Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report.

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia. CASE: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range. CONCLUSION: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.

Local Injection of Rapamycin-Loaded Pcl-Peg Nanoparticles for Enhanced Tendon Healing in Rotator Cuff Tears via Simultaneously Reducing Fatty Infiltration and Drug Toxicity.

As a common cause of shoulder pain, rotator cuff tears (RCTs) are difficult to treat clinically because of their unsatisfactory prognosis due to the fatty infiltration caused by muscle-derived stem cells (MDSCs). Previous studies have found that rapamycin (RAPA) can inhibit fatty infiltration. However, systemic administration of RAPA may cause complications such as infection and nausea, while local administration of RAPA may lead to the cytotoxicity of tendon cells, affecting the healing of rotator cuffs. In this study, biocompatible and clinically approved polycaprolactone-polyethylene glycol (PCL-PEG) is formulated into an injectable nanoparticle for the sustained release of RAPA. The results indicate that the RAPA/PCL-PEG nanoparticles (NPs) can efficiently prolong the release of RAPA and significantly reduce the cytotoxicity of tendon cells caused by RAPA. The study of the fatty infiltration model in rats with delayed rotator cuff repair shows that weekly intraarticular injection of RAPA/PCL-PEG NPs can more effectively reduce the fatty infiltration and muscle atrophy of rat rotator cuffs and leads to better mechanical properties and gait improvements than a daily intraarticular injection of RAPA. These findings imply that local injection of RAPA/PCL-PEG NPs in the shoulder joints can be a potential clinical option for RCTs patients with fatty infiltration.

Relationship between sodium-glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Aim: This study aims to assess the association between sodium-glucose cotransporter type-2 inhibitor (SGLT-2i) treatment and muscle atrophy in patients with type 2 diabetes mellitus (T2DM). Methods: We searched six databases from 1 January 2012 to 1 May 2023, without language restrictions. The primary outcome was muscle. Secondary outcomes were weight loss, weakness, malaise, or fatigue. Subgroup analyses were performed according to different definitions of muscle, treatment duration, and measurement methods. The quality of the studies was assessed using the Cochrane tool. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Results: Nineteen randomized controlled trials (RCTs) involving 1,482 participants were included. Compared with the control group, a meta-analysis showed that T2DM participants in the group treated with SGLT-2i demonstrated statistically significant reductions in lean body mass of 0.66 (95% confidence interval (CI), -1.05 to -0.27; p = 0.0009) and skeletal muscle mass of 0.35 (95% CI, -0.66 to -0.04; p = 0.03). No deaths or serious adverse events were reported. The quality of evidence in the included trials was low. Conclusions: SGLT-2i may lead to a reduction in muscle strength in the treatment of T2DM compared to the control group. However, there is still a lack of high-quality evidence to evaluate muscle atrophy caused by SGLT-2i. Systematic review registration: https://inplasy.com/inplasy-2022-12-0061/, identifier 2022120061.

Repetitive Sleep Starts in Allan-Herndon-Dudley Syndrome.

Allan-Herndon-Dudley syndrome (AHDS) is caused by mutations in the SLC16A2 gene, encoding for the monocarboxylate transporter 8 (MCT8). Central hypothyroidism and chronic peripheral thyrotoxicosis result in a severe phenotype, mainly characterized by poor growth, intellectual disability, spastic tetraparesis, and movement disorders, including paroxysmal ones (startle reaction and paroxysmal dyskinesias). Seizures are rarely reported. We conducted a retrospective analysis on video electroencephalography (EEG) recordings in four subjects with AHDS, focused on paroxysmal events. Among other manifestations recorded on EEG, we diagnosed repetitive sleep starts (RSS) in all subjects. RSS are a paroxysmal nonepileptic phenomenon occurring during sleep, similar to epileptic spasms in their clinical and electromyography characteristics, but not related to any EEG change. This is the first report on RSS in AHDS. We present video-EEG polygraphic documentation, suggesting that RSS could be underestimated or misdiagnosed. The importance of a correct diagnosis is crucial in a therapeutic perspective.

Lumbar Extensor and Flexor Muscle Structural Changes in Young Female Nurses with Chronic Bilateral Non-Specific Low Back Pain: A Case-Control Study.

BACKGROUND: Muscle structural studies on non-specific low back pain in young female nurses are rare. This study aimed to investigate the changes of lumbar extensor and flexor muscle cross-sectional area and fatty infiltration in young female nurses with chronic bilateral non-specific low back pain by lumbar spine magnetic resonance imaging to speculate on the possible pathogenesis. METHODS: The magnetic resonance imaging (MRI) data of 58 female nurses with chronic bilateral non-specific low back pain and 60 healthy female controls were analyzed retrospectively. The lumbar extensor and flexor muscle cross-sectional area/intervertebral disc cross-sectional area ratio, as well as magnetic resonance imaging signal intensity of lumbar extensor (erector spinae; multifidus) and flexor muscles (psoas muscle) were measured, calculated and compared between nurses and healthy controls by independent samples t-test. In addition, each mean MRI signal intensity of lumbar extensor or flexor muscles in nurses at different anatomical segments from lumbar vertebrae 2 (L2)-L3 to L5-sacral vertebrae 1 (S1) was also compared, and one-way Analysis of Variance (ANOVA) analyzed the mean MRI signal intensity between muscles in nurses with multiple comparisons. RESULTS: There was no significant difference in lumbar extensor and flexor muscle cross-sectional area/intervertebral disc cross-sectional area ratio between nurses with chronic bilateral non-specific low back pain and healthy controls, p > 0.01. The magnetic resonance imaging signal intensity in lumbar extensor and flexor muscle was significantly higher in nurses with chronic bilateral non-specific low back pain than in healthy controls, p < 0.01. The MRI signal intensity of lumbar extensor muscle at the lower lumbar segments was higher than at the upper ones. The magnetic resonance imaging signal intensity of the extensor muscle (erector spinae; multifidus) was significantly higher than that of the flexor muscle (psoas muscle), p < 0.01. CONCLUSIONS: This study showed that young nurses with chronic bilateral non-specific low back pain have lumbar extensor and flexor muscle fatty infiltration without muscle atrophy. We hypothesized that muscle fatty infiltration may occur prior to muscle atrophy. Therefore, the high fatty infiltration of the lumbar extensor and flexor muscle may be a cause or a result of chronic bilateral non-specific low back pain in young nurses.

Systematic review of sarcopenia in inflammatory bowel disease.

INTRODUCTION: There is growing evidence of increased muscle atrophy in IBD patients, likely resulting in a higher sarcopenia prevalence in IBD. The aims of this systematic review are A1; to estimate sarcopenia prevalence in IBD patients, A2; to investigate its impact on IBD patients, and A3; the effectiveness of nutritional interventions on muscle mass and/or strength in IBD patients. METHODS: On 28 July 2021, three electronic databases were used to identify eligible studies, including peer-reviewed studies (randomised controlled trials [RCTs], non-RCTs, observation studies) in adult (⩾ 18 years) IBD patients. For A1 and A2 only, studies defined low muscle mass and/or strength cut-off points. For A2, studies assessed association between sarcopenia and IBD complication. For A3, studies assessed the nutrition effect among IBD patients. RESULTS: 35 studies were included, 34 for A1, 20 for A2, and three for A3. 42% of adult IBD patients have myopenia, 34% have pre-sarcopenia, and 17% sarcopenia. Myopenic IBD was significantly associated with therapy failure including IBD-related surgery risk in six studies, risk of medical therapy failure in four studies, risk of hospitalisation in one study. A significant association existed with postoperative complications risk in IBD patients in four studies, reduction in BMD in two studies, and increased incidence of non-alcoholic fatty liver disease (NAFLD) in one study. Sarcopenia in IBD was significantly associated with a reduction in BMD in one study. Two studies found a personalised nutrition plan (high protein) in IBD patients significantly improved muscle mass. One study found a significant positive association between muscle mass and dietary intake including high protein intake. CONCLUSION: Over one third of adult IBD patients have myopenia and pre-sarcopenia, and nearly a fifth have sarcopenia. Myopeninc IBD is significantly associated with increased risk of IBD therapy failure, postoperative complications, and low BMD, with possible association with increased NAFLD risk. Nutritional therapy may play a role in reversing low muscle mass though yet unclear if this is through disease activity reversal. Further studies on adult IBD patients focusing on sarcopenia/myopenia are needed with recommended study designs of 1) standardised population-based definitions with recommended standard methods used to measure skeletal muscle mass, 2) prospective studies with IBD patients stratified by Montreal classification, disease activity, disease duration and concomitant medication to observe muscle changes, 3) mechanistic studies on sarcopenia aetiology, specifically focusing on protein handling atrophy and absorption, 4) properly designed RCT to assess nutrition intervention in sarcopenic IBD patients.

Skeletal muscle omics signatures in cancer cachexia: perspectives and opportunities.

Cachexia is a life-threatening complication of cancer that occurs in up to 80% of patients with advanced cancer. Cachexia reflects the systemic consequences of cancer and prominently features unintended weight loss and skeletal muscle wasting. Cachexia impairs cancer treatment tolerance, lowers quality of life, and contributes to cancer-related mortality. Effective treatments for cancer cachexia are lacking despite decades of research. High-throughput omics technologies are increasingly implemented in many fields including cancer cachexia to stimulate discovery of disease biology and inform therapy choice. In this paper, we present selected applications of omics technologies as tools to study skeletal muscle alterations in cancer cachexia. We discuss how comprehensive, omics-derived molecular profiles were used to discern muscle loss in cancer cachexia compared with other muscle-wasting conditions, to distinguish cancer cachexia from treatment-related muscle alterations, and to reveal severity-specific mechanisms during the progression of cancer cachexia from early toward severe disease.

Growth Hormone Improves Adipose Tissue Browning and Muscle Wasting in Mice with Chronic Kidney Disease-Associated Cachexia.

Cachexia associated with chronic kidney disease (CKD) has been linked to GH resistance. In CKD, GH treatment enhances muscular performance. We investigated the impact of GH on cachexia brought on by CKD. CKD was induced by 5/6 nephrectomy in c57BL/6J mice. After receiving GH (10 mg/kg/day) or saline treatment for six weeks, CKD mice were compared to sham-operated controls. GH normalized metabolic rate, increased food intake and weight growth, and improved in vivo muscular function (rotarod and grip strength) in CKD mice. GH decreased uncoupling proteins (UCP)s and increased muscle and adipose tissue ATP content in CKD mice. GH decreased lipolysis of adipose tissue by attenuating expression and protein content of adipose triglyceride lipase and protein content of phosphorylated hormone-sensitive lipase in CKD mice. GH reversed the increased expression of beige adipocyte markers (UCP-1, CD137, Tmem26, Tbx1, Prdm16, Pgc1α, and Cidea) and molecules implicated in adipose tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in CKD mice. Additionally, GH normalized the molecular markers of processes connected to muscle wasting in CKD, such as myogenesis and muscle regeneration. By using RNAseq, we previously determined the top 12 skeletal muscle genes differentially expressed between mice with CKD and control animals. These 12 genes' aberrant expression has been linked to increased muscle thermogenesis, fibrosis, and poor muscle and neuron regeneration. In this study, we demonstrated that GH restored 7 of the top 12 differentially elevated muscle genes in CKD mice. In conclusion, GH might be an effective treatment for muscular atrophy and browning of adipose tissue in CKD-related cachexia.

SENP7 deSUMOylase-governed transcriptional program coordinates sarcomere assembly and is targeted in muscle atrophy.

Disorganization of the basic contractile unit of muscle cells, i.e., the sarcomeres, leads to suboptimal force generation and is a hallmark of muscle atrophy. Here, we demonstrate that the nuclear role of SENP7 deSUMOylase is pivotal for sarcomere organization. SENP7 expression is temporally upregulated in mature muscle cells and directly regulates transcription of the myosin heavy chain (MyHC-IId) gene. We identify SENP7-dependent deSUMOylation of flightless-1 (Fli-I) as a signal for Fli-I association with scaffold attachment factor b1 (Safb1). SENP7 deficiency leads to higher Fli-I SUMOylation and lower chromatin residency of Safb1, thus generating transcriptionally incompetent chromatin conformation on MyHC-IId. Consequently, lower expression of MyHC-IId causes sarcomere disorganization and disrupted muscle cell contraction. Remarkably, cachexia signaling impedes the SENP7-governed transcriptional program, leading to muscle atrophy, with profound loss of motor protein MyHC-IId. We propose a SENP7-driven distinct transcription program as paramount for muscle cell function, which was found targeted in cachexia.

Identification of UBA1 as the causative gene of an X-linked non-Kennedy spinal-bulbar muscular atrophy.

BACKGROUND AND PURPOSE: Spinal-bulbar muscular atrophy (SBMA) (Kennedy's disease) is a motor neuron disease. Kennedy's disease is nearly exclusively caused by mutations in the androgen receptor encoding gene (AR). The results of studies aimed at identification of the genetic cause of a disease that best approximates SBMA in a pedigree (four patients) without mutations in AR are reported. METHODS: Clinical investigations included thorough neurological and non-neurological examinations and testing. Genetic analysis was performed by exome sequencing using standard protocols. UBA1 mutations were modeled on the crystal structure of UBA1. RESULTS: The clinical features of the patients are described in detail. A missense mutation in UBA1 (c.T1499C; p.Ile500Thr) was identified as the probable cause of the non-Kennedy SBMA in the pedigree. Like AR, UBA1 is positioned on chromosome X. UBA1 is a highly conserved gene. It encodes ubiquitin-like modifier activating enzyme 1 (UBA1) which is the major E1 enzyme of the ubiquitin-proteasome system. Interestingly, UBA1 mutations can also cause infantile-onset X-linked spinal muscular atrophy (XL-SMA). The mutation identified here and the XL-SMA causative mutations were shown to affect amino acids positioned in the vicinity of UBA1's ATP binding site and to cause structural changes. CONCLUSION: UBA1 was identified as a novel SBMA causative gene. The gene affects protein homeostasis which is one of most important components of the pathology of neurodegeneration. The contribution of this same gene to the etiology of XL-SMA is discussed.

Mechanical analysis of deep tissue injury during sitting in patients with spinal cord injury via parametric finite element model.

Spinal cord injury patients are prone to develop deep tissue injury because of long-term mechanical load. However, there is a lack of statistical research on the influence of tissue characteristics on the internal mechanical state of soft tissue. This study aimed to investigate the influence of tissue characteristics on the internal mechanical state of buttock in spinal cord injury patients. A three-dimensional reference buttock model was established and a visualization program was generated to modify the parameter values. Through changing the muscle atrophy, body mass index and the radius of curvature of the ischial tuberosity, 96 different model variants were simulated and validated in this study. With body mass index increasing from 16 to 40, the principal shear stress was 10.4 times principal compressive stress, the maximum shear strain and the max cluster volume increased by 1.2 (P < 0.001) and 8.8 times (P < 0.001), respectively. The interaction between BMI and muscle atrophy was significant when BMI was greater than or equal to 22.5 kg/m2. In all BMI stages, when the radius of curvature of the ischial tuberosity was 19 mm, the internal stress of the tissue always occupies the highest value. The results demonstrate that body mass index is the most important factor affecting the risk of buttock deep tissue injury. This study provides insights into investigation of inter-individual factors influencing the soft tissue response and assessment of deep tissue injury risk during sitting.

Molecular Mechanisms Underlying Intensive Care Unit-Acquired Weakness and Sarcopenia.

Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect-sarcopenia-the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism-mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology.

BACKGROUND: Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS: Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS: Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION: Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

A novel variant in SLC16A2 associated with typical Allan-Herndon-Dudley syndrome: a case report.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked recessive neurodegenerative disorder caused by mutations in the SLC16A2 gene that encodes thyroid hormone transporter. AHDS has been rarely reported in China. CASE PRESENTATION: This study reported a novel splicing mutation in the SLC16A2 gene in an 18-month-old male patient with AHDS. The patient was born to non-consanguineous, healthy parents of Chinese origin. He passed new-born screening for hypothyroidism, but failed to reach developmental milestones. He presented with hypotonia, severe mental retardation, dysarthria and ataxia. Genetic analysis identified a novel splicing mutation, NM_006517.4: c.431-2 A > G, in the SLC16A2 gene inherited from his mother. The patient received Triac treatment, (triiodothyroacetic acid), a thyroid hormone analogue for 3 months. Triac treatment effectively reduced serum TSH concentrations and normalized serum T3 concentrations in the patient. CONCLUSIONS: This study reported the first case of AHDS treated by Triac in China. And the study expanded the mutational spectrum of the SLC16A2 gene in AHDS patients.

Skeletal muscle atrophy and myosteatosis are not related to long-term aneurysmal subarachnoid hemorrhage outcome.

The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) is highly variable. This study aims to investigate whether skeletal muscle atrophy and myosteatosis are associated with poor outcome after aSAH. In this study, a cohort of 293 consecutive aSAH-patients admitted during a 4-year period was retrospectively analyzed. Cross-sectional muscle measurements were obtained at the level of the third cervical vertebra. Muscle atrophy was defined by a sex-specific cutoff value. Myosteatosis was defined by a BMI-specific cutoff value. Poor neurological outcome was defined as modified Rankin Scale 4-6 at 2 and 6-month follow-up. Patient survival state was checked until January 2021. Generalized estimating equation was performed to assess the effect of muscle atrophy / myosteatosis on poor neurological outcome after aSAH. Cox regression was performed to analyze the impact of muscle atrophy and myosteatosis on overall survival. The study found that myosteatosis was associated with poor neurological condition (WFNS 4-5) at admission after adjusting for covariates (odds ratio [OR] 2.01; 95%CI 1.05,3.83; P = .03). It was not associated with overall survival (P = .89) or with poor neurological outcomes (P = .18) when adjusted for other prognostic markers. Muscle atrophy was not associated with overall survival (P = .58) or neurological outcome (P = .32) after aSAH. In conclusion, myosteatosis was found to be associated with poor physical condition directly after onset of aSAH. Skeletal muscle atrophy and myosteatosis were however irrelevant to outcome in the Western-European aSAH patient. Future studies are needed to validate these finding.

Impact of myopenia and myosteatosis in patients undergoing abdominal surgery for chronic pancreatitis.

BACKGROUND: Surgery for chronic pancreatitis is associated with major morbidity and mortality. The aim of this study is to examine the role of preoperative muscle volume and quality on postoperative outcomes in patients with chronic pancreatitis. METHODS: All patients who underwent abdominal surgery for chronic pancreatitis between 2011 and 2018 were identified from an institutional surgical database. Patient demographics, clinical indices, and perioperative computed tomography scans were collected. Myopenia and myosteatosis were measured at the L3 vertebral level. Regression analysis was used to identify risk factors for major complications (Clavien-Dindo ≥3a) and length of stay. RESULTS: Seventy-five patients were identified. Toxic-metabolic or obstructive causes were the main underlying etiologies. Thirty patients were myopenic (40%), and 36 patients were myosteatotic (48%). Sixteen patients (21%) had a major complication. Median length of stay was 10 days. Both myopenia and myosteatosis were associated with major complications (hazard ratio = 7.85, 95% confidence interval: 1.91-32.29, P = .004 and hazard ratio = 4.351, 95% confidence interval: 1.22-15.52, P = .023). Myosteatosis was associated with increased length of stay (parameter estimate = 0.297, 95% confidence interval: 0.012-0.583, P = .041). CONCLUSION: Myopenia and myosteatosis were common and significant risk factors for adverse postoperative events. Preoperative muscle assessment may help in the risk stratification of surgical patients and identify patients that require preoperative nutritional and physical optimization.

Inflammation and physical dysfunction: responses to moderate intensity exercise in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. METHODS: This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n = 84, n = 43 males) and non-CKD controls (n = 26, n = 17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n = 21) or combined (CE, n = 20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. RESULTS: Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P = 0.01), Rectus femoris-cross sectional area (P = 0.002) and incremental shuttle walk test performance (P < 0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P = 0.006) and hand grip strength (P = 0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P = 0.02). Changes in inflammation were not associated with changes in physical performance. CONCLUSIONS: Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.

Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome.

BACKGROUND AND OBJECTIVES: MCT8 deficiency is a rare genetic leukoencephalopathy caused by a defect of thyroid hormone transport across cell membranes, particularly through blood brain barrier and into neural cells. It is characterized by a complex neurological presentation, signs of peripheral thyrotoxicosis and cerebral hypothyroidism. Movement disorders (MDs) have been frequently mentioned in this condition, but not systematically studied. METHODS: Each patient recruited was video-recorded during a routine outpatient visit according to a predefined protocol. The presence and the type of MDs were evaluated. The type of MD was blindly scored by two child neurologists experts in inherited white matter diseases and in MD. Dystonia was scored according to Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). When more than one MD was present, the predominant one was scored. RESULTS: 27 patients were included through a multicenter collaboration. In many cases we saw a combination of different MDs. Hypokinesia was present in 25/27 patients and was the predominant MD in 19. It was often associated with hypomimia and global hypotonia. Dystonia was observed in 25/27 patients, however, in a minority of cases (5) it was deemed the predominant MD. In eleven patients, exaggerated startle reactions and/or other paroxysmal non-epileptic events were observed. CONCLUSION: MDs are frequent clinical features of MCT8 deficiency, possibly related to the important role of thyroid hormones in brain development and functioning of normal dopaminergic circuits of the basal ganglia. Dystonia is common, but usually mild to moderate in severity, while hypokinesia was the predominant MD in the majority of patients.

Impact of Multifidus Muscle Atrophy on the Occurrence of Secondary Symptomatic Adjacent Osteoporotic Vertebral Compression Fractures.

To assess the potential influence of multifidus atrophy and fatty degeneration on the incidence of adjacent vertebral compression fractures within one year after the index fracture. In a retrospective cohort study, patients who underwent surgery for an OVCF were identified and baseline characteristics, fracture patterns and the occurrence of secondary adjacent fractures within one year were obtained by chart review. Multifidus muscle atrophy and fatty degeneration were determined on preoperative MRI or CT scans. In this analysis of 191 patients (mean age 77 years, SD 8, 116 female), OF type 3 was the most common type of OVCF (49.2%). Symptomatic adjacent OVCFs within one year after index fracture were observed in 23/191 patients (12%) at mean 12, SD 12 weeks (range 1-42 weeks) postoperatively. The mean multifidus muscle area was 264, SD 53 mm2 in patients with an adjacent vertebral fracture and 271, SD 92 mm2 in patients without a secondary fracture (p = 0.755). Mean multifidus fatty infiltration was graded Goutallier 2.2, SD 0.6 in patients with an adjacent fracture and Goutallier 2.2, SD 0.7 in patients without an adjacent fracture (p = 0.694). Pre-existing medication with corticosteroids was associated with the occurrence of an adjacent fracture (p = 0.006). Multifidus area and multifidus fatty infiltration had no significant effect on the occurrence of adjacent vertebral fractures within one year after the index fracture. Patients with a pre-existing medication with corticosteroids were more likely to sustain an adjacent fracture.

Bioinformatic analysis of the gene expression profile in muscle atrophy after spinal cord injury.

Spinal cord injury (SCI) is often accompanied by muscle atrophy; however, its underlying mechanisms remain unclear. Here, the molecular mechanisms of muscle atrophy following SCI were investigated. The GSE45550 gene expression profile of control (before SCI) and experimental (14 days following SCI) groups, consisting of Sprague-Dawley rat soleus muscle (n = 6 per group), was downloaded from the Gene Expression Omnibus database, and then differentially expressed gene (DEG) identification and Gene Ontology, pathway, pathway network, and gene signal network analyses were performed. A total of 925 differentially expressed genes, 149 biological processes, and 55 pathways were screened. In the pathway network analysis, the 10 most important pathways were citrate cycle (TCA cycle), pyruvate metabolism, MAPK signalling pathway, fatty acid degradation, propanoate metabolism, apoptosis, focal adhesion, synthesis and degradation of ketone bodies, Wnt signalling, and cancer pathways. In the gene signal network analysis, the 10 most important genes were Acat1, Acadvl, Acaa2, Hadhb, Acss1, Oxct1, Hadha, Hadh, Acaca, and Cpt1b. Thus, we screened the key genes and pathways that may be involved in muscle atrophy after SCI and provided support for finding valuable markers for this disease.