A Novel CLEIA for FGF23

Introduction: Measurement of fibroblast growth factor 23 (FGF23) has been reported to be clinically useful for the differential diagnosis of chronic hypophosphatemia. However, assays for research use only are available in Japan. Thus, the objective of this study was to examine the clinical utility of a novel and automated chemiluminescent enzyme immunoassay for the measurement of FGF23. Materials and Methods: Participants were recruited from July 2015 to January 2017 at six facilities in Japan. Thirty-eight patients with X-linked hypophosphatemic rickets (XLH; 15 males, 23 females, age 0–66 years), five patients with tumour-induced osteomalacia (TIO; 3 males, 2 females, age 60–73 years), and twenty-two patients with hypophosphatemia (11 males, 11 females, age 1–75 years) caused due to other factors participated in this study. Results: With the clinical cut-off value of FGF23 at 30.0 pg/mL indicated in the Diagnostic Guideline of Rickets/Osteomalacia in Japan, the sensitivity and specificity of FGF23-related hypophosphatemic rickets/osteomalacia without vitamin D deficiency (disease group-1) were 100% and 81.8%, respectively, which distinguished it from non-FGF23-related hypophosphatemia (disease group-2). Furthermore, the diagnostic sensitivity of FGF23-related hypophosphatemia with vitamin D deficiency remained at 100%. Among the four patients with FGF23 levels ≥ 30.0 pg/mL in disease group-2, two patients with relatively higher FGF23 values were suspected to have genuine FGF23-related hypophosphatemia, due to the ectopic production of FGF23 in pulmonary and prostate small cell carcinomas. Conclusion: The novel FGF23 assay tested in this study is useful for the differential diagnosis of hypophosphatemic rickets/osteomalacia in a clinical setting

BUROSUMAB IN TUMOR-INDUCED OSTEOMALACIA

Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated

FIELD SURVEYS OF EFFECTS OF THE MAINTENANCE FLOW DISCHRAGE CHANGE ON RIVER ENVIRONMENT IN THE OHYAMA RIVER

The maintenance flow discharge of the Ohyama River, which is located in the upper Chikugo River, had been restricted to 1.5m3/s by a hydroelectric dam. To improve the river environment, the river administrator has changed the maintenance flow discharge to 4.5m3/s in summer and to 1.8m3/s in winter. In this study, we aim at proposing an optimal control of the maintenance flow discharge for the river environment. Firstly, we carried out field surveys before and after reducing the river discharge in order to figure out effects on hydraulic conditions and attached algae. The results of the surveys show that hydraulic conditions become worse for ayu (plecoglossus altivelis) and attached algae. Also, there is a tendency to stagnate at the pool when the maintenance flow discharge decreases. Secondly, because it was reported that the length of ayu became larger than before changing the maintenance flow discharge, we attempted to analyze carbon and nitrogen stable isotope ratio of ayu and attached algae. We confirmed an obvious difference in food web structure between natural and cultured ayu

Appearance of Lipid-Laden Intima and Neovascularization After Implantation of Bare-Metal Stents Extended Late-Phase Observation by Intracoronary Optical Coherence Tomography

ObjectivesWe examined the neointimal characteristics of bare-metal stents (BMS) in extended late phase by the use of optical coherence tomography (OCT).BackgroundThe long-term neointimal features after BMS implantation have not yet been fully characterized.MethodsIntracoronary OCT observation of BMS segments was performed during the early phase (<6 months, n = 20) and late phase (≥5 years, n = 21) after implantation. Internal tissue of the BMS was categorized into normal neointima, characterized by a signal-rich band without signal attenuation, or lipid-leaden intima, with marked signal attenuation and a diffuse border. In addition, the presence of disrupted intima and thrombus was evaluated. Neovascularization was defined as small vesicular or tubular structures, and the location of the microvessels was classified into peristent or intraintima.ResultsNormal neointima proliferated homogeneously, and lipid-laden intima was not observed in the early phase. In the late phase, lipid-laden intima, intimal disruption, and thrombus frequently were found in comparison with the early phase (67% vs. 0%, 38% vs. 0%, and 52% vs. 5%, respectively; p < 0.05). Peristent neovascularization demonstrated a similar incidence between the 2 phases. The appearance of intraintima neovascularization was more prevalent in the late phase than the early phase (62% vs. 0%, respectively; p < 0.01) and in segments with lipid-laden intima than in nonlipidic segments (79% vs. 29%, respectively; p = 0.026).ConclusionsThis OCT study suggests that neointima within the BMS often transforms into lipid-laden tissue during an extended period of time and that expansion of neovascularization from peristent to intraintima contributes to atherosclerotic progression of neointima

DDD Pacing Therapy Could Serve as a Dual Purpose Treatment in Hypertrophic Obstructive Cardiomyopathy —A Case Report Which Suggests the Importance of Lead Position and the Mechanism—

We treated a patient with hypertrophic obstructive cardiomyopathy (HOCM) who underwent DDD pacing therapy. He suffered from attacks of paroxysmal atrial fibrillation (PAF) complicated by sick sinus syndrome. Initially, we were unable to decrease the left ventricular outflow tract (LVOT) gradient by pacing from the mid-distal portion of the right ventricular (RV) septum. However, by changing the pacing site to the apical portion guided by right ventriculography, it was possible to decrease the LVOT gradient and at the same time reduce the mitral regurgitation. Tissue Doppler imaging (TDI) revealed a marked motion delay of the ventricular septum during DDD pacing. The mechanism of the therapy for HOCM provided by the DDD pacing was clearly confirmed by TDI. Furthermore, a dramatic effect of preventing symptomatic PAF with the use of overdrive pacing in the region of Bachmann's bundle was also observed. This case report provides new insight into DDD pacing therapy for patients with HOCM