Superiority of high sensitivity cardiac troponin I over NT-proBNP and adiponectin for 7-year mortality in stable patients receiving haemodialysis.

Patients on haemodialysis (HD) have high mortality risk, and prognostic values of the major cardiovascular biomarkers cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and adiponectin should be ascertained over longer follow-up periods using higher-sensitivity assays, which we undertook. In 221 HD patients, levels of high-sensitivity (hs)-cTnI, NT-proBNP, and adiponectin, were measured using high-sensitivity assays, and their associations with all-cause mortality (ACM) and cardiovascular mortality (CVM) were prospectively investigated for 7 years. Higher hs-cTnI and NT-proBNP levels were significant risk factors for ACM and CVM in the Kaplan-Meier analysis. Multivariate Cox proportional hazards analyses in a model including hs-cTnI and NT-proBNP identified log hs-cTnI, but not log NT-proBNP, as an independent risk factor for ACM (HR 2.12, P < 0.02) and CVM (HR 4.48, P < 0.0005). Stepwise analyses identified a high hs-cTnI tertile as a risk factor for ACM (HR 2.31, P < 0.01) and CVM (HR 6.70, P < 0.001). The addition of hs-cTnI to a model including age, CRP, DM, and NT-proBNP significantly improved the discrimination of ACM and CVM each over 7 years. Conclusively, hs-cTnI was superior to NT-proBNP and adiponectin in predicting ACM and CVM over 7 years in HD patients, suggesting the significance of baseline hs-cTnI measurements in long-term management.

Diagnostic utility of Gold Coast criteria for amyotrophic lateral sclerosis in Asia.

Objective: This study aimed to reveal the diagnostic utility of Gold Coast (GC) criteria in Japanese patients with amyotrophic lateral sclerosis (ALS) by comparing the sensitivity/specificity with revised El Escorial (R-EE) and Awaji criteria, because its utility has not been studied in Asian ALS. Methods: Consecutive 639 patients (529 with ALS and 110 with ALS mimics), who were suspected of ALS and referred to three Japanese ALS centers, were enrolled. Diagnostic accuracy and characteristics of false positive and negative in GC criteria were compared with those of the Awaji and R-EE criteria. Patients were categorized as definite, probable or possible ALS according to each criterion. Results: The sensitivity of GC criteria (96.8%, 95% confidence interval [CI]: 95.3-98.3%) was higher than that of Awaji (89.6%, 95% CI: 87.0-92.2%) and R-EEC (89.2, 95% CI: 86.6-91.8%) criteria (both, p < 0.001). The specificity was also higher with GC criteria (77.3%, 95% CI: 69.5-85.1%) than Awaji (65.5%, 95% CI: 56.6-74.4%) and R-EEC (66.4, 95% CI: 57.6-75.2%) criteria (both, p < 0.01). Using GC criteria, patients with cervical spondylosis and Parkinson's syndrome tended to be diagnosed with ALS (i.e. "false positive"). Additionally, ALS patients diagnosed only by GC criteria less frequently had upper motor neuron (UMN) signs, compared with the other two criteria. Conclusion: Gold Coast criteria improve diagnostic accuracy for ALS in an Asian population, especially in patients with subtle UMN signs.

Exacerbation of Thymoma-Associated Myasthenia Gravis Following Efgartigimod Treatment Related to Anti-acetylcholine Receptor Antibody Overshoot: A Report of Two Cases.

Myasthenia gravis (MG), a chronic, autoimmune disease affecting the neuromuscular junction, arises from various autoantibodies, including those against the acetylcholine receptor (AChR). Recently, efgartigimod, a human IgG1 antibody Fc fragment engineered to reduce the pathogenic IgG autoantibody level, was developed as a treatment for MG. However, the long-term effects of the treatment are still unclear. The present report describes two novel cases of thymoma-associated MG exacerbation following efgartigimod treatment related to anti-AChR antibody overshoot. Both cases shared certain characteristics, including anti-AChR antibody positivity and post-thymectomy status. After a few cycles of efgartigimod treatment, their MG deteriorated, and their anti-AChR antibody titer exceeded the level before efgartigimod therapy. Prior studies show that anti-AChR antibody titer does not correlate with the disease severity of MG. However, previous studies have reported antibody overshoot following plasma exchange, which, like efgartigimod, reduces the level of plasma IgG and autoantibodies. Thus, MG exacerbation with anti-AChR antibody overshoot may be an adverse effect of both efgartigimod and plasma exchange. When clinical symptoms in patients with thymoma-associated MG receiving efgartigimod deteriorate despite low IgG, assessing the anti-AChR antibody level can be important for reconsidering the treatment strategy.

Renoprotective effects of extracellular fibroblast specific protein 1 via nuclear factor erythroid 2-related factor-mediated antioxidant activity.

Podocyte expression of fibroblast specific protein 1 (FSP1) is observed in various types of human glomerulonephritis. Considering that FSP1 is secreted extracellularly and has been shown to have multiple biological effects on distant cells, we postulated that secreted FSP1 from podocytes might impact renal tubules. Our RNA microarray analysis in a tubular epithelial cell line (mProx) revealed that FSP1 induced the expression of heme oxygenase 1, sequestosome 1, solute carrier family 7, member 11, and cystathionine gamma-lyase, all of which are associated with nuclear factor erythroid 2-related factor (Nrf2) activation. Therefore, FSP1 is likely to exert cytoprotective effects through Nrf2-induced antioxidant activity. Moreover, in mProx, FSP1 facilitated Nrf2 translocation to the nucleus, increased levels of reduced glutathione, inhibited the production of reactive oxygen species (ROS), and reduced cisplatin-induced cell death. FSP1 also ameliorated acute tubular injury in mice with cisplatin nephrotoxicity, which is a representative model of ROS-mediated tissue injury. Similarly, in transgenic mice that express FSP1 specifically in podocytes, tubular injury associated with cisplatin nephrotoxicity was also mitigated. Extracellular FSP1 secreted from podocytes acts on downstream tubular cells, exerting renoprotective effects through Nrf2-mediated antioxidant activity. Consequently, podocytes and tubular epithelial cells have a remote communication network to limit injury.

Effect of peripheral blood lymphocyte subsets and prognosis in autologous LAK cell treatment of advanced lung adenocarcinoma / 中国癌症杂志

Purpose:To study effect of peripheral blood lymphocyte subsets in autologous LAK cell treatment of advanced lung adenocarcinoma and to discuss the prognosis.Methods:21 surgically resected cases, were confirmed as primary lung adenocarcinoma stage Ⅲ or Ⅳ. The patients had received the treatment of IL 2 and two kinds of autologous LAK cells, every 2～3 months, for two years. The results of the three groups death in 2 years and survival over 2 years were analysed statistically as a whole.Results:In total,CD4 + decreased, t =2.817, P