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BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.
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Angioplastia com Balão , Artéria Femoral , Doença Arterial Periférica , Artéria Poplítea , Ultrassonografia de Intervenção , Grau de Desobstrução Vascular , Humanos , Ultrassonografia de Intervenção/métodos , Masculino , Angioplastia com Balão/métodos , Artéria Femoral/diagnóstico por imagem , Feminino , Artéria Poplítea/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/diagnóstico por imagem , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Materiais Revestidos Biocompatíveis , Resultado do Tratamento , AngiografiaRESUMO
BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.
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Anticoagulantes , Fibrilação Atrial , Clopidogrel , Stents Farmacológicos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Feminino , Humanos , Masculino , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/terapia , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Estudos Prospectivos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
AIM: This study evaluated the safety and efficacy of a moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. MATERIALS AND METHODS: In this post-hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high-density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high-intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72-1.32; p = .868). Lower rates of intolerance-related drug discontinuation or dose reduction (3.9% vs. 8.0%; p < .001) and lower low-density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p < .001) were observed with ezetimibe combination therapy versus high-intensity statin monotherapy. Furthermore, the rate of new-onset diabetes was 18.5% and 19.1% in each group (p = .822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. CONCLUSIONS: In patients with MetS and atherosclerotic cardiovascular disease, a moderate-intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high-intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low-density lipoprotein cholesterol levels, but there was no apparent between-group difference in new-onset diabetes.
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Anticolesterolemiantes , Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Metabólica , Humanos , Anticolesterolemiantes/efeitos adversos , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol , Diabetes Mellitus/tratamento farmacológico , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Síndrome Metabólica/complicações , Síndrome Metabólica/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND. Timely and accurate interpretation of chest radiographs obtained to evaluate endotracheal tube (ETT) position is important for facilitating prompt adjustment if needed. OBJECTIVE. The purpose of our study was to evaluate the performance of a deep learning (DL)-based artificial intelligence (AI) system for detecting ETT presence and position on chest radiographs in three patient samples from two different institutions. METHODS. This retrospective study included 539 chest radiographs obtained immediately after ETT insertion from January 1 to March 31, 2020, in 505 patients (293 men, 212 women; mean age, 63 years) from institution A (sample A); 637 chest radiographs obtained from January 1 to January 3, 2020, in 302 patients (157 men, 145 women; mean age, 66 years) in the ICU (with or without an ETT) from institution A (sample B); and 546 chest radiographs obtained from January 1 to January 20, 2020, in 83 patients (54 men, 29 women; mean age, 70 years) in the ICU (with or without an ETT) from institution B (sample C). A commercial DL-based AI system was used to identify ETT presence and measure ETT tip-to-carina distance (TCD). The reference standard for proper ETT position was TCD between greater than 3 cm and less than 7 cm, determined by human readers. Critical ETT position was separately defined as ETT tip below the carina or TCD of 1 cm or less. ROC analysis was performed. RESULTS. AI had sensitivity and specificity for identification of ETT presence of 100.0% and 98.7% (sample B) and 99.2% and 94.5% (sample C). AI had sensitivity and specificity for identification of improper ETT position of 72.5% and 92.0% (sample A), 78.9% and 100.0% (sample B), and 83.7% and 99.1% (sample C). At a threshold y-axis TCD of 2 cm or less, AI had sensitivity and specificity for critical ETT position of 100.0% and 96.7% (sample A), 100.0% and 100.0% (sample B), and 100.0% and 99.2% (sample C). CONCLUSION. AI identified improperly positioned ETTs on chest radiographs obtained after ETT insertion as well as on chest radiographs obtained of patients in the ICU at two institutions. CLINICAL IMPACT. Automated AI identification of improper ETT position on chest radiographs may allow earlier repositioning and thereby reduce complications.
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Inteligência Artificial , Intubação Intratraqueal , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Intubação Intratraqueal/métodos , Traqueia , RadiografiaRESUMO
Methods of selectively synthesizing diorganyl diselenides (R-Se-Se-R) without using harmful reducing agents are presented. We optimized the reaction conditions for the selective formation of the diselenide dianion (Se22-) and the corresponding diorganyl diselenides using basic reagents (e.g., KOH), while suppressing the formation of side products, such as diorganyl selenides (R-Se-R) or multiselenides (R-Sen-R; n ≥ 3). Furthermore, we have suggested and examined the reaction pathways responsible for the formation of the desired diorganyl diselenides 1 and side products 2 and 3. Consequently, the selective synthesis of diverse diorganyl diselenides was achieved with modest to excellent yields (33-99%) using various organyl halides under optimized conditions. The results provide a practical and efficient synthetic method for diorganyl diselenides as a representative class of organoselenium compounds.
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STUDY OBJECTIVE: Although the importance of primary percutaneous coronary intervention has been emphasized for ST-segment elevation myocardial infarction (STEMI), the appropriateness of the cardiac catheterization laboratory activation remains suboptimal. This study aimed to develop a precise artificial intelligence (AI) model for the diagnosis of STEMI and accurate cardiac catheterization laboratory activation. METHODS: We used electrocardiography (ECG) waveform data from a prospective percutaneous coronary intervention registry in Korea in this study. Two independent board-certified cardiologists established a criterion standard (STEMI or Not STEMI) for each ECG based on corresponding coronary angiography data. We developed a deep ensemble model by combining 5 convolutional neural networks. In addition, we performed clinical validation based on a symptom-based ECG data set, comparisons with clinical physicians, and external validation. RESULTS: We used 18,697 ECGs for the model development data set, and 1,745 (9.3%) were STEMI. The AI model achieved an accuracy of 92.1%, sensitivity of 95.4%, and specificity of 91.8 %. The performances of the AI model were well balanced and outstanding in the clinical validation, comparison with clinical physicians, and the external validation. CONCLUSION: The deep ensemble AI model showed a well-balanced and outstanding performance. As visualized with gradient-weighted class activation mapping, the AI model has a reasonable explainability. Further studies with prospective validation regarding clinical benefit in a real-world setting should be warranted.
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OBJECTIVES: To investigate clinical and CT factors associated with local resectability in patients with nonmetastatic pancreatic cancers after neoadjuvant chemotherapy ± radiation therapy (CRT). METHODS: This retrospective study included consecutive patients with nonmetastatic pancreatic cancers who underwent neoadjuvant CRT between June 2009 and June 2019. Tumor size, tumor-vascular contact with artery/vein, and local resectability categories (resectable, borderline resectable, or locally advanced) were assessed at baseline and post-CRT CT. Baseline and post-CRT carbohydrate antigen (CA) 19-9 levels were also assessed. Clinical or imaging features related to R0 resection were determined using logistic regression analysis. RESULTS: A total of 179 patients (mean age, 62.4 ± 9.3 years; 92 men) were included. After neoadjuvant CRT, 105 (58.7%) patients received R0 resection, while 74 (41.3%) did not. R0 resection rates were significantly different according to post-CRT CT resectability categories (p < 0.001): 82.8% (48/58), 70.1% (47/67), and 18.5% (10/54) for resectable, borderline resectable, and locally advanced disease, respectively. For post-CRT borderline resectable disease, ≥ 50% decrease in CA 19-9 was significantly associated with R0 resection (odds ratio (OR), 3.160; p = 0.02). For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm (OR, 9.668; p = 0.026) and decreased tumor-arterial contact (OR, 24.213; p = 0.022) were significantly associated with R0 resection. CONCLUSION: Post-CRT CT resectability categorization may be useful for the assessment of R0 resectability in patients with pancreatic cancer following neoadjuvant CRT. Additionally, ≥ 50% decrease in CA 19-9 was associated with R0 resection in post-CRT borderline resectable disease, while small post-CRT tumor size and decreased tumor-arterial contact were with locally advanced disease. KEY POINTS: ⢠R0 resection rates following neoadjuvant chemotherapy ± radiation therapy (CRT) were 82.8%, 70.1%, and 18.5% in resectable, borderline resectable, and locally advanced disease, respectively, at post-CRT CT (p < 0.001). ⢠For post-CRT borderline resectable disease, ≥ 50% decrease in carbohydrate antigen (CA) 19-9 was significantly associated with R0 resection. ⢠For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm and decreased tumor-arterial contact were significantly associated with R0 resection.
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Terapia Neoadjuvante , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Estudos RetrospectivosRESUMO
Studies on the selective synthetic method for dialkyl ditellurides 1, a representative class of organyl tellurium compounds, were presented. Considering the difficulty in conducting previous harsh reactions and in suppressing the formation of dialkyl tellurides 2 as side products, we optimized reaction conditions for selective syntheses of sodium ditelluride and the corresponding dialkyl ditellurides 1. We reduced tellurium to sodium ditelluride by using NaBH4 and subsequently, treated the obtained sodium ditelluride with alkyl halides (RX) to give the target compounds 1. Consequently, by applying various alkyl halides (RX) we achieved the selective syntheses of dialkyl ditellurides 1 (13 examples with 4 new compounds) in modest to good yields. We also suggested the mechanistic pathways to dialkyl ditellurides 1.
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TelúrioRESUMO
The syntheses of novel 1-acyloxyindole compounds 1 and the investigations on reaction pathways are presented. Nitro ketoester substrate 2, obtained in a two-step synthetic process, underwent reduction, intramolecular addition, nucleophilic 1,5-addition, and acylation to afford 1-acyloxyindoles 1 in one pot. Based on the systematic studies, we established the optimized reaction conditions for 1 focusing on the final acylation step of the intermediate 1-hydroxyindole 8. With the optimized conditions, we succeeded in synthesizing 21 examples of new 1-acyloxyindole derivatives 1 in modest yields (Y = 24 - 35%). Among the 1-acyloxyindole compounds, 1-acetoxyindole compounds 1x were generally unstable, and their yields were relatively lower than the other 1-acyloxyindoles. We expect that a bulkier alkyl or aromatic group on R2 could stabilize the 1-acyloxyindole compounds. Significantly, one-pot reactions of a four-step sequence successfully generated compounds 1 that are all new and might be difficult to be synthesized otherwise.
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Estrutura Molecular , AcilaçãoRESUMO
The studies on the selective synthesis of dialkyl selenide compounds 1 were presented. Overcoming the complexity and difficulty of selenides (R-Se-R) and/or multiselenides (R-Sen-R; n ≥ 2), we aimed to optimize the reaction condition for the tolerable preparation of sodium selenide (Na2Se) by reducing Se with NaBH4, and then to achieve selective syntheses of dialkyl selenides 1 by subsequently treating the obtained sodium selenide with alkyl halides (RX). Consequently, various dialkyl selenides 1 were efficiently synthesized in good-to-moderate yields. The investigations on reaction pathways and solvent studies were also described.
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Compostos de Selênio , SolventesRESUMO
OBJECTIVES: To investigate the oncological significance of a robot-assisted radical cystectomy (RARC)-related pentafecta in patients with bladder cancer. PATIENTS AND METHODS: Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien-Dindo grade 3-5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer-specific survival (CSS) using multivariate Cox proportional analysis was then carried out. RESULTS: Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow-up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non-attainment group (10-year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10-year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038). CONCLUSIONS: Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.
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Cistectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Duração da Cirurgia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
OBJECTIVE: Assess if deep learning-based artificial intelligence (AI) algorithm improves reader performance for lung cancer detection on chest X-rays (CXRs). METHODS: This reader study included 173 images from cancer-positive patients (n = 98) and 346 images from cancer-negative patients (n = 196) selected from National Lung Screening Trial (NLST). Eight readers, including three radiology residents, and five board-certified radiologists, participated in the observer performance test. AI algorithm provided image-level probability of pulmonary nodule or mass on CXRs and a heatmap of detected lesions. Reader performance was compared with AUC, sensitivity, specificity, false-positives per image (FPPI), and rates of chest CT recommendations. RESULTS: With AI, the average sensitivity of readers for the detection of visible lung cancer increased for residents, but was similar for radiologists compared to that without AI (0.61 [95% CI, 0.55-0.67] vs. 0.72 [95% CI, 0.66-0.77], p = 0.016 for residents, and 0.76 [95% CI, 0.72-0.81] vs. 0.76 [95% CI, 0.72-0.81, p = 1.00 for radiologists), while false-positive findings per image (FPPI) was similar for residents, but decreased for radiologists (0.15 [95% CI, 0.11-0.18] vs. 0.12 [95% CI, 0.09-0.16], p = 0.13 for residents, and 0.24 [95% CI, 0.20-0.29] vs. 0.17 [95% CI, 0.13-0.20], p < 0.001 for radiologists). With AI, the average rate of chest CT recommendation in patients positive for visible cancer increased for residents, but was similar for radiologists (54.7% [95% CI, 48.2-61.2%] vs. 70.2% [95% CI, 64.2-76.2%], p < 0.001 for residents and 72.5% [95% CI, 68.0-77.1%] vs. 73.9% [95% CI, 69.4-78.3%], p = 0.68 for radiologists), while that in cancer-negative patients was similar for residents, but decreased for radiologists (11.2% [95% CI, 9.6-13.1%] vs. 9.8% [95% CI, 8.0-11.6%], p = 0.32 for residents and 16.4% [95% CI, 14.7-18.2%] vs. 11.7% [95% CI, 10.2-13.3%], p < 0.001 for radiologists). CONCLUSIONS: AI algorithm can enhance the performance of readers for the detection of lung cancers on chest radiographs when used as second reader. KEY POINTS: ⢠Reader study in the NLST dataset shows that AI algorithm had sensitivity benefit for residents and specificity benefit for radiologists for the detection of visible lung cancer. ⢠With AI, radiology residents were able to recommend more chest CT examinations (54.7% vs 70.2%, p < 0.001) for patients with visible lung cancer. ⢠With AI, radiologists recommended significantly less proportion of unnecessary chest CT examinations (16.4% vs. 11.7%, p < 0.001) in cancer-negative patients.
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Inteligência Artificial , Neoplasias Pulmonares , Algoritmos , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Radiografia , Radiografia Torácica , Sensibilidade e EspecificidadeRESUMO
Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepared through a two-step synthetic sequence, underwent three consecutive reactions of nitro reduction, intramolecular condensation, and nucleophilic 1,5-addition to provide the intermediates, 1-hydroxyindoles 8, which then were alkylated in situ with alkyl halide to afford the novel target products 1. We optimized the reaction conditions for 1 focusing on the alkylation step, along with the consideration of formation of intermediates 8. The optimized condition was SnCl2·2H2O (3.3 eq) and alcohols (R1OH, 2.0 eq) for 1-2 h at 40 °C and then, base (10 eq) and alkyl halides (R2Y, 2.0 eq) for 1-4 h at 25-50 °C. Notably, all four step reactions were performed in one-pot to give 1 in good to modest yields. Furthermore, the mechanistic aspects were also discussed regarding the reaction pathways and the formation of side products. The significance lies in development of efficient one-pot reactions and in generation of new 1-alkoxyindoles.
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Álcoois/síntese química , Indóis/síntese química , Álcoois/química , Alquilação , Ciclização , Estrutura Molecular , Estereoisomerismo , Compostos de EstanhoRESUMO
BACKGROUND: Cystoid macular oedema (CMO) is an uncommon complication associated with hydroxychloroquine (HCQ) retinopathy threatening central vision. We report a patient with HCQ retinopathy and CMO, for which an intravitreal dexamethasone implant was used, which led to complete resolution of oedema. CASE PRESENTATION: A 57-year-old woman with systemic lupus erythematosus (SLE) complaining of blurred vision in both eyes was diagnosed with bilateral HCQ retinopathy and CMO based on characteristic photoreceptor defects and cystoid spaces on optical coherence tomography, hypo-autofluorescence on fundus autofluorescence, and corresponding visual field defects. After treatment with systemic acetazolamide and topical dorzolamide, CMO showed partial resolution in the right eye. Owing to worsening renal function, an intravitreal dexamethasone implant was placed in the right eye, which resulted in resolution of CMO and visual improvement from 20/50 to 20/30. CONCLUSION: Intravitreal dexamethasone implant may be effective for the treatment of CMO in HCQ retinopathy, particularly for the cases refractory to systemic or topical carbonic anhydrase inhibitors.
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Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Hidroxicloroquina/efeitos adversos , Edema Macular/tratamento farmacológico , Implantes de Medicamento , Feminino , Humanos , Edema Macular/etiologia , Pessoa de Meia-Idade , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/complicaçõesRESUMO
From May through July 2015, a total of 26 cases of Middle East Respiratory Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1 index case and 25 new cases. We examined the epidemiologic features of these cases and found an estimated median incubation period of 6.1 days (8.8 days in hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in hospital A and 3.0% in hospital B), and the attack rates among inpatients and caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case-fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of cohort quarantine may have played a role in preventing community spread, but additional transmission occurred among members of the hospital cohort quarantined together. Caregivers may have contributed in part to the transmission.
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Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Hospitais , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quarentena , República da Coreia/epidemiologiaRESUMO
OBJECTIVE: Preclinical studies have proved that beta-blocking agents inhibit several pathways for breast cancer progression and metastasis. We aimed to evaluate the association between beta-blocker use and prognosis of breast cancer. METHODS: A systematic search for studies from MEDLINE and EMBASE (inception to March 2014) was performed using the keywords "breast cancer" and "beta-blocker." In 2 groups of breast cancer patients (beta-blocker users and non-beta-blocker users), overall deaths (ODs), cancer-specific deaths (CSDs), and recurrences were compared. RESULTS: Six studies including 18,118 patients were eligible for this analysis. Two studies with 3,139 patients were included in the analysis of ODs. The random-effects model showed no significant difference in ODs between beta-blocker users and non-beta-blocker users (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.50-1.52, p = 0.49). Four studies with 13,782 patients were included in the measurement of CSDs. The difference in CSDs between beta-blocker users and non-beta-blocker users was not significant using the fixed-effect model (OR 0.93, 95% CI 0.82-1.06, p = 0.29). Three studies with 3,923 patients were included in the calculation of recurrences. Overall, beta-blockers did not affect the incidence of recurrence (OR 0.70, 95% CI 0.25-1.95, p = 0.49). CONCLUSION: Beta-blockers were not beneficial regarding ODs, CSDs, or recurrences. Further studies are needed to evaluate the associations between the effects of beta-blockers and subtypes of breast cancer.
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Antagonistas Adrenérgicos beta/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hipertensão/tratamento farmacológico , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Progressão da Doença , Feminino , Humanos , Hipertensão/complicações , Incidência , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Análise de Sobrevida , Resultado do TratamentoRESUMO
Mixed Zn(II)/Gd(III) oxide nanoparticles (~8 mole%Zn) with d(avg) of 2.1 nm were synthesized. The D-glucuronic acid coated Zn(II)/Gd(III) oxide nanoparticles showed a longitudinal water proton relaxivity (r1) of 12.3 s⻹mM⻹ with r2/r1 = 1.1, corresponding to an ideal condition for T1 MRI contrast agent. We attribute this to reduced magnetization of the mixed nanoparticles owing to non-magnetic Zn in the nanoparticles. Their effectiveness as a T1 MRI contrast agent was confirmed by acquiring In Vivo T1 MR images of a mouse after intravenous injection.
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Although tyrosine kinase inhibitor (TKI) therapies are highly effective in the treatment of chronic myeloid leukemia (CML), frequent recurrence limits their usage and demands new approaches for CML therapy. Stress-induced premature senescence (SIPS) is considered a potential anticancer treatment, but the underlying mechanism remains elusive. Here, we report that Sirtinol, a known SIRT1 inhibitor, induces premature senescence and growth arrest in K562 CML cells. Chromobox homolog 8 (CBX8) suppresses the Sirtinol-induced premature senescence, which is reversed by CBX8 knockdown. Upon Sirtinol treatment, the phosphorylation of AKT1, p27KIP1 and RB is severely downregulated. However, CBX8 overexpression enhances phosphorylation and, thereby, promotes the transcriptional activity of E2F1, both of which are impaired upon CBX depletion. These data suggest that CBX8 modulates SIPS through the RB-E2F1 pathway in CML cells and provide important insight into its application in CML treatment.
Assuntos
Benzamidas/administração & dosagem , Senescência Celular/efeitos dos fármacos , Fator de Transcrição E2F1/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Naftóis/administração & dosagem , Complexo Repressor Polycomb 1/metabolismo , Proteína do Retinoblastoma/metabolismo , Antineoplásicos/administração & dosagem , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Antagonismo de Drogas , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Proteína Oncogênica v-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
We report design, synthesis, and mechanistic studies of a new mitomycin tetramer 9 along with a new mitomycin dimer 10. Mitomycin 9 is a tetramer connected by the disulfide linker 11, and easily undergoes disulfide cleavage to provide two dimeric structures 9r that each contains a single thiol probe for activations. So, tetramer 9 as a precursor of 9r was specifically targeted to undergo double activations with a single probe. A tetramer 9 was synthesized using 1 and key intermediate 11, and a dimer 10 was synthesized from 1 and diamine 12. Activation studies revealed that 9 underwent effective double activations with a single probe by nucleophiles while the reference 10 did not. Evaluations of DNA ISC formations showed that 9 generated substantial levels of DNA ISC by nucleophilic activation while the references 10 and 2 did not. The effectiveness of 9 in activation and formation of DNA ISC per probe was verified by comparing with dimers 5-8 of double activations with two probes. These findings highlighted the role of a single thiol in 9r and demonstrated the intended double activations with a single probe, which marks the first case in mitomycin studies.
Assuntos
Alquilantes/química , Alquilantes/farmacologia , Adutos de DNA/química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Mitomicina/química , Mitomicina/farmacologia , Alquilantes/síntese química , DNA/química , Dimerização , Dissulfetos/síntese química , Dissulfetos/química , Dissulfetos/farmacologia , Desenho de Fármacos , Substâncias Intercalantes/síntese química , Mitomicina/síntese químicaRESUMO
We report the synthesis of novel 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins 3, and their biological evaluation using NADPH oxidase (NOX) 1 and 4. Based on structural and pharmacophore analyses of known inhibitors such as hydroxypyrazole 2, we envisioned interesting 2-thiohydantoin compounds, 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins 3 that would be expected to well match the structural features in 2. Efficient synthesis of eighteen target compounds 3 were achieved through the synthetic pathway of 4â11â3, established after consideration of several plausible synthetic pathways. The inhibitory activities of compounds 3 against NOX 1 and 4 were measured, with some of the target compounds showing similar or higher activities compared with reference 2; in particular, compounds 3bz, 3cz, and 3ez were found to be promising inhibitors of both NOX 1 and 4 with modest isozyme selectivities, which highlights the significance of the 2-thiohydantoin substructure for inhibition of NOX 1 and 4. This marks the first time these compounds have been applied to the inhibition of NOX enzymes.