Explore the vast range of titles available.

BackgroundNatural history of spinal muscular atrophy (SMA) in adult age has not been fully elucidated yet, including factors predicting disease progression and response to treatments. Aim of this retrospective, cross-sectional study, is to investigate motor function across different ages, disease patterns and gender in adult SMA untreated patients.MethodsInclusion criteria were as follows: (1) clinical and molecular diagnosis of SMA2, SMA3 or SMA4 and (2) clinical assessments performed in adult age (>18 years).ResultsWe included 64 (38.8%) females and 101 (61.2%) males (p=0.0025), among which 21 (12.7%) SMA2, 141 (85.5%) SMA3 and 3 (1.8%) SMA4. Ratio of sitters/walkers within the SMA3 subgroup was significantly (p=0.016) higher in males (46/38) than in females (19/38). Median age at onset was significantly (p=0.0071) earlier in females (3 years; range 0–16) than in males (4 years; range 0.3–28), especially in patients carrying 4 SMN2 copies. Median Hammersmith Functional Rating Scale Expanded scores were significantly (p=0.0040) lower in males (16, range 0–64) than in females (40, range 0–62); median revised upper limb module scores were not significantly (p=0.059) different between males (24, 0-38) and females (33, range 0–38), although a trend towards worse performance in males was observed. In SMA3 patients carrying three or four SMN2 copies, an effect of female sex in prolonging ambulation was statistically significant (p=0.034).ConclusionsOur data showed a relevant gender effect on SMA motor function with higher disease severity in males especially in the young adult age and in SMA3 patients.

Older adults lose muscle mass and strength at different speeds after the cessation of physical exercise, which might be genotype related. This study aimed to explore the genetic association with changes in muscle mass and strength one year after the cessation of structured training in an older population. Participants (n = 113, aged between 61 and 81 years) who performed one-year of combined fitness (n = 44) or whole-body vibration (n = 69) training were assessed one year after the cessation of the training. Whole-body skeletal muscle mass and knee strength were measured. Data-driven genetic predisposition scores (GPSs) were calculated and analysed in a general linear model with sex, age, body mass index and post-training values of skeletal muscle mass or muscle strength as covariates. Forty-six single nucleotide polymorphisms (SNPs) from an initial 170 muscle-related SNPs were identified as being significantly linked to muscular changes after cessation. Data-driven GPSs and over time muscular changes were significantly related (p < 0.01). Participants with higher GPSs had less muscular declines during the cessation period while data-driven GPSs accounted for 26–37% of the phenotypic variances. Our findings indicate that the loss of training benefits in older adults is partially genotype related.

Purpose Early identification and treatment of spinal muscular atrophy (SMA) are crucial but difficult. In this study, we aimed to assess the significance of compound motor action potential (CMAP) amplitude in patients identified through a newborn screening program. Methods We initiated a large-scale population newborn screening program for SMA in Taiwan in 2014. Patients had access to treatment through clinical trials or expanded use programs. Symptomatic patients were evaluated regularly, including CMAP exams. Results Among 364,000 screened newborns, 21 were diagnosed with SMA. The incidence of SMA was around 1 in 17,000 live births, and 70% developed SMA type 1. All infants with two SMN2 copies became symptomatic before the age of 1 month. CMAP amplitudes of 12 newborns were available, including 6 who were subsequently treated with nusinersen. We found that a rapid decrease of CMAP amplitude was an early predictor of symptom onset. Pretreatment CMAP and rapid increment of post-treatment CMAP could predict better treatment outcomes. Conclusion This study prospectively demonstrated the incidence of SMA and its types. Our results imply the importance of pretreatment CMAP amplitude and rapid reversal of post-treatment CMAP amplitude with regard to disease presentation and also treatment outcomes.

Background Studies show that low skeletal muscle index (SMI) and low skeletal muscle density (SMD) are negative prognostic factors and associated with more toxicity from systemic therapy in cancer patients. However, muscle depletion can be caused by a range of diseases, and many cancer patients have significant co‐morbidity. The aim of this study was to investigate whether there were associations between co‐morbidity and muscle measures in patients with advanced non‐small cell lung cancer. Methods Patients in a Phase III trial comparing two chemotherapy regimens in advanced non‐small cell lung cancer were analysed (n = 436). Co‐morbidity was assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS‐G), which rates co‐morbidity from 0 to 4 on 14 different organ scales. Severe co‐morbidity was defined as having any grades 3 and 4 CIRS‐G score. Muscle measures were assessed from baseline computed tomography slides at the L3 level using the SliceOMatic software. Results Complete data were available for 263 patients (60%). Median age was 66, 57.0% were men, 78.7% had performance status 0–1, 25.9% Stage IIIB, 11.4% appetite loss, 92.4% were current/former smokers, 22.8% were underweight, 43.7% had normal weight, 26.6% were overweight, and 6.8% obese. The median total CIRS‐G score was 7 (range: 0–16), and 48.2% had severe co‐morbidity. Mean SMI was 44.7 cm2/m2 (range: 27–71), and the mean SMD was 37.3 Hounsfield units (HU) (range: 16–60). When comparing patients with and without severe co‐morbidity, there were no significant differences in median SMI (44.5 vs. 44.1 cm2/m2; 0.70), but patients with severe co‐morbidity had a significantly lower median SMD (36 HU vs. 39 HU; 0.001), mainly due to a significant difference in SMD between those with severe heart disease and those without (32.5 vs. 37.9 HU; 0.002). Linear regression analyses confirmed the association between severe co‐morbidity and SMD both in the simple analysis (0.001) and the multiple analysis (0.037) adjusting for baseline characteristics. Stage of disease, gender, and body mass index (BMI) were significantly associated with SMI in both the simple and multiple analyses. Age and BMI were significantly associated with SMD in the simple analysis; and age, gender, and BMI were significantly associated in the multiple analysis. Conclusions There were no significant differences in SMI between patients with and patients without severe co‐morbidity, but patients with severe co‐morbidity had lower SMD than other patients, mainly due to severe heart disease. Co‐morbidity might be a confounder in studies of the clinical role of SMD in cancer patients.

Background Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients. Methods We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle–Ottawa Scale. Results Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% ( n  = 28/33) of the studies and computed tomography in the rest 15% ( n  = 5/33). During the first week of critical illness, patients lost every day −1.75% (95% CI −2.05, −1.45) of their rectus femoris thickness or −2.10% (95% CI −3.17, −1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%). Conclusion On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.

Key Points Muscle wasting is a debilitating condition that develops with ageing and more rapidly with inactivity (bed rest) and in various systemic diseases (for example, cancer, renal failure, chronic obstructive pulmonary disease, sepsis, HIV and trauma). Fibre atrophy primarily results from an acceleration of protein degradation, often combined with reduced protein synthesis. Treatments that prevent this activation of proteolysis or increase protein synthesis offer considerable promise to combat this debilitating process. Various types of rapid muscle wasting develop through a common transcriptional programme involving the induction of a set of atrophy-related genes (atrogenes) by forkhead box protein O (FOXO) transcription factors and reduced signalling by the PI3K–AKT–mTOR pathway. The resulting muscle weakness is a consequence of the degradation of myofibrils, which is catalysed by ubiquitin ligases that target different components of the contractile apparatus for proteasomal degradation. By contrast, the loss of endurance results from the breakdown of mitochondria via autophagy. Myostatin, an autocrine inhibitor of normal muscle growth, and its circulating homologue activin A, also trigger muscle protein loss in various catabolic states via the activation of SMAD2 and SMAD3, which function together with FOXO transcription factors. Antibodies against myostatin or activin A, or agents that block their receptor — activin A receptor, type IIB (ActRIIB) — in muscle could be a promising approach to combat muscle loss caused by cancer-associated cachexia, renal failure and ageing. Indeed, these treatments helped to preserve muscle and prolong longevity in tumour-bearing mice, and several of these treatments are currently in clinical trials. Glucocorticoids and various circulating inflammatory mediators, such as tumour necrosis factor-α (TNFα) and interleukin-6 (IL-6), have also been implicated in excessive muscle proteolysis in cachexia, but their roles in different catabolic states remain uncertain and controversial. Recent studies have increased our understanding of the biochemical mechanisms of atrophy and have identified many intracellular proteins that are crucial in muscle wasting (for example, SMADs, tripartate motif-containing protein 32 (TRIM32), nuclear factor-κB (NF-κB)) or that combat this process (for example, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), sirtuin1 (SIRT1) and JUNB). Their manipulation by small molecules offers many opportunities for the rational design of new treatments for this condition. Muscle atrophy can occur in patients with injuries or denervation of specific muscles, and muscle wasting occurs in patients with systemic diseases, including sepsis and cancer. This Review explains the pathophysiology of muscle wasting and discusses the progress of new therapies to treat this condition. Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.

Spinal muscular atrophy (SMA) is a monogenic disorder caused by loss of function mutations in the survival motor neuron 1 gene, which results in a broad range of disease severity, from neonatal to adult onset. There is currently a concerted effort to define the natural history of the disease and develop outcome measures that accurately capture its complexity. As several therapeutic strategies are currently under investigation and both the FDA and EMA have recently approved the first medical treatment for SMA, there is a critical need to identify the right association of responsive outcome measures and biomarkers for individual patient follow-up. As an approved treatment becomes available, untreated patients will soon become rare, further intensifying the need for a rapid, prospective and longitudinal study of the natural history of SMA Type 2 and 3. Here we present the baseline assessments of 81 patients aged 2 to 30 years of which 19 are non-sitter SMA Type 2, 34 are sitter SMA Type 2, 9 non-ambulant SMA Type 3 and 19 ambulant SMA Type 3. Collecting these data at nine sites in France, Germany and Belgium established the feasibility of gathering consistent data from numerous and demanding assessments in a multicenter SMA study. Most assessments discriminated between the four groups well. This included the Motor Function Measure (MFM), pulmonary function testing, strength, electroneuromyography, muscle imaging and workspace volume. Additionally, all of the assessments showed good correlation with the MFM score. As the untreated patient population decreases, having reliable and valid multi-site data will be imperative for recruitment in clinical trials. The pending two-year study results will evaluate the sensitivity of the studied outcomes and biomarkers to disease progression. ClinicalTrials.gov (NCT02391831).

Objective In order to assess their late benefits we present the long-term results of a comparison of treating cubital tunnel syndrome with anterior submuscular transposition or simple decompression. Methods Of 40 patients initially recruited to this study 33 were available for long term follow-up. Sixteen patients underwent anterior submuscular transposition (group A); simple decompression was performed in 17 of the patients (group B). The indications for inclusion were a typical clinical presentation confirmed by abnormal nerve conduction studies. The mean duration of the symptoms before operation was 13 months (range 2 to 84 months) in group A and 8.4 months (range 1.5 to 36 months) in group B. All patients were seen 2 months after surgery and at least 3 years later. The mean duration of follow-up was 63.1 month in the first group and 52 months in the second group. Results No complications were seen in either group. In the group treated by anterior transposition, ten of 16 patients were completely free of signs and symptoms; slight residual hypesthesia or paresthesia was observed in two patients. Paresis and atrophy was observed in only one person. In the simple decompression group, 11 of 17 patients were completely free of signs and symptoms. In five patients slight residual symptoms were observed; no paresis or atrophy was reported in any of this group. Conclusion These long-term results show that both surgical techniques have a good outcome. Thus, the less invasive simple decompression should be preferred.

Loss of muscle mass occurs rapidly during critical illness and negatively affects quality of life. The incidence of clinically significant muscle wasting in critically ill patients is unclear. This study aimed to assess the incidence of and identify predictors for clinically significant loss of muscle mass in this patient population. This was a single-center observational study. We used ultrasound to determine the rectus femoris cross-sectional area (RFcsa) on the first and seventh day of ICU stay. The primary outcome was the incidence of significant muscle wasting. We used a logistic regression model to determine significant predictors for muscle wasting. Ultrasound measurements were completed in 104 patients. Sixty-two of these patients (59.6%) showed ≥ 10% decreases in RFcsa. We did not identify any predictor for significant muscle wasting, however, age was of borderline significance (p = 0.0528). The 28-day mortality rate was higher in patients with significant wasting, but this difference was not statistically significant (30.6% versus 16.7%; p = 0.165). Clinically significant muscle wasting was frequent in our cohort of patients. Patient age was identified as a predictor of borderline significance for muscle wasting. The results could be used to plan future studies on this topic. Trial registration: ClinicalTrials.gov NCT03865095, date of registration: 06/03/2019.