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1.
J Thorac Dis ; 16(7): 4319-4328, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39144365

RESUMEN

Background: Cardiopulmonary bypass (CPB) can trigger a systemic inflammatory response during the perioperative period, which may lead to the consumption of the contact system and the production of neutrophil extracellular traps (NETs). This study attempted to determine whether the formation of NETs and contact activation are a vivid occurrence during CPB and whether they are related to post-operative atrial fibrillation (AF) and survival. Methods: A prospective observational study was conducted in 97 patients who underwent aortic valve and/or aorta replacement surgery with CPB. Circulating markers of NETs [histone-DNA complex, cell-free double stranded DNA (dsDNA), neutrophil elastase] and the contact system [prekallikrein, high molecular weight kininogen (HMWK), activated factor XII (FXIIa)] were measured at four-time points: before surgery (T0), immediately after surgery (T1), 1 day after surgery (T2), and 3 days after surgery (T3). Results: Elevated levels of circulating NETs markers were observed across post-CPB time. Significantly elevated levels of histone-DNA complex and cell-free dsDNA measured T3 were detected in patients with post-operative AF compared to those without. In logistic regression analysis, levels of histone-DNA complex and cell-free dsDNA measured at T3 were significant markers of risk for occurrence of AF. The levels of cell-free dsDNA measured T2 were significantly higher in non-survivors than in survivors. The level of cell-free dsDNA showed significant prognostic value. Conclusions: NETs markers may be useful for the assessment of risk for post-operative AF and mortality. Conduct of additional research regarding the role of NETs as clinical markers and as a therapeutic target in CPB is anticipated.

2.
Front Bioeng Biotechnol ; 12: 1392269, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100623

RESUMEN

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.

3.
Nutrients ; 16(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38999876

RESUMEN

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.


Asunto(s)
Leonurus , Extractos Vegetales , Probióticos , Humanos , Método Doble Ciego , Masculino , Femenino , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Persona de Mediana Edad , Leonurus/química , Probióticos/administración & dosificación , Lactobacillus plantarum , Anciano , Resultado del Tratamiento , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Adulto
4.
Sci Total Environ ; 949: 175051, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39067602

RESUMEN

This study conducted real-time monitoring of size-resolved particle concentrations ranging from 9 nm to 10 µm simultaneously at four sites on the park ground and the roof of a five-story apartment buildings in the upwind and downwind areas of the Olympic Expressway next to apartment complex areas of Seoul, Korea. Using a positive matrix factorization model for source apportionment, eight factors were resolved at each monitoring site: four exhaust emissions of vehicles, one non-exhaust emission of vehicle, two regional sources, and one unknown source. After categorizing monitoring data into three cases by wind conditions, impact and contribution of each vehicle-related source on the local road to the roadside pollution was quantified and characterized by subtracting the urban background concentrations. Throughout the measurement period, the contribution of vehicle-related sources to the particle number concentration at each monitoring site ranged from 61 % to 69 %, while that to the particle mass concentration ranged from 39 % to 87 %. During periods of steady traffic flow and wind blowing from the road to three downwind sites at speeds exceeding >0.5 m/s during working hours, the particle number concentrations at the downwind sites were 2.2-2.5 times higher than the average levels. Among vehicle-related sources, gasoline vehicles with multiple injections or high-emitting diesel vehicles showed the highest contribution to particle number concentrations at all sites. As wind speed increased, the number concentrations of particles from vehicle exhaust and non-exhaust emissions decreased and increased, respectively, probably due to enhanced dilution and transport, respectively. In addition, particle number concentrations showed a parabolic curve-like trend with traffic volumes increasing to approximately 10,000 vehicles/h, and then decreasing for both vehicle exhaust and non-exhaust emissions. These results can be utilized in numerical modeling studies and in establishing traffic-related environmental policies to reduce seasonal and temporal particle exposure near the roadsides.

5.
J Chem Phys ; 160(24)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38916268

RESUMEN

Here, we investigate the hypothesis that despite the existence of at least two high-density amorphous ices, only one high-density liquid state exists in water. We prepared a very-high-density amorphous ice (VHDA) sample and rapidly increased its temperature to around 205 ± 10 K using laser-induced isochoric heating. This temperature falls within the so-called "no-man's land" well above the glass-liquid transition, wherein the IR laser pulse creates a metastable liquid state. Subsequently, this high-density liquid (HDL) state of water decompresses over time, and we examined the time-dependent structural changes using short x-ray pulses from a free electron laser. We observed a liquid-liquid transition to low-density liquid water (LDL) over time scales ranging from 20 ns to 3 µs, consistent with previous experimental results using expanded high-density amorphous ice (eHDA) as the initial state. In addition, the resulting LDL derived both from VHDA and eHDA displays similar density and degree of inhomogeneity. Our observation supports the idea that regardless of the initial annealing states of the high-density amorphous ices, the same HDL and final LDL states are reached at temperatures around 205 K.

6.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892403

RESUMEN

Bakanae disease (BD), caused by the fungal pathogen Fusarium fujikuroi, is a serious threat to rice production worldwide. Breeding elite rice varieties resistant to BD requires the identification of resistance genes. Previously, we discovered a resistant quantitative trait locus (QTL), qFfR1, in a Korean japonica rice variety, Nampyeong. In this study, we fine-mapped qFfR1 with a Junam*4/Nampyeong BC3F3 population and delimited its location to a 37.1 kb region on chromosome 1. Complementation experiments with seven candidate genes in this region revealed that OsI_02728 is the gene for qFfR1. This gene encodes a protein with a typical leucine-rich repeat (LRR) receptor-like protein structure. RNA-sequencing-based transcriptomic analysis revealed that FfR1 induces the transcription of defense genes, including lignin and terpenoid biosynthesis genes, pathogenesis-related genes, and thionin genes. These results may facilitate investigations into the molecular mechanisms underlying BD resistance, including molecular patterns of Fusarium fujikuroi interacting with FfR1 and players working in signal transduction pathways downstream of FfR1, and the breeding of new BD-resistant varieties by providing a BD resistance gene with its precise selection marker. This will contribute to efficient control of BD, which is becoming more prevalent according to temperature rises due to climate change.


Asunto(s)
Mapeo Cromosómico , Resistencia a la Enfermedad , Fusarium , Oryza , Enfermedades de las Plantas , Sitios de Carácter Cuantitativo , Oryza/genética , Oryza/microbiología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Fusarium/patogenicidad , Clonación Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Cromosomas de las Plantas/genética
7.
J Thorac Dis ; 16(4): 2394-2403, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38738253

RESUMEN

Background: The strategy of treatment for tricuspid regurgitation (TR) induced by atrial fibrillation (AF) has not been established. The aim of this study was to evaluate the outcomes of surgical treatment for TR induced by AF. Methods: From 2000 to 2021, a total of 1,301 patients underwent tricuspid valve (TV) surgery. Among them 43 patients who diagnosed as AF induced TR were enrolled. The tricuspid valve-related events (TVRE) included cardiac death, TV reoperation, development of moderate or greater TV disease, congestive heart failure requiring re-admission, and major bleeding or thrombosis. The median follow-up duration was 42.0 months. Results: The interval from diagnosis of AF to more than moderate TR was 61.2 months, and the interval from initial diagnosis of severe TR to surgery was 2.4 months. Concomitant Cox-maze III procedure was performed in 39 patients. The operative mortality occurred in 1 patient, and there was no permanent pacemaker implantation. Overall survival rates at 1- and 5-year were 90.6% and 79.3%, respectively. The cumulative incidence of TVRE at 1- and 5-year were 16.3% and 26.5%, respectively. The cumulative incidences of AF recurrence at 1- and 3-year in the patients with surgical ablation were 29.7% and 67.6%. The TVRE was significantly associated with the longer interval from diagnosis of severe TR to surgery (hazard ratio: 1.023, 95% confidence interval: 1.005-1.042). Conclusions: TV surgery for TR induced by AF showed low surgical mortality and favorable mid-term outcomes. For these patients, early surgery after progress to severe TR can be helpful to decrease the occurrence of TVRE.

8.
Cancer Res Treat ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38697848

RESUMEN

Purpose: Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to two years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), 9 (26%), and 4 (12%) had a tumor proportion score of <1%, 1-50%, and ≥50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a five-year DFS rate of 29%. The OS rate was 86% at two years and 76% at five years. Patients with tumor recurrence within six months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion: Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

9.
Investig Clin Urol ; 65(3): 248-255, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38714515

RESUMEN

PURPOSE: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. MATERIALS AND METHODS: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. RESULTS: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). CONCLUSIONS: Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.


Asunto(s)
Adyuvantes Inmunológicos , Antimetabolitos Antineoplásicos , Vacuna BCG , Desoxicitidina , Gemcitabina , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Estudios Retrospectivos , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Masculino , Femenino , Administración Intravesical , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Persona de Mediana Edad , Adyuvantes Inmunológicos/administración & dosificación , Cistectomía/métodos , Medición de Riesgo , Uretra
10.
World Neurosurg ; 187: e963-e981, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38735564

RESUMEN

OBJECTIVE: The internet, particularly social media, has become a popular resource for learning about health and investigating one's own health conditions. The development of artificial intelligence (AI) chatbots has been fueled by the increasing availability of digital health data and advances in natural language processing techniques. While these chatbots are more accessible than before, they sometimes fail to provide accurate information. METHODS: We used representative chatbots currently available (Chat Generative Pretrained Transformer-3.5, Bing Chat, and Google Bard) to answer questions commonly asked by brain tumor patients. The simulated situations with questions were made and selected by the brain tumor committee. These questions are commonly asked by brain tumor patients. The goal of the study was introduced to each chatbot, the situation was explained, and questions were asked. All responses were collected without modification. The answers were shown to the committee members, and they were asked to judge the responses while blinded to the type of chatbot. RESULTS: There was no significant difference in accuracy and communication ability among the 3 groups (P = 0.253, 0.090, respectively). For empathy, Bing Chat and Google Bard were superior to Chat Generative Pretrained Transformer (P = 0.004, 0.002, respectively). The purpose of this study was not to assess or verify the relative superiority of each chatbot. Instead, the aim was to identify the shortcomings and changes needed if AI chatbots are to be used for patient medical purposes. CONCLUSION: AI-based chatbots are a convenient way for patients and the general public to access medical information. Under such circumstances, medical professionals must ensure that the information provided to chatbot users is accurate and safe.


Asunto(s)
Inteligencia Artificial , Neoplasias Encefálicas , Medios de Comunicación Sociales , Humanos , Consejo/métodos , Encuestas y Cuestionarios , Procesamiento de Lenguaje Natural
11.
Artículo en Inglés | MEDLINE | ID: mdl-38565405

RESUMEN

PURPOSE: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy. METHODS AND MATERIALS: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy. RESULTS: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535). CONCLUSIONS: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38442916

RESUMEN

BACKGROUND: As redo surgical aortic valve replacement (AVR) is relatively high risk, valve-in-valve transcatheter AVR has emerged as an alternative for failed prostheses. However, the majority of studies are outdated. This study assessed the current clinical outcomes of redo AVR. METHODS AND RESULTS: This study enrolled 324 patients who underwent redo AVR due to prosthetic valve failure from 2010 to 2021 in four tertiary centers. The primary outcome was operative mortality. The secondary outcomes were overall survival, cardiac death, and aortic valve-related events. Logistic regression analysis, clustered Cox proportional hazards models, and competing risk analysis were used to evaluate the independent risk factors. Redo AVR was performed in 242 patients without endocarditis and 82 patients with endocarditis. Overall operative mortality was 4.6% (15 deaths). Excluding patients with endocarditis, the operative mortality of redo AVR decreased to 2.5%. Multivariate analyses demonstrated that endocarditis (hazard ratio [HR]: 3.990, p = 0.014), longer cardiopulmonary bypass time (HR: 1.006, p = 0.037), and lower left ventricular ejection fraction (LVEF) (HR: 0.956, p = 0.034) were risk factors of operative mortality. Endocarditis and lower LVEF were independent predictors of overall survival. CONCLUSION: The relatively high risk of redo AVR was due to reoperation for prosthetic valve endocarditis. The outcomes of redo AVR for nonendocarditis are excellent. Our findings suggest that patients without endocarditis, especially with acceptable LVEF, can be treated safely with redo AVR.

13.
Clin Cancer Res ; 30(10): 2097-2110, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38457288

RESUMEN

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de Cabeza y Cuello , Terapia Neoadyuvante , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Persona de Mediana Edad , Femenino , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Neoadyuvante/métodos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Adulto , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos
14.
Cancer Sci ; 115(5): 1602-1610, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38480462

RESUMEN

Anti-programmed death-ligand 1 (PD-L1) Ab-based therapies have demonstrated potential for treating metastatic urothelial cancer with high PD-L1 expression. Urinary exosomes are promising biomarkers for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD-L1/Alix ratio to normalize exosomal PD-L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD-L1, and Alix on individual exosomes. On-disc ELISA was used to evaluate PD-L1 and Alix-normalized PD-L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On-disc ELISA was more reliable for detecting exosomal PD-L1 expression than standard plate ELISA-based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD-L1 in urine samples from patients with urothelial cancer.


Asunto(s)
Antígeno B7-H1 , Biomarcadores de Tumor , Exosomas , Humanos , Exosomas/metabolismo , Antígeno B7-H1/orina , Biomarcadores de Tumor/orina , Proteínas de Ciclo Celular/orina , Ensayo de Inmunoadsorción Enzimática/métodos , Masculino , Neoplasias de la Vejiga Urinaria/orina , Neoplasias de la Vejiga Urinaria/patología , Femenino , Anciano , Persona de Mediana Edad , Neoplasias Urológicas/orina , Neoplasias Urológicas/patología , Biopsia Líquida/métodos
15.
Eur J Cardiothorac Surg ; 65(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447184

RESUMEN

OBJECTIVES: To compare the early- and long-term clinical outcomes of concomitant surgical ablation (SA) for atrial fibrillation (AF) during isolated aortic valve replacement (AVR) using data from the Korean National Health Insurance Service Database. METHODS: Of 23,332 adult patients who underwent AVR between 2003 and 2019, those with underlying AF with or without concomitant SA were extracted, and propensity score matching analysis was performed. RESULTS: Overall, 1,741 patients with underlying AF with (n = 445, group A) or without (n = 1,296, group N) concomitant SA during isolated AVR were enrolled, from whom 435 pairs were matched in a 1:1 ratio using propensity score matching analysis. The operative mortality and early postoperative morbidities, including bleeding reoperation, stroke, permanent pacemaker implantation and acute kidney injury were comparable between the groups. The overall survival showed no differences between the groups. However, the cumulative incidence of new-onset late ischaemic stroke was significantly lower in group A than group N in propensity score-matched patients [2.3 vs 3.5 per 100 patient-years, adjusted hazard ratio (95% confidence interval) 0.64 (0.43-0.96), Group A versus Group N, respectively]. The cumulative incidence of other morbidities such as reoperation, permanent pacemaker implantation and progression to chronic renal failure showed no difference between groups. CONCLUSIONS: The incidence of late ischaemic stroke was significantly lower when concomitant SA was performed during isolated AVR in patients with underlying AF. Therefore, concomitant SA should be actively considered in patients with underlying AF undergoing isolated AVR to prevent the occurrence of late ischaemic stroke.


Asunto(s)
Fibrilación Atrial , Isquemia Encefálica , Implantación de Prótesis de Válvulas Cardíacas , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Válvula Aórtica/cirugía , Resultado del Tratamiento , Factores de Riesgo , Fibrilación Atrial/cirugía , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/cirugía , Estudios Retrospectivos
16.
Small ; 20(19): e2310873, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38279618

RESUMEN

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.


Asunto(s)
Ferroptosis , Nanopartículas , Ferroptosis/efectos de los fármacos , Humanos , Nanopartículas/química , Animales , Rayos X , Línea Celular Tumoral , Ratones , Apoptosis/efectos de los fármacos , Ácido Hialurónico/química , Terapia Combinada
17.
Artículo en Inglés | MEDLINE | ID: mdl-38213113

RESUMEN

While mechanical thrombectomy is known to be effective for distal medium vessel occlusion (DMVO) as well as large vessel occlusion, tortuous DMVO are predisposed to vessel injury during stent retriever thrombectomy. Furthermore, getting access to the thrombus may be difficult during suction thrombectomy using a dedicated suction catheter. Most studies describe DMVO treatment using stent retrievers and dedicated suction catheters, but there are limited studies reporting DMVO treated with suction thrombectomy using a microcatheter. Herein, we describe three cases of DMVO treated with suction thrombectomy that was performed using a microcatheter and subsequently showed good results. Therefore, suction thrombectomy using a microcatheter is a viable alternative treatment for tortuous DMVO.

18.
Stud Health Technol Inform ; 310: 1374-1375, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38270050

RESUMEN

A data pipeline was developed to send and receive patient blood management (PBM) data from all medical institutions in Korea. By incorporating the collected data with national big data, the system will be able to generate key performance index for each medical institution. The central PBM system also provides feedback to each individual medical institution.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Sistemas de Información en Hospital , Humanos , Macrodatos , Recolección de Datos , Transfusión Sanguínea
19.
Cancer Res Treat ; 56(1): 115-124, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37641819

RESUMEN

PURPOSE: This study aimed to determine the role of local ablative radiotherapy (LART) in oligometastatic/oligoprogressive lung adenocarcinoma. MATERIALS AND METHODS: Patients (n=176) with oligometastatic lung adenocarcinoma treated with LART were identified, and those treated with LART at the initial diagnosis of synchronous oligometastatic disease (OMD group) or treated with LART when they presented with repeat oligoprogression (OPD group) were included. RESULTS: In the OMD group (n=54), the 1- and 3-year progression-free survival (PFS) were 50.9% and 22.5%, respectively, whereas the 1- and 3-year overall survival in the OPD group were 75.9% and 58.1%, respectively. Forty-one patients (75.9%) received LART at all gross disease sites. Tyrosine kinase inhibitor (TKI) use and all-metastatic site LART were significant predictors of higher PFS (p=0.018 and p=0.046, respectively). In patients treated with TKIs at the time of LART (n=23) and those treated with all-metastatic site LART, the 1-year PFS was 86.7%, while that of patients not treated with all-metastatic site LART was 37.5% (p=0.006). In the OPD group (n=122), 67.2% of the patients (n=82) maintained a systemic therapy regimen after LART. The cumulative incidence of changing systemic therapy was 39.6%, 62.9%, and 78.5% at 6 months, 1 year, and 2 years after LART, respectively. CONCLUSION: Aggressive LART can be an option to improve survival in patients with oligometastatic disease. Patients with synchronous oligometastatic disease receiving TKI and all-metastatic site LART may have improved PFS. In patients with repeat oligoprogression, LART might potentially extend survival by delaying the need to change the systemic treatment regimen.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Adenocarcinoma del Pulmón/radioterapia , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/uso terapéutico
20.
Cancer Res Treat ; 56(2): 414-421, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37997326

RESUMEN

PURPOSE: Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey. MATERIALS AND METHODS: Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively. RESULTS: A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)-European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were 'too complicated' (66.0%), followed by 'insufficient supporting evidence' (30.0%), respectively. CONCLUSION: While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers.


Asunto(s)
Neoplasias Encefálicas , Oncología por Radiación , Humanos , Oncólogos de Radiación , Encuestas y Cuestionarios , República de Corea/epidemiología
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