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BACKGROUND: There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100â¯mg/m2 (33â¯mg/m2/days [d]1-3) every 3 weeks for two cycles. All patients were given oral aprepitant 125â¯mg once on d1, then 80â¯mg once on d2-5; ondansetron 8â¯mg once on d1; and dexamethasone 12â¯mg once on d1, then 8â¯mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δâ¯= 0.2 and αâ¯= 0.05, the expected CR rate was 80%. RESULTS: A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% confidence interval [CI]: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free and nausea-free responses in the overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related toxicity with antiemetic usage. CONCLUSION: The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy.
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Antieméticos , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antieméticos/efeitos adversos , Aprepitanto/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Dexametasona/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/prevenção & controle , Ondansetron/efeitos adversos , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Vômito/induzido quimicamente , Vômito/prevenção & controleRESUMO
PURPOSE: Concurrent chemoradiotherapy (CCRT) is a standard treatment choice for locally advanced hypopharyngeal carcinoma. The aim of this study was to investigate whether induction chemotherapy (IC) followed by CCRT is superior to CCRT alone to treat locally advanced hypopharyngeal carcinoma. METHODS AND MATERIALS: Patients (n = 142) were randomized to receive two cycles of paclitaxel/cisplatin/5-fluorouracil (TPF) IC followed by CCRT or CCRT alone. The primary end point was overall survival (OS). The secondary end points included the larynx-preservation rate, progression-free survival (PFS), distant metastasis-free survival (DMFS), and toxicities. RESULTS: Ultimately, 113 of the 142 patients were analyzed. With a median follow-up of 45.6 months (interquartile range 26.8-57.8 months), the 3-year OS was 53.1% in the IC + CCRT group compared with 54.8% in the CCRT group (hazard ratio, 1.004; 95% confidence interval, 0.573-1.761; P = 0.988). There were no statistically significant differences in PFS, DMFS, and the larynx-preservation rate between the two groups. The incidence of grade 3-4 hematological toxicity was much higher in the IC+ CCRT group than in the CCRT group (54.7% vs. 10%, P < 0.001). CONCLUSIONS: Adding induction TPF to CCRT did not improve survival and the larynx-preservation rate in locally advanced hypopharyngeal cancer, but caused a higher incidence of acute hematological toxicities. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03558035. Date of first registration, 15/06/2018.
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Quimiorradioterapia , Neoplasias Hipofaríngeas , Quimioterapia de Indução , Humanos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Hipofaríngeas/terapia , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Laringe , Intervalo Livre de ProgressãoRESUMO
BACKGROUND AND OBJECTIVES: Head and neck cancer patients often experience nutritional deterioration, which decreases their treatment tolerance and is associated with poor outcomes. We analyzed nutritional status in head and neck cancer patients before and during treatment, and its impact on clinical outcomes. METHODS AND STUDY DESIGN: Between January 2009 and April 2012, 336 head and neck cancer patients receiving radiotherapy or chemoradiotherapy were prospectively entered into the study. The Nutritional Risk Screening 2002 (NRS 2002) assessment was used to evaluate their nutritional status. RESULTS: A total of 227 patients with nasopharyngeal carcinoma and 109 patients with head and neck cancers were analyzed. The proportion of patients receiving radiotherapy or chemoradiotherapy at nutritional risk was 61.3%, with 11.9% at risk before treatment and 49.4% developing risk during treatment. In multivariate analysis, nutritional risk before treatment was associated with T stage for the two groups. Risk was significantly higher in patients receiving concurrent chemoradiotherapy during treatment for nasopharygeal carcinoma patients. The prognosis of pretreatment nutritional risk patients was worse than those becoming at risk during treatment and those without nutritional risk (3-year overall survival 62.9% vs 81.7% vs 80.6%, p=0.026; 3-year disease-free survival 64.8% vs 84.5% vs 84.4%, p=0.019). CONCLUSIONS: The incidence of nutritional risk is high in head and neck cancer patients receiving radiotherapy or chemoradiotherapy, especially during treatment. Pretreatment nutritional risk evaluated using the NRS 2002 can predict patient prognosis.
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Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Avaliação Nutricional , Estado Nutricional , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , PrognósticoRESUMO
Self-assembly of 1:1:2 MII (BF4 )2 (M=Zn or Fe), pyrazine-2,5-dicarbaldehyde (1) and 2-(2-aminoethyl)pyridine gave trimetallic triangle architectures rather than the anticipated tetrametallic [2×2] squares. Options for the nontrivial synthesis of 1 are considered, and synthetic details provided for both preferred routes. Rare cyclohelicate triangle architectures are observed for the pair of structurally characterized yellow-brown [Zn3 L3 ](BF4 )6 and dark green [Fe3 L3 ](BF4 )6 complexes of the neutral bis-terdentate Schiff base L. In order to form these pyrazine-edged triangles, the octahedral metal ions-with all 6 N-donors provided by the terdentate binding pockets of two L-are located 0.4-0.5â Å out of the plane of the bridging pyrazines, towards the center of the triangle. Density functional theory calculations confirm that simple particle counting entropic arguments, which predict triangles over squares, are correct here, with the triangles shown to be energetically favored over the corresponding squares. However, importantly, DFT analysis of these and related triangle versus square systems also show that vibrational contributions to entropy dominate and may significantly influence the preferred architecture, such that simple particle counting cannot in general be reliably employed to predict the observed architecture.
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Bromobenzyl compounds react selectively with phenols via the Williamson ether synthesis. An imidazolium charge-tagged bromobenzyl compound can be used to reveal phenol impurities in jet fuel by analysis via electrospray ionization mass spectrometry. The complex matrix as revealed by Cold EI GC/MS analysis is reduced to a few simple sets of compounds in the charge-tagged ESI mass spectrum, primarily substituted phenols and thiols. Examination of jet fuels treated by different refinery methods reveals the efficacy of these approaches in removing these contaminants.
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The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension.
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Carcinoma/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Encéfalo/patologia , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/secundário , Estudos de Casos e Controles , Feminino , Humanos , Hipotireoidismo , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , Estadiamento de Neoplasias , Pontuação de Propensão , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/mortalidade , Estudos Retrospectivos , Fatores Sexuais , Taxa de SobrevidaRESUMO
The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.
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Carcinoma de Células Escamosas , Quimiorradioterapia , Neoplasias Esofágicas , Esôfago , Radioterapia de Intensidade Modulada , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Esôfago/diagnóstico por imagem , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Planejamento de Assistência ao Paciente , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Critérios de Avaliação de Resposta em Tumores Sólidos , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Falha de TratamentoRESUMO
Complexation of 1,4-phenylenebis(methylene) diisonicotinate, L1, with cis-protected Pd(II) components, [Pd(L')(NO3 )2 ], in an equimolar ratio yielded binuclear complexes, 1 a-d of [Pd2 (L')2 (L1)2 ](NO3 )4 formulation where L' stands for ethylenediamine (en), tetramethylethylenediamine (tmeda), 2,2'-bipyridine (bpy), and phenanthroline (phen). The combination of 4,4'-bipyridine, L2, with the cis-protected Pd(II) units is known to yield molecular squares, 2 a-d. However, 2 b-d coexist with the corresponding molecular triangles, 3 b-d. Combination of an equivalent each of the ligands L1 and L2 with two equivalents of cis-protected Pd(II) components in DMSO resulted in the D-shaped heteroligated complexes [Pd2 (L')2 (L1)(L2)](NO3 )4 , 4 a-d. Two units of the D-shaped complexes interlock, in a concentration dependent fashion, to form the corresponding [2]catenanes [Pd2 (L')2 (L1)(L2)]2 (NO3 )8 , 5 a-d under aqueous conditions. Crystal structures of the macrocycle [Pd2 (tmeda)2 (L1)(L2)](PF6 )4 , 4 b'', and the catenane [Pd2 (bpy)2 (L1)(L2)]2 (NO3 )8 , 5 c, provide unequivocal support for the proposed molecular architectures.
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PURPOSE: The authors compared definitive intensity-modulated radiotherapy (IMRT) with definitive conventional radiotherapy (2D-RT) in cervical oesophageal squamous cell carcinoma (CESCC). MATERIALS AND METHODS: A total of 101 patients with CESCC treated with definitive radiotherapy from January 2001 to April 2012 were analysed. 37 patients were irradiated using 2D-RT, whereas 64 cases were treated using IMRT. RESULTS: The median follow-up time was 15.5 months for all the patients. For all patients, the overall 2-year local failure-free survival (LFFS), regional failure-free survival (RFFS), and overall survival (OS) rate was 67.4, 85.2 and 46.2%, respectively. The 2-year LFFS rate and the 2-year RFFS rate in the IMRT group were higher than the 2D-RT group, although no statistically significant difference was observed in LFFS and RFFS. No statistically significant difference was observed in overall survival (OS) between the groups. Compared with 2D-RT, the rate of grade 3 dysphagia after radiotherapy was lower (6.3 vs. 8.1%) and none had hypothyroidism requiring lifelong thyroxine replacement in the IMRT group. Matched-cases analysis did not show a statistical difference in terms of LFFS, RFFS and OS between the groups. CONCLUSIONS: Although no statistically significant difference was observed in OS, LFFS and RFFS between the IMRT group and the 2D-RT group, the incidence of late toxicity declined using IMRT, thereby resulting in an improved therapeutic ratio for patients with CESCC.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PescoçoRESUMO
A brain-computer interface (BCI) enables direct communication between the human brain and external devices. Electroencephalography (EEG) based BCIs are currently the most popular for able-bodied users. To increase user-friendliness, usually a small amount of user-specific EEG data are used for calibration, which may not be enough to develop a pure data-driven decoding model. To cope with this typical calibration data shortage challenge in EEG-based BCIs, this paper proposes a parameter-free channel reflection (CR) data augmentation approach that incorporates prior knowledge on the channel distributions of different BCI paradigms in data augmentation. Experiments on eight public EEG datasets across four different BCI paradigms (motor imagery, steady-state visual evoked potential, P300, and seizure classifications) using different decoding algorithms demonstrated that: (1) CR is effective, i.e., it can noticeably improve the classification accuracy; (2) CR is robust, i.e., it consistently outperforms existing data augmentation approaches in the literature; and, (3) CR is flexible, i.e., it can be combined with other data augmentation approaches to further improve the performance. We suggest that data augmentation approaches like CR should be an essential step in EEG-based BCIs. Our code is available online.
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Interfaces Cérebro-Computador , Eletroencefalografia , Eletroencefalografia/métodos , Humanos , Algoritmos , Encéfalo/fisiologia , Potenciais Evocados Visuais/fisiologia , Potenciais Evocados P300/fisiologia , Processamento de Sinais Assistido por Computador , Imaginação/fisiologiaRESUMO
Cross-subject electroencephalogram (EEG) based seizure subtype classification is very important in precise epilepsy diagnostics. Deep learning is a promising solution, due to its ability to automatically extract latent patterns. However, it usually requires a large amount of training data, which may not always be available in clinical practice. This paper proposes Multi-Branch Mutual-Distillation (MBMD) Transformer for cross-subject EEG-based seizure subtype classification, which can be effectively trained from small labeled data. MBMD Transformer replaces all even-numbered encoder blocks of the vanilla Vision Transformer by our designed multi-branch encoder blocks. A mutual-distillation strategy is proposed to transfer knowledge between the raw EEG data and its wavelets of different frequency bands. Experiments on two public EEG datasets demonstrated that our proposed MBMD Transformer outperformed several traditional machine learning and state-of-the-art deep learning approaches. To our knowledge, this is the first work on knowledge distillation for EEG-based seizure subtype classification.
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Epilepsia , Convulsões , Humanos , Convulsões/diagnóstico , Aprendizado de Máquina , Eletroencefalografia , Fontes de Energia ElétricaRESUMO
The objective of this research was to examine the correlation between the status of inactivated COVID-19 vaccination and self-reported confirmed SARS-CoV-2 infection among adults after China entered the "living with COVID" era. A cross-sectional online survey was conducted among parents or guardians of students attending all 220 kindergartens and 105 primary or secondary schools in Longhua District of Shenzhen, China during March 1 to 9, 2023. The participating schools invited all parents or guardians of their students to complete the online survey. The study focused on a sub-sample of 68,584 participants who were either unvaccinated (n = 2152) or only receiving inactivated COVID-19 vaccination (n = 66,432). Logistic regression was employed for data analysis. Prior to the implementation of the "living with COVID" policy, 83.5% of the participants received three doses of inactivated COVID-19 vaccines; 63.0% reported being infected with the SARS-CoV-2 after the policy change. In a multivariate analysis, participants who had received a third dose within the past 6 months were less likely to be infected with SARS-CoV-2, as compared to those who had not completed the primary vaccination series (4-6 months: AOR: 0.84, 95%CI: 0.77, 0.92; ≤3 months: AOR: 0.82, 95%CI: 0.73, 0.92). Despite the high coverage, our results suggested that three doses of inactivated COVID-19 vaccines did not provide adequate protection against SARS-CoV-2 infection among Chinese adults.
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BACKGROUND: Pneumococcal Polysaccharide Vaccine (PPV-23), designed to protect against the most common serotype of Streptococcus pneumoniae, is intended to protect the elderly and other high-risk groups. However, the immunogenicity of all 23 pneumococcal polysaccharide vaccines in older adults has not been thoroughly studied. OBJECTIVE: The purpose of this study is to look into the factors that influence the effect of the pneumonia vaccine on the elderly over 60 years old in Shenzhen, as well as their IgG antibody level against Streptococcus pneumoniae. METHODS: To determine the immune effectiveness of pneumococcal vaccination in older adults over 60 years old, we used the 3rd generation enzyme-linked immunosorbent assay to detect the antibody level of older adults to all 23 pneumococcal polysaccharide vaccines following pneumococcal immunization. RESULTS: Vaccination, the number of physical examinations, pneumonia knowledge, and the pneumonia vaccination policy of the elderly in Shenzhen were all positively correlated with Streptococcus pneumoniae antibody positivity. The distribution of subtypes did not differ between elderly adults (over 65) and younger adults (under 65). The GMCs of IgG antibodies to PPS were significantly lower in males than in females for types 7f, 18c and 19a. At the same time, we found that people with chronic respiratory disease have lower type 9n than people without chronic respiratory disease. Other chronic diseases, such as hypertension and diabetes, had no difference in subtype distribution. CONCLUSION: There was a statistically significant difference in antibody positivity rates for older people with more frequent medical check-ups in Shenzhen, indicating that publicity is playing a role. The effects of age, gender, and chronic diseases on naturally acquired anti-PPS IgG differ.
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Infecções Pneumocócicas , Pneumonia , Doenças Respiratórias , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Streptococcus pneumoniae , Imunoglobulina G , Vacinas Pneumocócicas , Anticorpos Antibacterianos , Doença Crônica , Polissacarídeos , Infecções Pneumocócicas/prevenção & controleRESUMO
BACKGROUND: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. METHODS: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). RESULTS: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I-II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III-IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. CONCLUSIONS: Radiotherapy improved local-regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments.
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Neoplasias de Cabeça e Pescoço , Tumores Neuroendócrinos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/mortalidade , Estudos Retrospectivos , Prognóstico , Adulto Jovem , Taxa de Sobrevida , Resultado do Tratamento , Terapia Combinada , Seguimentos , AdolescenteRESUMO
Objective Our objective was to compare the long-term outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies (SNMs). Methods Data for continuous patients with sinonasal squamous cell carcinoma and adenocarcinoma who received surgery (endoscopic or open surgery) combined with radiotherapy in our center between January 1999 and December 2016 were retrospectively reviewed. A 1:1 matching with propensity scores was performed. Overall survival (OS), progression-free survival (PFS), and local recurrence rate (LRR) were evaluated. Results We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS, and LRR were 69.9, 58.6, and 24.5% in the endoscopic group and 64.6, 54.4, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that the surgical approach was not associated with lower OS, PFS, or LRR. The overall postoperative complications were 13% in the endoscopic group, while 21.7% in the open group. Conclusion For patients with locally advanced SNMs, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.
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Given the multifactorial pathogenesis of atherosclerosis (AS), a chronic inflammatory disease, combination therapy arises as a compelling approach to effectively address the complex interplay of pathogenic mechanisms for a more desired treatment outcome. Here, we present cRGD/ASOtDON, a nanoformulation based on a self-assembled DNA origami nanostructure for the targeted combination therapy of AS. cRGD/ASOtDON targets αvß3 integrin receptors overexpressed on pro-inflammatory macrophages and activated endothelial cells in atherosclerotic lesions, alleviates the oxidative stress induced by extracellular and endogenous reactive oxygen species, facilitates the polarization of pro-inflammatory macrophages toward the anti-inflammatory M2 phenotype, and inhibits foam cell formation by promoting cholesterol efflux from macrophages by downregulating miR-33. The antiatherosclerotic efficacy and safety profile of cRGD/ASOtDON, as well as its mechanism of action, were validated in an AS mouse model. cRGD/ASOtDON treatment reversed AS progression and restored normal morphology and tissue homeostasis of the diseased artery. Compared to probucol, a clinical antiatherosclerotic drug with a similar mechanism of action, cRGD/ASOtDON enabled the desired therapeutic outcome at a notably lower dosage. This study demonstrates the benefits of targeted combination therapy in AS management and the potential of self-assembled DNA nanoformulations in addressing multifactorial inflammatory conditions.
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Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein-Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.
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PURPOSE: To determine the potential nodal drainage distances of nasopharyngeal carcinoma (NPC) by investigating spatial distribution of metastatic lymph nodes (LN). EXPERIMENTAL DESIGN: Patients with NPC harboring at least two ipsilateral metastatic LNs were enrolled. LN spreading distances were analyzed in nonrestricted direction, cranial-to-caudal direction, and between the two most caudal LNs. Euclidean distance (ED) and vertical distance (VD) between any two LNs were computed. The nearest-neighbor ED and VD covering 95% of LNs or patients (p95-ED and p95-VD) were considered drainage distances, and were further validated by independent internal and external cohorts with recurrent LNs. RESULTS: In all, 5,836 metastatic LNs in 948 patients were contoured. Corresponding to the three scenarios, per-LN level, the p95-EDs were 2.83, 3.28, and 3.55 cm, and p95-VDs were 2.17, 2.32, and 2.63 cm, respectively. Per-patient level, the p95-EDs were 3.25, 3.95, and 3.81 cm, and p95-VDs were 2.67, 2.81, and 2.73 cm, respectively. In internal validation, over 95% of recurred LNs occurred within ED of 2.91 cm and VD of 0.82 cm to the neighbor LN, and the corresponding distances in external validation were 2.77 and 0.67 cm, respectively. CONCLUSIONS: In NPC, the maximum LN drainage distance was 3.95 cm without considering the direction. Specifically, in cranial-to-caudal direction, the sufficient vertical drainage distance was 2.81 cm, indicating that a 3-cm extension from the most inferior node may be rational as caudal border of the prophylactic clinical target volume (CTV). These findings promote in-depth understanding of nodal spreading patterns, uncovering paramount evidence for individualized CTV.
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Linfonodos , Metástase Linfática , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/patologia , Feminino , Masculino , Linfonodos/patologia , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Adulto , Idoso , Planejamento da Radioterapia Assistida por Computador/métodos , Drenagem , PescoçoRESUMO
A method for the direct conversion of arylboronate esters to aryl fluorides under mild conditions with readily available reagents is reported. Tandem reactions have also been developed for the fluorination of arenes and aryl bromides through arylboronate ester intermediates. Mechanistic studies suggest that this fluorination reaction occurs through facile oxidation of Cu(I) to Cu(III), followed by rate-limiting transmetalation of a bound arylboronate to Cu(III). Fast C-F reductive elimination is proposed to occur from an aryl-copper(III)-fluoride complex. Cu(III) intermediates have been generated independently and identified by NMR spectroscopy and ESI-MS.
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Ácidos Borônicos/química , Complexos de Coordenação/química , Cobre/química , Ésteres/química , Fluoretos/química , Catálise , Complexos de Coordenação/síntese química , Halogenação , Oxirredução , Paládio/químicaRESUMO
PURPOSE: Nasopharyngeal adenoid cystic carcinomas (NACCs) are rare. No clear consensus is available regarding clinical characteristics and management approaches. The aim of this study was to summarize the clinical characteristics and evaluate the management approaches of NACC. MATERIALS AND METHODS: The experience of 1 institution with this tumor and the outcomes of treatment were examined. The medical records of 36 patients with NACC at 1 institution from 1963 through 2006 were reviewed. RESULTS: After a median follow-up of 65.8 months (1.8 to 245.2 mo), the 5- and 10-year overall survival, locoregional failure-free survival, and distant metastasis failure-free survival rates were 70.2% and 31.6%, 63.4% and 49.1%, and 65.0% and 59.6%, respectively. No significant differences were found in locoregional failure-free survival, distant metastasis failure-free survival, or overall survival rates between the group that received radiotherapy alone and the group that received combined modality therapy (radiotherapy plus surgery or surgery plus radiotherapy). CONCLUSIONS: NACC is a malignancy with a generally favorable prognosis. Radiotherapy alone or a combined modality therapy (radiotherapy plus surgery or surgery plus radiotherapy) is effective in the treatment of NACC.