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Background and Objectives: Geographical limitations in remote island medical facilities result in excessive wastage of blood products. To address this, we explored the feasibility of a novel blood rotation system, which enables the return and redelivery of blood products to/from the blood bank while ensuring the management of product quality, including temperature control. This study aimed to enhance the supply of blood products to these facilities. Materials and Methods: The Japan Red Cross Nagasaki Blood Center, Nagasaki Goto Chuoh Hospital (NGCH) and Nagasaki University Hospital collaborated to coordinate the transport and supply of red blood cell (RBC) products. Type O, RhD‐positive, irradiated RBC products were stored at a precise 4.0 ± 2.0°C in an active transport refrigerator (ATR). After transport from the Japan Red Cross Nagasaki Blood Center to NGCH, RBC products were held for 1 week in the ATR, and unused products were returned. Eligible returned products were reissued to the Nagasaki University Hospital. Results: All the returned RBC products met the redelivery criteria. Among the 103 redelivered RBC preparations, 101 bags (98.1%) were successfully used. NGCH utilized 597 RBC products and discarded 80 samples. The ATR supplied 107 type O RBC bags without any wastage. The overall wastage rate was 10.2% during the study period compared with 24.2% in the same period in the previous year. Conclusion: This innovative supply and operation system ensures a consistent and secure RBC product supply to remote islands while maximizing blood product use. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that perioperative fibrinogen level, platelet count, and rotational thromboelastometry (ROTEM) data values decrease in proportion to cardiopulmonary bypass (CPB) time, particularly in patients who underwent deep hypothermic circulatory arrest (DHCA). Methods: A total of 160 patients were enrolled and divided into the following three groups depending on CPB time: <2-h, 2– 3-h, and >3-h groups. Blood samples were obtained during CPB weaning. Platelet count, ROTEM data, fibrinogen level, and antithrombin level were determined. For propensity matching, we selected 15 patients who underwent DHCA and 15 patients who did not undergo DHCA and used propensity scores to match CPB time and other characteristics. Results: The <2-h, 2–3-h, and >3-h groups included 74, 63, and 23 patients, respectively. No significant differences in platelet count and fibrinogen level were observed between the groups. Antithrombin level and amplitude of clot firmness at 10 min in the EXTEM and FIBTEM tests were lowest in the >3-h group. Similarly, blood loss volume and transfusion volume were highest in the >3-h group. Significant differences in platelet count, ROTEM data, lowest esophageal and bladder temperatures, and transfusion volume were observed between patients who underwent DHCA and patients who did not undergo DHCA. Conclusions: The longer the CPB time, the greater the perioperative blood loss volume and transfusion volume, particularly if CPB time is greater than 3 hours. Sub-group analysis revealed that DHCA affects perioperative platelet count and function as well as blood loss volume. [ABSTRACT FROM AUTHOR]

Introduction: Accumulation of β2-microglobulin (B2M) in dialysis patients contributes to several comorbidities of end-stage kidney disease (ESKD). The LIXELLE® device adsorbs B2M from blood using sorbent bead technology. Studies in Japan showed that LIXELLE treatment during hemodialysis (HD) at blood flow rates up to 250 mL/min removes B2M above HD alone and is well tolerated. We investigated tolerance for LIXELLE treatment during HD at higher HD blood flow rates standard in the USA. Methods: A prospective, open-label, non-randomized, single-arm, early-feasibility study (EFS) assessed tolerance and safety of LIXELLE treatment during HD at blood flow rates up to 450 mL/min. ESKD patients (40–75 years old) on thrice weekly outpatient HD were eligible. After a 1-week HD run-in, patients received LIXELLE plus HD at a blood flow rate of 250 mL/min (1 week), followed by LIXELLE plus HD at a blood flow rate up to 450 mL/min (1 week). These blood flow rates were tested with three LIXELLE column sizes in sequence (treatment = 6 weeks). B2M removal was assessed for each combination. Results: Ten patients with a historic intradialytic hypotension (IDH) rate of 0.42 events/HD session/patient were enrolled. Nine patients completed all combinations without IDH events (treatment IDH rate: 0.56 events/HD session/patient). No treatment-emergent serious adverse events or significant changes in red blood cell, platelet, or complement indices except haptoglobin were reported. B2M reduction ratios and removal of select proteins (<40 kDa) increased with escalating column size and blood flow rate. Conclusion: LIXELLE plus HD across all column sizes was safe and well tolerated at blood flow rates up to 450 mL/min. Extent of B2M removal corresponded to column size-blood flow rate combinations. This EFS provides a risk profile to guide further studies of LIXELLE in ESKD patients at US-standard blood flow rates. [ABSTRACT FROM AUTHOR]

Introduction: The Atellica Hema (Siemens Healthineers, Tarrytown, NY, USA) is a new generation multi‐parameter analyzer for full blood count, 6‐part differential and reticulocyte testing by impedance variation and fluorescence flow cytometry. In this study, we verified the whole blood and limited body fluid modes of the Atellica Hema 580. Methods: We evaluated precision, linearity, carry‐over, throughput and performed a method comparison to assess the performance of the Atellica Hema 580. For comparison of the Atellica Hema 580 with the Sysmex XN‐1000 (Sysmex, Kobe, Japan), 140 samples from adult and pediatric patients including both normal and abnormal hematology profiles were analyzed in parallel. Results: The Atellica Hema 580 demonstrated acceptable imprecision within the manufacturer's specifications for whole blood and body fluid modes, good linearity for high and low ranges and no significant carryover. The full blood count, differential and reticulocyte correlated well with the Sysmex XN‐1000, except for mean cell hemoglobin concentration, basophil and large immature cells. The optical platelet count, reflexed in 34 samples with a platelet count <150 × 109/l, showed a strong correlation with the fluorescent platelet count on the Sysmex XN‐1000. The morphology flagging efficiency was 92% for white blood cells, 95% for red blood cells and 87% for platelets. Conclusion: The Atellica Hema 580 showed good analytical performance and workflow efficiency for a wide range of patient samples. [ABSTRACT FROM AUTHOR]

Background: The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. Methods: We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low (< 2.5 mmol/L), middle (≥ 2.5 and < 4.0 mmol/L), and high (≥ 4.0 mmol/L). We compared 28 days mortality and ICU-free and ventilator-free days using multiple linear regression among groups. Results: Of the 422 RESTRIC trial participants, 396 were analyzed, with low (n = 131), middle (n = 113), and high (n = 152) lactate. Across all lactate groups, 28 days mortality was similar between strategies. However, in the low lactate group, the restrictive approach correlated with more ICU-free (β coefficient 3.16; 95% CI 0.45 to 5.86) and ventilator-free days (β coefficient 2.72; 95% CI 0.18 to 5.26) compared to the liberal strategy. These findings persisted even after excluding patients with severe traumatic brain injury. Conclusions: Our results suggest that restrictive transfusion strategy might not have a significant impact on 28-day survival rates, regardless of lactate levels. However, the liberal transfusion strategy may lead to shorter ICU- and ventilator-free days for patients with low initial blood lactate levels. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for the treatment of RA in Japan in 1999 at a recommended dose of 6–8 mg/week. The approved maximum dose of MTX has been 16 mg/week since February 2011 when MTX was approved as a first-line drug in the treatment of RA. Recent evidence of MTX-polyglutamate concentration in the red blood cells of Japanese patients with RA justifies the current daily use of MTX in Japan. Additionally, after a nationwide clinical trial, a subcutaneous MTX injection formula (7.5–15 mg/week) was approved for RA treatment in September 2022. Therefore, in March 2023, a subcommittee of the Japan College of Rheumatology updated the guidance (formerly 'guidelines') for the use of MTX in Japanese patients with RA. This article, an abridged English translation summarizing the 2023 update of the Japan College of Rheumatology guidance for the use of MTX and management of patients with RA, will be helpful to both Japanese and global rheumatology communities. [ABSTRACT FROM AUTHOR]

Background: MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, Döhle body-like granulocyte inclusions, and nephropathy, which may progress to end-stage kidney disease (ESKD). However, information on the effects of renin-angiotensin system (RAS) inhibitors on kidney survival is currently lacking and the outcomes of kidney replacement therapy (KRT) in MYH9-RD are largely unknown. Methods: We conducted a cross-sectional nationwide survey by sending questionnaires to 145 institutions in Japan and analyzed data for 49 patients. Results: The median patient age was 27 years. Genetic analysis was performed in 37 (76%) patients. Twenty-four patients (65%) had MYH9 variants affecting the motor domain of non-muscle myosin heavy chain-IIA, and these patients had poorer kidney survival than those with variants affecting the tail domain (P = 0.02). There was no significant difference in kidney survival between patients treated with and without RAS inhibitors. Hemodialysis and peritoneal dialysis were performed in 16 and 7 patients, respectively. There were no major bleeding complications during the perioperative period or during follow-up, except for one patient. Most of the 11 patients who underwent kidney transplantation required perioperative red cell concentrate transfusions, but there was no graft loss during the median posttransplant observational period of 2.0 (interquartile range, 1.3–6.8) years. Conclusion: Our study demonstrated no beneficial effect of RAS inhibitors on kidney function in patients with MYH9-RD, indicating the need for further studies with more patients. All modalities of KRT are feasible options for MYH9-RD patients who progress to ESKD, with adequate attention to bleeding complications. [ABSTRACT FROM AUTHOR]

Background & Objectives: To evaluate immature granulocytes, a new inflammatory biomarker, and other markers in short- and long-term prognosis in patients with acute ischemic stroke (AIS). Methods: Laboratory information system data from a tertiary hospital in Turkiye were used in this retrospective study. Of the 327 patients with the diagnosis of AIS, 275 recovered, and 52 died. It was determined that 31 of these 275 patients, who were followed up retrospectively, died within 12 months after discharge. Routinely measured immature granulocyte (IG), other hemogram parameters in the Sysmex XN 1000 (XN-1000-Hematology-Analyzer-Sysmex Corporation, Japan), and demographic data were statistically compared in both groups. We tried to estimate the short- and long-term mortality from the blood samples of these patients at their first admission to the hospital. Results: Of the patients included in the study, 150 (45.9%) were female, and 177 (54.1%) were male. National Institutes Of Health Stroke Scale (NIHSS) (AUC=960), length of stay (AUC=791), red blood cell distribution width - standard deviation (RDW-CV) (AUC=728), and IG (AUC=712) were the most effective parameters in predicting short-term mortality, while age (AUC=764) in predicting long-term mortality was the most effective parameters. Conclusion: IG, together with NIHSS and length of stay, shows moderate and high predictive properties in prognosticating short-term mortality but is ineffective in prognosticating long-term mortality. Age was found to be the most predictive marker for long-term mortality. [ABSTRACT FROM AUTHOR]

The shelf life of red blood cell components (RBCs) in Japan was extended from 21 days to 28 days in March 2023, but still remains shorter than the 36 to 43 days in other countries. It is expected that extension of RBC shelf life will reduce wastage. However, irradiation of RBCs to avoid graft-versus-host disease may cause storage lesions. Here, we investigated whether the later irradiation of RBCs reduces the deterioration of RBC quality and contributes to the extension of shelf life. We irradiated RBCs on either day 2, 7, 14, or 21 post-collection during 42-day storage. We set the in vitro quality of RBCs irradiated on day 2 and stored until day 28 as the control. We compared the quality of RBCs irradiated later (days 7, 14, or 21) on days 28, 35, and 42, respectively, with the control. Late irradiation did not reduce the increased hemolysis or decreased ATP concentration on days 35 and 42. Only RBCs irradiated on day 21 and stored until day 35 had supernatant potassium concentrations equal to control values. RBCs irradiated on day 14 and stored until day 35, and those irradiated on day 21 and stored until day 42 showed deformability equal to control values. These results suggest that late irradiation is less effective in maintaining the quality of RBCs after 35 days storage and less useful for extension of the shelf life of RBCs. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to investigate whether consumption of sturgeon fillets reduces the oxidative stress marker urinary 8‐hydroxy‐2′‐deoxyguanosine (8OHdG) in top‐ranked Japanese female long‐distance runners. Methods: In a before‐and‐after study, nine professional long‐distance female athletes ate 100 g/day of sturgeon fillets for 2 weeks. Urinalysis (8OHdG, an oxidative stress marker, and creatinine), blood tests (fatty acids and 25‐hydroxyvitamin D [25OHD]), exercise intensity, subjective fatigue, muscle elasticity, muscle mass, body fat mass, and nutritional intake using image‐based dietary assessment (IBDA) were compared before, immediately after, and 1 month after the intervention. Results: Consumption of sturgeon fillets suppressed 8OHdG (p < 0.05) in the increased exercise intensity female athletes. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 25OHD levels in blood increased from before to immediately after and 1 month after the intervention (p < 0.05). IBDA showed that intake of n‐3 fatty acid increased after and one month after the intervention, whereas DHA, imidazole dipeptide and vitamin D intake increased after the intervention (p < 0.05) and then decreased after 1 month (p < 0.05). There were no significant changes in subjective fatigue, muscle elasticity, muscle mass, and body fat. Conclusions: The results suggest that eating sturgeon fillets during intense training may increase blood levels of EPA, DHA, and 25OHD, which may suppress urinary oxidative stress (8OHdG) in top‐ranked Japanese long‐distance runners. [ABSTRACT FROM AUTHOR]

Introduction: This study examined the association between hemoglobin (Hb) levels and all-cause mortality in community-dwelling individuals in Japan. Methods: Participants were 1,243 males (62 ± 14 years old) and 1,754 females (64 ± 12 years old). The research was based on a follow-up study with 7- and 19-year intervals. Results: The follow-up survey revealed 448 male deaths (36.0% of male participants) and 419 female deaths (23.9% of female participants). Male participants' hazard ratio (HR) for all-cause mortality was significantly higher for groups whose Hb level was < 11.0 g/dL (HR: 2.39; 95% confidence interval [CI]: 1.28-4.47) or in the range 11.0-11.9 g/dL (2.11; 1.23-3.62) or 12.0-12.9 g/dL (1.66; 1.15-2.41) than for the reference group (14.0-14.9 g/dL). For female participants, the HR for all-cause mortality was significantly higher in groups whose Hb level was < 11.0 g/dL (1.91; 1.19-3.05), in the range 11.0-11.9 g/dL (1.44; 1.03-2.03), or ≥15.0 g/dL (1.77; 1.10-2.85) than for the reference group (13.0-13.9 g/dL). Conclusions: The study revealed a linear positive association between Hb levels and the risk of all-cause mortality for male participants. However, this association formed a J-shaped curve for female participants. [ABSTRACT FROM AUTHOR]

Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported. We analyzed the genomic background of 23 patients from 20 Japanese families suspected of having DHSt using a target capture sequence and identified pathogenic/likely pathogenic variants of PIEZO1 or KCNN4 in 12 families. Hemolytic anemia: new variants in hereditary subtypes Genetic variants identified in 12 Japanese families are likely to be responsible for a rare hereditary condition causing red blood cells (RBCs) to rupture. Keiko Shimojima Yamamoto of Tokyo Women's Medical University, Japan, and colleagues conducted genetic analyses on blood samples from 23 people in 20 Japanese families with suspected dehydrated hereditary spherocytosis (DHSt), caused by RBC ion imbalances leading to dehydration and rupture. In 12 families, the analyses revealed probable disease-causing variants in two genes, PIEZO1 and KCNN4, some of which were identified for the first time. Both genes are related to RBC ion channels and the mutations lead to two slightly different forms of DHSt. Further understanding could improve treatment strategies. Comprehensive genomic analysis is a powerful tool for understanding the genetic cause of congenital hemolytic anemia. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, there are various opinions on the pros and cons of home transfusion because of safety concerns. We hence aimed to elucidate the safety and availability of home transfusion in Japan, which has not been clarified to date. Materials and Methods: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The analysis period was February to December 2019. Basic information about the clinics, their collaboration system with core hospitals, storage method of red blood cells (RBCs) and the system for the management of patient information regarding transfusion reactions were investigated. Results: Detailed information was obtained regarding the implementation of home transfusions by 51 clinics. The proportion of home care clinics performing home transfusions was 17.6%, and they were more frequently performed in urban regions. Approximately half of the clinics collaborated with a core hospital for emergency responses to transfusion reactions. At 84% of the clinics, RBC units were stored in refrigerators that were not exclusively allocated to blood storage. Nurses and family members were involved as patient attendants in 83% and 77% of the home transfusions, respectively. No serious transfusion reactions were reported among the 150 patients in 2019, nor the 623 patients up to 2018. Conclusion: From data on its availability and safety, home transfusions are considered to be in the developing phase in Japan. Increased cooperation between hospitals and clinics is crucial towards improving the home transfusion system in Japan in the future. [ABSTRACT FROM AUTHOR]

Stroke is a progressive disease with remissions and exacerbations; it significantly reduces the quality of life of patients and their family and caregivers. Primary prevention is necessary to reduce the growing incidence of stroke globally. In this study, we determined the risk factors for cerebral infarction in elderly Japanese residents and proposed a primary care strategy to prevent cerebral infarction. We investigated the relationship between the incidence of cerebral infarction and the results of checkups 10 years ago. Multivariate logistic regression analysis was performed to determine the variables related to the occurrence of cerebral infarction in biochemical tests and questionnaires administered ten years ago. Hypertension and abnormal creatinine levels were related to increased risk of cerebral infarction based on our findings of the health checkups conducted 10 years previously. Furthermore, weight gain or loss of >3 kg over the last year and habit of eating an evening meal within 2 h before going to bed were associated with an increased risk of cerebral infarction based on the questionnaire results from the specific health checkups. Long-term, large-scale prospective studies are required to determine the specific health items related to increased risk of cerebral infarction. [ABSTRACT FROM AUTHOR]

Background: Olaparib-induced anemia is a frequently occurring complication in patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and is associated with a marked deterioration in patients' health-related quality of life. This study aimed to clarify patient-specific risk factors for severe anemia in patients with advanced ovarian or breast cancer receiving olaparib monotherapy in a real-world setting. Methods: This multicenter, retrospective, observational study enrolled consecutively presenting patients with advanced ovarian or breast cancer who received olaparib monotherapy as maintenance or palliative treatment between April 2018 and December 2020 at three participating medical institutions in Japan. The primary endpoint was patient-associated risk factors underlying the onset of grade =3 anemia from olaparib treatment initiation to 90 days after treatment. Receiver operating characteristic curves were constructed and univariable and multivariable logistic regression analyses were performed to evaluate the association between patient-associated risk factors and grade =3 anemia. Results: Of 113 patients evaluated in this study, 32.7% (n = 37) had grade =3 anemia. Multivariable logistic regression analysis revealed that low baseline red blood cell (RBC) count (<3.3 × 106 cells/mL), low baseline hematocrit level (<35%), low baseline hemoglobin level (<11.6 g/dL), and breast cancer susceptibility (BRCA1/2) mutation were significantly associated with the onset of grade =3 anemia (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 1.28-9.62; P = 0.017, adjusted OR, 3.63; 95% CI, 1.28-11.64; P = 0.021, adjusted OR, 3.89; 95% CI, 1.39-12.21; P = 0.014, and adjusted OR, 4.09; 95% CI, 1.55-11.67; P = 0.006, respectively). Conclusions: Our findings suggest that low baseline RBC count, low baseline hematocrit level, and low baseline hemoglobin level might be the patientassociated risk factors for severe anemia induced by olaparib monotherapy. Additionally, BRCA1/2 mutation was suggested to be a patient-related risk factor for anemia regardless of severity. Therefore, applying these patientassociated risk factors would help classify and screen patients at risk of severe anemia. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection has been reported to be associated with a positive direct antiglobulin test (DAT). In this study, an analysis of 40 consecutive coronavirus disease 2019 (COVID-19) cases from December 2020 to September 2021 in Japan revealed that patients of 70 years and over were predisposed to a positive DAT. DAT positivity was related to a decrease in the hemoglobin level. Anemia in DAT-positive COVID-19 patients was attributed to hemolysis, which was corroborated by high reticulocyte counts and an increase in the red blood cell distribution width. Human leukocyte antigen (HLA)-DRB1*12:01 and DRB1*12:02 were exclusively found in DAT-positive COVID-19 patients. In silico assays for the Spike protein of SARS-CoV-2 predicted several common core peptides that met the criteria for a B cell epitope and strong binding to both HLA-DRB1*12:01 and DRB1*12:02. Among these peptides, the amino acids sequence TSNFR, which is found within the S1 subunit of SARS-CoV-2 Spike protein, is shared by human blood group antigen Rhesus (Rh) CE polypeptides. In vitro analysis showed that the expression of HLA-DR in CD4+ T cells and CD8+ T cells from a DAT-positive patient was increased after pulsation with TSNFR-sequence-containing peptides. In summary, positive DAT is related to enhanced anemia and to HLA-DR12 in the Japanese population. A peptide sequence within SARS-CoV-2 Spike protein may act as an epitope for IgG binding to RBCs in DAT-positive COVID-19 patients. [ABSTRACT FROM AUTHOR]

Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they are widely used in many fields, including the creation of humanized animal models, as well as regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size and can more easily undergo transplantation of various tissues and organs. Considering the absence of high-quality resources of immunodeficient rats, we used the CRISPR/Cas9 genome editing system to knock out the interleukin-2 receptor gamma chain gene (Il2rg) in F344/Jcl rats—alone or together with recombination activating gene 2 (Rag2)—to create a high-quality bioresource that researchers can freely use: severe combined immunodeficiency (SCID) rats. We selected one founder rat with frame-shift mutations in both Il2rg (5-bp del) and Rag2 ([1-bp del+2-bp ins]/[7-bp del+2-bp ins]), then conducted mating to establish a line of immunodeficient rats. The immunodeficiency phenotype was preliminarily confirmed by the presence of severe thymic hypoplasia in Il2rg-single knockout (sKO) and Il2rg/Rag2-double knockout (dKO) rats. Assessment of blood cell counts in peripheral blood showed that the white blood cell count was significantly decreased in sKO and dKO rats, while the red blood cell count was unaffected. The decrease in white blood cell count was mainly caused by a decrease in lymphocytes. Furthermore, analyses of lymphocyte populations via flow cytometry showed that the numbers of B cells (CD3- CD45+) and natural killer cells (CD3- CD161+) were markedly reduced in both knockout rats. In contrast, T cells were markedly reduced but showed slightly different results between sKO and dKO rats. Notably, our immunodeficient rats do not exhibit growth retardation or gametogenesis defects. This high-quality SCID rat resource is now managed by the National BioResource Project in Japan. Our SCID rat model has been used in various research fields, demonstrating its importance as a bioresource. [ABSTRACT FROM AUTHOR]

Background: In 2008, the Japanese government implemented a National Intervention Program for metabolic syndrome. Low-risk individuals were not direct targets of this intervention. Nevertheless, they were indirectly enlightened by this massive campaign. Documentation of the metabolic shifts in low-risk individuals following the program launch may inform public health policy regarding approaches to metabolic risks in the general population. Methods: We conducted a cross-sectional analysis of data from non-diabetic participants who underwent general health check-ups at the Physical Check-up Center of Sumitomo Hospital. Participants during 2007–2008 were pair-matched with those during 2015–2016 with respect to sex, age, smoking status, hemoglobin level, and red blood cell (RBC) count. Each participant was included only once in the study. Results: Totals of 3,140 men and 2,048 women were pair-matched. The non-diabetic participants showed lower waist circumference, blood pressure, heart rate, and serum lipid concentrations during the second study period. In contrast, the entire distributions of fasting plasma glucose (FPG) concentration in both sexes and glycated hemoglobin (HbA1c) in women were shifted upwards. In men, Δ FPG was +1.6 mg/dL (P < 0.001) and Δ HbA1c was ±0% (P = 0.6). In women, Δ FPG was +3.0 mg/dL (P < 0.001), and Δ HbA1c was +0.1% (P < 0.001). Δ Homeostasis model assessment of β-cell function was −6.6 in men (P < 0.001) and −10.3 in women (P < 0.001). The homeostasis model assessment of insulin resistance did not change significantly. Conclusions: The "glycemic set point" has increased in non-diabetic people in Japan during recent years. Lifestyle or environmental changes may have caused this metabolic shift through obesity-independent pathways, possibly through effects on pancreatic β-cell function. The underlying mechanism awaits further investigation. [ABSTRACT FROM AUTHOR]

Background: The automated haematology analyzer XN-31 prototype (XN-31p) is a new flow cytometry-based device developed to measure the number and the ratio of malaria-infected red blood cells (MI-RBC) with a complete blood count (CBC). The XN-31p can provide results in about one minute and also can simultaneously provide information on the malaria parasite (Plasmodium) species. In this study, clinical testing of the XN-31p was performed using blood samples from patients with imported malaria in Japan. Methods: Blood samples were collected from 80 patients who visited the hospital of the National Center for Global Health and Medicine, Tokyo, Japan, for malaria diagnosis from January 2017 to January 2019. The test results by the XN-31p were compared with those by other standard methods, such as microscopic observation, rapid diagnostic tests and the nested PCR. Results: Thirty-three patients were diagnosed by the nested PCR as being malaria positive (28 Plasmodium falciparum, 2 Plasmodium vivax, 1 Plasmodium knowlesi, 1 mixed infection of P. falciparum and Plasmodium malariae, and 1 mixed infection of P. falciparum and Plasmodium ovale), and the other 47 were negative. The XN-31p detected 32 patients as "MI-RBC positive", which almost matched the results by the nested PCR and, in fact, completely matched with the microscopic observations. The ratio of RBCs infected with malaria parasites as determined by the XN-31p showed a high correlation coefficient of more than 0.99 with the parasitaemia counted under microscopic observation. The XN-31p can analyse the size and nucleic acid contents of each cell, and the results were visualized on a two-dimensional cytogram termed the "M scattergram". Information on species and developmental stages of the parasites could also be predicted from the patterns visualized in the M scattergrams. The XN-31p showed a positive coincidence rate of 0.848 with the nested PCR in discriminating P. falciparum from the other species. Conclusions: The XN-31p could rapidly provide instructive information on the ratio of MI-RBC and the infecting Plasmodium species. It was regarded to be of great help for the clinical diagnosis of malaria. [ABSTRACT FROM AUTHOR]

This study aimed to produce a Theileria-free grazing system for Holstein heifers reared on a dairy farm in the Hita area, Kyushu, Japan. In the grazing area, spreading of T. orientalis infection was confirmed in 2009. To eradicate the T. orientalis infection, four measures were conducted: 1) 7-year deferred grazing; 2) grazing only T. orientalis-uninfected heifers; 3) anemia check by red blood cell parameters at least once per month; and 4) protecting heifers from bloodsucking T. orientalis-infected ticks. Grazing was restarted in 2017 in the same area and continued to 2021. During last 2 years of pasturing (2020-2021) all of the 129 heifers were confirmed to be T. orientalis-free. In summary, it is possible to establish a T. orientalis-free grazing system by conducting appropriate measures. [ABSTRACT FROM AUTHOR]

The objective of this single-center retrospective cohort study was to investigate the relationship between blood transfusion and persistent inflammation, immunosuppression, and catabolism syndrome (PIICS). The study was conducted at the Critical Care Center at Toho University Omori Medical Center, Japan. We included 391 patients in the PIICS group (hospitalization for > 15 days, C-reactive protein > 3.0 mg/dL or albumin < 3.0 mg/dL or lymph < 800/μL on day 14) and 762 patients in the non-PIICS group (hospitalization for > 15 days and not meeting the PIICS criteria). We performed univariate and multivariate logistic regression analyses using PIICS as the objective variable and red blood cell (RBC) or fresh frozen plasma or platelet (PLT) transfusion and other confounding factors as explanatory variables. In addition, we conducted a sensitivity analysis using propensity score matching analysis. The multivariate and propensity score analyses showed that RBC and PLT transfusions were significantly associated with PIICS. This is the first study to report an association between RBC and PLT transfusions and PIICS. Our findings have contributed to better understanding the risk factors of PIICS and suggest that physicians should consider the risk of PIICS occurrence when administering blood transfusions in intensive care unit (ICU) patients. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six in ANK1 [SPH1]; four in SPTB [SPH2]; and one in each of SPTA1 [SPH3], SLC4A1 [SPH4], and EPB42 [SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia. Blood disorder: Targeted sequencing helps diagnosis when symptoms vary Genetic testing can help accurately diagnose people suspected of having a rare blood disorder called hereditary spherocytosis, the clinical symptoms of which often vary. Researchers in Japan led by Keiko Shimojima Yamamoto from Tokyo Women's Medical University collected blood samples from 51 people with hemolytic anemia associated with/without morphological abnormalities in red blood cells. The researchers sequenced the DNA from five genes known to cause hereditary spherocytosis. They identified genetic defects, some never reported before, in 13 people, providing these individuals with a definitive diagnosis for their blood disorder. The researchers suggest more comprehensive genomic workups could help explain the cause of red blood cell shortages in the remaining study subjects. [ABSTRACT FROM AUTHOR]

Human norovirus (HuNoV) is a leading cause of infectious gastroenteritis. Since HuNoV shows resistance to alcohol, chlorine-based sanitizers are applied to decontaminate the virus on environmental surfaces. Chlorous acid water (CA) has been recently approved as a novel chlorine-based disinfectant categorized as a Type 2 OTC medicine in Japan. In this study, we aimed to evaluate the capability of CA to inactivate HuNoV. HuNoV (genogroups GII.2 and GII.4) was exposed to the test disinfectants including CA and sodium hypochlorite (NaClO), and the residual RNA copy was measured by reverse transcription quantitative PCR (RT-qPCR) after pretreatment with RNase. In addition, the log 10 reduction of HuNoV RNA copy number by CA and NaClO was compared in the presence of bovine serum albumin (BSA), sheep red blood cells (SRBC), polypeptone, meat extract or amino acids to evaluate the stability of these disinfectants under organic-matter-rich conditions. In the absence of organic substances, CA with 200 ppm free available chlorine provided >3.0 log 10 reduction in the HuNoV RNA copy number within 5 min. Even under high organic matter load (0.3% each of BSA and SRBC or 0.5% polypeptone), 200 ppm CA achieved >3.0 log 10 reduction in HuNoV RNA copy number while less than 1.0 log 10 reduction was observed with 1,000 ppm sodium hypochlorite (NaClO) in the presence of 0.5% polypeptone. CA reacted with only cysteine, histidine and glutathione while NaClO reacted with all of the amino acids tested. CA is an effective disinfectant to inactivate HuNoV under organic-matter-rich conditions. [ABSTRACT FROM AUTHOR]

Introduction: Developing prognostic markers can be useful for clinical decision‐making. Peripheral blood (PB) examination is simple and basic that can be performed in any facility. We aimed to investigate whether PB examination can predict prognosis in coronavirus disease (COVID‐19). Methods: Complete blood count (CBC) and PB cell morphology were examined in 38 healthy controls (HCs) and 40 patients with COVID‐19. Patients with COVID‐19, including 26 mild and 14 severe cases, were hospitalized in Juntendo University Hospital (Tokyo, Japan) between April 1 and August 6, 2020. PB examinations were performed using Sysmex XN‐3000 automated hematology analyzer and Sysmex DI‐60 employing the convolutional neural network‐based automatic image‐recognition system. Results: Compared with mild cases, severe cases showed a significantly higher incidence of anemia, lymphopenia, and leukocytosis (P <.001). Granular lymphocyte counts were normal or higher in mild cases and persistently decreased in fatal cases. Temporary increase in granular lymphocytes was associated with survival of patients with severe infection. Red cell distribution width was significantly higher in severe cases than in mild cases (P <.001). Neutrophil dysplasia was consistently observed in COVID‐19 cases, but not in HCs. Levels of giant neutrophils and toxic granulation/Döhle bodies were increased in severe cases. Conclusion: Basic PB examination can be useful to predict the prognosis of COVID‐19, by detecting SARS‐CoV‐2 infection‐induced multi‐lineage changes in blood cell counts and morphological anomalies. These changes were dynamically correlated with disease severity and may be associated with disruption of hematopoiesis and the immunological system due to bone marrow stress in severe infection. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) infection causes various extragastric diseases. Its transmission route has still not been clarified. However, no large‐scale studies have examined the extragastric diseases caused by H. pylori in adolescents. This study aimed to examine the association of H. pylori infection with anemia, serum cholesterol levels, physique, and birth delivery method (vaginal or cesarean) in a large number of Japanese adolescents. Methods: From 2016 to 2018, we screened 2,399 adolescents (aged 13–15 years) in their second and third years of junior high school using an enzyme‐linked immunosorbent assay‐based antibody test. Red blood cells, hemoglobin, hematocrit, total cholesterol, high‐density lipoprotein (HDL) cholesterol, and serum antibody levels were measured. Results: Hemoglobin and hematocrit levels were significantly lower in the H. pylori antibody‐positive group than in the H. pylori antibody‐negative group in both sexes (boys: P = 0.0004 and 0.0022; girls: P = 0.0019 and 0.0005, respectively). Total cholesterol and non‐HDL cholesterol levels were significantly higher in the H. pylori‐positive group than in the H. pylori‐negative group among boys (P = 0.0370 and 0.0293 respectively). There was no significant difference in body mass index percentile and birth delivery method between the H. pylori‐positive and H. pylori‐negative groups in both boys and girls. Conclusions: Among Japanese junior high school students, H. pylori antibody‐positive status was associated with anemia in both sexes while total cholesterol and non‐HDL cholesterol levels were associated among boys. There was no association between H. pylori antibody status, body mass index percentile, and birth‐delivery method. [ABSTRACT FROM AUTHOR]

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH; however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the <150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage. [ABSTRACT FROM AUTHOR]

Intra-operative autologous blood donation is a blood conservation technique with limited evidence. We evaluated the association between intra-operative autologous blood donation and decrease in peri-operative transfusion in cardiovascular surgery based on evidence from a Japanese administrative database. We extracted the data of patients who had undergone cardiovascular surgery from the Diagnosis Procedure Combination database in Japan (2016–2019). Based on the surgery type, we examined the association of intra-operative autologous blood donation with the transfusion rate and amount of blood used in cardiac and aortic surgeries using multilevel propensity score matching. We enrolled 32,433 and 4,267 patients who underwent cardiac and aortic surgeries and received 5.0% and 6.7% intra-operative autologous blood donation with mean volumes of 557.68 mL and 616.96 mL, respectively. The red blood cell transfusion rates of the control and intra-operative autologous blood donation groups were 60.6% and 38.4%, respectively, in the cardiac surgery cohort (p <.001) and 91.4%, and 83.8%, respectively, in the aortic surgery cohort (p =.037). The transfusion amounts for the control and intra-operative autologous blood donation groups were 5.9 and 3.5 units of red blood cells, respectively, for cardiac surgery patients (p <.001) and 11.9 and 7.9 units, respectively, for aortic surgery patients (p <.001). Intra-operative autologous blood donation could reduce the transfusion rate or amount of red blood cells and fresh frozen plasma for patients undergoing index cardiovascular surgery and could be an effective blood transfusion strategy in cardiovascular surgery for Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Currently, supplementary serological testing for β-D glucan (BDG) is often selected to diagnose deep mycosis in care covered by the health insurance in Japan. The Wako method used by our center has low sensitivity, and different studies have used different cut-off values due to factors that cause false positives and false negatives. One possible cause of false negatives is the use of platelet-rich plasma (PRP) as the sample material. Because phagocytic white blood cells (WBC) are precipitated by centrifugation and only plasma is measured, it seems unlikely that the actual amount of BDG is being measured when using PRP. Further, a frequent cause of false positives is contamination from blood products and gauze containing BDG. To resolve these issues, the blood cell separator, hydroxyethyl starch, is used to precipitate only the red blood cells to obtain leukocyte-rich plasma (LRP). We hypothesized that it might be possible to improve the diagnostic rate of deep mycosis by measuring the BDG content of plasma containing WBC and fungal components and by comparing the BDG content of PRP and LRP measured simultaneously. Materials and Methods: Healthy human blood, albumin-added blood, wrung-out gauze fluid-added blood, and fungal solution-added blood were prepared, and PRP and LRP were prepared using hydroxyethyl starch. The BDG content of each sample was measured using the Wako method and compared. In addition, PRP and LRP of fungal-added blood were Gramstained and examined under a microscope, and the number of WBCs and phagocytosed fungi was counted visually and compared. Results: Measuring the BDG content of LRP confirmed that there were no false positives with LRP, and in vitro experiments comparing albumin-added false-positive blood to fungal-added blood showed significant differences between PRP and LRP only in the fungal-added blood. Conclusion: Calculating the BDG-ratio (LRP/PRP) by measuring both LRP and PRP may eliminate false positives and false negatives of true deep mycosis and improve the diagnostic rate. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the effect of daily folic acid supplementation on methotrexate (MTX) toxicity and efficacy in Japanese patients with rheumatoid arthritis (RA). Methods: We followed 19 patients treated with MTX who switched from taking weekly 5mg folic acid supplementation (weekly regimen) to 1.25mg daily (daily regimen). White blood cell (WBC) and platelet (PLT) counts, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were collected for 24 weeks following the change. Results: We observed no significant changes in WBC or PLT counts. AST and ALT levels, which had exceeded the upper limits of their normal ranges at the beginning of the study, were improved significantly at weeks 4 and 8, no subsequent deterioration in liver function was found. Further, no significant changes in ESR and CRP levels were observed. Conclusion: Our data indicate that supplementing 1.25mg of folic acid daily rather than 5mg weekly reduces toxicity caused by MTX without affecting its efficacy. [ABSTRACT FROM AUTHOR]

Background: Severely burned patients often suffer white blood cell and platelet drop following the injury. Though coagulopathy after burn injury have been reported, the association between leukopenia or thrombopenia and mortality is still unrevealed. To determine whether early drastic drops in white blood cells (WBCs) and platelets following injury can be prognostic markers in patients with major burns.Methods: This is a retrospective cohort study setting in a single Burn Center in Japan. Data comprising patients' characteristics and blood cell counts (red blood cells [RBCs], WBCs including neutrophils, monocytes, and lymphocytes, and platelets) over the first 30 days after burn injury were serially collected from patients suffering major burn injury (≥20% TBSA) from January 1, 2006 to December 31, 2015. To determine blood cell counts affecting 60-day mortality, we used multivariable Cox proportional hazard analysis to assess associations between each blood cell count and mortality, adjusting for age and %TBSA as covariates, and evaluated predicted value of the hazard ratio (HR) of death.Results: We enrolled 280 patients. Following burn injury, all blood cell counts were high at admission, then decreased. RBCs diminished progressively and plateaued 2 weeks after injury. WBCs decreased suddenly 2 days after injury, then increased and stabilized. Platelets decreased more rapidly than WBCs to their nadir at 3 days, then continually increased. After covariate adjustment, low RBCs from day 1 (HR: 0.566, 95% C.I. 0.423, 0.759) to day 5 (HR: 0.524, 95% C.I. 0.175, 0.576) were predictors of mortality. Neutrophil count was not a risk factor, but day 3 lymphocyte count (HR: 0.131, 95% C.I. 0.026, 0.646) and day 10 monocyte count (HR: 0.044, 95% C.I. 0.005, 0.396) were risk factors. Low platelet counts from day 3 (HR: 0.545, 95% C.I. 0.300, 0.981) to day 30 following injury were always a predictor of mortality.Conclusions: Early thrombopenia and lymphopenia were independent risk factors for 60-day mortality, and prolonged thrombopenia and monocytopenia were independent risk factors for mortality. These findings might shed light on mechanisms of immune response following severe burns. [ABSTRACT FROM AUTHOR]

Background: Term infants can be categorized into 3 sub-groups: early term (37w0d to 38w6d), full term (39w0d to 40w6d), and late term (41w0d and beyond). However, the fatty acid composition among the 3 groups of term infants has not been investigated. The association between fatty acid composition and gestational period of term infants in Japan is unclear. Methods: We assessed the fatty acid composition of maternal erythrocyte membranes in the third trimester and of cord erythrocyte membranes at birth in 212 healthy term Japanese infants using data from a prospective hospital-based cohort study. Results: In maternal erythrocyte membranes, docosahexaenoic acid (DHA) levels and omega-3 index were significantly higher in the late-term group than in the early-term group. In cord erythrocyte membranes, DHA levels were not significantly different between the 3 groups; late-term infants showed significantly higher DHA/arachidonic acid (ARA) and lower 20: 3n-6 and ARA levels compared to early-term infants. Gestational period positively correlated with the DHA status in maternal and cord erythrocyte membranes. Conclusions: Fatty acid composition in maternal and cord erythrocyte membranes varies between early-, full-, and late-term infants, and the greater gestational period may contribute to the relatively high n-3 polyunsaturated fatty acids status in term infants. Furthermore, maternal DHA status in the third semester directly correlates with gestational period in pregnant Japanese women. [ABSTRACT FROM AUTHOR]

Background: Ammonia in the plasma usually does not pass through the blood-brain barrier (BBB). However, it can affect the brain as a neurotoxin in neonates with anemia of prematurity. Excess intake of ammonia should therefore be restricted in conditions involving BBB breakdown, such as in premature neonates. A potassium adsorption filter (PAF) can remove not only potassium, but also ammonia from red blood cell (RBC) solution. PAF for neonates (PAF-n) has been recently introduced using small satellite packs. We evaluated the effects of PAF-n on the removal of ammonia and potassium from RBC solution in small satellite packs.Study Design and Methods: RBC solutions were obtained from the Japanese Red Cross Society. Two units of RBC solution (280 mL) were divided into four satellite packs (70 mL/pack). The RBC solution was passed through PAF-n (Kawasumi Laboratories Inc.) that was primed with saline (100 mL) before use. The concentrations of ammonia and potassium were measured in the solution before and after filtration (four samples of 10 mL each of filtered RBC solution) by Biomedical Laboratories.Results: Approximately 47 to 82 and 84% to 93% of ammonia and potassium were removed from the RBC solution, respectively, without dilution with saline.Conclusion: PAF-n can remove ammonia and potassium from RBC solution in small satellite packs. PAF-n could therefore improve the clinical prognosis of neonates with poorly developed BBB by limiting the delivery of excess ammonia found in the RBC solution. [ABSTRACT FROM AUTHOR]

Background: In the past, blood products were not transported to the Ogasawara Islands because of the distance; the islands are approximately 1000 km from the mainland and lack an airport. The Ogasawara Blood Rotation system involves the routine, long-distance transportation of Type O, RhD-positive, irradiated red blood cells to rescue patients with acute hemorrhage and severe anemia and to reduce wastage from the expiration of red blood cell solution.Study Design and Methods: Blood transfusion and utilization in the Ogasawara blood rotation (BR) system were examined from December 2014 to March 2017. Two packs of RBC solution (one pack = 280 mL) were transported in an active transport refrigerator by scheduled ships between Tokyo City and the Ogasawara Islands.Results: Eight packs of red blood cell (RBC) solution were received as transfusions by four patients who had acute upper gastrointestinal bleeding or severe anemia (eight of 232 packs; 3.4%). The blood utilization rate at the time of re-use was 84.6% (196 of 232 packs), with neither adverse reactions nor wastage. Twenty-eight packs of RBC solution expired because of a delay in scheduled ships as the result of a typhoon (12.1%).Conclusion: The Ogasawara BR system was effectively capable of delivering RBC solution for transfusion in patients residing in distant islands and contributed to reducing the wastage of RBC solution by facilitating blood utilization at another hospital. [ABSTRACT FROM AUTHOR]

Introduction: The high-frequency antigen Jr (a-) is most frequently detected in Japan, northern Europe, between Bedouins and Mexicans, and gypsies in the central region of Czechoslovakia. The finding of an antibody against this high frequency antigen during pregnancy does not always cause hemolytic disease of the newborn and when it appears it is of moderate intensity. Patients and method: We present 4 cases of anti-Jrª detection in gypsy pregnant women of different families with hemolytic disease of the newborn in one case. Results: The investigation of alloantibodies in pregnant women allowed the identification of an anti-Jrª antibody. One case required transfusion due to the appearance of moderate hemolytic disease and no newborn presented sequelae Conclusion: In the management of pregnant women Jr (a-) the availability of red blood cell concentrates Jr (a-) must be guaranteed. [ABSTRACT FROM AUTHOR]

Objective: Docosahexaenoic acid (DHA) is an important nutrient required by pregnant women and fetuses. Several studies suggest that fatty acid composition changes during pregnancy. However, the association of longitudinal changes in erythrocyte fatty acid composition and dietary fatty acid intake during pregnancy is not well understood. We assessed the relationship between fatty acid composition of the erythrocyte membranes and fatty acid intake at each trimester in pregnant Japanese women. Methods: We conducted a prospective hospital-based cohort study. We investigated fatty acid composition of the erythrocyte membranes and intake of fatty acids during the three trimesters in 178 healthy, pregnant Japanese women. Results: The eicosapentaenoic acid and arachidonic acid percentage of the erythrocyte membranes significantly decreased. The percentages of linoleic acid and α-linolenic acid significantly increased during pregnancy. The DHA percentage in the erythrocyte membranes decreased from the second to the third trimester. The DHA percentage in the erythrocyte membranes positively correlated with DHA intake in the third trimester. Conclusion: In pregnant Japanese women, the fatty acid composition of the erythrocyte membranes markedly changed throughout pregnancy. The DHA intake in the third trimester may be insufficient to maintain DHA percentage in the maternal erythrocyte membranes. [ABSTRACT FROM AUTHOR]

Oketsu is a characteristic condition that plays an important role in Kampo, Japanese traditional medicine, and includes multiple aspects of hemodynamic disorders. This study aims to clarify the microcirculation of Oketsu and the pharmacological effect of Keishibukuryogan, an anti-Oketsu Kampo prescription, using live imaging techniques. Oral administration of Keishibukuryogan induced significant vasodilation of murine subcutaneous arterioles compared to the preadministration level. This vasodilatation peaked 60 min after administration and persisted for 90 min. The blood velocity in the subcutaneous capillary was also increased by Keishibukuryogan in generally the same manner. In rat mesenteric arterioles, Keishibukuryogan administration improved microhemodynamic parameters, including the resolution of erythrocyte congestion and the cell-free layer, which are representative of Oketsu pathology. Live imaging revealed an increase of diaminofluorescein-2 diacetate fluorescence, a nitric oxide (NO) specific reagent, in the arterial endothelium following Keishibukuryogan administration. This fluorescence was most remarkable at vascular bifurcations but was present throughout the mesenteric arterioles. This study demonstrates the successful imaging of Oketsu pathology with respect to microcirculation and the anti-Oketsu effects of Keishibukuryogan, namely, vasodilation of arterioles, increased blood velocity, and resolution of erythrocyte congestion. The anti-Oketsu effect of Keishibukuryogan is related to endothelial NO production. [ABSTRACT FROM AUTHOR]

Aims: Alcohol consumption increases the risk of colorectal adenoma and cancer. The fecal immunochemical test (FIT) is a widely used screening method for detecting colorectal neoplasia. We evaluated the results of screening and risk factors for colorectal neoplasia in individuals with alcohol dependence. Methods: Total colonoscopic screening was performed for 1006 Japanese men with alcohol dependence (462 FIT-positive and 544 FIT-negative). Advanced neoplasia was defined as neoplasia >10 mm, villous or tubulovillous adenoma, high-grade adenoma, or carcinoma. Results: The detection rates for non-advanced adenoma, advanced neoplasia and intramucosal or invasive carcinoma were 38.7%, 39.4% and 9.7% for the FIT-positive group, and 33.3%, 10.8% and 2.2% for the FIT-negative group, respectively. Advanced neoplasia, especially carcinoma, was detected more frequently in the distal colon than in the proximal colon in the FIT-positive group. The respective multivariate odds ratios (ORs; 95% confidence interval) for non-advanced adenoma and advanced neoplasia were 2.83 (2.06-3.88) and 9.13 (6.19-13.5) for a positive FIT (vs. negative), 1.68 (1.39-2.02) and 1.83 (1.45-2.30) for age (per +10 years), 1.54 (1.06-2.23) and 1.88 (1.17-3.03) for current smoking (vs. non-smokers), and 1.35 (0.96-1.92) and 1.59 (1.02-2.48) for the presence of marked macrocytosis (mean corpuscular volume ≥106fl vs. <106fl). Genetic polymorphisms of alcohol dehydrogenase-1 B and aldehyde dehydrogenase-2 did not affect the risk of colorectal neoplasia. Conclusion: The detection rate for advanced colorectal neoplasia was extremely high in the FIT-positive group but remained high even in the FIT-negative group. An older age, smoking and macrocytosis were predictors of advanced colorectal neoplasia. Short summary: Total colonoscopic screening was performed for 1006 Japanese alcoholic men (462 fecal immunochemical test [FIT]-positive and 544 FIT-negative). The detection rate for advanced colorectal neoplasia was extremely high in the FIT-positive group (39.4%) and high in the FIT-negative group (10.8%). Ageing, smoking and macrocytosis were predictors of advanced colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Background: The Japan Association of Obstetricians and Gynecologists (JAOG) recommends transfusion with a fresh-frozen plasma (FFP):red blood cell (RBC) ratio of 1 or more in postpartum hemorrhage. However, no global consensus exists concerning this, and little is known regarding the impact of FFP:RBC ratio on maternal mortality. This study evaluates the efficacy of transfusion with FFP:RBC ratio of 1 or more for amniotic fluid embolism (AFE) with coagulopathy.Study Design and Methods: The Maternal Death Exploratory Committee, established by the JAOG, conducted this retrospective nationwide case-control study in Japan. Women with AFE and coagulopathy were included in the study and were stratified into survival and death groups. Obstetric variables and therapy methods (hysterectomy, uterine artery embolism, and transfusion with FFP:RBC ratio ≥ 1) were compared between the survival and death groups.Results: A total of 54 women had AFE and coagulopathy (death group, n = 22; survival group, n = 32). Only nine (40.9%) women in the death group were transfused with FFP:RBC ratio of 1 or more, whereas 29 (90.6%) women in the survival group were transfused with FFP:RBC ratio of 1 or more. FFP:RBC ratio of 1 or more was found to be associated with better survival rate (adjusted odds ratio, 28.32; 95% confidence interval, 4.26-188.37). No difference was found in obstetric variables, hysterectomy, and uterine artery embolism between survival and death groups.Conclusion: Transfusion with FFP:RBC ratio of 1 or more is associated with higher survival rate in women with AFE with coagulopathy. [ABSTRACT FROM AUTHOR]

Conclusion:Red cell distribution width (RDW) can predict outcome in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Further studies are required to clarify the potential pathophysiological explanations for these findings. Objectives:RDW is one of the parameters reported in a complete blood count, and is elevated in direct proportion to variation in red cell size (anisocytosis). High RDW values are strongly associated with poor clinical outcomes in various diseases, including inflammatory and thrombotic diseases. To identify a prognostic biomarker that better predicts outcomes after ISSNHL, the association between RDW values at hospitalization and prognosis in patients with ISSNHL was assessed. Method:This study measured RDW and performed hearing assessments in 89 consecutive patients with ISSNHL. Patients were then divided into two groups (‘recovered’ and ‘unrecovered’), according to their response to the treatment, and further analysis undertaken. Results:Mean RDW was significantly higher in the unrecovered group (13.2% ± 1.0% compared with 12.7% ± 0.7% in the recovered group,p = 0.031). After adjusting for potentially confounding factors in a binary logistic regression model, only RDW was associated with recovery from ISSNHL (odds ratio = 2.33, 95% confidence interval = 1.20–4.51,p = 0.012). [ABSTRACT FROM PUBLISHER]

Objective: The arachidonic acid (ARA) and docosahexaenoic acid (DHA) contents in the infant formula influence on the growth and development of low-birth-weight infants (LBWI). In Japan, many infant formulas are fortified only with DHA. We investigated the safety and efficacy of an infant formula (H2025A) fortified with DHA and ARA (DHA/ARA ratio of 2:1, the same as that in Japanese breast milk). Methods: In this randomized double-blind trial, 35 LBWI were randomly allocated to 2 groups fed with H2025A or an infant formula fortified only with DHA (control formula) after discharge from the NICU. The duration of this study was one month, and the growth and fatty acid composition of the erythrocyte membrane were compared between the 2 groups. Results: No difference was found in the body weight gain, height gain and head circumstance gain development between the 2 groups, and no adverse event occurred in both groups. The ARA content of the erythrocyte membrane after feeding for 1 month was significantly higher in the H2025A group than in the control group. On analysis adjusted with the breast-fed ratio, the ARA and DHA contents were significantly higher in the H2025A group. Conclusion: It was suggested that H2025A significantly increased the ARA and DHA contents of the erythrocyte membrane of LBWI compared to the contents of the control formula. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies. [ABSTRACT FROM AUTHOR]

The red blood cell distribution width (RDW) is a quantitative measure of the variability in the size of circulating erythrocytes. We aimed to study whether higher levels of the RDW were associated with heart failure in a Fontan circulation and to analyze its clinical value compared to brain natriuretic peptide. This retrospective study included 38 consecutive pediatric patients with a Fontan circulation who underwent routine cardiac catheterization at the International Medical Center, Saitama Medical University from October 2010 to July 2014. We assessed the relation between the RDW and catheterization data such as the central venous pressure (CVP), mixed venous oxygen saturation (SvO2), and cardiac index (CI). The RDW was positively correlated with the CVP (p = 0.0002). The elevated RDW group had a significantly greater CVP than the normal RDW group (p = 0.0003). Also, the RDW was negatively correlated with the SvO2 (p = 0.0004). The elevated RDW group had a significantly less SvO2 than the normal RDW group (p <0.0001). The CI in the elevated RDW group was lower than that in the normal RDW group (p = 0.0421). In the multivariate regression analysis, the RDW was a significant independent predictor of the CVP and SvO2. The BNP level did not have any significant relation with the CVP, SvO2, or CI. The RDW is a convenient and powerful marker for detecting heart failure in a Fontan circulation. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to investigate the long-term fertility prognosis after B- Lynch sutures for post-partum hemorrhage ( PPH). Methods A retrospective observational study was conducted on patients who underwent B- Lynch sutures in our hospital between 2005 and 2010. Patient data was collected from hospital records. Information regarding subsequent pregnancies and menstrual complications were obtained by posted questionnaires and telephone interviews with patients who avoided hysterectomy. Results A total of 28 B- Lynch sutures were performed in 3976 deliveries, all in patients that underwent cesarean section. Twenty-two of the 26 patients who avoided hysterectomy answered our questionnaire or took part in an interview. All patients recovered regular menstruation with no severe complications. Of the 19 patients who wanted another child, 12 patients (63.2%) had 14 subsequent pregnancies in a mean follow-up period of 52.1 months. The results of pregnancies were nine uncomplicated term pregnancies, all delivered by elective cesarean section, two artificial abortions and three miscarriages. A significant difference was observed in the age of patients with subsequent pregnancies and those without pregnancies (30.8 vs 34.6 years, P = 0.04). Conclusion B- Lynch sutures for PPH do not appear to jeopardize fecundity. An older age was a risk factor for achieving subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Background: The criterion for performing a renal biopsy in children with idiopathic nephrotic syndrome (NS) showing microscopic hematuria at onset remains controversial. Methods: To determine an adequate renal biopsy criterion in children with NS showing hematuria, the optimal cutoff for the maximum red blood cell (RBC) range in urine sediment to separate minimal change disease (MCD) from other glomerular changes was obtained by receiver operating characteristic analysis. We studied 29 children with NS showing hematuria who were screened from 1,320 patients who underwent renal biopsies between January 2001 and September 2011. Patients were divided into two groups according to the cutoff value to verify its validity. Results: The optimal maximum RBC range was 30-49/high-power field (HPF). In group 1 (RBC ≤29/HPF, n = 14), 3 patients showed nephritis and the other 11 patients showed MCD. In group 2 (RBC ≥30/HPF, n = 15), 1 patient showed focal segmental glomerulosclerosis, 12 showed nephritis, and the other 2 showed MCD. These findings indicated that the ratio of non-MCD/MCD was significantly higher in group 2 than in group 1 ( P < 0.01). Conclusions: The use of maximum RBC range (30-49/HPF) for a criterion of renal biopsy in patients with NS showing hematuria may be reasonable for clinical practice. [ABSTRACT FROM AUTHOR]

Blood stasis syndrome is one of the pathological concepts of Oriental traditional medicine. In Oriental traditional medicine, blood is thought of as not only blood but also as a living component of the body. In fact, blood stasis syndrome is related to not just circulation disorders but dermatological and gynecological and other diseases. In Japan, the concept of blood stasis syndrome is based on the past literature, for instance, Synopsis of Golden Chamber (Jin Kui Yao Lue), etc. There are many signs of this syndrome, such as a dry mouth, fullness of the abdomen and rough skin. However, the levels of importance of these signs had been unclear. Therefore, in order to determine the levels of seriousness, a scoring system of blood stasis syndrome was made based on multivariate analysis by Dr. Terasawa (Terasawa's Blood Stasis Score). Using the scoring system, we have studied blood stasis syndrome mainly related to blood circulation using modern techniques of analysis. From the results, we found that patients with blood stasis syndrome showed hemorheological abnormalities, and an improvement in these abnormalities was shown after administration of removing-blood stasis formulae. Furthermore, we have studied blood stasis syndrome from the point of view of molecular biology. We searched for the specific protein expression in blood stasis syndrome by proteomic analysis, and found no specific protein expression. However, there may be a possibility of developing a diagnostic algorithm for blood stasis by construction of a decision tree. During the past few years, as one of the molecular biological factors affecting blood stasis syndrome, we have been studying hypoxia inducible factor, which is located in the upstream of many genes. Above all, blood stasis syndrome is more than just circulatory deficit but encompasses the pathological concept of constant multilateral change in the living body. [ABSTRACT FROM AUTHOR]

Background Oxidation of ethanol by alcohol dehydrogenase ( ADH) generates acetaldehyde (AcH), which is converted to acetate by aldehyde dehydrogenase-2 ( ALDH2). Roughly 40% of East Asians are ALDH2-deficient due to an inactive enzyme encoded by the ALDH2*2 allele. ALDH2-deficient individuals have a dramatically elevated risk of esophageal cancer from alcohol consumption. Methods We investigated the relationship between ALDH2*2, ADH1 B*2 (encoding a highly active ADH) and erythrocyte abnormalities, in a population of Japanese alcoholic men ( N = 1,238). Results Macrocytosis ( mean corpuscular volume [MCV] ≥100 fl) and macrocytic anemia ( MCV ≥100 fl and hemoglobin <13.5 g/dl) were found in 62.4 and 24.1% of the subjects, respectively. Age-adjusted daily alcohol consumption did not differ according to ADH1 B and ALDH2 genotypes. However, macrocytosis and macrocytic anemia were strongly associated with the ALDH2*1/*2 genotype multivariate odds ratios ( ORs; 95% confidence interval [CI] = 2.85 [1.95 to 4.18] and 3.68 [2.64 to 5.15], respectively, versus ALDH2*1/*1). In comparison with the ADH1 B*1/*1 and ALDH2*1/*1 genotype combination, the ADH1 B*1/*1 and ALDH2*1/*2 genotype combination and the ADH1 B*2 allele and ALDH2*1/*2 genotype combination increased stepwise the ORs (95% CI) for macrocytosis (1.65 [0.92 to 2.94] and 4.07 [2.33 to 7.11], respectively, p for difference in OR = 0.015) and macrocytic anemia (2.80 [1.52 to 5.15] and 5.32 [3.29 to 8.62], respectively, p for difference in OR = 0.045). Genotype effects were more prominent on the risks of the more advanced erythrocyte abnormalities. Older age, cigarette smoking, and low body mass index independently increased the risks of the erythrocyte abnormalities. Consumption of beer, which contains folate, decreased the risks, whereas consumption of alcoholic beverages lacking folate did not. Conclusions These results suggest that the erythrocyte abnormalities in alcoholics are attributable to high AcH exposure as well as to nutritional deficiencies and may be prevented by folate. [ABSTRACT FROM AUTHOR]

Alloimmunization to K11 is an extremely rare event. However, given the potential clinical significance of K11 alloantibodies, allocating antigen-negative red blood cell (RBC) units is a clinical necessity. In brief, we report a 39-year-old woman with multiple comorbidities including a right lower-extremity, below-the-knee amputation, who developed aggressive osteomyelitis associated with continuous bloody oozing, leading to anemia. To address these issues, the patient required extremity amputation. Surgery required addressing the concomitant critical anemia (hemoglobin <5 g/dL). However, with anti-K11 (in addition to anti-Jk a ) identified, no compatible units were immediately on hand and transfusing crossmatch-incompatible, antigen-positive units was deemed too high a risk. After a national search by the American Rare Donor Program (ARDP) was unsuccessful, the ARDP identified 2 irradiated, group O, K 0 (Kell null ), Jk(a-) RBC units in Japan that were predicted to be crossmatch-compatible with the patient's plasma. The units were successfully procured and infused, without evidence of adverse reactions, and the patient was able to safely undergo amputation to save her life. This case report reviews the complexities of anti-K11 detection and confirmation, as well as the processes by which K11- RBC units may be procured, which could help others in the global transfusion community should they be faced with similar challenging cases., (© 2022 J.V. Rodriguez et al., published by Sciendo.)