patients with SSc with sarcopenia had a poorer quality of life (mean difference -12.02; 95% CI -19.11 to -4.93) and higher C reactive protein (CRP) levels (standardised mean difference 0.67; 95% CI 0.35 to 1.00). CONCLUSIONS: Sarcopenia is common in patients with SSc. Patients with SSc with sarcopenia had a worse quality of life and higher CRP levels, based on our findings. Given the detrimental impact of sarcopenia on quality of life, future efforts aimed at early identification of sarcopenia in the clinical assessment of patients with SSc may have significance. PROSPERO REGISTRATION NUMBER: CRD42022368326.

Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism.

OBJECTIVE: Adrenal venous sampling (AVS) is recommended for identifying the subtype of primary aldosteronism before making a surgical treatment decision, but failed cannulation of one adrenal vein is common. To evaluate whether using results of one adrenal vein during AVS could accurately predict unilateral primary aldosteronism. METHODS: A retrospective study was conducted in primary aldosteronism patients receiving bilaterally or unilaterally successful AVS. The aldosterone-cortisol ratio from the adrenal vein divided by the aldosterone-cortisol ratio from the inferior vena cava (IVC) was calculated as the AV/IVC index. RESULTS: The study examined 455 patients with primary aldosteronism, including 347 patients with unilateral primary aldosteronism. Among them, 250 and 125 patients received non- adrenocorticotropic hormone (ACTH) and ACTH-stimulated AVS, respectively, and 80 patients received both forms of AVS. Under non-ACTH-stimulated AVS, AUC of the AV/IVC index to diagnose ipsilateral and contralateral primary aldosteronism were 0.778 and 0.924, respectively. The specificity was 100% for both, with sensitivities of 5 and 26%, respectively, when using cutoffs of 17.05 to diagnose ipsilateral primary aldosteronism and 0.15 to diagnose contralateral primary aldosteronism. When using cutoffs of 3.60 and 0.70, the specificity decreased, but if combined with CT results (ipsilateral or contralateral adrenal nodules larger than 10 mm), the specificity could be maintained at 99%, with sensitivities of 33 and 45%, respectively. Under ACTH-stimulated AVS, the AV/IVC index showed similar accuracy to diagnose ipsilateral and contralateral primary aldosteronism. CONCLUSION: The unilateral AV/IVC index can be used to diagnose unilateral primary aldosteronism during AVS. Combining CT results can increase the accuracy further.

Development and Validation of PRE-SARC (PREdiction of SARCopenia Risk in Community Older Adults) Sarcopenia Prediction Model.

OBJECTIVE: Reliable identification of high-risk older adults who are likely to develop sarcopenia is essential to implement targeted preventive measures and follow-up. However, no sarcopenia prediction model is currently available for community use. Our objective was to develop and validate a risk prediction model for calculating the 1-year absolute risk of developing sarcopenia in an aging population. METHODS: One prospective population-based cohort of non-sarcopenic individuals aged 60 years or older were used for the development of a sarcopenia risk prediction model and model validation. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia consensus. Stepwise logistic regression was used to identify risk factors for sarcopenia incidence within a 1-year follow-up. Model performance was evaluated using the area under the receiver operating characteristics curve (AUROC) and calibration plot, respectively. RESULTS: The development cohort included 1042 older adults, among whom 87 participants developed sarcopenia during a 1-year follow-up. The PRE-SARC (PREdiction of SARCopenia Risk in community older adults) model can accurately predict the 1-year risk of sarcopenia by using 7 easily accessible community-based predictors. The PRE-SARC model performed well in predicting sarcopenia, with an AUROC of 87% (95% CI, 0.83-0.90) and good calibration. Internal validation showed minimal optimism, with an adjusted AUROC of 0.85. The prediction score was categorized into 4 risk groups: low (0%-10%), moderate (>10%-20%), high (>20%-40%), and very high (>40%). The PRE-SARC model has been incorporated into an online risk calculator, which is freely accessible for daily clinical applications (https://sarcopeniariskprediction.shinyapps.io/dynnomapp/). CONCLUSIONS: In community-dwelling individuals, the PRE-SARC model can accurately predict 1-year sarcopenia incidence. This model serves as a readily available and free accessible tool to identify older adults at high risk of sarcopenia, thereby facilitating personalized early preventive approaches and optimizing the utilization of health care resources.

Screening for primary aldosteronism on and off interfering medications.

OBJECTIVE: To determine whether antihypertensives will affect diagnostic accuracy of the aldosterone-to-renin ratio (ARR) to an extent that is clinically relevant. METHODS: Confirmatory tests were used to confirm or exclude PA diagnosis. Area under the receiver operating characteristic curve (AUC), specificity and sensitivity of ARR performance in different conditions were calculated. RESULTS: 208 PA and 78 essential hypertension (EH), and 125 PA and 206 EH patients, were included in the retrospective and prospective cohort, respectively. AUC of ARR on interfering medications was comparable to ARR off interfering medications (retrospective: 0.82 vs. 0.87, p = 0.20; prospective: 0.78 vs. 0.84, p = 0.07). At a threshold of 20 pg/µIU, the sensitivity of ARR on interfering medications was lower (11.1-23.2%) while the specificity was higher (10.2-15.2%) than ARR off interfering medications. However, when the ARR threshold on interfering medications was lowered to 10 pg/µIU, both the sensitivity (retrospective: 0.91 vs. 0.90, p = 0.61; prospective: 0.86 vs. 0.82, p = 0.39) and specificity (retrospective: 0.49 vs. 0.59, p = 0.20; prospective: 0.58 vs. 0.66, p = 0.10) were comparable to the ARR threshold off interfering medications. CONCLUSION: Using ARR to screen for PA whilst taking interfering antihypertensive drugs is feasible in most cases, but the ARR threshold needs to be reduced. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04991961.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses.

BACKGROUND: Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. METHODS: We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. FINDINGS: In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09-6.32] in EIMDS, and 4.31 [1.39-13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05-1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. INTERPRETATION: Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes.

Combined associations of vitamin D and cognitive function with all-cause mortality among older adults in Chinese longevity areas: A prospective cohort study.

Objectives: While both vitamin D deficiency and cognitive impairment have individually been linked to a greater risk of all-cause mortality, the combined effects of these two different conditions have not previously been explored in this context. We aimed to investigate the combined impact of vitamin D concentration and cognitive impairment on all-cause mortality in older adults. Methods: The analyzed data were collected from community-dwelling adults ≥65 years of age that were enrolled in the Chinese Longitudinal Healthy Longevity Survey (n = 1,673). The Mini-Mental Status Examination (MMSE) was used to assess cognitive function, while the plasma 25-hydroxyvitamin D [25(OH)D] test was used to assess vitamin D status. The associations between vitamin D concentration, cognitive function, and all-cause mortality were assessed with Cox proportional hazards models. We used restricted cubic splines to examine the dose-response relationship between vitamin D and the risk of all-cause mortality and used joint effect testing to explore interactions between vitamin D concentration and cognitive function. Results: During a mean (SD) follow-up of 3.8 (1.9) years, 899 (53.7%) deaths occurred. A negative dose-response relationship was observed between 25(OH)D concentration and cognition impairment at baseline, as well as the odds of all-cause mortality during follow-up. Similarly, cognitive impairment was significantly related to all-cause mortality risk (HR 1.81, 95% CI: 1.54 to 2.12). The combined analyses showed positive associations, with the highest mortality risk observed in older adults with both low vitamin D and cognitive impairment (HR 3.04, 95% CI: 2.40 to 3.86). Moreover, the interaction between 25(OH)D concentration and cognitive function was found to be significant in relation to the risk of mortality (p for interaction <0.001). Conclusion: Lower plasma 25(OH)D and cognitive impairment were, respectively, associated with increased all-cause mortality risks. The 25(OH)D concentration and cognitive impairment exhibited a combined additive effect on all-cause mortality among older Chinese adults.

Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism: The ADOPA Randomized Clinical Trial.

Importance: Adrenal venous sampling (AVS) is usually recommended to distinguish between unilateral and bilateral primary aldosteronism (PA) before definitive surgical or medical treatment is offered. Whether a treatment decision based on AVS with or without corticotropin (ACTH) stimulation leads to different biochemical and clinical remission rates in patients with PA remains unclear. Objective: To evaluate whether treatment decisions based on AVS with or without ACTH stimulation lead to different biochemical and clinical remission rates in patients with PA. Design, Setting, and Participants: This randomized clinical trial (RCT) was conducted at a tertiary hospital in China from July 8, 2020, to February 20, 2023, among patients with PA aged 18 to 70 years. Patients were followed up for 12 months after the initiation of treatment. An intention-to-diagnose analysis was conducted. Interventions: Patients were randomly assigned to undergo either ACTH-stimulated or non-ACTH-stimulated AVS. Main Outcomes and Measures: The primary end point was the proportion of patients with complete biochemical remission after 12 months of follow-up. Secondary outcomes included the proportion of patients who achieved complete clinical remission after 12 months of follow-up, dosages of antihypertensive agents, rate of successful bilateral AVS, and adverse events. Results: Of 228 patients with PA, 115 were randomized to the non-ACTH-stimulated group (median age, 50.0 years [IQR, 41.0-57.0 years]; 70 males [60.9%]) and 113 to the ACTH-stimulated group (median age, 50.0 years [IQR, 43.5-56.5 years]; 63 males [55.8%]). A total of 68 patients (59.1%) underwent adrenalectomy in the non-ACTH group and 65 (57.5%) in the ACTH group. There was no significant difference in the proportion of patients with complete biochemical remission who were managed on the basis of AVS with vs without ACTH stimulation (with: 56 of 113 [49.6%]; without: 59 of 115 [51.3%]; P = .79). There also was no significant difference in the proportion of patients who achieved complete clinical remission between the non-ACTH and ACTH groups (26 of 115 [22.6%] and 31 of 113 [27.4%], respectively; P = .40). The intensity of therapy with antihypertensives, successful catheterization of bilateral adrenal veins, and incidence of adverse events did not significantly differ between the non-ACTH and ACTH groups. Conclusions and Relevance: In this RCT, treatment of PA on the basis of non-ACTH-stimulated or ACTH-stimulated AVS did not lead to significant differences in clinical outcomes for the patients. These results suggest that ACTH stimulation during AVS may not have clinical benefit, at least in the Chinese population. Trial Registration: ClinicalTrials.gov Identifier: NCT04461535.

Phosphoproteomics Reveals the Wolframin-Calcium Axis as an Important Pathogenic Signaling Node in Primary Aldosteronism.

BACKGROUND: Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown. METHODS: We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line. RESULTS: The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411, P<0.001). Among 97 APA cases for validation, a higher expression level of wolframin was associated with a higher plasma aldosterone concentration postcaptopril challenge test and a higher systolic blood pressure. In vitro, the secretion of aldosterone was enhanced by wolframin overexpression, while aldosterone secretion in response to potassium or angiotensin II was inhibited by the knockdown of wolframin. Further in vivo and in vitro data demonstrated the wolframin-calcium axis as an important regulator of CYP11B2 expression and aldosterone production. CONCLUSIONS: Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion.

Combined Vision and Hearing Impairment is Associated with Frailty in Older Adults: Results from the West China Health and Aging Trend Study.

Objective: Hearing and vision loss have been independently associated with frailty in older adults, but the relationship between concurrent hearing and visual impairment (dual sensory impairment) and frailty is not well understood. Therefore, we aimed to examine whether dual sensory impairment is associated with frailty in older adults. Methods: This cross-sectional study was based on the data from the West China Health and Aging Trend (WCHAT) study of community-dwelling individuals aged 60 years and older. Frailty status was evaluated by the FRAIL scale and categorized as robust, prefrail and frail. Hearing and vision functions were based on self-report. We used multinomial regression models to explore the association between dual sensory impairment and frailty. Results: Of 3985 participants, 1655 (41.5%) were male and the median age was 66 years (interquartile range: 61-68). Overall, 7.6% of participants reported hearing impairment only, 32.7% reported vision impairment only, and 28.6% reported dual sensory impairment. The prevalence of prefrailty and frailty was 60.7% and 6.1%, respectively. After adjustment for confounding variables, results from the multinomial regression analysis showed that dual sensory impairment was significantly associated with greater odds of becoming frail (OR = 2.17, 95% CI = 1.40-3.38) compared with no impairment. When stratified by gender, dual sensory impairment was significantly associated with frailty in women (OR = 2.42, 95% CI = 1.40-4.20) but not in men (OR = 1.30, 95% CI = 0.58-2.91). Conclusion: Older adults with dual sensory impairment are more likely to be frail than those with no impairment, suggesting that interventions to improve sensory function may potentially help reduce the risk of frailty in older adults.

Diagnosis, prevalence, and mortality of sarcopenia in dialysis patients: a systematic review and meta-analysis.

There is no consensus on the prevalence of sarcopenia or its impact on mortality in end-stage renal disease patients undergoing dialysis. This review aimed to summarize the diagnostic criteria of sarcopenia and its prevalence and impact on the mortality of end-stage renal disease patients undergoing dialysis. Embase, MEDLINE, PubMed, and Cochrane Library were searched from inception to 8 May 2021 to retrieve eligible studies that assessed muscle mass by commonly used instruments, such as dual-energy X-ray absorptiometry, bioelectrical impedance analysis, magnetic resonance imaging, and body composition monitor. Two assessment tools matched to study designs were employed to evaluate study quality. Pooled sarcopenia prevalence was calculated with 95% confidence interval (CI), and heterogeneity was estimated using the I2 test. Associations of sarcopenia with mortality were expressed as hazard ratio (HR) and 95% CI. The search identified 3272 studies, and 30 studies (6162 participants, mean age from 47.5 to 77.5 years) were analysed in this review. The risk of bias in the included studies was low to moderate. Twenty-two studies defined sarcopenia based on low muscle mass (LMM) plus low muscle strength and/or low physical performance, while eight studies used LMM alone. Muscle mass was assessed by different instruments, and a wide range of cut-off points were used to define LMM. Overall, sarcopenia prevalence was 28.5% (95% CI 22.9-34.1%) and varied from 25.9% (I2  = 94.9%, 95% CI 20.4-31.3%; combined criteria) to 34.6% (I2  = 98.1%, 95% CI 20.9-48.2%; LMM alone) (P = 0.247 between subgroups). The statistically significant differences were not found in the subgroups of diagnostic criteria (P > 0.05) and dialysis modality (P > 0.05). Additionally, the sarcopenia prevalence could not be affected by average age [regression coefficient 0.004 (95% CI: -0.005 to 0.012), P = 0.406] and dialysis duration [regression coefficient 0.002 (95% CI -0.002 to 0.005), P = 0.327] in the meta-regression. The pooled analyses showed that combined criteria of sarcopenia were related to a higher mortality risk [HR 1.82 (I2  = 26.3%, 95% CI 1.38-2.39)], as was LMM [HR 1.61 (I2  = 26.0%, 95% CI 1.31-1.99)] and low muscle strength [HR 2.04 (I2  = 80.4%, 95% CI 1.19-3.5)]. Although there are substantial differences in diagnostic criteria, sarcopenia is highly prevalent in dialysis patients and is linked to increased mortality. The standardization of sarcopenia diagnostic criteria would be beneficial, and future longitudinal studies are needed to investigate the prevalence and prognostic value of sarcopenia in dialysis patients.

Prevalence of Sarcopenia in Pain Patients and Correlation Between the Two Conditions: A Systematic Review and Meta-Analysis.

OBJECTIVES: Sarcopenia is a generalized and progressive skeletal muscle disorder and has been proven to be associated with many diseases; however, the correlation between sarcopenia and pain has not yet been systematically clarified. This review aimed to investigate the prevalence of sarcopenia in patients with pain and to ascertain whether pain is independently associated with sarcopenia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: A systematic literature search was performed from the Cochrane Central Register of Controlled Trials, Embase, MEDLINE and Epub Ahead of Print, In-Process, In-Data-Review, and Other Non-Indexed Citations, Daily and Versions for observational studies from inception until February 2021, and our search was updated on December 31, 2021. METHODS: Sarcopenia prevalence was calculated according to the corresponding number of patients with sarcopenia and pain. We performed meta-analyses with random effects models to calculate the pooled prevalence of sarcopenia in pain and its correlations. Subgroup analyses were also performed based on pain classification, pain location, and diagnostic criteria for sarcopenia. Heterogeneity between the studies was described using the I2 statistic. RESULTS: Fourteen observational studies (13,953 participants, 44% women, and mean age from 40.1 to 76.6 years) were included. Study quality was rated moderate to high. The overall sarcopenia prevalence in patients with pain was 0.11 (95% CI 0.07-0.15, P < .001; I2 = 92.3%). People with pain were independently associated with a higher risk of sarcopenia than those without pain [odds ratio (OR) 1.35; 95% CI 1.17-1.56; P = .025; I2 = 51.1%]. Subgroup analyses showed that the cumulative prevalence and effect measures of sarcopenia were increased when individuals suffered secondary musculoskeletal pain (Prevalence = 12%; OR 1.45; 95% CI 1.19-1.78) and low back pain (Prevalence = 21%; OR 1.95; 95% CI 1.22-3.12). CONCLUSIONS AND IMPLICATIONS: The prevalence of sarcopenia in patients with pain is relatively high, and pain is significantly associated with sarcopenia in older adults. Attention is needed to screen sarcopenia among patients with pain and optimize its early detection and management in clinical practice.

Association Between Geriatric Nutritional Risk Index and Frailty in Older Hospitalized Patients.

OBJECTIVE: Previous studies have explored the association between malnutrition and frailty, but no study has investigated whether the Geriatric Nutritional Risk Index (GNRI), a simple and objective nutritional risk screening tool, is associated with the frailty of older adults. The study aimed to examine the relationship between nutrition-related risk, as assessed by the GNRI, and frailty among older hospitalized patients. METHODS: A cross-sectional study was conducted in the West China Hospital of Sichuan University with 740 patients aged ≥70 years between March 2016 and Jan 2017. Nutritional and frailty status was evaluated with the GNRI and FRAIL scale, respectively. The adjusted and unadjusted ordinal logistic regression analyses were used to examine the relationship between nutritional risk and frailty. The ability of GNRI in detecting frailty was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: The prevalence of low, moderate, and severe nutritional risk among frail patients were 30.1%, 27.6%, and 12.5%, respectively. Ordinal logistic regression analysis showed that malnutrition assessed by the GNRI had a significant association with frailty after adjustment of age, sex, polypharmacy, comorbidity, vision impairment, hearing impairment, cognitive impairment, and depression. In the ROC analysis, the area under the curve for GNRI identifying frailty was 0.698 (95% CI: 0.66-0.74; P<0.001), and the optimal cut-point value was 97.16 (sensitivity: 64.3%; specificity: 66.9%). CONCLUSION: Nutrition-related risk screened by the GNRI was independently associated with frailty. The GNRI could be used as a simple tool in detecting nutritional risk and frailty status of older patients.

Effects of anti-osteoporosis therapy on plasma aldosterone and renin.

OBJECTIVE: This study aimed to investigate the effect of anti-osteoporosis therapy on plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the aldosterone/renin ratio (ARR) in patients with postmenopausal osteoporosis. METHODS: In 60 patients with postmenopausal osteoporosis, bone mineral density (BMD), PAC and PRC were measured before and after treatment with alendronate (70 mg/week, n=22) or recombinant human parathyroid hormone (20 µg/day, n=35) for 48 weeks. RESULTS: PAC was negatively correlated with the T-score of lumbar spine BMD and femoral neck BMD (lumbar r=-0.386, p<0.01; femoral neck r=-0.262, p<0.05). With the improvement in lumbar BMD after anti-osteoporosis treatment (T-score -3.4±0.5 vs. -3.1 ±0.4, p<0.0001), PAC decreased from 182.8±53.2 to 143.7±68.6 pg/mL (p<0.0001), PRC increased from 7.8±11.6 to 39.2±50.0 µIU/mL (p<0.0001) and the ARR decreased from 74.8±75.2 to 13.1±17.1 pg/µIU (p<0.0001). At baseline, 58% (35/60) of the patients had an ARR >37 pg/µIU, and the proportion decreased to 8% (5/57) after treatment. CONCLUSION: Treatment with alendronate or parathyroid hormone causes decreased PAC and increased PRC, resulting in a decreased ARR in postmenopausal women with osteoporosis.