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1.
Artigo em Inglês | MEDLINE | ID: mdl-38997400

RESUMO

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

2.
bioRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38979192

RESUMO

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer Disease (AD), and recent proteomic studies highlight a disruption of glial carbohydrate metabolism with disease progression. Here, we report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN) in the first step of the kynurenine pathway, rescues hippocampal memory function and plasticity in preclinical models of amyloid and tau pathology by restoring astrocytic metabolic support of neurons. Activation of IDO1 in astrocytes by amyloid-beta 42 and tau oligomers, two major pathological effectors in AD, increases KYN and suppresses glycolysis in an AhR-dependent manner. Conversely, pharmacological IDO1 inhibition restores glycolysis and lactate production. In amyloid-producing APP Swe -PS1 ΔE9 and 5XFAD mice and in tau-producing P301S mice, IDO1 inhibition restores spatial memory and improves hippocampal glucose metabolism by metabolomic and MALDI-MS analyses. IDO1 blockade also rescues hippocampal long-term potentiation (LTP) in a monocarboxylate transporter (MCT)-dependent manner, suggesting that IDO1 activity disrupts astrocytic metabolic support of neurons. Indeed, in vitro mass-labeling of human astrocytes demonstrates that IDO1 regulates astrocyte generation of lactate that is then taken up by human neurons. In co-cultures of astrocytes and neurons derived from AD subjects, deficient astrocyte lactate transfer to neurons was corrected by IDO1 inhibition, resulting in improved neuronal glucose metabolism. Thus, IDO1 activity disrupts astrocytic metabolic support of neurons across both amyloid and tau pathologies and in a model of AD iPSC-derived neurons. These findings also suggest that IDO1 inhibitors developed for adjunctive therapy in cancer could be repurposed for treatment of amyloid- and tau-mediated neurodegenerative diseases.

3.
Ann Gastroenterol ; 37(4): 442-448, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974087

RESUMO

Background: Frailty has major health implications for affected patients and is widely used in the perioperative risk assessment. The Hospital Frailty Risk Score (HFRS) is a validated score that utilizes administrative billing data to identify patients at higher risk because of frailty. We investigated the utility of the HFRS in patients with Clostridioides difficile infection (CDI) to determine whether they were at risk for worse outcomes and higher healthcare resource utilization. Methods: Using the 2017 National Inpatient Sample, we identified all adults with a primary diagnosis of CDI. We classified patients into 2 groups: those who had an HFRS <5 (NonFrailCDI) and those with a score ≥5 (FrailCDI). We assessed differences in hospital outcomes and healthcare resource utilization based on frailty status. Results: We identified 93,810 hospitalizations, of which 54,300 (57.88%) were FrailCDI. FrailCDI patients were at higher risk for fulminant CDI (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.6-2.3), requiring colectomy (OR 4.1, 95%CI 1.5-11.2), and inpatient mortality (OR 4.5, 95%CI 2.8-7.1). Furthermore, FrailCDI patients had higher odds of requiring Intensive Care Unit admission (OR 13.7, 95%CI 6.3-29.9) or transfer to another facility on discharge (OR 2.2, 95%CI 2.0-2.4), and had longer hospital stays and higher total charges when compared with NonFrailCDI. Conclusions: Frailty as defined by the HFRS is an independent factor for worse outcomes and higher healthcare utilization in adults admitted for CDI. Risk stratifying patients by frailty may improve outcomes.

4.
Biomed Pharmacother ; 177: 117062, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971009

RESUMO

Smoking remains a significant health problem in patients with type 2 diabetes mellitus. This study compared intracellular Ca2+ ([Ca2+]i) in microglia, neurons, and astrocytes in the presence of high glucose (HG) and nicotine and evaluated the effects of Lavandula angustifolia Mill. essential oil (LEO) on this process. [Ca2+]i concentrations were measured by monitoring the fluorescence of Fura-2 acetoxymethyl ester. Treatment with HG and nicotine significantly increased [Ca2+]i in both microglia and neurons through Ca2+ influx from extracellular sources. This increased Ca2+ influx in microglia, however, was significantly reduced by LEO, an effect partially inhibited by the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms.

5.
Nutrients ; 16(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38999876

RESUMO

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.


Assuntos
Leonurus , Extratos Vegetais , Probióticos , Humanos , Método Duplo-Cego , Masculino , Feminino , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Pessoa de Meia-Idade , Leonurus/química , Probióticos/administração & dosagem , Lactobacillus plantarum , Idoso , Resultado do Tratamento , Microbioma Gastrointestinal/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Adulto
6.
Artigo em Inglês | MEDLINE | ID: mdl-39010759

RESUMO

The efficiency of copper indium gallium selenide (CIGS) solar cells that use transparent conductive oxide (TCO) as the top electrode decreases significantly as the device area increases owing to the poor electrical properties of TCO. Therefore, high-efficiency, large-area CIGS solar cells require the development of a novel top electrode with high transmittance and conductivity. In this study, a microgrid/TCO hybrid electrode is designed to minimize the optical and resistive losses that may occur in the top electrode of a CIGS solar cell. In addition, the buffer layer of the CIGS solar cells is changed from the conventional CdS buffer to a dry-processed wide-band gap ZnMgO (ZMO) buffer, resulting in increased device efficiency by minimizing parasitic absorption in the short-wavelength region. By optimizing the combination of ZMO buffer and the microgrid/TCO hybrid electrode, a device efficiency of up to 20.5% (with antireflection layers) is achieved over a small device area of 5 mm × 5 mm (total area). Moreover, CIGS solar cells with an increased device area of up to 20 mm × 70 mm (total area) exhibit an efficiency of up to 19.7% (with antireflection layers) when a microgrid/TCO hybrid electrode is applied. Thus, this study demonstrates the potential for high-efficiency, large-area CIGS solar cells with novel microgrid electrodes.

7.
Med Sci Monit ; 30: e944913, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961611

RESUMO

Vital signs are crucial for monitoring changes in patient health status. This review compared the performance of noncontact sensors with traditional methods for measuring vital signs and investigated the clinical feasibility of noncontact sensors for medical use. We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database for articles published through September 30, 2023, and used the key search terms "vital sign," "monitoring," and "sensor" to identify relevant articles. We included studies that measured vital signs using traditional methods and noncontact sensors and excluded articles not written in English, case reports, reviews, and conference presentations. In total, 129 studies were identified, and eligible articles were selected based on their titles, abstracts, and full texts. Three articles were finally included in the review, and the types of noncontact sensors used in each selected study were an impulse radio ultrawideband radar, a microbend fiber-optic sensor, and a mat-type air pressure sensor. Participants included neonates in the neonatal intensive care unit, patients with sleep apnea, and patients with coronavirus disease. Their heart rate, respiratory rate, blood pressure, body temperature, and arterial oxygen saturation were measured. Studies have demonstrated that the performance of noncontact sensors is comparable to that of traditional methods of vital signs measurement. Noncontact sensors have the potential to alleviate concerns related to skin disorders associated with traditional skin-contact vital signs measurement methods, reduce the workload for healthcare providers, and enhance patient comfort. This article reviews the medical use of noncontact sensors for measuring vital signs and aimed to determine their potential clinical applicability.


Assuntos
COVID-19 , Sinais Vitais , Humanos , Sinais Vitais/fisiologia , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , COVID-19/diagnóstico , SARS-CoV-2 , Frequência Cardíaca/fisiologia , Pressão Sanguínea/fisiologia
8.
Biomacromolecules ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014545

RESUMO

Hydrogels are promising materials for biomedical applications, particularly in drug delivery and tissue engineering. This study highlights thermoresponsive hydrogels, specifically poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA triblock copolymers, and introduces a feed rate-controlled polymerization (FRCP) method. By utilizing an organic catalyst and regulating the monomer feed rate, the sequence distribution of PLGA within the triblock copolymer is controlled. Various analyses, including 13C NMR and rheological measurements, were conducted to investigate the impact of sequence distribution. Results show that altering sequence distribution significantly influences the sol-gel transition, hydrophobicity-hydrophilicity balance, and drug release profile. Increased sequence uniformity lowers the glass transition temperature, raises the sol-gel transition temperature due to enhanced hydrophilicity, and promotes a more uniform drug (curcumin) distribution within the PLGA domain, resulting in a slower release rate. This study emphasizes the importance of PLGA sequence distribution in biomedical applications and the potential of FRCP to tailor thermoresponsive hydrogels for biomedical advancements.

9.
J Korean Med Sci ; 39(27): e213, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39015004
10.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000152

RESUMO

Global public health is facing a major issue with emerging resistance to antimicrobial agents. Antimicrobial agents that are currently on the market are strong and efficient, but it has not been ruled out that these medications will eventually cause resistance to bacteria. Exploring novel bioactive compounds derived from natural sources is therefore, crucial to meet future demands. The present study evaluated the mode of action of the antimicrobial potential protease enzyme SH21. Protease SH21 exhibited antimicrobial activity, strong heat stability (up to 100 °C), and pH stability (pH 3.0 to 9.0). In terms of mode of action, we found that protease SH21 was able to disrupt the bacterial cell membrane as the results of the nucleotide leakage and cell membrane permeability assay. In addition, we also checked inner membrane permeability by PI uptake assay which suggested that protease SH21 has the ability to enter the bacterial cell membrane. Our results revealed that the antimicrobial protease SH21 might be a promising candidate for treating microbial infections.


Assuntos
Bacillus , Testes de Sensibilidade Microbiana , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Peptídeo Hidrolases/metabolismo , Concentração de Íons de Hidrogênio , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/metabolismo , Estabilidade Enzimática
11.
Cancer Imaging ; 24(1): 84, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965621

RESUMO

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.


Assuntos
Imageamento Tridimensional , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Broncoscopia/métodos , Endossonografia/métodos , Aprendizado de Máquina
12.
J Am Coll Radiol ; 21(6S): S286-S291, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823950

RESUMO

Abdominal aortic aneurysm (AAA) is a significant vascular disease found in 4% to 8% of the screening population. If ruptured, its mortality rate is between 75% and 90%, and it accounts for up to 5% of sudden deaths in the United States. Therefore, screening of AAA while asymptomatic has been a crucial portion of preventive health care worldwide. Ultrasound of the abdominal aorta is the primary imaging modality for screening of AAA recommended for asymptomatic adults regardless of their family history or smoking history. Alternatively, duplex ultrasound and CT abdomen and pelvis without contrast may be appropriate for screening. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Assuntos
Aneurisma da Aorta Abdominal , Medicina Baseada em Evidências , Programas de Rastreamento , Sociedades Médicas , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Estados Unidos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas
13.
J Am Coll Radiol ; 21(6S): S268-S285, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823949

RESUMO

Pulmonary arteriovenous malformations (PAVMs) occur in 30% to 50% of patients with hereditary hemorrhagic telangiectasia. Clinical presentations vary from asymptomatic disease to complications resulting from the right to left shunting of blood through the PAVM such as paradoxical stroke, brain abscesses, hypoxemia, and cardiac failure. Radiology plays an important role both in the diagnosis and treatment of PAVM. Based on different clinical scenarios, the appropriate imaging study has been reviewed and is presented in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Assuntos
Medicina Baseada em Evidências , Artéria Pulmonar , Veias Pulmonares , Sociedades Médicas , Humanos , Estados Unidos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/anormalidades , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/anormalidades , Malformações Arteriovenosas/diagnóstico por imagem , Fístula Arteriovenosa/diagnóstico por imagem
14.
Front Med (Lausanne) ; 11: 1421901, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933102

RESUMO

The continuous monitoring of the health status of patients is essential for the effective monitoring of disease progression and the management of symptoms. Recently, health monitoring using non-contact sensors has gained interest. Therefore, this study aimed to investigate the use of non-contact sensors for health monitoring in hospital settings and evaluate their potential clinical applications. A comprehensive literature search was conducted using PubMed to identify relevant studies published up to February 26, 2024. The search terms included "hospital," "monitoring," "sensor," and "non-contact." Studies that used non-contact sensors to monitor health status in hospital settings were included in this review. Of the 38 search results, five studies met the inclusion criteria. The non-contact sensors described in the studies were radar, infrared, and microwave sensors. These non-contact sensors were used to obtain vital signs, such as respiratory rate, heart rate, and body temperature, and were then compared with the results from conventional measurement methods (polysomnography, nursing records, and electrocardiography). In all the included studies, non-contact sensors demonstrated a performance similar to that of conventional health-related parameter measurement methods. Non-contact sensors are expected to be a promising solution for health monitoring in hospital settings.

15.
Int J Mol Sci ; 25(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38928069

RESUMO

An ischemic stroke, one of the leading causes of morbidity and mortality, is caused by ischemia and hemorrhage resulting in impeded blood supply to the brain. According to many studies, blueberries have been shown to have a therapeutic effect in a variety of diseases. Therefore, in this study, we investigated whether blueberry-treated mesenchymal stem cell (MSC)-derived extracellular vesicles (B-EVs) have therapeutic effects in in vitro and in vivo stroke models. We isolated the extracellular vesicles using cryo-TEM and characterized the particles and concentrations using NTA. MSC-derived extracellular vesicles (A-EVs) and B-EVs were round with a lipid bilayer structure and a diameter of ~150 nm. In addition, A-EVs and B-EVs were shown to affect angiogenesis, cell cycle, differentiation, DNA repair, inflammation, and neurogenesis following KEGG pathway and GO analyses. We investigated the protective effects of A-EVs and B-EVs against neuronal cell death in oxygen-glucose deprivation (OGD) cells and a middle cerebral artery occlusion (MCAo) animal model. The results showed that the cell viability was increased with EV treatment in HT22 cells. In the animal, the size of the cerebral infarction was decreased, and the behavioral assessment was improved with EV injections. The levels of NeuN and neurofilament heavy chain (NFH)-positive cells were also increased with EV treatment yet decreased in the MCAo group. In addition, the number of apoptotic cells was decreased with EV treatment compared with ischemic animals following TUNEL and Bax/Bcl-2 staining. These data suggested that EVs, especially B-EVs, had a therapeutic effect and could reduce apoptotic cell death after ischemic injury.


Assuntos
Mirtilos Azuis (Planta) , Vesículas Extracelulares , AVC Isquêmico , Células-Tronco Mesenquimais , Vesículas Extracelulares/metabolismo , Animais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , AVC Isquêmico/metabolismo , AVC Isquêmico/terapia , AVC Isquêmico/patologia , Mirtilos Azuis (Planta)/química , Masculino , Modelos Animais de Doenças , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/metabolismo
16.
Haematologica ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38841794

RESUMO

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

17.
J Korean Med Sci ; 39(21): e183, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38832482
18.
Artigo em Inglês | MEDLINE | ID: mdl-38863389

RESUMO

BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), P = 0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, P < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, P = 0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all P < 0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38934039

RESUMO

Background: The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse. Methods: For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them. Results: We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN. Conclusion: Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

20.
Addict Behav ; 157: 108077, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38851142

RESUMO

INTRODUCTION: This study assessed quit attempts among adults who use cigarettes either exclusively or with e-cigarettes in Mexico, where non-daily smoking predominates. METHODS: An open cohort of Mexican adults who smoke was surveyed every four months from November 2018 to March 2021. Participants followed to the next survey were analyzed (n = 2220 individuals, 4560 observations). Multinomial logistic models regressed smoking quit attempts reported at the followup survey (ref = no attempt; tried to quit; sustained attempt of ≥30 days) on e-cigarette use frequency (none = ref; 1-2 days/week; ≥3 days/week), adjusting for sociodemographics and smoking-related variables. Additional models subdivided e-cigarette users by intentions to quit smoking in the next six months (i.e., yes/no), use of nicotine (i.e., yes/no), and vaping device used (i.e., open/closed). RESULTS: At 4-month follow-up, 32.7 % had tried to quit, and 2.9 % had quit for 30 days or more. Compared to those who smoke exclusively, occasional, and frequent e-cigarette users were more likely to try to quit (Adjusted Relative Risk Ratio or ARRR = 1.26 and 1.66, respectively) but no more likely to sustain their quit attempt. Among those who intended to quit smoking, e-cigarette users were no more likely to either try or sustain quit attempts. Furthermore, use of e-cigarettes with nicotine (59.6 %) was unassociated with cessation except that those who frequently used e-cigarettes with nicotine were more likely to try to quit than those who smoke exclusively (ARRR = 1.88). Device type used was not differentially associated with outcomes. CONCLUSIONS: Mexicans who smoke and use e-cigarettes appear more likely than those who smoke exclusively to try to quit but not to sustain abstinence.

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