Development of pure red cell aplasia by transmission and persistent infection of parvovirus B19 through a kidney allograft.

We report a case of pure red cell aplasia (PRCA) caused by parvovirus B19 (PVB19) infection, which was transmitted through a kidney allograft. The patient underwent a living-donor kidney transplant from his wife at the age of 60. Despite successful engraftment with a normal creatinine level, he developed severe anemia that required frequent blood transfusions 2 months after transplantation. Renal anemia was unlikely as his serum erythropoietin level was extremely high. A bone marrow aspiration test demonstrated the existence of large proerythroblasts. Although anti-PVB19 IgM antibody levels were not increased, polymerase chain reaction (PCR) detected PVB19 DNA in his serum. Thus, he was diagnosed as having PRCA induced by PVB19 infection. PCR analysis of total DNA isolated from 0-hour biopsy sections showed the existence of PVB19 DNA. Furthermore, PVB19 proteins was detected on renal tubules of 0-hour allograft by immunoperoxidase staining. Thus, transmission of PVB19 through the allograft was confirmed. A single course of intravenous immunoglobulin (IVIG) therapy resulted in substantial improvement; however, the effect was limited, and severe anemia relapsed after 5-6 months. Several courses of IVIG with adjustment of immunosuppressive drugs resulted in long-term remission. Our case demonstrates that donor-transmitted PVB19 infection should be suspected in kidney transplant recipients who develop refractory anemia during the early post-operative phase.

Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach.

Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases. Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0. Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin. Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.

Silica-Induced Protein (Sip) in Thermophilic Bacterium Thermus thermophilus Responds to Low Iron Availability.

UNLABELLED: Thermus thermophilus HB8 expresses silica-induced protein (Sip) when cultured in medium containing supersaturated silicic acids. Using genomic information, Sip was identified as a Fe(3+)-binding ABC transporter. Detection of a 1-kb hybridized band in Northern analysis revealed that sip transcription is monocistronic and that sip has its own terminator and promoter. The sequence of the sip promoter showed homology with that of the σ(A)-dependent promoter, which is known as a housekeeping promoter in HB8. Considering that sip is transcribed when supersaturated silicic acids are added, the existence of a repressor is presumed. DNA microarray analysis suggested that supersaturated silicic acids and iron deficiency affect Thermus cells similarly, and enhanced sip transcription was detected under both conditions. This suggested that sip transcription was initiated by iron deficiency and that the ferric uptake regulator (Fur) controlled the transcription. Three Fur gene homologues (TTHA0255, TTHA0344, and TTHA1292) have been annotated in the HB8 genome, and electrophoretic mobility shift assays revealed that the TTHA0344 product interacts with the sip promoter region. In medium containing supersaturated silicic acids, free Fe(3+) levels were decreased due to Fe(3+) immobilization on colloidal silica. This suggests that, because Fe(3+) ions are captured by colloidal silica in geothermal water, Thermus cells are continuously exposed to the risk of iron deficiency. Considering that Sip is involved in iron acquisition, Sip production may be a strategy to survive under conditions of low iron availability in geothermal water. IMPORTANCE: The thermophilic bacterium Thermus thermophilus HB8 produces silica-induced protein (Sip) in the presence of supersaturated silicic acids. Sip has homology with iron-binding ABC transporter; however, the mechanism by which Sip expression is induced by silicic acids remains unexplained. We demonstrate that Sip captures iron and its transcription is regulated by the repressor ferric uptake regulator (Fur). This implies that Sip is expressed with iron deficiency. In addition, it is suggested that negatively charged colloidal silica in supersaturated solution absorbs Fe(3+) ions and decreases iron availability. Considering that geothermal water contains ample silicic acids, it is suggested that thermophilic bacteria are always facing iron starvation. Sip production may be a strategy for surviving under conditions of low iron availability in geothermal water.