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PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5â¯Σâ¯+ 0.7â¯σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITVâ©PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8â¯mm (LR), 2.2â¯mm (AP), and 5.3â¯mm (SI). Four healthy volunteers participated for validation. A margin of 3â¯mm (AP) and 5â¯mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3â¯mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.
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Tomografia Computadorizada de Feixe Cônico , Glote , Neoplasias Laríngeas , Imagem Cinética por Ressonância Magnética , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Imagem Cinética por Ressonância Magnética/métodos , Glote/diagnóstico por imagem , Masculino , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/radioterapia , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Movimentos dos Órgãos , Sistemas Computacionais , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Vertical migration behaviour, which is integral to marine energy circulation, is a prevalent trait among marine organisms. However, the behaviour of phytoplankton, particularly beyond diel vertical migration (DVM), remain underexplored compared to groups like zooplankton. Through the lens of the harmful alga Heterosigma akashiwo, which exhibits active vertical migrations and unique fluctuating bloom dynamics, this study aimed to explore the ecological intricacies and diverse benefits of phytoplankton vertical migration behaviours. During the bloom period of H. akashiwo, we unexpectedly observed a dense concentration of cells at bottom layer during daytime. This phase coincided with the emergence of cells related to this species' sexual reproduction. Laboratory experiments further showed an elevated frequency of sexual reproduction in the cell populations that migrated to deeper depths compared to those at the surface. This finding implies a connection between dense bottom accumulation (BA) and the life cycle transitions of the species. This BA phase persisted for two days, after which the populations returned to their standard DVM behaviour, providing insight into the unique fluctuating bloom dynamics of H. akashiwo. Our study suggests that phytoplankton vertical migrations are not strictly dictated by DVM, revealing diverse vertical migration behaviours that may contribute to the complexity of harmful algal bloom patterns.
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Proliferação Nociva de Algas , Fitoplâncton , Reprodução , Fitoplâncton/fisiologia , Fitoplâncton/crescimento & desenvolvimentoRESUMO
Recently, alopecia areata (AA) treatment via the Janus kinase (JAK)-signal transducer and activator of transcription pathway has been reported. However, as baricitinib, a JAK1/2 inhibitor is only approved for adult patients, children, and adolescent patients still lack treatment options. We present a case that showed improvement of severe AA in an adolescent patient on upadacitinib, which has been approved by the Food and Drug Administration (FDA) for use in patients with rheumatoid disease or atopic dermatitis (AD) in children aged 12 years or older and weighing 40 kg or more. Herein, we suggest that upadacitinib can be a good alternative for adolescent patients with AA, particularly those who may also have AD.
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Alopecia em Áreas , Inibidores de Janus Quinases , Estados Unidos , Adulto , Criança , Humanos , Adolescente , Alopecia em Áreas/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Janus Quinases/metabolismo , Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/uso terapêuticoRESUMO
BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in paediatric patients, with infectious agents being the main cause. This study aimed to determine whether there are differences in the clinical manifestations of KD between patients with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. METHODS: From January 1, 2021 to August 15, 2022, 82 patients with analysable echocardiographic data were diagnosed with KD. Twelve patients with multisystem inflammatory syndrome in children were excluded. Serologic tests were performed by chemiluminescence immunoassay for both the nucleocapsid (N) and the spike (S) proteins in blood samples. Among the 70 patients diagnosed with KD at Jeonbuk University Children's Hospital, the SARS-CoV-2 antibody test was performed in 41 patients. RESULTS: The SARS-CoV-2 antibody test results for the N antigen were positive in 12 patients, while those for S protein were positive in 14 patients. N antigen SARS-CoV-2 antibody-positive KD was different from N antigen SARS-CoV-2 antibody-negative KD in terms of sex (male predominance in the positive group, 83.3% vs. female predominance in the negative group 62.1%, P = 0.008) and the incidence of refractory KD (41.7% vs. 10.3%, P = 0.034). The pro-B-type natriuretic peptide level was lower in the N-antigen SARS-CoV-2 antibody-positive KD group than that in the negative group (518.9 ± 382.6, 1,467.0 ± 2,417.6, P = 0.049). No significant differences in the echocardiographic findings between both groups were noted. In the multi-variable analysis, SARS-CoV-2 antibody (N antigen) was the only predictor of refractory KD (odds ratio, 13.70; 95% confidence interval, 1.63-115.44; P = 0.016). CONCLUSION: High incidence of intravenous immunoglobulin-refractory KD may occur in up to 40% of the patients having recent history of coronavirus disease 2019. For patients having KD with N-type SARS-CoV-2 antibody positivity, adjunctive treatment, such as corticosteroids, can be considered as the first line of treatment.
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COVID-19 , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Masculino , Feminino , SARS-CoV-2 , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Anticorpos Antivirais , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
BACKGROUND: A proper depth of percutaneous central venous catheter (PCVC) is very important to reduce procedural time and prevent various complications in very low birth weight (VLBW) infants who require minimal handling or have a sensitive skin. The objective of this study was to suggest a formula for faster and proper insertion of PCVC in VLBWIs to prevent unintended consequences of patients' conditions. METHODS: Prospective data of VLBW infants admitted from June 2015 to January 2018 who had PCVC inserted via the great saphenous vein within seven days after birth were analyzed. Correlations of length of inserted PCVC with body weight, body length, and postmenstrual age at the date of PCVC insertion were determined with a linear regression analysis. Using results of this analysis, a formula to determine the optimal insertion length of PCVC was derived. Coefficient of determination was used to assess how well outcomes were replicated by the formula. RESULTS: The formula to predict the proper insertion length of PCVC via the great saphenous vein at popliteal crease level was obtained as follows: Optimal Length (cm) = 3.8 × Body Weight (kg) + 11.1. With everyday movements such as flexion and extension of the lower extremities, the mean difference in catheter tip position was 7.0 ± 3.9 mm, which was not significant enough to escalate the risk of catheter tip displacement. The rate of catheter-related complications was as low as 4.9% in this study. CONCLUSIONS: The formula derived from this study to predict the optimal PCVC insertion length could benefit VLBW infants by reducing procedural time and lowering the risk of complications.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Recém-Nascido , Lactente , Humanos , Estudos Prospectivos , Veia Safena/diagnóstico por imagem , Cateterismo Venoso Central/métodos , Recém-Nascido de muito Baixo Peso , Peso CorporalRESUMO
Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice's survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and ß), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.
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Enterovirus Humano B/imunologia , Infecções por Enterovirus/imunologia , Imunidade Inata , Miocardite/imunologia , Miocárdio/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Doença Aguda , Animais , Enterovirus Humano B/genética , Infecções por Enterovirus/genética , Células HeLa , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/virologia , Camundongos , Camundongos Knockout , Miocardite/genética , Miocardite/virologia , Proteínas Proto-Oncogênicas c-akt/genéticaRESUMO
African swine fever virus (ASFV), a highly contagious virus, can cause diseases with high mortality rates in pigs, making it a pathogen of social and economic significance. ASFV has been reported to show potential long-term survival in living livestock, such as pigs, but also in leftover cooking meat and undercooked pork meat. Hence, it is possible that there could be direct reinfection or secondary infection through feed produced from household food waste and treatment facilities. Many polymerase chain reaction (PCR)-based molecular diagnostic techniques to detect ASFV in clinical swine samples have been reported. However, those with applicability for food waste samples, which contain relatively low viral copy numbers and may contain various unknown inhibitors of PCR, are still lacking. In this study, we developed a conventional PCR-based diagnostic system that can detect ASFV with high sensitivity from food waste sample types. The technique shows a 10-100 times higher limit of detection compared to that of previously reported methods based on conventional PCR and quantitative real-time PCR. It is also capable of amplifying a sequence that is approximately 751 nucleotides, which is advantageous for similarity analysis and genotyping. Moreover, a ASFV-modified positive material different from ASFV that could synthesize 1400 nucleotide amplicons was developed to identify false-positive cases and thus enhance diagnostic accuracy. The method developed herein may be applicable for future ASFV monitoring, identification, and genotyping in food waste samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01007-y.
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Atopic dermatitis is a typical chronic inflammatory skin disease that affects all age groups and requires basic skin care for treatment. Anti-inflammatory and antiallergy steroids are the most frequently used treatments but they are limited due to their side effects caused by a weakening of the immune system. Many consumers focus on performance as a criterion for selecting cosmetics. However, steroids have been illegally used to improve the performance of cosmetics, and consumers have been adversely affected by the corresponding side effects. In this paper, we propose a simple and rapid method using liquid chromatography-tandem mass spectrometry to simultaneously analyze ten non-permitted atopic therapeutic compounds in cosmetic products: chlorpheniramine maleate, ketotifen fumarate, doxepin hydrochloride, azelastine hydrochloride, bufexamac, clotrimazole, tranilast, fusidic acid, tacrolimus, and pimecrolimus. Additionally, the major characteristic fragment ions for tacrolimus, pimecrolimus, and clotrimazole were identified by time-of-flight mass spectrometry. The specificity, linearity, limit of detection, limit of quantification, recovery, precision, accuracy, and stability of the proposed method were validated. The limit of detection and quantification were in the ranges of 5.05-203.30 pg/mL and 15.15-609.90 pg/mL, respectively. The proposed analysis method could help improve the safety management of cosmetics.
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Anti-Inflamatórios não Esteroides/análise , Cosméticos/química , Bufexamac/análise , Clorfeniramina/análise , Cromatografia Líquida de Alta Pressão , Clotrimazol/análise , Doxepina/análise , Ácido Fusídico/análise , Cetotifeno/análise , Ftalazinas/análise , Tacrolimo/análogos & derivados , Tacrolimo/análise , Espectrometria de Massas em Tandem , ortoaminobenzoatos/análiseRESUMO
BACKGROUND: The aim of this study is to investigate the long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome (PSS). METHODS: In this retrospective case series study, a total of 98 patients with PSS from January 2014 to February 2019 were included in this study. Initial presentations and follow-up data were obtained from medical records. Vision-related quality of life (VR-QoL) was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire. RESULTS: Of the 98 patients included in the study, 66 (67%) presented with glaucoma, and among them, 21 (32%) required glaucoma surgery. The mean follow-up time was 50.1 months (range 1-263 months). Iris involvement was noted in 46 (46.9%) eyes; 26 (26.5%) had sectoral iris changes and 20 (20.4%) showed diffuse iris changes. Eyes with iris involvement had a significantly higher number of acute attacks of uveitis than those without (p = 0.010). The 5-year glaucoma surgery-free interval was 77.8% according to Kaplan-Meier analysis. Significant predictors of glaucoma surgery included iris involvement (hazard ratio [HR] = 5.215; confidence interval [CI] = 1.387-19.610), highest number of anti-glaucoma agents (HR = 5.069; CI = 1.848-13.905), baseline average retinal nerve fiber layer thickness (RNFLT) thickness (HR = 0.949; CI = 0.917-0.982), and disease duration (HR = 0.977; CI = 0.957-0.996). Overall complete surgical success and qualified success at 2 years was 35.3% and 75.5%, respectively. Patients with iris involvement, glaucoma surgery, and thinner average RNFLT had significantly poorer VR-QoL (all, p < 0.05). CONCLUSIONS: Patients with PSS and glaucoma required glaucoma surgery in a high rate. Iris involvement increased the probability of surgical treatment and lowered the VR-QoL of PSS patients.
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Glaucoma de Ângulo Aberto , Glaucoma , Glaucoma/diagnóstico , Glaucoma/etiologia , Humanos , Pressão Intraocular , Prognóstico , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.
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Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Lesões por Radiação/epidemiologia , Radiocirurgia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Lesões por Radiação/etiologia , Radiocirurgia/métodos , Taxa de SobrevidaRESUMO
BACKGROUND: Long-term side effects after radiotherapy for organ preservation 'could deteriorate' the laryngeal function. This study intended to identify the incidence of severe late dysphagia following the multimodal treatment for stage III/IV laryngeal and hypopharyngeal cancer 'to evaluate the function of larynx'. METHODS: The medical records of patients successfully treated for laryngeal and hypopharyngeal cancer with a multimodal approach, including radiotherapy, were retrospectively analyzed. 'Functional larynx was defined as tolerable oral diet without severe late dysphagia or tracheostoma'. RESULTS: The study included 99 patients with a median follow-up period of 72 months. 'Tracheostomy during the follow-up period was required in only one patient due to aspiration pneumonia, and dysphagia is the main determinant for functional larynx'. The probability of maintaining functional larynx was 63% for 10 years, when the treatment was started with radiotherapy or concurrent chemoradiotherapy. In upfront surgery (operation first and adjuvant radiotherapy/concurrent chemoradiotherapy) group, 37% of patients required total laryngectomy as primary treatment and 43% of patients could maintain laryngeal function for 10 years. And severe late dysphagia in the latter group developed mainly after laryngeal preservation surgery. The patients aged ≥65 years showed significantly higher incidence of dysphagia. Severe late dysphagia was very rare in laryngeal cancer successfully cured with radiotherapy/concurrent chemoradiotherapy (1/25, 4%); however, it gradually increased over time in hypopharyngeal cancer patients showing a statistically significant difference from laryngeal cancer patients (P = 0.040). CONCLUSION: Severe late dysphagia occurred in 19.2% of patients treated for laryngeal and hypopharyngeal cancers, regardless of whether treatment started with radiotherapy/concurrent chemoradiotherapy or surgery.
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Transtornos de Deglutição/etiologia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Terapia Combinada/efeitos adversos , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Neoplasias Hipofaríngeas/fisiopatologia , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/fisiopatologia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Laringectomia/métodos , Laringe/fisiopatologia , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Mucin family members mucin 1 (MUC1) and mucin 4 (MUC4) play an important role in transformation and adhesion, and are known markers for the detection of cancer. However, the pathophysiology of endometriosis associated with the mucin gene is unclear. In this study, we analyzed the relationship between MUC1 and MUC4 single-nucleotide polymorphisms (SNPs) and the risk for endometriosis. METHODS: We performed a case-controlled study of 29 endometriosis clinical samples and 27 functional cysts as control. Sixteen SNPs (rs145224844, rs139620330, rs144273480, rs1611770, rs146141676, rs201798179, rs201815857, rs199840128, rs200788986, rs141460657, rs183700327, rs199768496, rs191544901, rs200639498, rs148332231, and rs11465209) of MUC1 gene and eight SNPs (rs1104760, rs1106502, rs882605, rs2291651, rs2291652, rs2291653, rs2291654, and rs375068067) of the MUC4 gene were identified. We amplified SNP sites by polymerase chain reaction (PCR) using specific primer sets followed by DNA sequencing. RESULTS: The single mutation analysis of MUC4 showed that MUC4 mutations had no effect on the risk for endometriosis, but the frequencies of haplotypes [T/T + T/T + C/C] (rs2291653, 2291654 and rs375068067) were associated with endometriosis. CONCLUSION: The MUC1 genotype may not be correlated with endometriosis susceptibility. However, MUC4 polymorphisms are associated with the risk for endometriosis in Korean women.
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Endometriose/genética , Mucinas/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , República da CoreiaRESUMO
LESSONS LEARNED: Induction chemotherapy with Genexol-PM and cisplatin demonstrated modest tumor response in locally advanced head and neck squamous cell carcinoma.Considering favorable toxicity profiles and promising survival data, further studies on this regimen are warranted in patients with head and neck squamous cell carcinoma. BACKGROUND: Genexol-PM is a polymeric micellar formulation of paclitaxel without Cremophor EL. We investigated the efficacy and safety of Genexol-PM plus cisplatin as induction chemotherapy (IC) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Patients received Genexol-PM (230 mg/m2) and cisplatin (60 mg/m2) every 3 weeks as IC. After three cycles of IC, definitive treatment of either concurrent chemoradiotherapy (CCRT) with weekly cisplatin (30 mg/m2) or surgery was performed. The primary endpoint was overall response rate (ORR) after IC. RESULTS: Of 52 patients enrolled, 47 completed three cycles of IC, and the ORR was 55.8% (95% confidence interval, 42.3-69.3). Although there was one treatment-related death, toxicity profiles to Genexol-PM and cisplatin were generally favorable, and the most common grade 3 or 4 toxicities were neutropenia (15.4%), anorexia (7.7%), and general weakness (7.7%). Fifty-one patients received definitive treatment (CCRT [n = 44] or radical surgery [n = 7]). The rate of complete response following CCRT was 81.8% (36/44). After a median follow-up of 39 months, estimates of progression-free survival (PFS) and overall survival (OS) at 3 years were 54.3% and 71.3%, respectively. CONCLUSION: IC with Genexol-PM and cisplatin demonstrated modest tumor response with well-tolerated toxicity profiles for patients with LA-HNSCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Paclitaxel/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Paclitaxel/análogos & derivados , Paclitaxel/química , Veículos Farmacêuticos/química , Polímeros/química , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Purpose To elucidate the radiosensitizing effect and underlying mechanism of a new kind of DNA methyltransferase (DNMT) inhibitor with biological availability. Methods A novel non-nucleoside compound, designated as MA-17, was recently derived from a phthalimido alkanamide structure. DNMT expressions were confirmed in cultured human lung cancer (A549) and normal astrocyte (NHA) cells, radiosensitivity was measured using clonogenic assay, and assays of cell cycle alteration, apoptosis, DNA damage repair, and differential gene expression were undertaken. Results MA-17 significantly radiosensitized A549 cells with a mean dose enhancement ratio (DER) of 1.43 at the surviving fraction of 0.2 (p < 0.05 by one-tailed ratio paired t-test). MA-17 did not affect normal astrocytes (mean DER0.2, 1.016; p = 0.420). MA-17 demonstrated a mean half-life of 1.0 h in vivo and a relatively even distribution in various tissues. Pretreatment with MA-17 increased sub-G1 fractions and inhibited the repair of DNA double-strand breaks, which are induced by irradiation. We found that MA-17 also down-regulated DNA homologous recombination and the Fanconi anemia pathway (FANCA, BRCA1, and RAD51C) in A549 cells. This bioinformatics finding was confirmed in validation Western blot to evaluate the expression of vital proteins. Conclusions A novel phthalimido alkanamide derivative, a DNMT inhibitor, possessed both biostability and favorable and substantial radiosensitizing effects by augmenting apoptosis or inhibiting DNA damage repair.
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Metilases de Modificação do DNA/antagonistas & inibidores , Ftalimidas/farmacologia , Radiossensibilizantes/farmacologia , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Metilases de Modificação do DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Recombinação Homóloga/efeitos dos fármacos , Recombinação Homóloga/efeitos da radiação , Humanos , Tolerância a Radiação/efeitos dos fármacos , Raios XRESUMO
Red-emitting phosphor-in-glass (PiG) materials with a high luminescence efficiency were developed by co-firing commercial red-emitting (Sr,Ca)AlSiN3:Eu2+ (SCASN) phosphor and our original glass frits with a composition of Li2O-Na2O-ZnO-Al2O3-B2O3-P2O5, which has a low Tg (271°C) and Ts (380°C) temperatures. By optimizing the sintering temperature and the content of the phosphor, the highest luminous efficacy was obtained for the 3 wt.% SCASN-based PiG sintered at 400°C, which showed a luminous efficacy of 25 lm/W rad by combining the PiG materials with a blue light-emitting diode (LED) chip-on-board (COB, incident power = 100 mA). The internal quantum efficiency of this sample under excitation at 450 nm was 53%. The PiG-based LED maintained a high luminous efficacy when the incident power of the blue COB increased up to 5.5 W (47 lm).
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Experiments show that the Cooper pair transport in the insulator phase that forms at thin film superconductor to insulator transitions (SIT) is simply activated. The activation energy T_{0} depends on the microscopic factors that drive Cooper pair localization. To test proposed models, we investigated how a perturbation that weakens Cooper pair binding, magnetic impurity doping, and phase frustration affects T_{0}. The data show that T_{0} decreases monotonically with doping in films tuned farther from the SIT and increases and peaks in films that are closer to the SIT critical point. The observations provide strong evidence that the bosonic SIT in thin films is a Mott transition driven by Coulomb interactions that are screened by virtual quasiparticle excitations. This dependence on underlying fermionic degrees of freedom distinguishes these SITs from those in microfabricated Josephson Junction arrays, cold atom systems, and likely in high temperature superconductors with nodes in their quasiparticle density of states.
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PURPOSE: In the present study, the ability of adjuvant trastuzumab to reduce locoregional recurrence in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer receiving adjuvant chemotherapy and radiotherapy (RT) was investigated. MATERIALS AND METHODS: We retrospectively included 520 patients with HER2-overexpressing breast cancer who received surgery followed by adjuvant RT and cytotoxic chemotherapy from 2003 to 2011. Adjuvant trastuzumab was administered to 286 patients. Propensity score matching was conducted to compare trastuzumab-treated and non-treated cohorts. RESULTS: Median follow-up duration was 7.1 years (range 1.1-14.1 years). Propensity score matching yielded 171 matched pairs of patients with no significantly different clinical factors. An improved 7-year locoregional control (LRC) rate was observed in the trastuzumab-treated cohort compared with the non-treated cohort (95.6% vs. 89.9%, p = 0.014). Based on multivariate analysis, hormone receptor negativity (hazard ratio [HR] = 5.348, p = 0.007), positive lymph node ratio > 0.25 (HR = 2.549, p = 0.040), and lack of adjuvant trastuzumab (HR = 3.401, p = 0.017) were identified as significant risk factors for poor LRC. Adjuvant trastuzumab significantly reduced the locoregional recurrence rate in patients with one or two risk factors (7-year LRC = 95.0% vs. 84.2%, p = 0.007); however, the benefit of adjuvant trastuzumab was non-significant in patients with no risk factors (7-year LRC = 95.8% vs. 97.9%, p = 0.75). CONCLUSIONS: Adjuvant trastuzumab improved LRC in patients with HER2-overexpressing breast cancer receiving adjuvant RT and cytotoxic chemotherapy, especially in hormone receptor-negative, HER2-enriched subtype, and high positive lymph node ratio breast cancer.
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Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Expressão Gênica , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Adulto , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pontuação de Propensão , Receptor ErbB-2/metabolismo , Retratamento , Estudos Retrospectivos , Tempo para o Tratamento , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Falha de Tratamento , Resultado do TratamentoRESUMO
PURPOSE: In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). METHODS: The data from the patients participating in two South Korean multi-institutional studies (KROG 14-22; N = 1842 and KROG 14-23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. RESULTS: The median follow-up time was 72.2 months (range 0.8-125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. CONCLUSIONS: The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.
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Neoplasias da Mama/diagnóstico , Parede Torácica/patologia , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Período Pós-Operatório , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Carga Tumoral , Adulto JovemRESUMO
PURPOSE: To investigate and to prevent irradiation outside the treatment field caused by an electron stream in the air generated by the magnetic field during magnetic resonance image-guided accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: In all, 20 patients who received APBI with a magnetic resonance image-guided radiation therapy (MR-IGRT) system were prospectively studied. The prescription dose was 38.5 Gy in 10 fractions of 3.85 Gy and delivered with a tri-cobalt system (the ViewRay system). For each patient, primary plans were delivered for the first five fractions and modified plans with different gantry angles from those of the primary plan (in-treatment plans) were delivered for the remaining five fractions to reduce the skin dose. A 1 cm thick bolus was placed in front of the patient's jaw, ipsilateral shoulder, and arm to shield them from the electron stream. Radiochromic EBT3 films were attached to the front (towards the breast) and back (towards the head) of the bolus during treatment. Correlations between the measured values and the tumor locations, treatment times, and tumor sizes were investigated. RESULTS: For a single fraction delivery, the average areas of the measured isodoses of 14% (0.54 Gy), 12% (0.46 Gy), and 10% (0.39 Gy) at the front of the boluses were as large as 3, 10.4, and 21.4 cm2, respectively, whereas no significant dose could be measured at the back of the boluses. Statistically significant but weak correlations were observed between the measured values and the treatment times. CONCLUSION: During radiotherapy for breast cancer with an MR-IGRT system, the patient must be shielded from electron streams in the air generated by the interaction of the magnetic field with the beams of the three-cobalt treatment unit to avoid unwanted irradiation of the skin outside the treatment field.
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Ar , Neoplasias da Mama/radioterapia , Elétrons/efeitos adversos , Imageamento por Ressonância Magnética/efeitos adversos , Mamografia/efeitos adversos , Lesões por Radiação/prevenção & controle , Radioterapia Guiada por Imagem/efeitos adversos , Adulto , Fracionamento da Dose de Radiação , Feminino , Dosimetria Fotográfica , Humanos , Pessoa de Meia-Idade , Imagens de Fantasmas , Estudos Prospectivos , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estatística como Assunto , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: This study aimed to examine predictors and clinical outcomes of periprocedural myocardial infarction (PMI) after chronic total occlusion (CTO) intervention. BACKGROUND: There are limited data on the clinical implications of PMI after CTO intervention in the new-generation drug-eluting stent (DES) era. METHODS: We enrolled 337 patients who underwent CTO intervention and met the study criteria. We evaluated the incidence and predictors of PMI, defined as an increase in creatine kinase-MB ≥3× the upper limit of normal (ULN) after intervention and compared the occurrence rates of major adverse cardiac and cerebrovascular events (MACCE, defined as the composite of cardiac death, myocardial infarction, stent thrombosis, target-vessel revascularization, or cerebrovascular accidents) between the PMI and non-PMI groups. RESULTS: PMI occurred in 23 (6.8%) patients after CTO intervention. Significant independent predictors were previous bypass surgery [odds ratio (OR) = 5.52, 95% confidence interval (CI) = 1.17-25.92; P = 0.03], Japan-CTO score ≥3 (OR = 7.06, 95%CI = 2.57-19.39; P < 0.001), side branch occlusion (OR = 4.21, 95%CI = 1.13-15.66; P = 0.03), and longer procedure time (OR = 4.18, 95%CI = 1.35-12.99; P = 0.01). During a median follow-up of 29.6 months, the PMI group had a significantly higher MACCE rate than the non-PMI group (23.7 vs. 5.6%, P = 0.008 by log-rank test). PMI was an independent predictor of MACCE (HR = 4.26, 95%CI = 1.35-13.43; P = 0.01). The MACCE rate gradually increased in a CK-MB-dependent fashion and was highest in patients with ≥10× ULN (P = 0.005). CONCLUSION: Previous bypass surgery, high Japan-CTO score, side branch occlusion, and longer procedure time were strongly related to PMI occurrence after CTO intervention. PMI was significantly associated with worse clinical outcomes in the new-generation DES era.