Accuracy management survey of nucleic acid amplification tests using inactivated SARS-CoV-2 in Hiroshima Prefecture

At the beginning of 2020, the number of laboratories performing SARS-CoV-2 testing increased with the rapid expansion of COVID-19 in Hiroshima Prefecture. Thus, it is necessary to compare and verify the validity of the test results among local laboratories. In this study, we distributed the same standard samples to laboratories that performed COVID-19 testing using the nucleic acid amplification method and confirmed the accuracy of the tests. The SARS-CoV-2 strain distributed by the National Institute of Infectious Diseases (NIID), Japan, was used for testing. As measured by RT-qPCR, a specific amount of the virus was inactivated by ethanol and dried as specimens for distribution. This study included 27 tests performed at 15 laboratories conducting or planning to conduct nucleic acid amplification tests (RT-qPCR and LAMP methods) for SARSCoV-2. The detection limit of each test method was set at the value provided by the NIID. The accuracy of the tests was examined to determine whether they met the required accuracy criteria. SARS-CoV-2 genomic RNA was reliably detected in all 27 tests. The inactivated specimens used in this study were safe to distribute and could be used as positive controls for all methods.This study was supported by a grant from the Government-Academia Collaboration of Hiroshima Prefecture and by a research grant for COVID-19 from AMED, Japan under Grant Number 20he0622011h0001(to J. T.)

Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial

[Objectives:] We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). [Methods:] From 2013 to 2016, 42 patients with a median age of 58 (range 42–65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. [Results:] Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%−97.5%) and 62.6% (95% CI: 45.8%−75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. [Conclusion:] VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan

An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions.

First online: 06 March 2014[Background]Lipocalin 2 (LCN2 or neutrophil gelatinase-associated lipocalin) is a secretory protein discovered from neutrophils, which accumulates in the blood and urine during acute kidney injury (AKI) and in the blood by bacterial infection. Little is known about the tissue source and molecular forms of this protein under normal and pathophysiologic conditions. [Methods]By sandwich ELISA, serum and urinary LCN2 levels were measured in 36 patients with hematologic malignancies who transiently became neutropenic by stem cell transplantation (SCT). To evaluate contribution of neutrophil-derived LCN2 in the physiologic blood LCN2 concentrations, we examined CCAAT/enhancer-binding protein ε (C/EBPε) knockout mice, which lack mature neutrophils. [Results]In patients without AKI and bacterial infection, at 1 week after SCT, the median blood neutrophil counts became zero and serum LCN2 levels were decreased by 76 ± 6 % (p 100 kDa), while urinary LCN2 was mainly in low molecular weight forms. [Conclusion]Our findings suggest that neutrophils are the major source of circulating LCN2 in normal and infected conditions, whereas blood and urinary LCN2 mainly derive from the kidney during AKI, and that the molecular forms and regulation of blood and urinary LCN2 are clearly distinct