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BACKGROUND: No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma. METHODS: We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight intravenously on days 1 and 8) and pembrolizumab (at a dose of 200 mg intravenously on day 1) (enfortumab vedotin-pembrolizumab group) or gemcitabine and either cisplatin or carboplatin (determined on the basis of eligibility to receive cisplatin) (chemotherapy group). The primary end points were progression-free survival as assessed by blinded independent central review and overall survival. RESULTS: A total of 886 patients underwent randomization: 442 to the enfortumab vedotin-pembrolizumab group and 444 to the chemotherapy group. As of August 8, 2023, the median duration of follow-up for survival was 17.2 months. Progression-free survival was longer in the enfortumab vedotin-pembrolizumab group than in the chemotherapy group (median, 12.5 months vs. 6.3 months; hazard ratio for disease progression or death, 0.45; 95% confidence interval [CI], 0.38 to 0.54; P<0.001), as was overall survival (median, 31.5 months vs. 16.1 months; hazard ratio for death, 0.47; 95% CI, 0.38 to 0.58; P<0.001). The median number of cycles was 12 (range, 1 to 46) in the enfortumab vedotin-pembrolizumab group and 6 (range, 1 to 6) in the chemotherapy group. Treatment-related adverse events of grade 3 or higher occurred in 55.9% of the patients in the enfortumab vedotin-pembrolizumab group and in 69.5% of those in the chemotherapy group. CONCLUSIONS: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma, with a safety profile consistent with that in previous reports. (Funded by Astellas Pharma US and others; EV-302 ClinicalTrials.gov number, NCT04223856.).
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Anticorpos Monoclonais , Antineoplásicos , Carcinoma de Células de Transição , Neoplasias Urológicas , Humanos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Neoplasias da Bexiga Urinária , Gencitabina/administração & dosagem , Gencitabina/efeitos adversos , Gencitabina/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Análise de Sobrevida , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/secundárioRESUMO
Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, western blotting, viability assays, wound healing assays, verteporfin treatment, and xenograft assays were conducted using melanoma cell lines B16F1 and B16F10 subjected to YapS127A transfection and siYap knockdown. Nuclear YAP localization was identified in 63 tumors (45.0%) and was more frequent than cytoplasmic YAP in acral lentiginous and nodular subtypes (P = .007). Compared with cytoplasmic YAP melanomas, melanomas with nuclear YAP had higher mitotic activity (P = .016), deeper invasion (P < .001), and more frequently metastasized to lymph nodes (P < .001) and distant organs (P < .001). Patients with nuclear YAP melanomas had poorer disease-free survival (P < .001) and overall survival (P < .001). Nuclear YAP was an independent risk factor for distant metastasis (hazard ratio: 3.206; 95% CI, 1.032-9.961; P = .044). Proliferative ability was decreased in siYapB16F1 (P < .001) and siYapB16F10 (P = .001) cells and increased in YapS127AB16F1 (P = .003) and YapS127AB16F10 (P = .002) cells. Cell cycle analysis demonstrated relative G1 retention in siYapB16F1 (P < .001) and siYapB16F10 (P < .001) cells and S retention in YapS127AB16F1 cells (P = .008). Wound healing assays showed that Yap knockdown inhibited cell invasion (siYapB16F1, P = .001; siYapB16F10, P < .001), whereas nuclear YAP promoted it (YapS127AB16F, P < .001; YapS127AB16F1, P = .017). Verteporfin, a direct YAP inhibitor, reduced cellular proliferation in B16F1 (P = .003) and B16F10 (P < .001) cells. Proliferative effects of nuclear YAP were confirmed in xenograft mice (P < .001). In conclusion, nuclear YAP in human melanomas showed subtype specificity and correlated with proliferative activity and proinvasiveness. It is expected that YAP becomes a useful prognostic marker, and its inhibition may be a potential therapy for melanoma patients.
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Proteínas Adaptadoras de Transdução de Sinal , Núcleo Celular , Melanoma , Neoplasias Cutâneas , Fatores de Transcrição , Proteínas de Sinalização YAP , Animais , Feminino , Humanos , Masculino , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Progressão da Doença , Melanoma/metabolismo , Melanoma/patologia , Melanoma Maligno Cutâneo , Camundongos Nus , Fosfoproteínas/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP/metabolismoRESUMO
BACKGROUND: Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP). PATIENTS AND METHODS: Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib. RESULTS: Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses. CONCLUSIONS: Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.
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Melanoma , Mutação , Proteínas Proto-Oncogênicas B-raf , Humanos , Melanoma/genética , Melanoma/tratamento farmacológico , Melanoma/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Proteínas Proto-Oncogênicas B-raf/genética , GTP Fosfo-Hidrolases/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-raf/genética , Idoso de 80 Anos ou mais , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Seed dormancy is a biological mechanism that prevents germination until favorable conditions for the subsequent generation of plants are encountered. Therefore, this mechanism must be effectively established during seed maturation. Studies investigating the transcriptome and miRNAome of rice embryos and endosperms at various maturation stages to evaluate seed dormancy are limited. This study aimed to compare the transcriptome and miRNAome of rice seeds during seed maturation. RESULTS: Oryza sativa L. cv. Nipponbare seeds were sampled for embryos and endosperms at three maturation stages: 30, 45, and 60 days after heading (DAH). The pre-harvest sprouting (PHS) assay was conducted to assess the level of dormancy in the seeds at each maturation stage. At 60 DAH, the PHS rate was significantly increased compared to those at 30 and 45 DAH, indicating that the dormancy is broken during the later maturation stage (45 DAH to 60 DAH). However, the largest number of differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) were identified between 30 and 60 DAH in the embryo and endosperm, implying that the gradual changes in genes and miRNAs from 30 to 60 DAH may play a significant role in breaking seed dormancy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses confirmed that DEGs related to plant hormones were most abundant in the embryo during 45 DAH to 60 DAH and 30 DAH to 60 DAH transitions. Alternatively, most of the DEGs in the endosperm were related to energy and abiotic stress. MapMan analysis and quantitative real-time polymerase chain reaction identified four newly profiled auxin-related genes (OsSAUR6/12/23/25) and one ethylene-related gene (OsERF087), which may be involved in seed dormancy during maturation. Additionally, miRNA target prediction (psRNATarget) and degradome dataset (TarDB) indicated a potential association between osa-miR531b and ethylene biosynthesis gene (OsACO4), along with osa-miR390-5p and the abscisic acid (ABA) exporter-related gene (OsMATE19) as factors involved in seed dormancy. CONCLUSIONS: Analysis of the transcriptome and miRNAome of rice embryos and endosperms during seed maturation provided new insights into seed dormancy, particularly its relationship with plant hormones such as ABA, auxin, and ethylene.
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MicroRNAs , Oryza , Dormência de Plantas/genética , Oryza/genética , Transcriptoma , Reguladores de Crescimento de Plantas/metabolismo , Germinação/genética , Sementes/genética , Ácido Abscísico/metabolismo , Etilenos/metabolismo , Ácidos Indolacéticos/metabolismo , MicroRNAs/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Lymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer. METHODS: We included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed. RESULTS: Among 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 - 9 (CA 19 - 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728. CONCLUSION: Our newly developed prediction model using age, CA 19 - 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer.
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Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Metástase Linfática , Pancreaticoduodenectomia , Humanos , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Masculino , Feminino , Metástase Linfática/patologia , Pessoa de Meia-Idade , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/patologia , Idoso , Estudos Retrospectivos , Fatores de Risco , Prognóstico , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Linfonodos/patologia , Linfonodos/cirurgia , Adulto , Antígeno CA-19-9/sangue , Período Pré-Operatório , Excisão de Linfonodo , Idoso de 80 Anos ou maisRESUMO
Ubiquitination is a representative post-translational modification that tags target proteins with ubiquitin to induce protein degradation or modify their functions. Deubiquitinating enzymes (DUBs) play a crucial role in reversing this process by removing ubiquitin from target proteins. Among them, USP2a has emerged as a promising target for cancer therapy due to its oncogenic properties in various cancer types, but its inhibitors have been limited. In this study, our aim was to optimize the structure of ML364, a USP2a inhibitor, and synthesize a series of its derivatives to develop potent USP2a inhibitors. Compound 8v emerged as a potential USP2a inhibitor with lower cytotoxicity compared to ML364. Cellular assays demonstrated that compound 8v effectively reduced the levels of USP2a substrates and attenuated cancer cell growth. We confirmed its direct interaction with the catalytic domain of USP2a and its selective inhibitory activity against USP2a over other USP subfamily proteins (USP7, 8, or 15). In conclusion, compound 8v has been identified as a potent USP2a inhibitor with substantial potential for cancer therapy.
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Endopeptidases , Ubiquitina , Endopeptidases/química , Proteólise , Ubiquitina/metabolismo , UbiquitinaçãoRESUMO
BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.
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Biomarcadores , Morte Súbita Cardíaca , Parada Cardíaca Extra-Hospitalar , Sistema de Registros , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Masculino , Feminino , Vitamina D/sangue , Vitamina D/análogos & derivados , Pessoa de Meia-Idade , Estudos de Casos e Controles , Medição de Risco , Idoso , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Fatores de Risco , Biomarcadores/sangueRESUMO
OBJECTIVES: The effect of the case volume of emergency medical services (EMS) on the clinical outcomes of trauma is uncertain. The purpose of this study was to evaluate the association between the case volume of an ambulance station and clinical outcomes in moderate to severe trauma patients. METHODS: Adult trauma patients with injury severity scores greater than 8 who were transported by the EMS between 2018 and 2019 were analyzed. The main exposure was the annual case volume of moderate to severe trauma at the ambulance station where the patient-transporting ambulance was based: low-volume (less than 60 cases), intermediate-volume (between 60 and 89 cases), and high-volume (equal or greater than 90 cases). The primary outcome was in-hospital mortality. Multilevel multivariable logistic regression analysis was conducted to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs), with the high-volume group used as the reference. RESULTS: In total, 21,498 trauma patients were analyzed. The high-volume group exhibited lower in-hospital mortality, 447 (9.0%), compared to 867 (14.1%) in the intermediate-volume group and 1,458 (14.1%) in the low-volume group. There were a significantly higher odds of in-hospital mortality: the low-volume group (AOR 95% CI: 1.20 (0.95-1.51)) and intermediate-volume group (AOR 95% CI: 1.29 (1.02-1.64)) when compared to the high-volume group. CONCLUSIONS: The case volume at an ambulance station is associated with in-hospital mortality in patients with moderate to severe trauma. These results should be considered when constructing an EMS system and education program for prehospital trauma care.
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BACKGROUND: Major trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear. METHODS: We conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups. RESULTS: The sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups. CONCLUSIONS: sFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients.
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Serviços Médicos de Emergência , Febre Grave com Síndrome de Trombocitopenia , Ferimentos e Lesões , Adulto , Humanos , Adolescente , Triagem , Estudos Retrospectivos , Escala de Gravidade do Ferimento , Centros de Traumatologia , Ferimentos e Lesões/diagnósticoRESUMO
PURPOSE: This study aimed to evaluate the symptomatic response and side effects of ventriculolumbar perfusion (VLP) methotrexate chemotherapy with a low perfusion rate in patients with leptomeningeal metastasis. METHODS: Patients in a single-arm, two-stage phase II trial based on Simon's minimax design received VLP with a reduced (15 cc/h) perfusion rate with the purpose of decreasing constitutional side effects such as nausea/vomiting, insomnia, and confusion. The primary outcome was control of increased intracranial pressure (ICP). The secondary outcome was an occurrence of side effects. The results were compared with those of a previous trial of VLP with a 20-cc/h perfusion rate. RESULTS: Total 90 patients were enrolled. Out of 65 patients with increased ICP, 32 achieved normalized ICP after VLP chemotherapy (bias-adjusted response rate = 51%). The incidence of moderate-to-severe nausea/vomiting was reduced to 46% from 64% in the previous study, and that of sleep disturbance was increased to 13% from 9%, but both failed to reach statistical significance. The incidence of moderate-to-severe confusion was significantly reduced to 12% from 23% in the previous study (p = 0.04). Median overall survival was better among patients with controlled ICP than among those who remained with increased ICP (193 days vs. 94 days, p = 0.013). CONCLUSION: Compared with a higher perfusion rate, the low perfusion rate failed to provide non-inferior ICP control or improved side effects, except for confusion. The relationship between VLP perfusion rate and ICP control needs to be evaluated in future trials adjusting for bias from uncompleted protocol due to poor general condition.
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Carcinomatose Meníngea , Humanos , Carcinomatose Meníngea/tratamento farmacológico , Carcinomatose Meníngea/secundário , Metotrexato/uso terapêutico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Perfusão , Vômito/induzido quimicamente , Vômito/tratamento farmacológicoRESUMO
Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.
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Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Metotrexato/farmacologia , Metotrexato/uso terapêutico , MicroRNAs/genética , MicroRNAs/uso terapêutico , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologiaRESUMO
In Korea, decommissioning of nuclear power plants and transportation of the decommissioning waste are expected to expand in the near future. It is necessary to confirm that radiological risks to the public and workers are not significant through radiological safety assessment. The objective of this study is to assess the radiological safety for transportation of RPV waste, which is a major decommissioning waste with relatively high level of radioactivity. It was assumed that the waste would be transported to the Gyeongju disposal facility by land transportation. First, the source term and transportation method of the RPV waste were determined, and the external dose rates from the waste were calculated using MCNP. Then, transportation scenarios were assumed under both normal and accident conditions. Under the scenarios, radiation doses were calculated using the RADTRAN. Under normal operation scenarios without a transportation accident, assuming 40 shipments per year, the average individual doses for the public ranged from 6.56×10-6to 2.18×10-2mSv yr-1. The maximum individual doses for only a single shipment ranged from 2.43×10-6to 3.14×10-1mSv. For cargo handlers and vehicle crew members, the average doses were 2.26×101mSv yr-1and 2.95 mSv yr-1, respectively. Under transportation accident scenarios, average individual radiological risks which are product of the radiation doses and the annual accident rates ranged from 1.14×10-11to 1.61×10-10mSv yr-1by transportation route segment when considering the transportation accident rate. Average individual doses assuming transportation accident occurrence ranged from 2.62×10-4to 1.42×10-3mSv. The maximum individual dose under accident conditions was 7.99×10-2mSv. The calculated doses were below the regulatory limits in Korea. However, relatively high doses were observed for cargo handlers and vehicle crew members because of conservative assumptions. This study results can be used as basic data for the radiological safety assessment for the decommissioning waste transportation in the future.
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Acidente Nuclear de Fukushima , Monitoramento de Radiação , Humanos , Centrais Nucleares , Doses de Radiação , Monitoramento de Radiação/métodos , República da CoreiaRESUMO
Warts caused by the human papillomavirus (HPV) are generally treated with cryotherapy, CO2 laser ablation, interferon injections, and bleomycin injections. However, it is sometimes difficult to treat children because the treatment can be painful. In addition, recurrence may occur after treatment. In this study, warts completely disappeared following the administration of herbal medicine in two children, with warts in multiple parts of the hands and around the nails. Two pediatric patients visited the hospital for treatment of warts around their fingers and nails. Both patients received Taeeumjowi-tang (TJT) as a decoction for 60 days. TJT was performed twice per day for the 11-year-old patient and once per day for the 7-year-old patient. Patient progress was observed monthly, and the visual condition of the warts was photographed during the visits. After approximately two months of treatment, the warts disappeared from the fingers and nails of both patients. This case study suggests that the oral administration of TJT may be effective for pediatric patients with warts. Further studies are required to determine the efficacy and safety of these therapies.
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Lipomas are one of the most common mesenchymal tumors in the human body, exhibiting a heightened prevalence between the ages of 40 and 60 years. However, primary intraoral lipomas are rare. Myxoid lipoma, which is characterized by abundant mucoid components, is a particularly rare histological subtype of lipoma. This study presents two cases of myxoid lipoma that occurred outside the common age range for occurrence, one in the right submandibular area of a 67-year-old male and the other in the lower lip of a 3-year-old child. Through these case reports, the aim was to introduce myxoid lipoma, a rare subtype affecting facial areas, and provide a brief review to assist in the differential diagnosis, emphasizing the importance of pathological assessment. Even in age groups and anatomical locations not typically associated with lipomas, it is crucial to emphasize the necessity of careful evaluation.
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We have examined whether the copper reduction slag (CRS) generated after recovering valuable metals from copper slag (CS) by reduction process can be used as supplementary cementitious materials (SCMs). According to the test results, the Cu secondary slag with low Fe, Cu, and heavy metal contents had a suitable oxide composition for using as a SCM. CRS showed better grinding efficiency than that of ground blast furnace slag (GGBS). Ground CRS contributed to the formation of tobermorite under autoclaved curing conditions. The compressive strength of CRS mortar replacing 50 % of OPC generated 93 % of that of the OPC mortar. Based on the results of this study, we found that the CRS has highly appropriate engineering characteristics for using as SCMs for concrete. In addition, it is judged that the method of using secondary slag as a material for precast concrete produced under hydrothermal conditions can greatly contribute to the construction process of buildings by securing mechanical performance.
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This study aimed to assess the predictive ability of the shock index (SI) and the shock index, pediatric age-adjusted (SIPA) for mortality among pediatric patients with trauma (aged ≤ 18 years). A systematic search used PubMed, Embase, and Cochrane Library databases to identify pertinent articles published from their inception to 13 February 2023. For each SI and SIPA, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals were calculated. We planned a priori meta-regression analyses to explore heterogeneity using the following covariates: country, clinical setting, type of center, data source, and cutoff value. Twelve studies were included based on the inclusion criteria. Among them, nine studies with 195,469 patients were included for the SIPA at the hospital, four studies with 4,970 patients were included for the pre-hospital SIPA, and seven studies with 606,445 patients were included to assess the ability of the SI in predicting mortality. The pooled sensitivity and specificity with 95% confidence interval for predicting mortality were as follows: 0.58 (0.44-0.70) and 0.72 (0.60-0.82), respectively, for the SIPA at the hospital; 0.61 (0.47-0.74) and 0.67 (0.61-0.73), respectively, for the pre-hospital SIPA; and 0.71 (0.59-0.81) and 0.45 (0.31-0.59), respectively for the SI. The DOR were 3.80, 3.28, and 2.06 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The AUC were 0.693, 0.689, and 0.618 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The SI and SIPA are simple predictive tools with sufficient accuracy that can be readily applied to pediatric patients with trauma, but SIPA and SI should be utilized cautiously due to their limited sensitivity and specificity, respectively.
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Choque , Ferimentos e Lesões , Humanos , Criança , Choque/mortalidade , Choque/diagnóstico , Ferimentos e Lesões/mortalidade , Adolescente , Curva ROC , Pré-Escolar , PrognósticoRESUMO
Rituximab is a monoclonal antibody that targets CD20 antigen in B cells. For pemphigus, rituximab has been highly effective in steroid-sparing therapy for moderate to severe cases. Originator rituximab has demonstrated favorable treatment effects in patients with pemphigus, but its high cost remains a challenge. Biosimilar rituximab is expected to offer a potential solution. However, it is required for the comparative study of efficacy and safety between biosimilar and originator because all biosimilars may not be identical to the originator. In this study, we compared the treatment effects and safety of biosimilar (Truxima) and originator (MabThera) rituximab in patients with pemphigus. A final cohort of 52 patients in the MabThera group and 72 patients in the Truxima group was enrolled. Except for the intravenous immunoglobulin administration rate, there were no differences in baseline characteristics between the two groups, and for the purpose of comparing efficacy, investigations into time to complete remission, total steroid intake to complete remission, and total steroid intake for 6 months following rituximab treatment revealed no significant differences between the two groups. Truxima can be considered a relatively affordable alternative treatment option for pemphigus, offering cost-effectiveness to patients who are indicated for the treatment with MabThera.
Assuntos
Medicamentos Biossimilares , Pênfigo , Rituximab , Humanos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Pênfigo/tratamento farmacológico , Pênfigo/imunologia , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/economia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Idoso , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/administração & dosagem , Indução de Remissão/métodos , Estudos RetrospectivosRESUMO
INTRODUCTION: It is unclear whether emergency medical service (EMS) agencies with good out-of-hospital cardiac arrest (OHCA) quality indicators also perform well in treating other emergency conditions. We aimed to evaluate the association of an EMS agency's non-traumatic OHCA quality indicators with prehospital management processes and clinical outcomes of major trauma. METHODS: This retrospective cross-sectional study analyzed data from registers of nationwide, population-based OHCA (adult EMS-treated non-traumatic OHCA patients from 2017 to 2018) and major trauma (adult, EMS-treated, and injury severity score ≥16 trauma patients in 2018) in South Korea. We developed a prehospital ROSC prediction model to categorize EMS agencies into quartiles (Q1-Q4) based on the observed-to-expected (O/E) ROSC ratio for each EMS agency. We evaluated the national EMS protocol compliance of on-scene management according to O/E ROSC ratio quartile. The association between O/E ROSC ratio quartiles and trauma-related early mortality was determined in a multi-level logistic regression model by adjusted odds ratios (OR) and 95 % confidence intervals (95 % CI). RESULTS: Among 30,034 severe trauma patients, 4,836 were analyzed. Patients in Q4 showed the lowest early mortality rate (5.6 %, 5.5 %, 4.8 %, and 3.4 % in Q1, Q2, Q3, and Q4, respectively). In groups Q1 to Q4, increasing compliance with the national EMS on-scene management protocol (trauma center transport, basic airway management for patients with altered mentality, spinal motion restriction for patients with spinal injury, and intravenous access for patients with hypotension) was observed (p for trend <0.05). Multivariable multi-level logistic regression analysis showed significantly lower early mortality in Q4 than in Q1 (adjusted OR [95 % CI] 0.56 [0.35-0.91]). CONCLUSION: Major trauma patients managed by EMS agencies with high success rates in achieving prehospital ROSC in non-traumatic OHCA were more likely to receive protocol-based care and exhibited lower early mortality.