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This study investigated the relationship between walking ability and age-related muscle atrophy of the lower limbs in elderly women. The subjects comprised 20 young women and 37 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into three groups according to their walking ability. The muscle thickness of the following ten lower limb muscles were measured by B-mode ultrasound: the gluteus maximus, gluteus medius, gluteus minimus, psoas major, rectus femoris, vastus lateralis, vastus intermedius, biceps femoris, gastrocnemius and soleus. Compared to the young group, muscle thicknesses of all muscles except the soleus muscle were significantly smaller in all the elderly groups. There were no significant differences between the fast- and slow-walking groups in the thickness of any muscle. In the dependent elderly group, noticeable muscle atrophy was observed in the quadriceps femoris muscle. The results of this study suggest that the elderly who are capable of locomotion, regardless of their walking speed, show a moderate degree of age-related atrophy, while those who do not walk exhibit more severe atrophy, especially in the quadriceps femoris muscle.

ObjectiveTo investigate the characteristics of beta parapapillary atrophy (β-PPA) in patients with primary angle-closure suspect (PACS).Methods and analysisIn total, 215 and 259 eyes with PACS and non-PACS (NPACS), respectively, were enrolled in this observational, cross-sectional study. Stereoscopic fundus and optical coherence tomography images were used to characterise β-PPA; the former was also used to measure the major β-PPA parameters. Univariate and multiple logistic regression analyses were used to identify the factors correlated with the presence of β-PPA and with β-PPA parameters.ResultsThe β-PPA occurrence rates were 48.80% and 44.40% in the PACS and NPACS groups, respectively, with no significant difference between groups. Compared with that in the NPACS group, the β-PPA area was significantly larger (p=0.005) in the PACS group, but the angular extent and maximum radial length did not differ between groups (p=0.110 and 0.657, respectively) after adjusting for age and axial length. The presence of β-PPA was associated with older age (OR 1.057, 95% CI 1.028 to 1.088, p<0.001) and larger disc area (OR 1.716, 95% CI 1.170 to 2.517, p=0.006). A larger β-PPA area was associated with older age (p=0.014), greater vertical cup-to-disc ratio (p=0.028), larger disc area (p<0.001) and PACS diagnosis (p=0.035).Conclusion48.80% of participants with PACS had β-PPA, which is slightly larger than NPACS. The area of β-PPA was larger in PACS, while the angular extent and maximum radial length did not differ between groups.

Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by CAG repeat expansion in the androgen receptor gene. Patients with this disease have low concentrations of insulin-like growth factor-1 (IGF-1), and studies of overexpression and administration of IGF-1 showed benefit in a transgenic model; thus the IGF-1 pathway presents as a potential treatment target. We assessed safety, tolerability, and preliminary efficacy of BVS857, an IGF-1 mimetic, in patients with spinal and bulbar muscular atrophy. In this randomised, double-blind, placebo-controlled trial, we recruited patients from neuromuscular centres in Denmark (Copenhagen), Germany (Ulm), Italy (Padova), and three sites within the USA (Bethesda, MD; Irvine, CA; and Columbus, OH). Eligible patients were 18 years or older with a confirmed genetic diagnosis of spinal and bulbar muscular atrophy, were ambulatory, had symptomatic weakness, and had serum IGF-1 concentrations of 170 ng/mL or lower. Patients were randomly assigned (2:1) to study drug or placebo by a number scheme. Patients, investigators, and study personnel were masked to treatment assignment. After a safety and tolerability assessment with eight patients, BVS857 was administered once a week (0·06 mg/kg intravenously) for 12 weeks. Primary outcome measures were safety, tolerability, and the effects of BVS857 on thigh muscle volume (TMV) measured by MRI. The ratio of TMV at day 85 to baseline was analysed with ANCOVA per protocol. Secondary outcomes of muscle strength and function were measured with the Adult Myopathy Assessment Tool, lean body mass through dual energy x-ray absorptiometry, and BVS857 pharmacokinetics. This trial was registered with ClinicalTrials.gov, NCT02024932. 31 patients were assessed for eligibility, 27 of whom were randomly assigned to either BVS857 treatment (n=18) or placebo (n=9), and 24 were included in the preliminary efficacy analysis (BVS857 group, n=15; placebo group, n=9). BVS857 was generally safe with no serious adverse events. No significant differences were found in adverse events between the BVS857 and placebo groups. Immunogenicity was detected in 13 (72%) of 18 patients in the BVS857 group, including crossreacting antibodies with neutralising capacity to endogenous IGF-1 in five patients. TMV decreased from baseline to day 85 in the placebo group (–3·4% [–110 cm3]) but not in the BVS857 group (0% [2 cm3]). A significant difference in change in TMV was observed in the BVS857 group versus the placebo group (geometric-mean ratio 1·04 [90% CI 1·01–1·07]; p=0·02). There were no differences between groups in measures of muscle strength and function. TMV remained stable in patients with spinal and bulbar muscular atrophy after being given BVS857 for 12 weeks. The intervention was associated with high incidence of immunogenicity and did not improve muscle strength or function. Additional studies might be needed to assess the efficacy of activating the IGF-1 pathway in this disease. Novartis Pharmaceuticals and the US National Institutes of Health.

ObjectiveAutoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer risk of patients with AIG consistently tested H. pylori-negative (naïve H. pylori-negative subjects).DesignTwo-hundred eleven naïve H. pylori-negative patients (tested by serology, histology, molecular biology) with AIG (F:M=3.15:1; p<0.001) were prospectively followed up with paired biopsies (T1 vs T2; mean follow-up years:7.5 (SD:4.4); median:7). Histology distinguished non-atrophic versus atrophic AIG. Atrophy was further subtyped/scored as non-metaplastic versus metaplastic (pseudopyloric (PPM) and intestinal (IM)). Enterochromaffin-like-cell (ECL) status was categorised as diffuse versus adenomatoid hyperplasia/dysplasia, and type 1 neuroendocrine tumours (Type1-NETs).ResultsOver the long-term histological follow-up, AIG consistently featured oxyntic-predominant-mononuclear inflammation. At T1, PPM-score was greater than IM (200/211 vs 160/211, respectively); IM scores increased from T1 to T2 (160/211 to 179/211), with no changes in the PPM prevalence (T1=200/211; T2=201/211). At both T1/T2, the prevalence of OLGA-III-stage was <5%; no Operative Link on Gastritis Assessment (OLGA)-IV-stage occurred. ECL-cell-status progressed from diffuse to adenomatoid hyperplasia/dysplasia (T1=167/14 vs T2=151/25). Type1-NETs (T1=10; T2=11) always coexisted with extensive oxyntic-atrophy, and ECL adenomatoid-hyperplasia/dysplasia. No excess risk of gastric or other malignancies was found over a cumulative follow-up time of 10 541 person years, except for (marginally significant) thyroid cancer (SIR=3.09; 95% CI 1.001 to 7.20).ConclusionsOxyntic-restricted inflammation, PPM (more than IM), and ECL-cell hyperplasia/neoplasia are the histological AIG hallmarks. Compared with the general population, corpus-restricted inflammation/atrophy does not increase the GC risk. The excess of GC risk reported in patients with AIG could plausibly result from unrecognised previous/current H. pylori comorbidity.

The small molecule risdiplam increased the expression of SMN protein in blood in 21 infants with type 1 spinal muscular atrophy. Post hoc clinical features of sitting ability and respiratory status were reported.

Aims  To provide a clinical update on the hereditary optic neuropathies. Methods  Review of the literature. Results  The hereditary optic neuropathies comprise a group of disorders in which the cause of optic nerve dysfunction appears to be hereditable, based on familial expression or genetic analysis. In some hereditary optic neuropathies, optic nerve dysfunction is typically the only manifestation of the disease. In others, various neurologic and systemic abnormalities are regularly observed. Conclusion  The most common hereditary optic neuropathies are autosomal dominant optic atrophy (Kjer's disease) and maternally inherited Leber's hereditary optic neuropathy. We review the clinical phenotypes of these and other inherited disorders with optic nerve involvement.

Background Chronic low back pain (LBP) is common and associated with lumbar disc herniation. The purpose of this study was to investigate if the grade of lumbar disc degeneration correlates with the degree of lumbar multifidus muscle (LMM) fatty atrophy. Methods A retrospective analysis on 16 males and 19 females with chronic LBP and a mean age of 47.2 years. Using MRI, the grade of lumbar intervertebral discs degeneration was assessed according to the Pfirrmann classification at L4/L5 and L5/S1 levels. Fatty infiltration of the LMM was graded as normal, mild, moderate and severe. Adobe Photoshop CS6 was used for qualitative image analysis by measuring the Cross-sectional area (CSA) of the pure fat component of LMM. Results There was a low correlation (R = 0.37) and significant association (ANOVA, p  = 0.001, 95% CI 2.07–8.14) between the grade of lumbar disc degeneration and the degree of LMM fatty atrophy. Mean value of intervertebral disc degeneration was 2.9 for the L4/L5 level and 3.2 for L5/S1 respectively. The percentage of fat infiltration of the LMM at both studied levels showed a mean value of 22.91+/− 13.19% for L4/L5 and a higher mean value of 26.37+/− 12.89% for L5/S1. There were higher fatty atrophy scores in women and more disc degeneration in men. Conclusion The percentage of LMM atrophy is higher in the lower levels (L5/S1) and shows a low correlation with the grade of disc degeneration.

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).

A prematurely aged phenotype is a common characteristic of chronic kidney disease (CKD) and other chronic organ diseases, including heart failure and rheumatoid arthritis. In this opinion article, the authors suggest four major pathophysiological mechanisms that may underlie premature ageing in CKD. Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing—treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training—reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

Bone fractures in older adults are often preceded by a loss of muscle mass and strength. Likewise, bone loss with prolonged bed rest, spinal cord injury, or with exposure to microgravity is also preceded by a rapid loss of muscle mass. Recent studies using animal models in the setting of hindlimb unloading or botulinum toxin (Botox) injection also reveal that muscle loss can induce bone loss. Moreover, muscle-derived factors such as irisin and leptin can inhibit bone loss with unloading, and knockout of catabolic factors in muscle such as the ubiquitin ligase Murf1 or the myokine myostatin can reduce osteoclastogenesis. These findings suggest that therapies targeting muscle in the setting of disuse atrophy may potentially attenuate bone loss, primarily by reducing bone resorption. These potential therapies not only include pharmacological approaches but also interventions such as whole-body vibration coupled with resistance exercise and functional electric stimulation of muscle.