Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

INAUGURAL ARTICLE by a Recently Elected Academy Member:Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn^−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass.     

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

鄂托克前旗马场井村改水降氟15年病情防治效果分析

目的：了解改水降氟后地氟病的防治效果。方法：水氟，尿氟测定均为电极法，氟斑牙诊断为Dean‘s法。结果：该村自1985年改饮低氟水，水氟含量由改水前的6.05mg/L降至改水后的0.48mg/L。改水后未出现新的氟骨症患者，8-12岁儿童氟斑牙患病率呈逐年下降趋势，改水后7-15年间氟斑牙病率均已稳定，表明病情得到有效控制，且达到稳定控制状态，结论：坚持长年饮用低氟水，地方性氟中毒就能得到有效控制。     

Long-term results of surgical treatment of dysphagia secondary to cervical diffuse idiopathic skeletal hyperostosis

Background contextLarge, prominent osteophytes along the anterior aspect of the cervical spine have been reported as a cause of dysphagia. Improvement of swallowing after surgical resection has been reported in a few case reports with short-term follow-up. The current report describes outcomes of a series of five patients with surgical treatment for this rare disorder, with a long-term follow-up.PurposeTo study the clinical and radiographic outcomes of a case series of patients surgically treated for dysphagia secondary to cervical diffuse idiopathic skeletal hyperostosis (DISH).Study designRetrospective review of a case series.Patient sampleFive cases from a University Hospital.Outcome measuresClinical and imagenological follow-up.MethodsThe records of five patients with dysphagia who had undergone anterior surgical resection of prominent osteophytes secondary to DISH were reviewed. Extrinsic esophageal compression secondary to anterior cervical osteophytes was radiographically confirmed via preoperative barium esophagogram swallowing study. All patients underwent anterior cervical osteophytes resection without fusion. Postoperatively, patients were followed-up clinically and radiographically with routine lateral cervical radiographs.ResultsPreoperative esophagogram showed that the esophageal obstruction was present at one level in three cases and two levels in two cases. The C3–C4 level was involved in three cases, C4–C5 in three cases, and C5–C6 in one case. There were no postoperative complications, including recurrent laryngeal nerve palsy, wound infection, or hematomas. All patients had resolution of dyphagia soon after surgery (within 2 weeks). Postoperative radiographs demonstrated complete removal of osteophytes. At final follow-up, ranging from 1 to 9 years (average 59.8 months, median 53 months), no patients reported recurrence of dysphagia. Final radiographic examination demonstrated minimal regrowth of the osteophytes.ConclusionsAlthough rarely indicated, surgical resection of anterior cervical osteophytes from DISH causing dyphagia produces good clinical and radiographical outcomes. After thorough evaluation to rule out other intrinsic or extrinsic causes of swallowing difficulty, surgical treatment of this uncommon condition might be considered.     

Screening vs. individual detection of industrial fluorosis: a decision analysis model

In preventive medicine and occupational health, decision-makers face uncertainty, divergent opinions, and varying needs. In the Swiss aluminum industry, screening for industrial fluorosis illustrates how decision analysis and cost-effectiveness analysis can provide rational and explicit models of decision-making in such contexts. Data on fluoride-exposed potroom workers are used to compare the cost-effectiveness of two strategies: mass screening of fluorosis versus individual detection of the disease on the basis of the worker's symptoms. A decision-analysis and a sensitivity analysis are performed to assess the impact of the screening program for different levels of expected prevalence of the disease. The optimal decision, in economic terms, is the one that minimizes the pension and screening-related costs and maximizes the number of years of full working capacity. Swiss data suggest that a diagnosis of clinical fluorosis is unlikely before 10 years of exposure to fluoride. Between 10 and 30 years of exposure to fluoride, mass screening may be more cost-effective than individual detection of the disease, even when the expected prevalence of the disease in a given industrial setting is less than 10%.