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Background: The sharp increase in fungal infections, insufficient diagnostic and treatment capabilities for fungal infections, poor prognosis of patients with fungal infections as well as the increasing drug resistance of fungi are serious clinical problems. It is necessary to explore the implementation and evaluation methods of antifungal stewardship (AFS) to promote the standardized use of antifungal drugs. Methods: The AFS programme was implemented at a tertiary first-class hospital in China using a plan-do-check-act (PDCA) quality management tool. A baseline investigation was carried out to determine the utilization of antifungal drugs in pilot hospitals, analyse the existing problems and causes, and propose corresponding solutions. The AFS programme was proposed and implemented beginning in 2021, and included various aspects, such as team building, establishment of regulations, information construction, prescription review and professional training. The management effectiveness was recorded from multiple perspectives, such as the consumption of antifungal drugs, the microbial inspection rate of clinical specimens, and the proportion of rational prescriptions. The PDCA management concept was used for continuous improvement to achieve closed-loop management. Results: In the first year after the implementation of the AFS programme, the consumption cost, use intensity and utilization rate of antifungal drugs decreased significantly (P < 0.01). The proportion of rational antifungal drug prescriptions markedly increased, with the proportion of prescriptions with indications increasing from 86.4% in 2019 to 97.0% in 2022, and the proportion of prescriptions with appropriate usage and dosage increased from 51.9 to 87.1%. In addition, after the implementation of the AFS programme, physicians' awareness of the need to complete microbial examinations improved, and the number of fungal cultures and serological examinations increased substantially. Statistics from drug susceptibility tests revealed a decrease in the resistance rate of Candida to fluconazole. Conclusion: This study indicated that the combination of AFS and the PDCA cycle could effectively reduce antifungal consumption and promote the rational use of antifungal drugs, providing a reference for other health care systems to reduce the overuse of antifungal drugs and delay the progression of fungal resistance. [ABSTRACT FROM AUTHOR]

Financial toxicity during cancer survival has been studied mainly in the United States; 47-49% of cancer survivors reported financial hardships and 12-63% reported debt owing to treatment costs. Financial toxicity is influenced by each country's economic status and healthcare system. We aimed to review the evidence on financial toxicity in Japan. A systematic search was performed using PubMed and Ichushi databases. We included English or Japanese peer-reviewed articles that (1) explored the experiences of cancer patients facing financial toxicity due to cancer diagnosis and treatment, (2) were specific to Japan, and (3) focused on the experiences of financial toxicities among cancer patients. Data were extracted focusing on the experiences of patients, families, and healthcare providers. The main themes were synthesized based on a previous study. The search yielded 632 citations from PubMed and 21 from Ichushi, and non-duplicates were identified. Of these, 31 articles were selected for full-text review. Literature was divided into studies describing the following elements: (a) risk factors for financial toxicity, (b) description of financial toxicity, (c) psychological reactions, (d) coping strategies for financial toxicity, and (e) impact on treatment outcomes. Only three studies reported comprehensive financial toxicity scores. Furthermore, treatment costs influenced physicians' treatment decisions, and patients and their families adopted various strategies to cope with treatment costs. Two studies showed that low current income and younger age were high-risk factors. As for utilization of the support system, approximately 70% of the patients used the high-cost medical expense system, 20% used the sickness benefit system, and 40% used the medical expense deduction system. Many cancer patients in Japan suffer from financial toxicity during cancer survival. One reason for this is that the awareness of the system supporting financial toxicity is insufficient and actual utilization is low. It is necessary to actively encourage patients to ask healthcare providers questions, improve the link between patients and the support system, reconstruct the support system design, and improve the method of publicizing the system. [ABSTRACT FROM AUTHOR]

Reduced-intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non-Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced-dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low-dose melphalan (80 or 100 mg/m 2 ; Flu/Mel80-100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end-point was the 5-year overall survival (OS). The 5-year OS was 53.8% (95% CI, 47.6-59.6) and 42.4% (95% CI, 35.6-49.0) in the Flu/Bu2 and Flu/Mel80-100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80-100 group for 5-year OS was 0.77 (95% CI, 0.60-0.99, p = 0.046), 0.97 (95% CI, 0.78-1.21, p = 0.798) for 5-year progression-free survival, 0.65 (95% CI, 0.45-0.94, p = 0.022) for 5-year cumulative risk of non-relapse mortality and 1.25 (95% CI, 0.95-1.64, p = 0.115) for 5-year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non-relapse mortality than those who received Flu/Mel80-100., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background and Objectives: A more restrictive blood donation criterion has been applied in Japan, with a maximum volume of whole blood (WB) donation of 400 mL, allowing twice a year for female donors and thrice a year for male donors. However, iron deficiency was as high as 20.5% among female donors prior to donation, increasing to 37.7% after blood donation. More than 20 years have passed since then, so we set out to investigate the present situation., Materials and Methods: A total of 2659 (male/female: 1496/1163) donors of 400 mL WB who gave informed consent to join the study were enrolled. Serum ferritin (sFer) of first-time/reactivated (FT/RA) donors were compared with those of repeat donors, according to gender and age; those who returned for subsequent donations during the study period were also followed up., Results: About one-third of FT/RA female donors had iron deficiency, possibly reflecting its high incidence among the general population. Interestingly, although sFer levels were low among pre-menopausal FT/RA female donors, these values were not much different in repeat donors, whereas significant differences were observed between FT/RA and repeat donors among post-menopausal females and in most age groups among males. As expected, donors with a normal initial sFer (≥26 ng/mL) recovered faster than those with a low initial sFer., Conclusion: Female donors, especially, have iron deficiency even before donation, and the rate increased compared to what was found previously. Measures to prevent iron deficiency of blood donors is required, and studies are going on in Japan., (© 2024 International Society of Blood Transfusion.)

This article examines Japan's COVID-19 medication policy, specifically focusing on three approved oral drugs: molnupiravir, nirmatrelvir, and ensitrelvir. The study suggests that there may be a bias favoring domestic drugs, potentially influenced by politics rather than patient health. The article highlights the importance of regulatory processes based on international cooperation and scientific evidence. It also raises concerns about the effectiveness and safety of certain drugs, particularly ensitrelvir, which was widely prescribed despite unclear effectiveness and controversial clinical trial protocols. The article emphasizes the need to prioritize patient health over nationalistic priorities and to critically review drug approval and regulatory processes. [Extracted from the article]

Purpose: This study compares doctor staffing level and the scale of medical education in China with those of other countries and proposes policy recommendations for future adjustments to the scale of China's medical education. Design/Approach/Methods: This study employs a literature review and descriptive analysis. Findings: China had 1.98 medical doctors per 1,000 people in 2018, ranking 85th out of the 193 member-states of the World Health Organization (WHO). In 2017, China had 1.99 practicing doctors per 1,000 people, only ranking above Turkey (1.88) in Organisation for Economic Co-operation and Development (OECD) countries. China had only 10.28 medical graduates per 100,000 people--placing in the bottom third of OECD countries. China's provision of 1.4 medical schools per 10 million people was also significantly lower than the global average (3.9). However, the average number of students enrolled in medical schools (509) in China was significantly higher than the global average (160). Originality/Value: Although the scale of admission in undergraduate medical education must be expanded in China, this needs to be achieved while controlling the average number of medical students per school and reducing enrollment in low-quality medical schools. Furthermore, it is necessary to establish new medical schools while improving the operating level of existing ones. [ABSTRACT FROM AUTHOR]

We evaluated 413 adult patients with lymphoma who underwent unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning between 2002 and 2017 to investigate longitudinal changes in outcomes and the optimal melphalan dose and graft-versus-host disease (GVHD) prophylaxis regimen. Outcomes were compared between FM80/100 (melphalan dose: 80 or 100 mg/m2) and FM140 (melphalan dose: 140 mg/m2), as well as between calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved over time (OS: 27% in 2000s vs. 42% in 2010s, p < 0.001; NRM: 43% in 2000s vs. 26% in 2010s, p < 0.001). Multivariable analysis showed that in the 2000s, melphalan dose and GVHD prophylaxis regimen did not affect any outcomes. In the 2010s, FM80/100 (vs. FM140) related to better OS (hazard ratio [HR] 0.62, p = 0.01) and NRM (HR 0.52, p = 0.016). MTX + CNI and CNI alone (vs. CNI + MMF) related to worse OS (CNI + MTX, HR 2.01, p < 0.001; CNI alone, HR 2.65, p < 0.001) and relapse/progression (CNI + MTX, HR 2.40, p < 0.001; CNI alone, HR 2.13, p = 0.023). In recent years, the use of FM80/100 and CNI + MMF significantly reduced the risk of NRM and relapse/progression, respectively, and resulted in better OS after UCBT for lymphoma. [ABSTRACT FROM AUTHOR]

The present study aimed to clarify the characteristics of young evacuees who had missed the Comprehensive Health Check of the Fukushima Health Management Survey (FHMS) after the Great East Japan Earthquake in 2011. The FHMS has been conducted as a prospective cohort study to evaluate the health status of evacuees annually after the great earthquake in 2011. This study focused on the annual participation rate in the Comprehensive Health Check of evacuees aged between 20 and 37 years in 2011 who evacuated due to the Fukushima Daiichi Nuclear Power Plant accident. The characteristics of subjects who did not participate after the second survey year were identified with a multivariate logistic regression model. The participation rate was estimated at 26.6% (9720 among 36,502 residents) and 15.6% (5691 residents) in 2011 and 2012, respectively. The logistic regression model revealed the following characteristics at baseline as independent predictors of non-participation after the second year of the survey: age ≤ 24 years (adjusted odds ratio 2.11, 95% CI 1.84–2.42), 25–29 years of age (1.28, 1.13–1.45), men (1.52, 1.38–1.69), evacuation outside the municipality but within Fukushima prefecture (1.54, 1.40–1.70), evacuation outside the Fukushima prefecture (1.40, 1.21–1.63), anemia (1.23, 1.06–1.43), smoking habit (1.34, 1.21–1.48), and drinking habit (1.20, 1.09–1.32). A medical history of heart disease showed opposite odds ratios, which indicate the association with continuous participation (0.43, 0.26–0.72, respectively). We observed deteriorated participation in the prospective study of the Comprehensive Health Check of the FHMS among evacuees of a younger age group, men, those evacuated outside their municipalities, and those with history of anemia, smoking and drinking habits. Hence, the cohort study may have missed certain population groups with worse health behaviors. Thus, it is necessary to consider various measures to increase the participation rate in the disaster cohort study to understand the long-term health effects of disasters on younger residents in evacuation zones. [ABSTRACT FROM AUTHOR]

BACKGROUND: Drawing blood from the fingertips for glucose testing is painful and likely to cause tissue damage over time. Earlobes are an alternative site for glucose measurement. OBJECTIVE: This work aims to validate the earlobe as an alternate test site for blood glucose testing by demonstrating valid and reliable statistically significant differences between the earlobes and standard reference sites. METHODS: Blood glucose concentrations from 50 volunteers were measured and statistically analysed from the reference sites (forearm and fingertip) and earlobe. The analysis included: 1) one-way analysis of variance (ANOVA), 2) regression analysis, 3) Bland Altman analysis, and 4) Clarke Error Grid analysis. RESULTS: The results indicated that there is no statistically significant difference between the three blood glucose-testing methods. For the forearm-earlobe and fingertip-earlobe, all measurements were grouped around the mean of 3.7 ± 1.96 SD and 2.96± 1.96 SD, respectively. Error grid analysis showed > 97% of all earlobe and references measurements fell in Zones A and B and were in the clinically acceptable level. CONCLUSIONS: The results have shown that the earlobe is a valid substitute for blood glucose measurements. [ABSTRACT FROM AUTHOR]

A cancer diagnosis can have significant financial impacts for patients, often resulting from unexpected out‐of‐pocket expenses and a reduced capacity to work. These financial implications have been well characterised quantitatively in common cancers. However, less is known about the lived experience of financial stress, particularly outside the United States and in rarer cancers. This study aimed to explore the perceived financial impact of acute myeloid leukaemia (AML)—a rare haematological malignancy where patients may be particularly vulnerable to financial stress due to the lengthy, specialised and centralised care. The findings provide insight into the patients' lived experience of the personal financial impact of the disease. This Australian qualitative study was undertaken with 11 adults in remission from AML and recruited from their treating hospital. Semi‐structured interviews were transcribed, and data were managed using NVivo. Themes were identified through inductive and deductive analysis using open, axial and thematic coding. Four themes were identified: burden of AML‐attributable costs (e.g. out‐of‐pocket parking and medication expenses); accommodating the AML‐impact on paid work (e.g. early retirement and modifying job tasks); the consequence of financial strain from AML (e.g. using savings and accessing Government welfare) and concerns about the future and future familial financial burden (e.g. securing finances and worry about depleting financial resources). A reduction in or stopping work was perceived as the most burdensome to their current and future finances. The findings demonstrate people with AML experience financial difficulty even within a publically funded healthcare system. Opportunities exist for health services to alleviate some financial burden through reducing or abolishing parking fees for oncology patients and ensuring adequate access to social workers to facilitate access to Government welfare. Improving patients' financial difficulties contributes to improved quality of life, which is congruent to cancer survivorship. [ABSTRACT FROM AUTHOR]

Objectives: To survey the utilization of social media (SoMe) in patients with urological disease and their families., Methods: Among the panel members registered in NEO Marketing Inc. (Tokyo, Japan), 300 people who or whose families were visiting the urological department regularly were included. Study subjects were randomly chosen and surveyed using the questionnaire over the internet., Results: This study included 203 (68%) males and 97 (32%) females. The mean age was 62 (21-85) in males and 49 (22-75) in females. One hundred and ten subjects (37%) had no account for any SoMe. The account holders of YouTube, Twitter, Facebook, Instagram, and TikTok were 119 (40%), 117 (39%), 101 (34%), 90 (30%), and 33 (11%), respectively. The proportions of account holders were different depending on gender, age, and platforms. Frequent viewers on YouTube, Twitter, Facebook, Instagram, and TikTok were 100 (84%), 89 (76%), 63 (62%), 66 (73%), and 24 (73%), respectively. Of 190 who had accounts for any SoMes, 64 (34%) found any information about urological diseases of themselves or their families. Among the all subjects, 162 (54%) thought that they would like to view the medical contents on SoMes submitted by medical societies., Conclusions: Patients with urological disease and their families in Japan occasionally utilize SoMe to obtain information on their diseases and prefer professional medical information on SoMe. The gender and age of SoMe users and the optimal platform should be considered when posting medical information on SoMe., (© 2023 The Japanese Urological Association.)

Iron-deficiency-induced anemia is associated with poor neurological development, including decreased learning ability, altered motor functions, and numerous pathologies. Siderophores are iron chelators with low molecular weight secreted by microorganisms. The proposed catechol-type pathway was identified based on whole-genome sequences and bioinformatics tools. The intended pathway consists of five genes involved in the biosynthesis process. Therefore, the isolated catechol-type siderophore (Sid) from Streptomyces tricolor HM10 was evaluated through an anemia-induced rat model to study its potential to accelerate recovery from anemia. Rats were subjected to an iron-deficient diet (IDD) for 42 days. Anemic rats (ARs) were then divided into six groups, and normal rats (NRs) fed a standard diet (SD) were used as a positive control group. For the recovery experiment, ARs were treated as a group I; fed an IDD (AR), group II; fed an SD (AR + SD), group III, and IV, fed an SD with an intraperitoneal injection of 1 μg Sid Kg−1 (AR + SD + Sid1) and 5 μg Sid Kg−1 (AR + SD + Sid5) twice per week. Group V and VI were fed an iron-enriched diet (IED) with an intraperitoneal injection of 1 μg Sid Kg−1 (AR + IED + Sid1) and 5 μg Sid Kg−1 (AR + IED + Sid5) twice per week, respectively. Weight gain, food intake, food efficiency ratio, organ weight, liver iron concentration (LIC) and plasma (PIC), and hematological parameters were investigated. The results showed that ~50–60 mg Sid L−1 medium could be producible, providing ~25–30 mg L−1 purified Sid under optimal conditions. Remarkably, the AR group fed an SD with 5 μg Sid Kg−1 showed the highest weight gain. The highest feed efficiency was observed in the AR + SD + Sid5 group, which did not significantly differ from the SD group. Liver, kidneys, and spleen weight indicated that diet and Sid concentration were related to weight recovery in a dose-dependent manner. Liver iron concentration (LIC) in the AR + IED + Sid1 and AR + IED + Sid5 groups was considerably higher than in the AR + SD + Sid1 AR + SD + Sid5 groups or the AR + SD group compared to the AR group. All hematological parameters in the treated groups were significantly closely attenuated to SD groups after 28 days, confirming the efficiency of the anemia recovery treatments. Significant increases were obtained in the AR + SD + Sid5 and AR + IED + Sid5 groups on day 14 and day 28 compared to the values for the AR + SD + Sid1 and AR + IED + Sid1 groups. The transferrin saturation % (TSAT) and ferritin concentration (FC) were significantly increased with time progression in the treated groups associatively with PIC. In comparison, the highest significant increases were noticed in ARs fed IEDs with 5 μg Kg−1 Sid on days 14 and 28. In conclusion, this study indicated that Sid derived from S. tricolor HM10 could be a practical and feasible iron-nutritive fortifier when treating iron-deficiency-induced anemia (IDA). Further investigation focusing on its mechanism and kinetics is needed. [ABSTRACT FROM AUTHOR]

Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein–Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA. Prognostication can be based on presentation parameters (age, stage, lymph node involvement, clinical subtypes, and EBV DNA), which represent patient factors and lymphoma load; and dynamic parameters during treatment (serial plasma EBV DNA and interim/end-of-treatment PET/CT), which reflect response to therapy. Therapeutic goals are to achieve undetectable plasma EBV DNA and normal PET/CT (Deauville score ≤ 3). NK/T-cell lymphomas express the multidrug resistance phenotype, rendering anthracycline-containing regimens ineffective. Stage I/II nasal cases are treated with non-anthracycline asparaginase-based regimens plus sequential/concurrent radiotherapy. Stage III/IV nasal, and non-nasal and aggressive leukaemia/lymphoma cases are treated with asparaginase-containing regimens and consolidated by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable patients. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment. [ABSTRACT FROM AUTHOR]

Autoimmune disease (AD) may occur after allogeneic hematopoietic stem cell transplantation (HSCT). The autoimmune mechanism seems to be related to an imbalance of the immune regulation effect of T-regulatory lymphocytes on autoreactive T-lymphocytes. ADs include hematological ADs (HADs) and nonhematologic ADs (NHADs) involving organs such as thyroid, peripheral and central nervous system, skin, liver, connective tissue, gastrointestinal tract, and kidney. To identify the risk factors for ADs, to report their clinical characteristics, and to discuss new approaches represent the areas covered in this review. Some risk factors for HAD and NHAD are common and include nonmalignant diseases, young age, cord blood as a stem cell source, conditioning regimens without total body irradiation, alemtuzumab, antithymocyte globulin, T-cell-depleted transplant, some viral infection, mixed chimerism, and chronic Graft versus Host Disease. In NHADs, the detection of autoantibodies is more frequent and the transfer of autoimmunity from the donor to the recipient represents the pathogenetic mechanism responsible for these complications. New therapeutic approaches such as bortezomib, daratumumab, sirolimus, eculizumab, and eltrombopag appear to be promising in terms of better efficacy and reduced toxicity compared to traditional therapies. New horizons based on personalized therapies will allow us to improve the prognosis of AD. [ABSTRACT FROM AUTHOR]

We report a case of donor-derived leukemia (DDL) occurring 34 months after double-unit cord blood transplantation (CBT). Molecular analysis using short tandem repeat (STR) sequences proved the acute myeloid leukemia (AML) to be of dominant cord blood origin. Karyotype was normal and molecular analysis showed WT1 and EVI1 overexpression. Cytological and molecular remission were achieved with only induction and consolidation chemotherapy. Relapse occurred after 6 years of remission from one clone with only WT1 overexpression. Potential etiologies for donor cell leukemogenesis in the recipient are discussed, including occult leukemia in the donor or genetic predisposition to hematologic malignancies, impaired immune surveillance, induced or inherited stromal abnormalities, transformation of donor cells during engraftment via altered signals of the host tissues, and fusion of donor cells with residual leukemic cells leading to acquisition of oncogenes. Although cases of DDL occurring after umbilical CBT have already been reported, very few cases have been described arising after double-unit CBT. DDL cases following CBT previously described in the literature have been reviewed. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is the third most common cancer worldwide, with high mortality rates. The programmed cell death 1 (PD-1)/(PD-1 ligand) PD-L1 has been reported to be an effective indicator in cancer development. In this study, we aim to explore the role of PD-1/PD-L1 in the evaluation of concurrent chemoradiotherapy (CCRT) efficacy and prognosis in CC patients. Methods: We included 55 CC patients in this study. Immunohistochemistry and flow cytometry were employed to detect the expression of PD-1, Treg cells, CD8, and CD68 in tumor tissues, and the contents of PD-1+ CD8+ T cells, PD-1+ CD4+ T cells, and PD-1+ Treg cells in the peripheral blood. The relationships of these indexes with CCRT efficacy were measured by Spearman correlation analysis, overall survival (OS), and disease-free survival (DFS) of patients were analyzed by Kaplan–Meier estimator, and the diagnostic values of these indexes in CC were assessed by a receiver operating characteristic (ROC) curve. Results: The clinical effectivity rate of CCRT was 89.10%. The positive expressions of PD-L1, Treg cells, PD-1+ CD8+ T cells, PD-1+ CD4+ T cells, and PD-1+ Treg cells were reduced after CCRT, while the CD8 and CD68 increased. All 7 indexes had diagnostic values in evaluating CCRT efficacy and were considered the influencing factors of OS, DFS, and the prognosis of CC patients. Conclusion: These findings indicate that PD-1/PD-L1 may be a potential indicator for the efficacy evaluation of CCRT and the prognosis of CC. This study may offer potential targets for CC treatment. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess whether longer indwelling time of peripherally inserted central catheters (PICC) increases risk of central line associated bloodstream infections (CLABSI) in haematology patients. Methods: Multicentre retrospective cohort study among haematology patients receiving PICCs between 2013 and 2015. Occurrence of CLABSI based on CDC definitions was assessed. We calculated incidence rates, determined risk factors for CLABSI and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time. We compared diagnoses and treatment characteristics between 2013–2015 and 2015–2020. Results: 455 PICCs placed in 370 patients were included, comprising 19,063 catheter days. Median indwelling time was 26 days (range 0–385) and CLABSI incidence was 4.0 per 1000 catheter days, with a median time to CLABSI of 33 days (range 18–158). Aplastic anaemia (AA) was associated with an increased risk of CLABSI; patients undergoing autologous stem cell transplantation (SCT) were less likely to develop CLABSI. In the unadjusted analysis, PICCs with an indwelling time of 15–28 days, 29–42 days, 43–56 days and > 56 days each had an increased CLABSI incidence rate ratio of 2.4 (1.2–4.8), 2.2 (0.95–5.0), 3.4 (1.6–7.5) and 1.7 (0.9–3.5), respectively, compared to PICCs in place for < 15 days. However, after adjusting for AA and SCT, there was no significant difference in incidence rates between dwell times (p 0.067). Conclusions: Our study shows that risk of CLABSI does not appear to increase with longer PICC indwelling time. Routine replacement of PICCs therefore is unlikely to prevent CLABSI in this population. [ABSTRACT FROM AUTHOR]

Background: Although several epigenetic drugs have been reported to have therapeutic efficacy for some hematologic neoplasms (HNs) in clinical trials, few achieved disease-free survival benefit. The traditional drug discovery pathway is costly and time-consuming, and thus, more effective strategies are required. We attempted to facilitate epigenetic drug repositioning for therapy of HNs by screening the Human Epigenetic Drug Database (HEDD) in the web, conducting a bench-work cytotoxicity test and a retrospective nationwide cohort study prior to a clinical trial. Methods: Four FDA-approved epigenetic drugs with antitumor properties and completion of clinical phase II trials were selected from HEDD. Hydralazine (HDZ) and valproate (VAL) among the four were selected with higher cytotoxicity to HN cells, no matter whether carrying the JAK2V617F mutation or not. Both of them were chosen for a cohort study using the Longitudinal Health Insurance Database (LHID) 2000–2015 (N = 1,936,512), a subset of the National Health Insurance Research Database (NHIRD, N= 25.68 millions) in Taiwan. Results: In the initial cohort, HDZ or VAL exposure subjects (11,049) and matching reference subjects (44,196) were enrolled according to maximal daily consumption (300/2,100 mg per day of HDZ/VAL). The HN incidence in HDZ and VAL exposure groups reduced from 4.97% to 3.90% (p <.001) and 4.45% (p =.075), respectively. A further cohort study on HDZ at a lower range of the WHO defined daily dose (<34 mg per day) and HN incidence of HDZ exposure subjects (75,612) reduced from 5.01% to 4.16% (p = 1.725 × 10 -18) compared to the reference subjects (302,448). Conclusions: An association of a chronically prescribed HDZ, even prescribed low dose, with reduction of overall incidence rate and in most subgroups of HN was observed in our study. Repositioning HDZ for HN management may be feasible. This is the first nationwide cohort study of the epigenetics-associated risk evaluation of overall HN in the existing literature, showing an effective method with a wider scope to inform contemporary clinical trials of epigenetic drugs in the future. [ABSTRACT FROM AUTHOR]

Fludarabine with intravenous busulfan (6.4 mg/kg; FB2) and fludarabine with intermediate-dose melphalan (140 mg/m2; FM140) are the most widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation. FM140 generally has a lower relapse rate and higher non-relapse mortality (NRM), resulting in overall survival (OS) comparable to that seen with FB2. To evaluate the effect of reducing the melphalan dose, we retrospectively compared transplant outcomes in 156 patients who received FB2 (n = 103) or FM80 (n = 53) at our center (median age: 63 years; range 27–72 years). All patients received 4-Gy total body irradiation. Three-year OS, the cumulative incidence of relapse, and NRM were comparable between groups (FB2 vs. FM80, 58% vs. 47%, p = 0.24; 30% vs. 36%, p = 0.57; 17% vs. 21%, p = 0.44, respectively). There was no significant difference in the cumulative incidence of graft-versus-host disease (GVHD) at day 100, chronic GVHD at 3 years, or the 3-year GVHD-free/relapse-free survival rate. In the high-risk disease group, patients receiving FM80 tended to have lower 3-year OS (FB2 vs. FM80, 48% vs. 17%, p = 0.06). In summary, transplant outcomes following FB2 or FM80 were comparable except in patients with high-risk disease. [ABSTRACT FROM AUTHOR]

Background: Large numbers of patients with diseases preventable by voluntary vaccines have been reported in Japan. However, it is difficult to analyze the impact of voluntary vaccination on disease prevention, as governments do not aggregate the number of recipients of vaccines that are not included in the national immunization program. This study investigated the association between the coverage rates of two voluntary vaccines (rotavirus and mumps vaccines) and the incidence of the diseases preventable by these vaccines. Methods: We performed a prospective questionnaire‐based observational study to investigate the presumptive coverage rates of the rotavirus vaccine in infancy and the mumps vaccine at 1 year of age in Kitakyushu City from 2015 to 2018. The number of children admitted to a secondary medical institution for rotavirus‐associated gastroenteritis and the incidence of mumps infection in sentinel medical institutions were also analyzed during the investigation period. Results: The rotavirus and mumps vaccine coverage rates since 2016 were 61‐63% and late 28‐30%, respectively (52.6% and 20.3% in 2015, respectively). The yearly number of children hospitalized for rotavirus‐associated gastroenteritis from 2015 to 2018 declined by 41.4% compared with that during the pre‐vaccination period (2009–2011). The incidence of mumps infection remained unchanged during the investigation period. Conclusion: The coverage rates of two voluntary vaccines were not high enough to control the infections. The incorporation of voluntary vaccines into the routine immunization program should be considered as the one of the effective ways to increase vaccination coverage. [ABSTRACT FROM AUTHOR]

The article discusses Japan's emergency approval system for drugs and vaccines during the COVID-19 pandemic. Previously, pharmaceutical companies in Japan could only import approved drugs from overseas, but a new emergency approval system was implemented in May 2022 to encourage domestic production. The first domestically produced oral COVID-19 medication, ensitrelvir fumaric acid (Xocoba), was granted emergency approval in November. However, there are concerns about the limited clinical data and the government's contract with the manufacturer before approval. The article questions whether Japan's regulatory policy prioritizes citizens' health or domestic company profits and suggests a need for evidence-based regulatory science. [Extracted from the article]

We investigated whether maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status increases the risk for long-term oncologic morbidity of their offspring up to the age of 18 years. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical center. Our study included: HBV carriers (n = 588), HCV carriers (n = 183) and non-carriers (n = 241,570. No significant differences regarding oncologic morbidity were found between offspring of HBV carriers (0.2%), HCV carriers (0%) and non-carriers (0.6%; p = 0.216, respectively). To conclude: maternal HBV or HCV carrier status is not a risk factor for long-term oncologic morbidity of the offspring. [ABSTRACT FROM AUTHOR]

We estimate elastic and anelastic parameters and their evolution during laboratory rock deformation experiments, while developing a Monte Carlo waveform inversion. The transducer‐to‐transducer one‐source one‐station active seismic data of dry and water‐saturated samples are obtained from Zaima and Katayama (2018), https://doi.org/10.1029/2018JB016377. We first performed a trial‐and‐error estimate of the boundary conditions in order to suppress its influence on waveforms. The synthetic seismic data were generated using equivalent homogeneous models with different combinations of elastic and anelastic parameters with the aid of spectral element method. We compared them with the laboratory experimental data. Based on the comparisons, we obtained the time‐lapse variations of seismic velocities and attenuation of rock samples during deformation experiments, which we interpreted as crack developments. Our simultaneous estimation of elastic and anelastic parameters allowed us to detail the dynamics prior to the rock failure. Plain Language Summary: We developed a novel methodology to monitor the rock deformation in the laboratory using active seismic waveforms, comparing them against 3D synthetic seismograms. Our methodology can invert for the P‐ and S‐wave velocity changes as well as their attenuation quality factors. Changes in velocity and attenuation show the different trends especially just before rock failure, indicating the complexity of microcracks' evolution. Key Points: 3D numerical modeling with proper physical setting can simulate the waveforms in laboratory rock experimentsMonte Carlo waveform inversion for velocity and attenuation structure can image velocity and attenuation changes during rock deformationChanges in velocity and attenuation show the different trends especially before rock failure [ABSTRACT FROM AUTHOR]

Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. Patients (pts) with relapsed/refractory disease after Asparaginase (ASPA)-based chemotherapy have a dismal prognosis. To better define the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), we conducted a retrospective analysis of data shared with the European Society for Blood and Marrow Transplantation (EBMT) and cooperating Asian centers. We identified 135 pts who received allo-HSCT between 2010 and 2020. Median age was 43.4 years at allo-HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) Asian. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% previous auto-HSCT, and 74.1% ASPA-containing regimens prior to allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. With a median follow-up of 4.8 years, 3-year progression-free(PFS) and overall survival were 48.6% (95%-CI:39.5-57%) and 55.6% (95%-CI:46.5-63.8%). Non-relapse mortality at 1 year was 14.8% (95%-CI:9.3-21.5%) and 1-year relapse incidence 29.6% (95%-CI:21.9-37.6%). In multivariate analyses, shorter time interval (0-12 months) between diagnosis and allo-HSCT [HR = 2.12 (95%-CI:1.03-4.34); P = 0.04] and transplantation not in CR/PR [HR = 2.20 (95%-CI:0.98-4.95); P = 0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased GVHD nor impacted survival. We demonstrate that allo-HSCT can achieve long-term survival in approximately half of pts allografted for NKTCL., (© 2023. The Author(s).)

It is therefore impossible to know whether their cancer was caused by their abnormal lipid values or by statin treatment A more accurate appraisal is therefore to relate the number of cancer cases to the achieved blood cholesterol concentration, as in the study by Matsuzaki et al. ([18]). Keywords: cancer; LDL-cholesterol; ox-LDL; lipid-lowering treatment; microorganisms; immune system EN cancer LDL-cholesterol ox-LDL lipid-lowering treatment microorganisms immune system 1 3 3 05/05/22 20220502 NES 220502 Introduction As demonstrated by Deng et al. ([1]), the association between cancer and LDL-cholesterol is an utterly complicated issue. Cancer, LDL-cholesterol, ox-LDL, lipid-lowering treatment, microorganisms, immune system. [Extracted from the article]

Dear Editor, Intravascular large B cell lymphoma (IVLBCL) is a rare type of diffuse large B cell lymphoma (DLBCL) that is characterized by extranodal disease, with infiltration and proliferation of lymphoma cells within blood vessels. Although chimeric antigen receptor T cell therapy has been a useful treatment approach for DLBCL patients relapsing after auto-SCT [[7]], allo-SCT remains a potentially curative treatment option with graft-versus-lymphoma effect. [Extracted from the article]

Neurological complications (NCs) represent a diagnostic and clinical challenge in allogeneic hematopoietic stem cell transplant (alloHSCT) patients. We retrospectively analyzed NC incidence, etiology, timing, characteristics, outcome, and long-term effects in 2384 adult patients transplanted in seven Italian institutions between January 2007 and December 2019. Ninety-three (3.9%) patients were affected by 96 NCs that were infectious (29.2%), immune/inflammatory (26%), drug-related (12.5%), cerebrovascular (5.2%), metabolic (3.1%), related to central nervous system disease relapse (11.5%) and malignancy (3.1%), or undefined (9.4%). Six patients (6.4%) had neurological manifestations of chronic graft-versus-host disease (GVHD). NCs occurred on average at day +128 (from -5 to +4063). Early (< day +120) and late NCs had similar frequencies (46.9% vs 53.1%, p = 0.39). Thirty-one patients (33.3%) were affected by acute or chronic GVHD at the NC onset. With a median follow-up of 25.4 (0.4-163) months, the overall mortality due to NCs was 22.6%. The median time between NC onset and death was 36 (1-269) days. Infectious NCs were the main cause (61.9%) of NC-related mortality. A persistent neurological impairment occurred in 20.4% patients, 57.9% of whom being affected by immune/inflammatory NCs. This study highlights the rare, yet severe impact of alloHSCT-associated NCs on patient survival and long-term functional ability., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Hand-foot syndrome (HFS) is a typical skin disorder caused by the use of cytotoxic anticancer drugs and molecular targets. Similarly, various anticancer drugs have been used as a conditioning regimen for hematopoietic stem cell transplantation (HSCT), and skin disorders such as HFS have been reported. The aim of this study was to determine retrospectively the frequency of HFS in recipients who have received a first allogeneic HSCT and the risk factors for HFS occurrence., Methods: We retrospectively investigated the medical records of recipients who received their first allogeneic HSCT and neutrophil engraftment at Shizuoka Cancer Center from January 1, 2011, to December 31, 2019., Results: The occurrence of HFS was confirmed in 78 cases (48.1%), and no grade 3 HFS was confirmed. The median occurrence of HFS was 8 (- 3 to 19) days. In recipients with and without confirmed HFS, the median neutrophil engraftment day was 16.5 (10-33) and 15.0 (11-26) days, respectively (p = 0.013). Multivariate analysis indicated that the frequency of HFS was statistically significantly higher in women (p = 0.032), recipients administered busulfan (Bu) four times daily (p = 0.011), and recipients previously treated with anthracycline (p = 0.002)., Conclusion: Attention should be paid to HFS that occurs due to the conditioning regimen for HSCT in women, recipients who received 0.8 mg/kg of Bu four times a day, and recipients with a history of anthracycline administration, as HFS may affect the duration to neutrophil engraftment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Apart from the Epstein-Barr virus (EBV), the etiology of the hematologic malignancy Hodgkin lymphoma (HL) is not well defined. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with some lymphoproliferative diseases with similarities to HL., Methods: We performed a systematic review and meta-analysis, by searching Embase, MEDLINE, and Web of Science databases on March 9, 2021, for studies reporting a measure of association for HBV and HL or HCV and HL. We calculated pooled relative risks (RR) and their 95% confidence intervals (CI)., Results: Pooling nine HBV studies with 1,762 HL cases yielded an RR of 1.39 (95% CI, 1.00-1.94) and pooling 15 HCV studies with 4,837 HL cases resulted in an RR of 1.09 (95% CI, 0.88-1.35). Meta-analyzing by study design, hepatitis detection method, and region revealed two subgroups with statistically significant associations-HCV studies that used hospital-based controls and/or were conducted in the West Pacific. No included study assessed age or EBV tumor status in relation to HL., Conclusions: Although we did not find an association between HBV or HCV and HL, research assessing the impact of age and EBV tumor status was lacking., Impact: The effect of HBV or HCV infection in the development of HL remains unclear., (©2021 American Association for Cancer Research.)

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of 'beyond lipid-lowering'. [ABSTRACT FROM AUTHOR]

The Ministry of Health, Labour and Welfare (MHLW) of Japan has conducted two national surveillance systems for approximately 20 years to monitor antimicrobial resistance (AMR) in bacteria: the National Epidemiological Surveillance of Infectious Diseases (NESID) and the Japan Nosocomial Infections Surveillance (JANIS). Data accumulated for 20 years by these two surveillance systems have helped depict the epidemiology of the representative AMR bacteria in Japan chronologically. The epidemiology of methicillin-resistant Staphylococcus aureus teaches us that once AMR bacteria have established their high endemicity, controlling such AMR bacteria requires time and is challenging. On the other hand, the epidemiology that multidrug-resistant Acinetobacter sp. exhibits when a strict containment policy for AMR bacteria was introduced in the early phase of its emergence and spread reveals that it is possible to control it. Detailed epidemiology provided by these two different national surveillance systems in Japan enabled us to set up the goal for controlling each AMR bacteria at the hospital level to the prefecture/national level. It is the public health authorities' responsibility to maintain a good surveillance system for AMR bacteria and share the data and findings with healthcare professionals and academicians. [ABSTRACT FROM AUTHOR]