Universal nucleic acid donor screening revealed epidemiological features of hepatitis E and prevented transfusion-transmitted infection in Japan.

BACKGROUND: More than 45 cases of transfusion-transmitted hepatitis E virus infection (TT-HEV) have been reported in Japan. Therefore, in 2020, universal individual donation nucleic acid amplification testing (ID-NAT) was implemented for HEV. STUDY DESIGN AND METHODS: We characterized HEV NAT-positive blood donors. The number of new HEV infections and the asymptomatic infection rate were estimated using the HEV NAT-positive rate. HEV RNA quantitation, phylogenetic analysis, and antibody tests were performed, and the residual risk of TT-HEV was assessed based on the lookback study results. RESULTS: A total of 5,075,100 blood donations were screened with ID-NAT during the first year of implementation, among which 2804 (0.055%; males: 0.060%, females: 0.043%) were NAT-positive with regional differences. Approximately 270,000 new HEV infection cases were estimated to occur annually in Japan, with an asymptomatic infection rate of 99.9%. The median HEV RNA concentration, excluding cases below the limit of quantification, was 205 IU/mL. Among the 1113 cases where the genotype could be determined, HEV-3 and HEV-4 accounted for 98.8% (1100) and 1.2% (13), respectively. The maximum duration of HEV viremia, including the pre- and post-ID-NAT window periods, was estimated to be 88.2 days. Within the 3 years since ID-NAT implementation, no confirmed cases of breakthrough TT-HEV were observed. DISCUSSION: Multiple indigenous HEV strains are prevalent in Japan, infecting a significant number of individuals. However, since the implementation of ID-NAT, TT-HEV has been prevented due to the test's high sensitivity.

Risk of transfusion-transmitted infection with severe acute respiratory syndrome coronavirus 2 from blood donors in Japan.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) essentially affects respiratory organs and tissues. SARS-CoV-2 RNAemia is often associated with more severe cases of coronavirus disease 2019 (COVID-19) compared to cases without RNAemia. To determine the impact of the pandemic on transfusion medicine, particularly transfusion-related infection, we examined the frequency of blood donation with RNAemia, the viral RNA (vRNA) concentration, and any possibility of transfusion-transmitted infection (TTI) among transfusion recipients. STUDY DESIGN AND METHODS: vRNA was examined in plasma/serum samples from 496 of 513 blood donors who reported having been infected with SARS-CoV-2 within 2 weeks of donation among a total of ca. 9.9 million blood donations in Japan between January 15, 2020, and December 31, 2021. The clinical course of patients transfused with the blood component containing vRNA was also examined. RESULTS: vRNA was detected in 23 of 496 samples. The median period from blood donation to COVID-19 onset was 1 day in 16 RNAemia-positive donors. Most samples had vRNA concentrations below the limit of quantification. Three patients were transfused with either a packed red blood cell or platelet concentrate that tested positive for vRNA, showing no COVID-19 symptoms and testing negative for vRNA in post-transfusion blood. CONCLUSION: The rate of RNAemia was 4.6% among blood donors who were found to be infected with SARS-CoV-2 shortly after donation, and vRNA concentrations in their donated blood were extremely low. There was no evidence of TTI in the recipients transfused with RNAemia-positive blood components. TTI risk in SARS-CoV-2 is negligible.

Transfusion-transmitted HBV infection with isolated anti-HBs-positive blood.

BACKGROUND: Hepatitis B virus (HBV)-positive individuals with isolated anti-HBs are found among HBV vaccine recipients and healthy blood donors with no vaccination history. HBV infectivity from blood transfusions derived from such individuals remains unclear. CASE PRESENTATION: A male patient who received transfusion with blood negative for individual donation-NAT, HBsAg and anti-HBc but weakly positive for anti-HBs developed typical transfusion-transmitted (TT)-HBV with anti-HBc response. The responsible blood donor was a frequent repeat donor showing a marked increase in anti-HBs titer without anti-HBc response 84 days after index donation. Test results for his past donations showed transient viremia with very low viral load and fluctuating low-level anti-HBs. The HBV vaccination history of this donor was unknown. DISCUSSION: Anti-HBs and anti-HBc kinetics of the donor suggest a second antibody response to new HBV challenge, representing a vaccine breakthrough case. On the other hand, transient low-level viremia and fluctuating anti-HBs in the test results of past donations suggested chronic occult HBV infection with isolated anti-HBs. CONCLUSION: Whatever the basic infection state, blood donors with isolated weak anti-HBs may include a small population with a risk of causing TT-HBV. Identifying individuals harboring such TT-HBV risk among individuals positive only for anti-HBs is difficult under current screening strategies. Active surveillance for the occurrence of TT-HBV with blood positive only for anti-HBs is necessary.

Marked reduction in the incidence of transfusion-transmitted hepatitis B virus infection after the introduction of antibody to hepatitis B core antigen and individual donation nucleic acid amplification screening in Japan.

BACKGROUND: In Japan, 41 million blood donations have been screened for hepatitis B virus (HBV) during the past 8.4 years using individual donation nucleic acid amplification testing (ID-NAT) and antibody to hepatitis B core antigen (anti-HBc) screening. STUDY DESIGN AND METHODS: Transfusion-transmitted HBV infection (TT-HBV) incidence was examined. Donated blood implicated in TT-HBV was analyzed for infection stage and DNA levels. Causative HBV strains were phylogenetically analyzed. RESULTS: Among 5162 (0.013%) ID-NAT positives, window period (WP) and occult HBV infection (OBI) accounted for 3.4% (176) and 11.5% (594), respectively. No OBI-related TT-HBV occurred. Seven blood donations caused eight TT-HBV cases, six of which were in the pre-ID-NAT WP, leaving one with an unresolved infection stage. Seven cases were caused by platelet concentrate (180 mL plasma) and one case by fresh-frozen plasma (200 mL plasma), which contained estimated infectious doses varying between 2 and 2300 HBV virions. HBV subgenotypes in five cases were HBV/A2. Complete genome sequences of the transmitting A2 strains were nearly identical (99.6%-100%) and clustered in a group that included HBV/HIV-1 coinfections and a higher proportion of donors in the acute infection phase (69%) than the other group of HBV/A2 sequences (5%). DISCUSSION: The incidence of observed TT-HBV cases has significantly reduced to 0.19 per million in the ID-NAT screening period. OBI-related TT-HBV was eliminated by anti-HBc screening. Established TT-HBV cases were caused by blood products with large plasma volumes containing extremely low HBV concentrations derived from blood donors at a very early infection stage.

Performance evaluation of in vitro diagnostic kits for hepatitis B virus infection using the regional reference panel of Japan.

BACKGROUND: Hepatitis B virus (HBV) infection is a global public health concern. Precise and sensitive detection of viral markers, including HBV DNA and HBs antigen (Ag), is essential to determine HBV infection. METHODS: The sensitivities and specificities of 5 HBV DNA and 14 HBsAg kits were evaluated using World Health Organization International Standards (WHO IS) and the Regional Reference Panel (RRP) consisting of 64 HBsAg-negative and 80 HBsAg-positive specimens. RESULTS: All 5 HBV DNA kits detected HBV DNA in the WHO IS at a concentration of 10 IU/mL. The sensitivity and specificity to the RRP were 98.8-100% and 96.9-100%, respectively. HBV DNA titers were well correlated among the 5 kits regardless of HBV genotype. However, discordance of the HBV DNA titer was found in 5 specimens measured by CAP/CTM HBV v2.0. Among 12 automated HBsAg kits, the minimum detectable concentrations in the WHO IS varied from 0.01 to 0.1 IU/mL. Two lateral flow assays were positive for WHO IS concentrations greater than or equal to 1.0 and 0.1 IU/mL, respectively. When analyzed by the RRP, 12 automated kits exhibited a sensitivity of 98.8-100%, and 2 lateral flow assays showed sensitivities of 93.8% and 100%. The specificities of HBsAg kits were 100%. In the quantification of HBsAg, some kits showed a poor correlation of measurements with each other and showed up to a 1.7-fold difference in the regression coefficient of HBsAg titers. There were variations in the correlations of measurements among HBsAg kits when analyzed by genotype. CONCLUSIONS: Five HBV DNA kits showed sufficient sensitivity and specificity to determine HBV infection. HBV DNA titers were compatible with each other irrespective of HBV genotypes. HBsAg kits had enough sensitivity and specificity to screen for HBV infection. One of the lateral flow assays had a nearly equivalent sensitivity to that of the automated HBsAg kit. HBsAg titers quantified by the evaluated kits were not compatible across the kits. Genotype-dependent amino acid variations might affect the quantification of HBsAg titers.

Two cases of Streptococcus dysgalactiae subspecies equisimilis infection transmitted through transfusion of platelet concentrate derived from separate blood donations by the same donor.

BACKGROUND: Transfusion-transmitted bacterial infections (TTBIs) in Japan have been largely prevented due to a short shelf life of 3.5 days after blood collection for platelet concentrate (PC) and washed PCs (WPCs; PC in which 95% plasma is replaced by platelet additive solution). CASE PRESENTATION: Case 1: In January 2018, a woman in her 50s with aplastic anaemia who received WPC transfusion and developed a fever the next day and Streptococcus dysgalactiae subspecies equisimilis (SDSE) was detected in the residual WPC. Case 2: In May 2018, a man in his 60s with a haematologic malignancy who received PC transfusion and developed chills during the transfusion. SDSE was detected in the patient's blood and residual PC. The contaminated platelet products were both manufactured from blood donated by the same donor. The multi-locus sequencing typing revealed that SDSE detected in case 1 was identical to that from case 2; however, whole blood subsequently obtained from the donor was culture negative. CONCLUSION: WPC and PC produced from two blood donated 106 days apart by the same donor were contaminated with SDSE of the same strain and both caused TTBIs. Safety measures should be considered regarding blood collection from a donor with a history of bacterial contamination.

Seroepidemiology of hepatitis A virus infection in Japan: An area of very low endemicity.

The incidence of hepatitis A virus (HAV) infection has declined significantly worldwide, including in Japan. A nationwide seroepidemiological study on hepatitis A in Japan has taken place almost every 10 years since 1973, and the last study was performed in 2003. In the present study, we describe the latest seroepidemiological pattern of hepatitis A in Japan using 7867 serum specimens obtained from healthy individuals collected between 2013 and 2017, approximately 10 years after the last study. Among them, 223 were anti-HAV positive. About 68% of individuals aged 60 years and older had anti-HAV antibodies, whereas only 1.1% of those aged below 60 years old had immunity; thus, almost all individuals younger than 60 years of age were HAV susceptible. In comparison with previous investigations, the susceptible population has increased and aged. According to data from the National Epidemiological Surveillance of Infectious Diseases (NESID) program, between 1989 and 2016, the proportion of patients with hepatitis A aged 60 years and older continuously increased with each year. The NESID data also suggested that recently, typical large foodborne outbreaks of hepatitis A have become rare, and cases tend to be reported among at-risk groups; overseas travelers contributed to 25% of hepatitis A cases, and in 2018, the first nationwide hepatitis A outbreak that affected mostly men who have sex with men was reported. The purpose of this study was to determine the current status of HAV infection in Japan, based on both seroepidemiology and the national surveillance data from the NESID.

Evaluation of human T-cell leukemia virus in vitro diagnostics using plasma specimens collected in Japan.

BACKGROUND: In vitro diagnostics (IVDs) for primary detection test/screening of human T-cell leukemia virus (HTLV) have recently been updated to new-generation products in Japan. In this study, the performance of these products was evaluated and discussed in terms of the usability of HTLV diagnosis in Japan. METHODS: The performance of 10 HTLV IVDs for primary detection test and confirmatory/discriminatory test was evaluated. Plasma specimens that had been declared ineligible for transfusion were provided by the Japanese Red Cross Blood Center. RESULTS: The diagnostic specificity of the IVDs was 100% (160/160). Six sandwich assays resulted in all HTLV-1/HTLV-positive specimens being positive (46/46). On the other hand, one sandwich assay, IVD under development 2 (UD2), resulted in one HTLV-1-positive and one HTLV-positive specimen being negative (44/46, 95.7%). One indirect assay, HISCL HTLV-1, could not detect one HTLV-positive specimen (45/46, 97.8%), but the updated product, UD1, correctly detected it (46/46, 100%). Serodia HTLV-I, based on a particle agglutination assay, resulted in 44 of the 46 positive specimens, but could not detect two specimens (44/46, 95.7%). ESPLINE HTLV-I/II, based on an immunochromatography assay (ICA), was able to diagnose all specimens as positive (46/46, 100%). CONCLUSIONS: Six sandwich assays and an ICA demonstrated high diagnostic sensitivity and specificity and are recommended for use in HTLV diagnosis in conjunction with confirmatory/discriminatory test using the INNO-LIA HTLV-I/II Score.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Association of Staphylococcus aureus in platelet concentrates with skin diseases in blood donors: Limitations of cultural bacterial screening.

BACKGROUND: Bacterial contamination in platelet concentrates (PCs) is a major problem in transfusion medicine. Contamination with Staphylococcus aureus is occasionally missed, even with cultural screening. STUDY DESIGN AND METHODS: Donors implicated in S. aureus-contaminated PC were followed up. Skin and nasal swab specimens from six donors and S. aureus isolated from PCs related to these donors were subjected to multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to determine the identity of bacteria. To evaluate the validity of the screening method using BacT/ALERT 3D, we spiked S. aureus and three other bacterial species as comparisons into PCs and investigated their growth pattern. RESULTS: S. aureus was isolated from all nasal specimens and from the arm skin specimens of three donors with atopic dermatitis. In all cases, the S. aureus strains isolated from the PC and those from the nasal and skin specimens of the same donor showed concordant results using MLST and PFGE. In the spiking study, S. aureus showed irregular detectability over 24 to 48 h post-spike periods, whereas the three other bacterial species were detected in all culture bottles after a 24-h post-spike period. DISCUSSION: The strain identity of S. aureus between donor and PC suggests that the contaminants were derived from those colonized in the donor. Furthermore, S. aureus yielded false-negative results using BacT/ALERT 3D.

Trends in hepatitis E virus infection: Analyses of the long-term screening of blood donors in Hokkaido, Japan, 2005-2019.

BACKGROUND: After experiencing several cases of transfusion-transmitted hepatitis E (TT-HE) in Hokkaido, Northern Japan, hepatitis E virus (HEV) screening in blood donors, using a nucleic acid amplification test (NAT), was introduced in 2005. STUDY DESIGN AND METHODS: The frequency of HEV RNA-positive donations (2005-2019) was investigated, and the HEV RNA-positive specimens were phylogenetically analyzed. In August 2014, the 20-pooled NAT (20P-NAT) was replaced with an individual-NAT (ID-NAT) system. RESULTS: Until 2019, the frequency of HEV RNA-positive donors was 0.011% (289/2,638,685) with 20P-NAT and 0.043% (597/1,379,750) with ID-NAT, and no TT-HE cases were observed in Hokkaido. The prevalence among male, but not female donors, increased significantly between 2015 and 2019. Eighty-nine percent of HEV isolates from donors were genotype 3 and the remainder were genotype 4, and many clusters existed in each genotype. ALT levels at the time of donation were significantly higher in donors with genotype 4. Four subgenotypes, namely 3a (37%), 3b (41%), 3e (6%), and 4c (10%), comprised 94% of the total. During this period, the most identified subgenotype, 3a, transitioned to 3b. Majority of the HEV strains within the same clusters were detected in the same geographical region around the same period. Many of the human HEV isolates were shown to coexist closely with animal HEV isolates phylogenetically. CONCLUSION: In Hokkaido, multiple divergent HEV strains have been circulating, and small outbreaks of hepatitis E have occurred in the last 15 years. The results suggested that HEV NAT can contribute significantly in ensuring safety during blood transfusions.

How we secured a COVID-19 convalescent plasma procurement scheme in Japan.

BACKGROUND: In order to tackle the COVID-19 pandemic, a COVID-19 convalescent plasma (CCP) procurement program was initiated in Japan in April 2020. The program was a collaboration between a government-managed national hospital, an infectious disease research institute, and a blood banking organization. Each party assumed different responsibilities: recruitment, SARS-CoV-2 antibody profiling, and plasmapheresis; conduction of screening tests; and SARS-CoV-2 blood testing, respectively. METHODS: We adopted a two-point screening approach before the collected CCP was labeled as a CCP product for investigational use, for which we mainly tested anti-SARS-CoV-2 antibody eligibility and blood product eligibility. Anti-SARS-CoV-2 spike protein titer was measured using enzyme-linked immunosorbent assay, and the IC50 value was denoted as the neutralizing activity. Blood donor eligibility was extended beyond the normal blood donation guidelines to include a broader range of participants. After both eligibility criteria were confirmed, participants were asked to revisit the hospital for blood donation, which is a unique aspect of the Japanese CCP program, as most donations are taking place in normal blood donation venues in other countries. Some donors were re-scheduled for repeat plasma donations. As public interest in anti-SARS-CoV-2 antibodies increased, test results were given to the participants. RESULTS: As of September 17, 2020, our collection of CCP products was sufficient to treat more than 100 patients. As a result, projects for administration and distribution are also being conducted. CONCLUSIONS: We successfully implemented a CCP procurement scheme with the goal to expand to other parts of the country to improve treatment options for COVID-19.

Evaluation of Geenius HIV-1/2 Confirmatory Assay for the confirmatory and differential diagnosis of HIV-1/HIV-2 in Japan and reliability of the Geenius Reader in the diagnosis of HIV-2.

BACKGROUND: NEW LAV BLOT I and II (LAV I and LAV II), they were only option for human immunodeficiency virus (HIV) confirmatory test, following HIV screening test using HIV Ag/Ab combination test in Japan. We evaluated the performance of Geenius HIV-1/2 Confirmatory Assay (Geenius), both as a confirmatory test and for differentiation between HIV-1 and HIV-2, in comparison with LAV I and LAV II. METHODS: Eighty-nine HIV-1-positive plasma specimens, one anti-HIV-1 low-titer performance panel, 10 seroconversion panels, and two anti-HIV-1/2 combo performance panels were tested. The results were read with the Geenius Reader and by visual reading. RESULTS: All 89 HIV-1-positive plasma specimens were identified as HIV-1-positive using Geenius; this 100% success rate was superior to that with LAV I (95.5% using WHO criteria, 98.9% using CDC criteria). The HIV-1-positive specimens showed low cross-reactivity with HIV-2 lines in Geenius. The sensitivity of Geenius for HIV-1 detection was the same as or greater than that of LAV I, but less than that of Genscreen HIV Ag-Ab ULT, in our analysis of the commercial performance and seroconversion panels. In contrast, five of the 13 HIV-2-positive specimens that had been identified as HIV-positive untypable by visual reading because of their cross-reactivity to HIV-1 lines were successfully identified by the Geenius Reader as HIV-2-positive with cross-reactivity. CONCLUSIONS: Geenius provides strong performance for HIV confirmatory tests and HIV-1 differentiation tests. However, when visual reading is used, its performance in HIV-2 differentiation is less reliable. Because HIV-2 infection has been sporadically reported in Japan, the use of the Geenius Reader is preferable to ensure more reliable HIV-1/HIV-2 differentiation.

IFN-λ3 as a host immune response in acute hepatitis E virus infection.

BACKGROUND AND AIM: Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E. METHODS: IFN-λ3 and HEV RNA levels in the sera of patients with acute HEV infection and in the supernatant of HEV-inoculated cells were measured, using an in-house high-sensitivity method and reverse transcription-polymerase chain reaction, respectively. RESULTS: High serum IFN-λ3 levels were found in the early phase of acute HEV infection, which normalized after resolution. Interestingly, serum IFN-λ3 levels correlated well with serum HEV RNA titers in the same sera, both of which showed the peak before the robust increase of transaminases. In vitro experiments demonstrated that HEV replicated well in the cells with little IFN-λ3 induction (Caco-2, A549) and recombinant IFN-λ3 inhibited HEV replication in a dose-dependent manner. In contrast, in HT-29 cells, a colon cancer cell line, HEV poorly replicated and induced IFN-λ3 in a titer-dependent manner. CONCLUSIONS: These clinical and experimental observations suggest that HEV induced IFN-λ3 as a host innate immune response, which may play a protective role against HEV.

Different growth kinetics in blood components and genetic analysis of Lactococcus garvieae isolated from platelet concentrates.

BACKGROUND: In 2014, we experienced the first isolation of Lactococcus garvieae from a platelet concentrate (PC). Thereafter, L. garvieae contamination of PCs occurred in two more cases in Japan. It is rare that bacterial contamination with uncommon strains like this species occurs frequently within a short period. Therefore, we performed a detailed analysis of the characteristics of these strains. STUDY DESIGN AND METHODS: Three bacterial strains were identified by biochemical testing and molecular analysis. Genomic diversity was characterized by multilocus sequence typing (MLST). To observe growth kinetics in blood components, PCs were inoculated with the three different strains. RESULTS: All three strains were identified as L. garvieae by molecular analysis. Each strain belonged to a different phylogenetic group according to MLST analysis. In the spiking trial, the three strains demonstrated differences in their final concentrations and changes in appearance of PCs. CONCLUSION: In this study, all three L. garvieae strains were correctly identified by molecular analysis. Since the three strains were collected in different regions of Japan and belonged to different phylogenetic groups according to MLST analysis, it is suggested that L. garvieae have a wide distribution with diversity in Japan. In PCs, the three L. garvieae strains showed clear differences in growth kinetics and changes in appearance of PCs. These differences may have been the primary determinant of whether PC contamination was detected before transfusion. Moreover, L. garvieae represents an emerging foodborne bacterium that can cause transfusion-transmitted bacteremia. Understanding our cases may help prevent bacterial contamination of blood products.

Platelet safety strategies in Japan: impact of short shelf life on the incidence of septic reactions.

BACKGROUND: Transfusion-transmitted bacterial infections (TTBIs) often have serious consequences for patients. The Japanese Red Cross (JRC) has not implemented culture screening for platelet concentrate (PC), but it has maintained a shelf life of 85 hours for PC. STUDY DESIGN AND METHODS: The JRC collected reports of suspected TTBI and investigated causal relationships using PC samples and patient blood samples. PCs showing apparent abnormalities were retrieved and cultured and analyzed for bacterial growth. RESULTS: The JRC analyzed 86 samples available from 135 transfused PCs with suspected TTBIs that were collected over the past 12 years; 17 (19.8%) were culture-positive. One, 6, and 10 TTBIs developed in patients on Days 1, 2, and 3 after PC collection, respectively. Assuming that PC is transfused on the day of issue, the TTBI risk was fourfold higher on Day 3 than on Day 2, after adjusting the TTBI incidence for the number of PCs issued per day. Compared with the model of issuing all PCs on Day 3, issuing PCs with the current distribution of storage time could have decreased the TTBI incidence by 56%. During the past 8 years, the JRC retrieved 960 PC units because of apparent abnormalities, 2.8% of which were culture-positive. CONCLUSION: The short shelf life of PC is associated with a low incidence of reported TTBIs, more than half of which occurred on Day 3 relative to earlier time points. Visual inspection of PC before transfusion is crucial in detecting bacterially contaminated PC despite its low positive predictive value.

Hepatitis A virus and hepatitis E virus prevalence relates to human immunodeficiency virus infection in Japanese male blood donors.

Hepatitis A virus (HAV) has begun to spread globally among men who have sex with men (MSM). Hepatitis E virus (HEV) also may be transmitted through sexual contact among MSM. To assess the current status of these viruses among MSM in Japan, the seroprevalence of both viruses using 503 plasma samples collected between 2009 and 2018 from human immunodeficiency virus (HIV)-positive male donors who were presumed to be mainly MSM was investigated. Our results suggested that HAV may be spreading within this population, as reported elsewhere. By contrast, the spread of HEV was confirmed only among younger HIV-positive donors.

[Pulmonary Artery Catheter-induced Massive Tracheal Hemorrhage during Aortic Valve Surgery;Report of a Case].

We report a case of pulmonary artery catheter (PAC)-induced massive intratracheal hemorrhage during aortic valve surgery. An 81-year-old woman underwent aortic valve replacement and pulmonary vein isolation. Operative procedures were uneventful, but active and massive intratracheal hemorrhage started just after cardiopulmonary bypass was discontinued. We immediately resumed cardiopulmonary bypass and replaced the endotracheal tube with a double-lumen one, keeping the airway pressure high (20 cmH2O). Those maneuvers reduced intratracheal hemorrhage and maintained oxygenation, and then cardiopulmonary bypass was disconnected without lung lobectomy. Mechanical ventilation with high positive end expiratory pressure for 6 days in the intensive care unit let her good recovery. A postoperative enhanced computed tomography revealed a thrombosed right pulmonary artery pseudoaneurysm possibly induced by PAC. After close observation the patient left the hospital on foot.

[Treatment Strategy for Stanford Type A Acute Aortic Dissection].

The fundamental treatment of Stanford type A acute aortic dissection is a lifesaving emergency surgery in our hospital. We perform hemiarch replacement with a focus on entry tear, but an extended surgery is also performed only when resection of the entry tear is difficult. The outcomes of current therapeutic policy, along with the short-term and the long-term outcomes of different sites of entry tear, were examined retrospectively. Three hundred and twenty surgery of Stanford type A acute aortic dissection were performed between 1991 and 2015 at our hospital. Their short-term and long-term outcomes were examined after dividing them into 7 groups according to their entry sites. We also investigated surgical methods and effects of presence/absence of residual entry tear. As a result, overall hospital mortality was 13.1%. There was no significant difference in either shortterm or long-term outcome among the groups. Likewise, no significant difference was observed in the surgical methods or the presence/absence of residual entry tear. Recently, minimally invasive procedures, such as stent-grafting, have been applied to manage the residual entry tear. Therefore, an aggressive extended surgery is no longer inevitable and our current therapeutic policy is considered reasonable.

Optimal titer of anti-HBs in blood components derived from donors with anti-HBc.

BACKGROUND: The ultimate strategy to cope with transfusion-transmitted hepatitis B virus (HBV) infection caused by transfusion of blood from donors with historical HBV infection is to reject all donors having anti-HBV core antigen (anti-HBc). However, this strategy would result in a huge loss of blood donors and subsequent blood inventory collapse. On the other hand, anti-HBc-positive blood is reportedly not infectious when containing more than 100 mIU/mL of anti-HBV surface antigen (anti-HBs). STUDY DESIGN AND METHODS: In Japan, anti-HBc-positive blood has been used for transfusion if it contained 200 mIU/mL or more of anti-HBs. First, to verify the screening policy, clinical outcomes for transfusion of such blood were analyzed for the 2008-2012 period. Second, human hepatocyte-repopulated severe combined immunodeficiency mice were inoculated with HBV preincubated with varying doses of anti-HBs, then viremic status was followed. The effects of anti-HBs across different HBV genotypes were also investigated. RESULTS: Twenty-three transfusion-transmitted HBV infections related to anti-HBc-positive blood components were identified. None of the blood responsible for these cases contained 200 mIU/mL or more of anti-HBs. When 100 µL of plasma containing 104 copies of HBV and 20 mIU of anti-HBs was injected into severe combined immunodeficiency mice, no viremia was detected within 13 weeks. Genotype C anti-HBs was capable of total inhibition of genotype A HBV replication, whereas genotype A anti-HBs inhibited genotype C HBV to a lesser extent. CONCLUSION: Anti-HBc-positive blood containing 200 mIU/mL or more of anti-HBs appears safe as a transfusion component. HBV vaccination seems effective between HBV genotypes A and C.