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Background. Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. Methods. We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. Results. Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). Conclusions. Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV. [ABSTRACT FROM AUTHOR]

Background Reactivation of hepatitis B virus ( HBV) infection, reverse seroconversion ( RS), is a serious complication after allogeneic stem cell transplantation (allo HSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV- RS. This report is an update of the hepatitis B vaccine study. Methods In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. Results None of the 21 patients in the vaccine group developed HBV- RS and 12 controls developed HBV- RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody ( HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. Conclusion These results demonstrated the long-term effects of HBV vaccine for preventing HBV- RS after allo HSCT. Of note, no HBV- RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination. [ABSTRACT FROM AUTHOR]

A. Shigematsu, S. Yamamoto, J. Sugita, T. Kondo, M. Onozawa, K. Kahata, T. Endo, S. Shiratori, S. Ota, K. Yamaguchi, K. Wakasa, M. Takahata, H. Goto, S. Ito, R. Takemura, J. Tanaka, S. Hashino, M. Nishio, T. Koike, M. Asaka, M. Imamura. Increased risk of bacterial infection after engraftment in patients treated with allogeneic bone marrow transplantation following reduced-intensity conditioning regimen. Transpl Infect Dis 2010: 12: 412-420. All rights reserved Although bacterial infection is a major cause of death even after reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), little is known about the epidemiology and risk factors. The incidence of bacterial infection in 43 patients who received allogeneic bone marrow transplantation (BMT) using a RIC regimen was compared with that in 68 patients who received BMT using a myeloablative conditioning regimen, and risk factors for bacterial infection were identified. Before engraftment, incidences of febrile neutropenia (FN) and documented infections (DI) were significantly decreased in RIC patients (FN: 59.5% vs. 89.6%, P<0.01, DI: 4.8% vs. 17.9%, P<0.01). However, incidence of bacterial infection was significantly increased in RIC patients in the post-engraftment phase (53.8% vs. 11.1%, log-rank, P<0.01). Blood stream was the most frequent focus of infection in both groups. In multivariate analysis, RIC and acute graft-versus-host disease were revealed to be significant risk factors for bacterial infection in this phase. In summary, risk of bacterial infection after engraftment was significantly higher in RIC patients, although infection was decreased before engraftment, and we need to develop a RIC-specific strategy against bacterial infection after RIC SCT. [ABSTRACT FROM AUTHOR]

A 43-year-old woman with severe aplastic anemia (SAA) received anti-thymocyte globulin and cyclosporin A (CyA) and achieved hematological remission. Although she had maintained hematological remission, the disease relapsed 10 months after arbitrary discontinuance of maintenance therapy with CyA. Resumption of CyA therapy was not effective, and her condition became complicated with progressive sinusitis with bone destruction, which was refractory to antibiotics, antifungal agents, granulocyte colony-stimulating factor, and surgical drainage. Because of the necessity for early neutrophil recovery (to resolve the infection), we proceeded with a combination therapy using allogeneic peripheral blood stem cell transplantation (PBSCT) promptly followed by granulocyte transfusion (GTX) from the same human leukocyte antigen-identical donor rather than carrying out a second immunosuppressive therapy. The patient showed temporal resolution of infection on the second day after a single GTX. Although the patient had pneumonia on day 11, it was resolved promptly after engraftment on day 16. This report suggests the clinical utility of a salvage therapy with allogeneic PBSCT followed by GTX in a particular case of recurrent SAA with refractory infections. [ABSTRACT FROM AUTHOR]

Aims: Linezolid is primarily used to treat of methicillin-resistant Staphylococcus aureus and multidrug-resistant tuberculosis infections. Thrombocytopenia due to linezolid usage is a concern, and therapeutic drug monitoring has been reported to be effective in its prevention. Plasma concentrations provide valuable information for treatment decisions; however, collecting plasma samples can be burdensome for both patients and healthcare providers. Therefore, there is interest in saliva as an alternative for monitoring, considering its potential to replace plasma samples., Methods: Patients hospitalized at Hokkaido University Hospital and Hokkaido Spinal Cord Injury Center between April 2022 and July 2024, who received oral or intravenous linezolid treatment, were enrolled. The concentrations of linezolid were simultaneously measured in plasma and saliva samples. We determined the concentration profiles of linezolid in the saliva and examined the correlation between saliva and plasma linezolid concentrations., Results: Eighteen patients receiving linezolid were enrolled. The average of saliva/plasma (S/P) concentration ratios of linezolid were 1.018. A strong correlation was found between the salivary and plasma concentrations of linezolid (R = .833, P < .001). Notably, in patients receiving intravenous administration of linezolid, the correlation was even more pronounced (R = .885, P < .001). Additionally, when focusing on the S/P ratio of the trough concentrations in the morning and at night, the S/P ratios at night were much closer to 1.0., Conclusion: The concentrations of linezolid in plasma and saliva were similar, indicating their potential applicability in clinical settings. The monitoring of linezolid concentrations in saliva has been shown to be particularly suitable for patients receiving intravenous administration., (© 2024 British Pharmacological Society.)

Prolonged SARS-CoV-2 infection in immunocompromised individuals has been scattered, but the details remain unclear. We conducted a prospective study with 26 COVID-19 patients with haematological malignancies to determine viral shedding kinetics and characteristics. We obtained nasopharyngeal swabs from the patients 21-28 days post-onset for a PCR test and performed virus isolation from the PCR-positive samples. A viable virus was detected in five patients (19.2%), all of whom had malignant lymphoma. Those patients had significantly lower CD4 + T-cell counts than the PCR-negative patients. A comparison of previous chemotherapy showed that anti-CD20 antibodies and bendamustine may be risk factors for prolonged viral shedding., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Background The major underlying mechanisms contributing to acute coronary syndrome are plaque rupture, plaque erosion, and calcified nodule. Artery-to-artery embolic myocardial infarction (AAEMI) was defined as ST-segment-elevation myocardial infarction caused by migrating thrombus formed at the proximal ruptured plaque. The aim of this study was to investigate the prevalence and clinical features of AAEMI by using optical coherence tomography. Methods and Results This study retrospectively enrolled 297 patients with ST-segment-elevation myocardial infarction who underwent optical coherence tomography before percutaneous coronary intervention. Patients were divided into 4 groups consisting of plaque rupture, plaque erosion, calcified nodule, and AAEMI according to optical coherence tomography findings. The prevalence of AAEMI was 3.4%. The culprit vessel in 60% of patients with AAEMI was right coronary artery. Minimum lumen area at the culprit site was larger in AAEMI compared with plaque rupture, plaque erosion, and calcified nodule (4.0 mm 2 [interquartile range (IQR), 2.2-4.9] versus 1.0 mm 2 [IQR, 0.8-1.3] versus 1.0 mm 2 [IQR, 0.8-1.2] versus 1.1 mm 2 [IQR, 0.7-1.6], P <0.001). Lumen area at the rupture site was larger in patients with AAEMI compared with patients with plaque rupture (4.4 mm 2 [IQR, 2.5-6.7] versus 1.5 mm 2 [IQR, 1.0-2.4], P <0.001). In patients with AAEMI, the median minimum lumen area at the occlusion site was 1.2 mm 2 (IQR, 1.0-2.1), 40% of them had nonstent strategy, and the 3-year major adverse cardiac event rate was 0%. Conclusions AAEMI is a rare cause for ST-segment-elevation myocardial infarction and has unique morphological features of plaque including larger lumen area at rupture site and smaller lumen area at the occlusion site.

The objective of this study was to investigate the immunomodulatory effects of heat-killed Enterococcus faecalis TH10 (hk-TH10) and its signal transduction on murine macrophage RAW264 cells. RAW264 cells produced nitric oxide (NO) following hk-TH10 treatment. In order to investigate the mechanisms underlying hk-TH10-stimulated NO production, we further measured NO production in RAW264 cells treated with Toll-like receptor (TLR) 4 inhibitor peptide, NF-κB inhibitor, TLR1-siRNA, TLR2-siRNA, and TLR-6 siRNA. Furthermore, the activation of TLR2-TLR1/6 pathway molecules was analyzed by Western blotting. The result of this study showed that hk-TH10 stimulates NO in RAW264 cells through the activation of the TLR2-TLR1/6 pathway. From our findings, we can conclude that hk-TH10 isolated from a traditional side-dish fermented food (tempeh) may facilitate host immunomodulation., (© 2012 The Authors. Published by Blackwell Publishing Ltd.)

Objective: Glucocorticoid (GC) therapy is associated with increased risk of fracture in patients with rheumatoid arthritis (RA). To elucidate the cause of this increased risk, we examined the effects of chronic erosive inflammatory arthritis and GC treatment on bone quality, structure, and biomechanical properties in a murine model., Methods: Mice with established arthritis and expressing human tumor necrosis factor α (TNFα) transgene (Tg) and their wild-type (WT) littermates were continually treated with GC (prednisolone 5 mg/kg/day via subcutaneous controlled-release pellet) or placebo for 14, 28, or 42 days. Microstructure, biomechanical properties, chemical composition, and morphology of the tibiae and lumbar vertebral bodies were assessed by micro-computed tomography, biomechanical testing, Raman spectroscopy, and histology, respectively. Serum markers of bone turnover were also determined., Results: TNF-Tg and GC treatment additively decreased mechanical strength and stiffness in both the tibiae and the vertebral bodies. GC treatment in the TNF-Tg mice increased the ductility of tibiae under torsional loading. These changes were associated with significant alterations in the biochemical and structural composition of the mineral and organic components of the bone matrix, a decrease in osteoblast activity and bone formation, and an increase in osteoclast activity., Conclusion: Our findings indicate that the concomitant decrease in bone strength and increase in bone ductility associated with chronic inflammation and GC therapy, coupled with the significant changes in the bone quality and structure, may increase the susceptibility of the bone to failure under low-energy loading. This may explain the mechanism of symptomatic insufficiency fractures in patients with RA receiving GC therapy who do not have radiographic manifestations of fracture., (Copyright © 2012 by the American College of Rheumatology.)

Reduced intensity conditioning (RIC) regimens are widely used in allogeneic stem cell transplantation (SCT). In this study, we retrospectively investigated the clinical outcomes of RIC with fludarabine (Flu; 180 mg/m(2)), intravenous busulfan (BU; 6.4 mg/kg) or oral BU (8 mg/kg), and low-dose total body irradiation (TBI; 4 Gy) (Flu-BU2-TBI) in 66 patients (median age: 54.5 years) with various hematological malignancies. Thirty-eight patients (58%) were high-risk patients (median age: 56 years). The overall survival rate at 2 years of the high-risk patients was 64.5%, which was comparable to the survival rate of 70.9% in standard-risk patients (P = 0.68). The relapse rates at 2 years in the standard-risk and high-risk patients were 16 and 28%, respectively, and day 100 treatment-related mortality rates were 0 and 6%, respectively. The Flu-BU2-TBI regimen for high-risk patients showed therapeutic effects equivalent to those for standard-risk patients and favorable outcomes compared with those of other previous RIC regimens.

The functional contributions of amino acid residue Asp87 of Escherichia coli gyrase A protein (GyrA) was analyzed by site-directed mutagenesis. We generated a series of mutants, in which Asp87 of GyrA was changed to Ala, Val, Phe, Asn, Ser, and Lys. By genetic analysis of gyrA genes in a gyrA temperature-sensitive (Ts) background, it was shown that all these mutations caused the quinolone-resistance. These results indicate that the 87th amino acid of E. coli GyrA must have negative charge in expressing the phenotype of quinolone sensitivity. These findings also suggest that the carboxyl group of Asp87 may interact with quinolone drugs.