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Background: Acute kidney injury (AKI) is a well-known complication of critical illnesses, significantly affecting morbidity and the risk of death. Diuretics are widely used to ameliorate excess fluid accumulation and oliguria associated with AKI. Their popularity stems from their ability to reduce the energy demands of renal tubular cells by inhibiting transporters and flushing out intratubular casts. Numerous studies have assessed the effects of diuretics in the context of AKI prevention and treatment. However, a comprehensive systematic review addressing this topic has yet to be conducted., Objectives: This review aimed to explore the benefits and harms of diuretics for both the prevention and treatment of AKI., Search Methods: The Cochrane Kidney and Transplant Register of Studies was searched up to May 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov., Selection Criteria: We selected randomised controlled trials (RCTs) and quasi-RCTs in which diuretics were used to prevent or treat AKI., Data Collection and Analysis: Two authors independently extracted data using standardised data extraction forms. Dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment, the standardised mean difference (SMD) was used. The primary review outcomes for AKI prevention studies were the incidence of AKI and any use of kidney replacement therapy (KRT). For treatment studies, the primary outcome was any use of KRT. The certainty of evidence was assessed per outcome using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach., Main Results: We included 64 studies (83 reports, 9871 participants): 53 prevention studies (8078 participants) and 11 treatment studies (1793 participants). Studies were conducted in the following World Health Organization regions: the Americas (15), Eastern Mediterranean (9), Europe (25), South-East Asia (2), and the Western Pacific (13). Thirty-six studies were single-centre studies, 19 were multicentre, and the setting was unclear in nine studies. Diuretics were compared to placebo, no treatment or conventional therapy, saline solutions (isotonic or hypotonic), 5% dextrose, 5% glucose, Hartmann's solution, and Ringer's acetate. Overall, the risk of bias was low in one study, high in 19 studies, and of some concern in 41 studies. Three studies could not be assessed because they did not report any outcomes of interest. For AKI prevention, compared to control, diuretics may reduce the risk of AKI (38 studies, 5540 participants: RR 0.75, 95%, CI 0.61 to 0.92; I 2 = 77%; low-certainty evidence) and probably reduce any use of KRT (32 studies, 4658 participants: RR 0.63, 95% CI 0.43 to 0.91; I 2 = 0%, moderate-certainty evidence) and death (33 studies, 6447 participants: RR 0.73, 95% CI 0.59 to 0.92; I 2 = 0%; moderate-certainty evidence). The use of diuretics may result in little or no difference in the need for permanent dialysis (2 studies, 956 participants: RR 0.52, 95% CI 0.08 to 3.47; I 2 = 21%; low-certainty evidence), hypotension (7 studies, 775 participants: RR 1.27, 95% CI 0.87 to 1.86; I 2 = 0%; low-certainty evidence) and hypokalaemia (6 studies, 1383 participants: RR 1.20, 95% CI 0.88 to 1.73; I 2 = 43%; low-certainty evidence), and had uncertain effects on arrhythmias (13 studies, 3375 participants: RR 0.77, 95% CI 0.57 to 1.04; I 2 = 53%; very-low certainty evidence). Diuretics may make little or no difference to changes in SCr within 30 days (8 studies, 646 participants: SMD 0.41, 95% CI -0.01, to 0.83; I 2 = 82%; low-certainty evidence) but it was uncertain whether diuretics increased urinary output (8 studies, 1155 participants: SMD 1.87, 95% CI -0.20 to 3.95; I 2 = 99%; very low-certainty evidence). For AKI treatment, diuretics may make little or no difference to any use of KRT (8 studies, 1275 participants: RR 0.93, 95% CI 0.83 to 1.04; I 2 = 2%; low-certainty evidence) or death (14 studies, 2052 participants: RR 1.08, 95% CI 0.96 to 1.22; I 2 = 0%; low-certainty evidence). Diuretics may increase hypotension (2 studies, 720 participants: RR 1.99, 95% CI 1.16 to 3.41; I 2 = 90%; low-certainty evidence) and probably increase arrhythmias (6 studies, 1011 participants: RR 1.62, 95% CI 1.12 to 2.33; I 2 = 0%; moderate-certainty evidence). Diuretics may result in little or no difference in hypokalaemia (3 studies, 478 participants: RR 1.52, 95% CI 0.70 to 3.31; I 2 = 0%; low-certainty evidence). It was uncertain whether diuretics increased urinary output (3 studies, 329 participants: SMD 4.40, 95% CI -0.94 to 9.74; I 2 = 99%; very low-certainty evidence). The need for permanent dialysis and changes in serum creatinine were not reported., Authors' Conclusions: When used for the prevention of AKI, diuretics may reduce the risk of AKI. However, our confidence in the effect estimate is limited. Diuretics probably reduce the incidence of KRT use, and we are moderately confident in the effect estimate. When used for the treatment of AKI, diuretics may make little or no difference to any use of KRT, and our confidence in the effect estimate is limited. More RCTs are needed to explore the role of diuretics for treating established AKI., (Copyright © 2025 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The etiology of Kawasaki disease (KD) has not yet been completely elucidated. We evaluated the temporal association between respiratory pathogens and KD incidence and the association between respiratory pathogens and treatment responsiveness in patients with KD. This retrospective study was conducted to compare the number of symptomatic children with pathogens detected using multiplex PCR tests with the number of KD cases. Logistic analysis was performed to assess whether the presence of at least one respiratory virus was associated with immunoglobulin non-responsiveness in patients with KD. A statistically significant temporal association was found between the number of KD patients and the number of patients with a positive respiratory pathogen (Pearson correlation coefficient +0.595; p=0.003). The adjusted odds ratio of respiratory pathogen detection for immunoglobulin responsiveness was 1.24 (95% confidence interval 0.38-4.11) (p=0.721). Our study demonstrated a temporal association between the total number of respiratory infections and KD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2025 Elsevier Inc. All rights reserved.)

Cisplatin (CDDP) remains a key drug for patients with advanced bladder cancer (BC), despite the emergence of new therapeutic agents; thus, the identification of factors contributing to CDDP treatment resistance is crucial. As acidity of the tumor microenvironment has been reported to be associated with treatment resistance and poor prognosis across various cancer types, our objectives in this study were to investigate the effects of an acidic environment on BC cells and elucidate the mechanisms behind CDDP resistance. Our findings show that BC cells cultured under acidic conditions developed cisplatin resistance as acidity increased. Notably, CDDP administered to BC cells in a pH 6.0 environment required double the concentration, compared to those in a pH 7.5 environment, to achieve equivalent toxicity. Using chloroquine and navitoclax, we identified the involvement of the Bcl-2 and LC3B pathways in the acquisition of CDDP resistance under acidic conditions. A Western blot analysis revealed that the activations of Bcl-2 and XIAP expression appear to inhibit both apoptotic and autophagic cell death. Taken together, these results suggest that alleviating the acidity of the tumor microenvironment in clinical settings might enhance BC sensitivity to CDDP.

[Purpose] The safety and physiological effects of combined training with breathing resistance and sustained physical exertion in middle-aged and older adults remain unclear. This pilot study investigated the safety and physiological benefits of this training method in older adults. [Participants and Methods] Participants aged 55-75 without respiratory, circulatory, or metabolic diseases were randomly divided into two groups: a combined breathing and physical training group and a control group. All participants were assessed for respiratory function and metabolic parameters before and after a 6-week training period. [Results] Two participants with hypertension were excluded from the study, leaving 24 participants who were randomly assigned to the combined training group (14 participants) or the control group (10 participants). All participants completed the 6-week training, except for three who withdrew due to adverse health events. In the combined training group, maximal minute ventilation significantly increased post-intervention compared to pre-training levels. [Conclusion] Six weeks of combined breathing and physical training was safely conducted in middle-aged and older adults. The results suggest that this method is more effective than conventional training in improving respiratory function. Therefore, this approach could be a novel method for enhancing respiratory function in middle-aged and older adults., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (2025©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background: Efforts to promote antimicrobial stewardship aimed at reducing antimicrobial resistance are necessary regardless of hospital scale owing to delays in new antimicrobial development. We aimed to evaluate the effects of pharmacist-driven interventions on broad-spectrum antimicrobial usage and the prognosis of patients with bacteremia in a medium-sized hospital lacking infectious disease physicians and a microbiology laboratory., Methods: This single-center, retrospective, pragmatic, quasi-experimental study was conducted to compare pre- and post-intervention effects at Saiseikai Futsukaichi Hospital. We analyzed the days of therapy (DOT) for carbapenems and days of antibiotic spectrum coverage (DASC) for antimicrobials using an interrupted time series analysis. Cox proportional hazards analysis was performed to assess 30-day mortality using propensity score and inverse probability of treatment weighting in patients with bacteremia., Results: Pharmacist-driven interventions significantly reduced the DOT (incidence rate ratio [IRR]: 0.53, 95 % confidence intervals [CI]: 0.33-0.81, p = 0.003) and DASC (IRR: 0.87, 95 % CI: 0.78-0.97, p = 0.016). The 30-day mortality due to bacteremia did not significantly differ between pre- and post-intervention in all patients (adjusted hazard ratio [HR]: 0.92, 95 % CI: 0.56-1.51, p = 0.74). Conversely, pharmacist-driven interventions significantly reduced the 30-day mortality owing to bacteremia with Pitt bacteremia score (PBS) ≥4 (adjusted HR: 0.52, 95 % CI: 0.28-0.99, p = 0.047)., Conclusions: Pharmacist-driven interventions may represent a valuable approach for optimizing antimicrobial treatment and improving prognosis, especially in patients with PBS ≥4, which will potentially benefit patients in similar healthcare environments facing challenges related to antimicrobial stewardship and patient prognosis., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: De novo chronic myeloid leukemia in blastic phase (CML-BP) showing lymphoid immunophenotype mimics Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). Although upfront allogeneic hematopoietic cell transplantation (HCT) is considered in both diseases, it is not yet clear whether the transplant outcomes are also similar., Methods: Using a registry database, the transplant outcomes between de novo CML-BP and Ph-positive ALL in negative-minimal residual disease (MRD), positive MRD, and nonremission cohorts were compared, respectively. All of the included patients had received tyrosine kinase inhibitor therapy before HCT and underwent HCT between 2002 and 2021. Regarding Ph-positive ALL, patients with p210 transcripts were excluded because there was concern that this group might include patients with de novo CML-BP., Results: Although most of the outcomes were comparable, in patients with positive MRD at HCT, de novo CML-BP was significantly associated with superior disease-free survival (DFS) (hazard ratio [HR] 0.6, p = .0032), overall survival (HR 0.66, p = .027), and a lower risk of relapse (HR 0.48, p = .0051). In subgroup analyses, BCR::ABL1 mutation status had a significant interaction with the disease (p for interaction = .0027). De novo CML-BP seemed to be associated with superior disease-free survival in a BCR::ABL1 mutation-positive cohort, whereas this association was not observed in a mutation-negative cohort., Conclusions: Considering previous reports that showed inferior outcomes for de novo CML-BP compared to Ph-positive ALL, the data suggested that allogeneic HCT could overcome the poor prognosis of de novo CML-BP. These findings highlight the importance of distinguishing de novo CML-BP from Ph-positive ALL., (© 2024 American Cancer Society.)

Indium compounds are used in manufacturing displays of mobile phones and televisions. These compounds cause interstitial pneumonia in workers and lung cancer in animals, but their precise mechanisms are unclear. In this study, we performed microarray analysis of gene expression in lung tissues of indium-exposed rats. Male Wistar rats (8-week-old) were exposed to indium oxide (In 2 O 3 , mean particle diameter 0.14 μm) and indium-tin oxide (ITO, mean particle diameter 0.95 μm) by intratracheal instillation (10 mg indium/kg body weight/instillation) twice a week and five times in total. These rats were sacrificed immediately, 3 weeks and 12 weeks after the last instillation. Hematoxylin and eosin and Masson's trichrome staining showed that indium compounds induced infiltration of neutrophils and macrophages into alveolar space, and fibrosis around bronchial epithelium and in alveolar wall. Microarray analysis revealed that In 2 O 3 and ITO significantly upregulated 233 and 676 genes at 12 weeks, respectively (> twofold, p < 0.05 by ANOVA + Tukey's test). In 2 O 3 and ITO largely upregulated Lcn2 (lipocalin-2) (49.4- and 91.8-fold), S100a9 (30.2- and 46.5-fold) and S100a8 (11.5- and 22.0-fold), respectively. Metascape database predicted that these genes participate in immunomodulatory and inflammatory responses. Real-time PCR confirmed that these genes were upregulated by indium compounds throughout the experiments. In Western blotting, S100A9 expression was significantly increased by indium exposure, whereas LCN2 expression was only slightly increased. Fluorescent immunohistochemistry revealed that S100A9 and S100A8 were expressed in alveolar epithelial cells and neutrophils in indium-exposed rats. These results suggest that S100 proteins contribute to indium-induced lung diseases via neutrophil-mediated inflammatory responses., Competing Interests: Declarations. Conflict of interest: No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interests to declare., (© 2024. The Author(s).)

Ganciclovir and foscarnet are two representative anti-cytomegalovirus (CMV) agents. A previous regional study revealed a lower risk of chronic graft-versus-host disease (GVHD) in patients who received pre-emptive foscarnet. We conducted a retrospective nationwide study to confirm the results. A total of 8890 patients aged 16 or older with hematological malignancies who received foscarnet (n = 1555) or ganciclovir (n = 7335) during their first hematopoietic stem cell transplantation (HSCT) were included. The risks of chronic GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.13-1.40; P < 0.001) and extensive chronic GVHD (HR, 1.16; 95% CI, 1.01-1.33; P = 0.033) were higher with ganciclovir. Among male patients with a female donor, the incidence of extensive chronic GVHD 3 years after HSCT was clearly lower with foscarnet (13%; 95% CI, 9-16%) than with ganciclovir (27%; 95% CI, 25-29%; P < 0.001). In male patients who received HSCT from female donors, foscarnet recipients showed significantly lower incidence of extensive chronic GVHD than ganciclovir recipients, regardless of donor source or previous acute GVHD. While caution is necessary, these results indicate that foscarnet affects alloimmunization and might reduce the incidence of chronic GVHD., Competing Interests: Declarations. Conflict of interest: The authors declare that there are no competing financial interest to report. S. Terakura and Y.K are editors of International Journal of Hematology., (© 2024. Japanese Society of Hematology.)

Introduction: A clonal shift from staphylococcal cassette chromosome mec (SCCmec) type II/ST5 methicillin-resistant Staphylococcus aureus (MRSA) to SCCmec type IV/clonal complex (CC)1 MRSA has occurred rapidly in Japan. Our previous research in a geriatric hospital found SCCmec type IV/CC1 MRSA prevalence in long-term care wards. Due to intensive personal care requirements, frequent contact with healthcare providers can potentially cause unintentional nosocomial MRSA transmission. We performed polymerase chain reaction-based open reading frame typing (POT) and core genome multilocus sequence typing (cgMLST) to investigate the occurrence of nosocomial transmission and to compare the results of these methods., Methods: POT and whole genome sequencing were performed in 83 MRSA isolates. Commercial automated software (Ridom SeqSphere+) was used to perform cgMLST. MRSA isolates with 0-8 allelic differences were considered related, and medical records were consulted in these cases., Results: SCCmec type IV/CC1 MRSA was the most frequently detected clone (n = 56, 67.5 %), which was divided into 14 POT types, followed by SCCmec type I/ST8 (n = 9) and SCCmec type IV/ST8 (n = 8). Identical POT types were found across 7 of 11 wards. However, cgMLST analysis identified only three cases (six strains) of high genetic similarity, indicating nosocomial transmission; only one involved SCCmec type IV/CC1 (two strains). The mean allelic difference in the core genomes between strains with identical POT types in the same ward was 55.3 ± 22.0., Conclusions: The cgMLST method proved more effective for identifying nosocomial transmissions compared to POT, highlighting its utility in tracking MRSA spread in healthcare settings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)