JCSM: growing together with cachexia and sarcopenia research Fröhlich, Ann‐Kathrin; Diek, Monika; Denecke, Corinna ...
Journal of cachexia, sarcopenia and muscle,
December 2021, 2021-12-00, 20211201, 2021-12-01, Letnik:
12, Številka:
6
Journal Article
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The impact factor of a journal is calculated by counting all citations in a given year towards articles published in the two preceding years, and divided by the number of original articles and ...reviews published in the two preceding years. ...the rise in the impact factor shows that JCSM continues to publish research that is important and of interest to the scientific community. Original articles in JCSM are mainly about different wasting disorders such as sarcopenia, cachexia, malnourishment, anorexia, and lipolysis—often in connection with weight loss—but it also focuses on many different chronic illnesses: that is, heart failure, COPD, and cancer among many others. Table 1 Top 20 cited JCSM articles published (of all time) Rank Authors Title Article type Times cited 1 von Haehling, S; Anker, SD 2 Cachexia as a major underestimated and unmet medical need: facts and numbers Editorial 582 2 Malmstrom, TK; Miller, DK; Simonsick, EM; Ferrucci, L; Morley, JE 3 SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes Original Article 259 3 Morley, JE; Anker, SD; von Haehling, S 4 Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology—update 2014 Editorial 251 4 Anker, SD; Morley, JE; von Haehling, S 5 Welcome to the ICD-10 code for sarcopenia Editorial 229 5 Buckinx, F; Landi, F; Cesari, M; Fielding, RA; Visser, M; Engelke, K; Maggi, S; Dennison, E; Al-Daghri, NM; Allepaerts, S; Bauer, J; Bautmans, I; Brandi, ML; Bruyere, O; Cederholm, T; Cerreta, F; Cherubini, A; Cooper, C; Cruz-Jentoft, A; McCloskey, E; Dawson-Hughes, B; Kaufman, JM; Laslop, A; Petermans, J; Reginster, JY; Rizzoli, R; Robinson, S; Rolland, Y; Rueda, R; Vellas, B; Kanis, JA 6 Pitfalls in the measurement of muscle mass: a need for a reference standard Original Article 210 6 Dalton, JT; Barnette, KG; Bohl, CE; Hancock, ML; Rodriguez, D; Dodson, ST; Morton, RA; Steiner, MS 7 The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial Original Article 203 7 Tieland, M; Trouwborst, I; Clark, BC 8 Skeletal muscle performance and ageing Review 180 8 Wakabayashi, H; Sakuma, K 9 Rehabilitation nutrition for sarcopenia with disability: a combination of both rehabilitation and nutrition care management Review 176 9 Montano-Loza, AJ; Angulo, P; Meza-Junco, J; Prado, CMM; Sawyer, MB; Beaumont, C; Esfandiari, N; Ma, M; Baracos, VE 10 Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis Original Article 169 10 Bowen, TS; Schuler, G; Adams, V 11 Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training Review 168 11 Elkina, Y; von Haehling, S; Anker, SD; Springer, J 12 The role of myostatin in muscle wasting: an overview Review 166 12 Fanzani, A; Conraads, VM; Penna, F; Martinet, W 13 Molecular and cellular mechanisms of skeletal muscle atrophy: an update Review 164 13 Cesari, M; Fielding, RA; Pahor, M; Goodpaster, B; Hellerstein, M; Van Kan, GA; Anker, SD; Rutkove, S; Vrijbloed, JW; Isaac, M; Rolland, Y; M'Rini, C; Aubertin-Leheudre, M; Cedarbaum, JM; Zamboni, M; Sieber, CC; Laurent, D; Evans, WJ; Roubenoff, R; Morley, JE; Vellas, B 14 Biomarkers of sarcopenia in clinical trials—recommendations from the International Working Group on Sarcopenia Original Article 156 14 Patel, SS; Molnar, MZ; Tayek, JA; Ix, JH; Noori, N; Benner, D; Heymsfield, S; Kopple, JD; Kovesdy, CP; Kalantar-Zadeh, K 15 Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature Review 154 15 von Haehling, S; Anker, SD 16 Prevalence, incidence and clinical impact of cachexia: facts and numbers—update 2014 Editorial 151 16 Lenk, K; Schuler, G; Adams, V 17 Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training Review 150 17 Dasarathy, S 18 Consilience in sarcopenia of cirrhosis Review 144 18 Mak, RH; Ikizler, AT; Kovesdy, CP; Raj, DS; Stenvinkel, P; Kalantar-Zadeh, K 19 Wasting in chronic kidney disease Review 144 19 Brown, JC; Harhay, MO; Harhay, MN 20 Sarcopenia and mortality among a population-based sample of community-dwelling older adults Original Article 130 20 Morley, JE; von Haehling, S; Anker, SD; Vellas, B 21 From sarcopenia to frailty: a road less traveled Editorial 130 Table 2 Top 20 cited JCSM articles published in 2020 Rank Authors Title Article type Times cited 1 Prado, CM; Purcell, SA; Laviano, A 23 Nutrition interventions to treat low muscle mass in cancer Review 51 2 Morley, JE; Kalantar-Zadeh, K; Anker, SD 24 COVID-19: a major cause of cachexia and sarcopenia? Editorial 39 3 Wang, DXM; Yao, J; Zirek, Y; Reijnierse, EM; Maier, AB 25 Muscle mass, strength, and physical performance predicting activities of daily living: a meta-analysis Review 39 4 Kirk, B; Zanker, J; Duque, G 26 Osteosarcopenia: epidemiology, diagnosis, and treatment—facts and numbers Editorial 30 5 Peixoto da Silva, S; Santos, J; Costa e Silva, MP; Gil da Costa, RM; Medeiros, R 27 Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia Review 26 6 Nishida, Y; Nawaz, A; Kado, T; Takikawa, A; Igarashi, Y; Onogi, Y; Wada, T; Sasaoka, T; Yamamoto, S; Sasahara, M; Imura, J; Tokuyama, K; Usui, I; Nakagawa, T; Fujisaka, S; Kunimasa, Y; Tobe, K 28 Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of AMPK pathway Original Article 19 7 Capitanio, D; Moriggi, M; Torretta, E; Barbacini, P; De Palma, S; Viganò, A; Lochmüller, H; Muntoni, F; Ferlini, A; Mora, M; Gelfi, C 29 Comparative proteomic analyses of Duchenne muscular dystrophy and Becker muscular dystrophy muscles: changes contributing to preserve muscle function in Becker muscular dystrophy patients Original Article 19 8 Zhou, H; Meng, J; Malerba, A; Catapano, F; Sintusek, P; Jarmin, S; Feng, L; Lu-Nguyen, N; Sun, L; Mariot, V; Dumonceaux, J; Morgan, JE; Gissen, P; Dickson, G; Muntoni, F 30 Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy Original Article 17 9 Sipilä, S; Törmäkangas, T; Sillanpää, E; Aukee, P; Kujala, UM; Kovanen, V; Laakkonen, EK 31 Muscle and bone mass in middle-aged women: role of menopausal status and physical activity Original Article 16 10 Chiappalupi, S; Sorci, G; Vukasinovic, A; Salvadori, L; Sagheddu, R; Coletti, D; Renga, G; Romani, L; Donato, R; Riuzzi, F 32 Targeting RAGE prevents muscle wasting and prolongs survival in cancer cachexia Original Article 15 11 Koutnik, AP; Poff, AM; Ward, NP; DeBlasi, JM; Soliven, MA; Romero, MA; Roberson, PA; Fox, CD; Roberts, MD; D'Agostino, DP 33 Ketone bodies attenuate wasting in models of atrophy Original Article 15 12 Rong, S; Wang, L; Peng,
Aims
Viral‐induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)‐like syndromes. COVID‐19 can lead to myocardial damage and vascular injury. We hypothesised ...that COVID‐19 patients frequently develop a HFpEF‐like syndrome, and designed this study to explore this.
Methods and results
Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID‐19 patients from April–November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID‐19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA‐PEFF score. A low (0–1 points), intermediate (2–4 points), and high (5–6 points) HFA‐PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID‐19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P = 0.0002). High HFA‐PEFF scores were more frequent in COVID‐19 patients than controls (25% vs. 4%, P = 0.001). In COVID‐19 patients, the HFA‐PEFF score significantly correlated with age, estimated glomerular filtration rate, high‐sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H2FPEF score (all P < 0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA‐PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA‐PEFF scores median 5 (interquartile range 3–6) vs. 1 (0–3), P < 0.001 and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P < 0.001).
Conclusion
Hospitalized COVID‐19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID‐19 patients.
Health-related quality of life (HRQoL) is highly relevant in cancer and often assessed with the EORTC QLQ-C30. Cardiovascular HRQoL in cancer can be measured with the ESC HeartQoL questionnaire. We ...compared these instruments and examined their prognostic value.
Summary scores for EORTC QLQ-C30 (0-100 points) and HeartQoL (0-3 points) questionnaires were prospectively assessed in 290 patients with mostly advanced cancer (stage 3/4: 81%, 1-year mortality: 36%) and 50 healthy controls (similar age and sex). Additionally, physical function and activity assessments were performed.
Both questionnaires demonstrated reduced HRQoL in patients with cancer vs controls (EORTC QLQ-C30: 67±20 vs 91±11, p<0.001; ESC HeartQoL: 1.8±0.8 vs 2.7±0.4, p<0.001). The instruments were strongly correlated with each other (summary scores (r=0.76), physical (r=0.81), and emotional subscales (r=0.75, all p<0.001)) and independently associated with all-cause mortality (best cut-offs: EORTC QLQ-C30 <82.69: hazard ratio (HR) 2.33, p=0.004, HeartQoL <1.50: HR 1.85, p=0.004 - adjusted for sex, age, left ventricular ejection fraction, NT-proBNP, hsTroponinT, cancer stage/type), with no differences in the strength of the association by sex (p-interaction>0.9). Combining both questionnaires identified three risk groups with highest mortality in patients below both cut-offs (vs. patients above both cut-offs: HR 3.60, p<0.001). Patients with results below both cut-offs, showed higher NT-proBNP and reduced physical function and activity.
EORTC QLQ-C30 and ESC HeartQoL - assessing cancer and cardiovascular HRQoL - are both associated with increased mortality in cancer patients, with even greater stratification by combing both. Reduced HRQoL scores were associated with elevated cardiovascular biomarkers and decreased functional status. This article is protected by copyright. All rights reserved.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin gene. The neuropathology of HD is characterized by the ...decline of a specific neuronal population within the brain, the striatal medium spiny neurons (MSNs). The origins of this extreme vulnerability remain unknown. Human induced pluripotent stem cell (hiPS cell)-derived MSNs represent a powerful tool to study this genetic disease. However, the differentiation protocols published so far show a high heterogeneity of neuronal populations in vitro. Here, we compared two previously published protocols to obtain hiPS cell-derived striatal neurons from both healthy donors and HD patients. Patch-clamp experiments, immunostaining and RT-qPCR were performed to characterize the neurons in culture. While the neurons were mature enough to fire action potentials, a majority failed to express markers typical for MSNs. Voltage-clamp experiments on voltage-gated sodium (Nav) channels revealed a large variability between the two differentiation protocols. Action potential analysis did not reveal changes induced by the HD mutation. This study attempts to demonstrate the current challenges in reproducing data of previously published differentiation protocols and in generating hiPS cell-derived striatal MSNs to model a genetic neurodegenerative disorder in vitro.
Spinal muscular atrophy (SMA) is a neurodegenerative disorder that is characterized by progressive weakness, respiratory insufficiency, and dysphagia. Due to symptom burden and disease progress, its ...care management and impact on daily life can severely burden the families of affected children. The objectives of this study are (1) to explore the health care experiences and (2) to investigate the psychosocial needs of the parents of children with SMA. In total, 29 parents of patients with SMA participated in our study. All children received supportive therapy (e.g., physiotherapy) and most were dependent on medical equipment. Parents perceived the health care positively regarding team quality, communication and access to medical care. An assessment of the impact of the child's health on the family (e.g., stressors, burden, consequences) is not routinely integrated into care. On average, parents reported low to medium levels of psychosocial needs. Due to the complex health care needs of SMA patients, the health care experiences of parents can provide relevant information on care delivery. To enhance the inclusion of psychosocial and emotional issues, as well as family impact, into routine health care, health care providers should be sensitive towards parental needs for consistency in the health care team and emotional aspects and, if applicable, address them proactively.
Spinal muscular atrophy (SMA) is a neuromuscular disease, causing progressive muscle weakness due to loss of lower motoneurons. Since 2017, three therapies, two modifying gene transcription and one ...adding the defective gene, have been approved with comparable efficacy on motor outcome. Data on cognitive outcomes of treated SMA type 1 patients is limited. The aim of this study was to evaluate cognitive function in symptomatic and presymptomatic SMA type 1 patients with two or three SMN2 copies who received SMN-modifying or gene-addition therapy in the first year of life.
Cognitive testing was performed in 20 patients, including 19 symptomatic SMA type 1 patients with up to three SMN2 copies and 1 pre-symptomatically treated patient. Children were tested using Bayley Scales of Infant Development (BSID-III) at the age of 2 or 3 years or the Wechsler Preschool and Primary Scale of Intelligence (WPSII-IV) at the of age of 5 years.
11/20 patients showed subnormal cognitive development. Boys had significantly lower cognitive scores. Patients requiring assisted ventilation or feeding support were more likely to have cognitive deficits. Achieving more motor milestones was associated with a better cognitive outcome.
Treated patients with SMA type 1 have heterogeneous cognitive function with 55 % of patients showing deficits. Risk factors for cognitive impairment in our cohort were male gender and need for assisted ventilation or feeding support. Therefore, cognitive assessment should be included in the standard of care to allow early identification of deficits and potential therapeutic interventions.
•Data on cognitive function in SMA type 1 patients is limited.•55 % of tested SMA patients showed cognitive impairment.•Boys scored significantly lower than girls.•Cognitive testing should be implemented in standard care of SMA patients.
Given the novelty of gene replacement therapy with onasemnogene abeparvovec in spinal muscular atrophy, efficacy and safety data are limited, especially for children older than 24 months, those ...weighing more than 8·5 kg, and those who have received nusinersen. We aimed to provide real-world data on motor function and safety after gene replacement therapy in different patient subgroups.
We did a protocol-based, multicentre prospective observational study between Sept 21, 2019, and April 20, 2021, in 18 paediatric neuromuscular centres in Germany and Austria. All children with spinal muscular atrophy types 1 and 2 receiving onasemnogene abeparvovec were included in our cohort, and there were no specific exclusion criteria. Motor function was assessed at the time of gene replacement therapy and 6 months afterwards, using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and Hammersmith Functional Motor Scale-Expanded (HFMSE) scores. Additionally, in children pretreated with nusinersen, motor function was assessed before and after treatment switch. Off-target adverse events were analysed with a focus on liver function, thrombocytopaenia, and potential cardiotoxicity.
76 children (58 pretreated with nusinersen and 18 who were nusinersen naive) with spinal muscular atrophy were treated with onasemnogene abeparvovec at a mean age of 16·8 months (range 0·8-59·0, IQR 9-23) and a mean weight of 9·1 kg (range 4·0-15·0, IQR 7·4-10·6). In 60 patients with available data, 49 had a significant improvement on the CHOP-INTEND score (≥4 points) and HFMSE score (≥3 points). Mean CHOP INTEND scores increased significantly in the 6 months after therapy in children younger than 8 months (n=16; mean change 13·8 SD 8·5; p<0·0001) and children aged between 8 and 24 months (n=34; 7·7 SD 5·2; p<0·0001), but not in children older than 24 months (n=6; 2·5 SD 5·2; p=1·00). In the 45 children pretreated with nusinersen and had available data, CHOP INTEND score increased by 8·8 points (p=0·0003) at 6 months after gene replacement therapy. No acute complications occurred during infusion of onasemnogene abeparvovec, but 56 (74%) patients had treatment-related side-effects. Serious adverse events occurred in eight (11%) children. Liver enzyme elevation significantly increased with age and weight at treatment. Six (8%) patients developed acute liver dysfunction. Other adverse events included pyrexia (n=47 62%), vomiting or loss of appetite (41 54%), and thrombocytopenia (n=59 78%). Prednisolone treatment was significantly prolonged with a mean duration of 15·7 weeks (IQR 9-19), mainly due to liver enzyme elevation. Cardiac adverse events were rare; only two patients had abnormal echocardiogram and echocardiography findings.
This study provides class IV evidence that children with spinal muscular atrophy aged 24 months or younger and patients pretreated with nusinersen significantly benefit from gene replacement therapy, but adverse events can be severe and need to be closely monitored.
None.
For the German translation of the abstract see Supplementary Materials section.
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