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Epicardial adipose tissue (EAT) have been shown to be associated with several heart disease, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). It is reported that the quality of EAT, represented by fat attenuation determined using computed tomography (CT) imaging, can detect the histologically-assessed remodeled EAT. We tested the hypothesis that quality of EAT would predict major adverse cerebral and cardiovascular events (MACCE) following transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS). A total of 125 consecutive severe AS patients who underwent TAVI were enrolled (39 male, mean 85.4 ± 4.0 years). Using CT imaging before TAVI, we measured the average CT fat attenuation of EAT (EAT attenuation) and investigated the association with MACCE. During the mean follow up period of 567 ± 371 days, 21 cases of MACCE were observed. Patients with MACCE had greater levels of EAT attenuation compared to those without (- 74 ± 3.7 Hounsfield Units (HU) vs - 77 ± 5.5 HU, p = 0.010). Based on the ROC curves, the high EAT attenuation was defined as > - 74.3 HU. According to this cut-off index, 44 patients were classified into the high EAT attenuation group (28 female, mean age 87 ± 3.6 years), whereas 81 patients were classified into the low EAT attenuation group (13 female, 85 ± 4.1 years). Kaplan-Meier survival curve demonstrated that the patients in the high EAT attenuation group showed greater prevalence of MACCE (log-rank 6.64, p = 0.010). Cox proportional hazards regression analysis revealed that EAT attenuation and Logistic EuroSCORE were independently associated with the incidence of MACCE. Our results suggest that quality of EAT, assessed by EAT attenuation detected by CT imaging, can predict the cerebral and cardiovascular events after TAVI in patients with AS.
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Tejido Adiposo , Estenosis de la Válvula Aórtica , Pericardio , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Masculino , Femenino , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Pericardio/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Tejido Adiposo/diagnóstico por imagen , Anciano de 80 o más Años , Factores de Riesgo , Estudios Retrospectivos , Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Medición de Riesgo/métodos , Anciano , Tomografía Computarizada por Rayos X , Índice de Severidad de la Enfermedad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Curva ROC , Japón/epidemiología , Valor Predictivo de las Pruebas , Estudios de Seguimiento , Resultado del Tratamiento , Tomografía Computarizada Multidetector , Factores de Tiempo , Tejido Adiposo EpicárdicoRESUMEN
OBJECTIVES: The COVID-19 pandemic has had variable effects on the rates of STIs reported across the globe. This study sought to assess how the number of STI reports changed during the pandemic in Japan. METHODS: We used national infectious disease surveillance data from the National Institute of Infectious Diseases (Tokyo, Japan) for the period between January 2013 and December 2021. We compared reported rates of chlamydia, gonorrhoea, condyloma acuminata and genital herpes, as well as total notifications for HIV/AIDS and syphilis during the pandemic versus previous years in Japan. We used a quasi-Poisson regression to determine whether any given week or month between January 2018 and December 2021 had a significant excess or deficit of STIs. Notification values above or below the 95% upper and lower prediction thresholds were considered as statistically significant. The start of the pandemic was defined as January 2020. RESULTS: Chlamydia generally remained within predicted range during the pandemic period. Reporting of gonorrhoea was significantly higher than expected throughout early-to-mid 2021 but otherwise generally remained within predicted range prior to 2021. Condyloma, herpes and HIV/AIDS reporting were transiently significantly lower than expected throughout the pandemic period, but no significant periods of higher-than-expected reporting were detected. Syphilis showed widespread evidence of significantly lower-than-predicted reporting throughout 2020 but eventually reversed, showing significantly higher-than-predicted reporting in mid-to-late 2021. CONCLUSIONS: The COVID-19 pandemic was associated with variable changes in the reporting of STIs in Japan. Higher-than-predicted reporting was more likely to be observed in the later phases of the pandemic. These changes may have been attributable to pandemic-related changes in sexual behaviour and decreased STI clinic attendance and testing, but further research on the long-term impact of the pandemic on STIs is necessary.
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Síndrome de Inmunodeficiencia Adquirida , COVID-19 , Infecciones por Chlamydia , Chlamydia , Condiloma Acuminado , Gonorrea , Infecciones por VIH , Enfermedades de Transmisión Sexual , Sífilis , Humanos , Sífilis/epidemiología , Gonorrea/epidemiología , Pandemias , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Japón/epidemiología , Infecciones por VIH/epidemiología , COVID-19/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Condiloma Acuminado/epidemiología , Infecciones por Chlamydia/epidemiologíaRESUMEN
Accurately estimating the timing of pathogen exposure plays a crucial role in outbreak control for emerging infectious diseases, including the source identification, contact tracing, and vaccine research and development. However, since surveillance activities often collect data retrospectively after symptoms have appeared, obtaining accurate data on the timing of disease onset is difficult in practice and can involve "coarse" observations, such as interval or censored data. To address this challenge, we propose a novel likelihood function, tailored to coarsely observed data in rapid outbreak surveillance, along with an optimization method based on an ε $$ \varepsilon $$ -accelerated EM algorithm for faster convergence to find maximum likelihood estimates (MLEs). The covariance matrix of MLEs is also discussed using a nonparametric bootstrap approach. In terms of bias and mean-squared error, the performance of our proposed method is evaluated through extensive numerical experiments, as well as its application to a series of epidemiological surveillance focused on cases of mass food poisoning. The experiments show that our method exhibits less bias than conventional methods, providing greater efficiency across all scenarios.
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INTRODUCTION: During the COVID-19 pandemic, the incidence of many droplet-transmitted infections decreased due to increased mask-wearing and social distancing. Contrastingly, there has been concern that COVID-19 countermeasures, such as lockdowns, may increase legionellosis incidence via water stagnation. During the pandemic in Japan, four state of emergency declarations were imposed between 2020 and 2021, which makes it particularly suitable to test this hypothesis. METHODS: We use country-level surveillance data from the National Institute of Infectious Diseases to track the relative incidence of legionellosis compared to invasive pneumococcal disease (IPD) during the COVID-19 pandemic in Japan, with a focus on the periods just after state of emergency declarations were lifted. RESULTS: The absolute number of legionellosis and IPD cases decreased in 2020 and 2021 compared to previous years. The average relative incidence of legionellosis as well as the variance of the relative incidence significantly increased during the pandemic compared to previous years. There were no increases in the relative incidence of legionellosis during the periods immediately following emergency declaration liftings, but the relative incidence did increase considerably during the first two states of emergency. CONCLUSIONS: COVID-19 countermeasures appear more effective at decreasing the incidence of human-to-human transmitted infections, such as IPD, compared to environmentally-transmitted infections, such as legionellosis. Though no evidence was found to suggest that legionellosis cases increased after state of emergency declarations, public health efforts should continue to emphasize the importance of routine sanitation and water system maintenance to prevent water stagnation and Legionella spp. contamination.
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COVID-19 , Legionelosis , Infecciones Neumocócicas , Humanos , COVID-19/epidemiología , Pandemias , Incidencia , Japón/epidemiología , Control de Enfermedades Transmisibles , Legionelosis/epidemiología , Infecciones Neumocócicas/epidemiología , AguaRESUMEN
[Figure: see text].
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Proteína Morfogenética Ósea 4/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Insuficiencia de la Válvula Mitral/metabolismo , Válvula Mitral/efectos de los fármacos , Infarto del Miocardio/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Redes Reguladoras de Genes , Antígenos Comunes de Leucocito/genética , Masculino , Válvula Mitral/metabolismo , Válvula Mitral/patología , Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/genética , Insuficiencia de la Válvula Mitral/patología , Insuficiencia de la Válvula Mitral/fisiopatología , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Mapas de Interacción de Proteínas , Oveja Doméstica , Transducción de Señal , Transcriptoma , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
BACKGROUND: Interrupted time series (ITS) analysis has become a popular design to evaluate the effects of health interventions. However, the most common formulation for ITS, the linear segmented regression, is not always adequate, especially when the timing of the intervention is unclear. In this study, we propose a new model to overcome this limitation. METHODS: We propose a new ITS model, ARIMAITS-DL, that combines (1) the Autoregressive Integrated Moving Average (ARIMA) model and (2) distributed lag functional terms. The ARIMA technique allows us to model autocorrelation, which is frequently observed in time series data, and the decaying cumulative effect of the intervention. By contrast, the distributed lag functional terms represent the idea that the intervention effect does not start at a fixed time point but is distributed over a certain interval (thus, the intervention timing seems unclear). We discuss how to select the distribution of the effect, the model construction process, diagnosing the model fitting, and interpreting the results. Further, our model is implemented as an example of a statement of emergency (SoE) during the coronavirus disease 2019 pandemic in Japan. RESULTS: We illustrate the ARIMAITS-DL model with some practical distributed lag terms to examine the effect of the SoE on human mobility in Japan. We confirm that the SoE was successful in reducing the movement of people (15.0-16.0% reduction in Tokyo), at least between February 20 and May 19, 2020. We also provide the R code for other researchers to easily replicate our method. CONCLUSIONS: Our model, ARIMAITS-DL, is a useful tool as it can account for the unclear intervention timing and distributed lag effect with autocorrelation and allows for flexible modeling of different types of impacts such as uniformly or normally distributed impact over time.
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COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Análisis de Series de Tiempo Interrumpido , Modelos Lineales , Pandemias/prevención & control , Factores de TiempoRESUMEN
BACKGROUND: Increases in human mobility have been linked to rises in novel coronavirus disease 2019 (COVID-19) transmission. The pandemic era in Japan has been characterized by changes in inter-prefectural mobility across state of emergency (SOE) declarations and travel campaigns, but they have yet to be characterized. METHODS: Using Yahoo Japan mobility data extracted from the smartphones of more than 10 million Japanese residents, we calculated the monthly number of inter-prefectural travel instances, stratified by residential prefecture and destination prefecture. We then used this adjacency matrix to calculate two network connectedness metrics, closeness centrality and effective distance, that reliably predict disease transmission. RESULTS: Inter-prefectural mobility and network connectedness decreased most considerably during the first SOE, but this decrease dampened with each successive SOE. Mobility and network connectedness increased during the Go To Travel campaign. Travel volume between distant prefectures decreased more than travel between prefectures with geographic proximity. Closeness centrality was found to be negatively correlated with the rate of COVID-19 infection across prefectures, with the strength of this association increasing in tandem with the infection rate. Changes in effective distance were more visible among geographically isolated prefectures (Hokkaido and Okinawa) than among metropolitan, central prefectures (Tokyo, Aichi, Osaka, and Fukuoka). CONCLUSION: The magnitude of reductions in human mobility decreased with each subsequent state of emergency, consistent with pandemic fatigue. The association between network connectedness and rates of COVID-19 infection remained visible throughout the entirety of the pandemic period, suggesting that inter-prefectural mobility may have contributed to disease spread.
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COVID-19 , Pandemias , Humanos , COVID-19/epidemiología , Japón/epidemiología , Viaje , TokioRESUMEN
OBJECTIVE: Excessive salt intake raises blood pressure and increases the risk of non-communicable diseases (NCD), such as CVD, chronic kidney disease and stomach cancer. Reducing the Na content of food is an important public health measure to control the NCD. This study quantifies the amount of salt reduced by using umami substances, i.e. glutamate, inosinate and guanylate, for adults in the USA. DESIGN: The secondary data analysis was performed using data of the US nationally representative cross-sectional dietary survey, the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Per capita daily salt intake corresponding to the NHANES food groups was calculated in the four hypothetical scenarios of 0 %, 30 %, 60 % and 90 % market share of low-Na foods in the country. The salt reduction rates by using umami substances were estimated based on the previous study results. SETTING: The USA. PARTICIPANTS: 4139 individuals aged 20 years and older in the USA. RESULTS: Replacing salt with umami substances could help the US adults reduce salt intake by 7·31-13·53 % (7·50-13·61 % for women and 7·18-13·53 % for men), which is equivalent to 0·61-1·13 g/d (0·54-0·98 g/d for women and 0·69-1·30 g/d for men) without compromising the taste. Approximately, 21·21-26·04 % of the US adults could keep their salt intake below 5 g/d, the WHO's recommendation in the scenario where there is no low-Na product on the market. CONCLUSIONS: This study provides essential information that the use of umami substances as a substitute for salt may help reduce the US adults' salt intake.
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BACKGROUND: Hybrid endovascular repair for thoracoabdominal aortic aneurysm (TAAA) is a less invasive alternative treatment than conventional open repair. However, disseminated intravascular coagulation (DIC) and hemorrhagic complications can occur postoperatively. We investigated risk factors for hemorrhagic complications after hybrid endovascular TAAA repair. METHODS: Sixty-one patients who underwent elective hybrid endovascular TAAA repair between 2007 and 2020 were included. Laboratory data before and after placing stent graft were collected, and DIC was diagnosed using a scoring system established by the Japanese Association for Acute Medicine. The length of the stent graft used to cover the aorta was defined as the aortic coverage length, which was measured using the first postoperative computed tomography image. Predictors of unexpected hemorrhagic complications were evaluated. RESULTS: Postoperative thrombocytopenia was observed in 57 (93%) patients, and their platelet count decreased significantly after stent graft placement (14.3 [9.5-18.0] vs. 8.2 [5.4-10.9] × 104/µL, P < 0.001). Fifteen (25%) and 45 patients (74%) were diagnosed with DIC before and after stent graft placement, respectively. Hemorrhagic complications were observed in 21 patients (34%). Multivariate logistic regression analysis revealed that aortic coverage length was an independent risk factor for hemorrhagic complications (odds ratio 1.441/50 mm increase; 95% confidence interval, 1.041-1.994, P = 0.027). The cutoff value for aortic coverage length obtained from the receiver operating characteristic curve (area under the curve = 0.72) was 304.4 mm (sensitivity 0.76, specificity 0.70). CONCLUSION: Aortic coverage length is a risk factor for hemorrhagic complications. Patients undergoing extensive aortic coverage greater than 304 mm should be closely monitored.
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Implantación de Prótesis Vascular/efectos adversos , Prótesis Vascular , Coagulación Intravascular Diseminada/etiología , Procedimientos Endovasculares/efectos adversos , Hemorragia Posoperatoria/etiología , Anciano , Aneurisma de la Aorta Torácica , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Stents , Trombocitopenia/etiologíaRESUMEN
To provide insight into the mortality burden of coronavirus disease (COVID-19) in Japan, we estimated the excess all-cause deaths for each week during the pandemic, January-May 2020, by prefecture and age group. We applied quasi-Poisson regression models to vital statistics data. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the 1-sided prediction interval. A total of 208-4,322 all-cause excess deaths at the national level indicated a 0.03%-0.72% excess in the observed number of deaths. Prefecture and age structure consistency between the reported COVID-19 deaths and our estimates was weak, suggesting the need to use cause-specific analyses to distinguish between direct and indirect consequences of COVID-19.
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COVID-19/mortalidad , COVID-19/diagnóstico , Causas de Muerte , Humanos , Japón/epidemiología , Mortalidad , SARS-CoV-2RESUMEN
The demand for rapid surveillance and early detection of local outbreaks has been growing recently. The rapid surveillance can select timely and appropriate interventions toward controlling the spread of emerging infectious diseases, such as the coronavirus disease 2019 (COVID-19). The Farrington algorithm was originally proposed by Farrington et al (1996), extended by Noufaily et al (2012), and is commonly used to estimate excess death. However, one of the major challenges in implementing this algorithm is the lack of historical information required to train it, especially for emerging diseases. Without sufficient training data the estimation/prediction accuracy of this algorithm can suffer leading to poor outbreak detection. We propose a new statistical algorithm-the geographically weighted generalized Farrington (GWGF) algorithm-by incorporating both geographically varying and geographically invariant covariates, as well as geographical information to analyze time series count data sampled from a spatially correlated process for estimating excess death. The algorithm is a type of local quasi-likelihood-based regression with geographical weights and is designed to achieve a stable detection of outbreaks even when the number of time points is small. We validate the outbreak detection performance by using extensive numerical experiments and real-data analysis in Japan during COVID-19 pandemic. We show that the GWGF algorithm succeeds in improving recall without reducing the level of precision compared with the conventional Farrington algorithm.
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COVID-19 , Pandemias , Algoritmos , Brotes de Enfermedades/prevención & control , Humanos , Funciones de Verosimilitud , SARS-CoV-2RESUMEN
In the COVID-19 era, movement restrictions are crucial to slow virus transmission and have been implemented in most parts of the world, including Japan. To find new insights on human mobility and movement restrictions encouraged (but not forced) by the emergency declaration in Japan, we analyzed mobility data at 35 major stations and downtown areas in Japan-each defined as an area overlaid by several 125-meter grids-from September 1, 2019 to March 19, 2021. Data on the total number of unique individuals per hour passing through each area were obtained from Yahoo Japan Corporation (i.e., more than 13,500 data points for each area). We examined the temporal trend in the ratio of the rolling seven-day daily average of the total population to a baseline on January 16, 2020, by ten-year age groups in five time frames. We demonstrated that the degree and trend of mobility decline after the declaration of a state of emergency varies across age groups and even at the subregional level. We demonstrated that monitoring dynamic geographic and temporal mobility information stratified by detailed population characteristics can help guide not only exit strategies from an ongoing emergency declaration, but also initial response strategies before the next possible resurgence. Combining such detailed data with data on vaccination coverage and COVID-19 incidence (including the status of the health care delivery system) can help governments and local authorities develop community-specific mobility restriction policies. This could include strengthening incentives to stay home and raising awareness of cognitive errors that weaken people's resolve to refrain from nonessential movement.
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COVID-19 , Pandemias , Humanos , Japón/epidemiología , Estudios Longitudinales , SARS-CoV-2RESUMEN
OBJECTIVE: To estimate the effect of airline travel restrictions on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) importation. METHODS: We extracted passenger volume data for the entire global airline network, as well as the dates of the implementation of travel restrictions and the observation of the first case of coronavirus disease (COVID-19) in each country or territory, from publicly available sources. We calculated effective distance between every airport and the city of Wuhan, China. We modelled the risk of SARS-CoV-2 importation by estimating survival probability, expressing median time of importation as a function of effective distance. We calculated the relative change in importation risk under three different hypothetical scenarios that all resulted in different passenger volumes. FINDINGS: We identified 28 countries with imported cases of COVID-19 as at 26 February 2020. The arrival time of the virus at these countries ranged from 39 to 80 days since identification of the first case in Wuhan. Our analysis of relative change in risk indicated that strategies of reducing global passenger volume and imposing travel restrictions at a further 10 hub airports would be equally effective in reducing the risk of importation of SARS-CoV-2; however, this reduction is very limited with a close-to-zero median relative change in risk. CONCLUSION: The hypothetical variations in observed travel restrictions were not sufficient to prevent the global spread of SARS-CoV-2; further research should also consider travel by land and sea. Our study highlights the importance of strengthening local capacities for disease monitoring and control.
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Control de Enfermedades Transmisibles/métodos , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Viaje/legislación & jurisprudencia , Aeronaves/legislación & jurisprudencia , Aeropuertos/normas , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/transmisión , Humanos , Modelos Estadísticos , Neumonía Viral/transmisión , Medición de Riesgo , SARS-CoV-2 , Factores de TiempoRESUMEN
BACKGROUND: The World Health Organization declared the novel coronavirus outbreak (COVID-19) to be a pandemic on March 11, 2020. Large-scale monitoring for capturing the current epidemiological situation of COVID-19 in Japan would improve preparation for and prevention of a massive outbreak. METHODS: A chatbot-based healthcare system named COOPERA (COvid-19: Operation for Personalized Empowerment to Render smart prevention And care seeking) was developed using the LINE app to evaluate the current Japanese epidemiological situation. LINE users could participate in the system either though a QR code page in the prefectures' websites or a banner at the top of the LINE app screen. COOPERA asked participants questions regarding personal information, preventive actions, and non-specific symptoms related to COVID-19 and their duration. We calculated daily cross correlation functions between the reported number of infected cases confirmed using polymerase chain reaction and the symptom-positive group captured by COOPERA. RESULTS: We analyzed 206,218 participants from three prefectures reported between March 5 and 30, 2020. The mean age of participants was 44.2 (standard deviation, 13.2) years. No symptoms were reported by 96.93% of participants, but there was a significantly positive correlation between the reported number of COVID-19 cases and self-reported fevers, suggesting that massive monitoring of fever might help to estimate the scale of the COVID-19 epidemic in real time. CONCLUSIONS: COOPERA is the first real-time system being used to monitor trends in COVID-19 in Japan and provides useful insights to assist political decisions to tackle the epidemic.
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Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Brotes de Enfermedades/prevención & control , Monitoreo Epidemiológico , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We developed a surgical hemostatic film using Hydrofit® (Hydrofit® film). This film is prepared by reacting Hydrofit® with water in advance, and it can be used in the same way as an accessory silicone sheet. In addition, unlike the silicone sheet, there is no need to remove the Hydrofit® film from the body. In the present study, we describe the hemostatic effect of our new method using Hydrofit® film. We created a pulsatile flow circuit model using a ventricular assist device and a vascular graft. The circuit was filled with water, and the systolic pressure was adjusted to ≥ 130 mmHg. The artificial blood vessel was punctured by an 18-G needle. Operations to prevent water from leaking were attempted through either a conventional method using a silicone sheet or our new method using Hydrofit® film. In the 180-s trial, 14 attempts (93.3%) with the Hydrofit® film were successful. In the silicone sheet group, 13 attempts (86.7%) were successful before the silicone sheet was peeled off, and hemostasis was maintained in 10 (66.5%) cases after the silicone sheet was removed. After short-duration hemostasis for 60 s, good waterproofing was obtained in the Hydrofit® film group (success in 17 cases [85%]). In contrast, in the silicone sheet group, 10 attempts (50%) were successful before the silicone sheet was peeled off, and hemostasis was maintained in only 7 (35%) cases after the silicone sheet was removed. Hydrofit® film showed good hemostatic performance in the pulsatile flow circuit model.
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Pérdida de Sangre Quirúrgica/prevención & control , Hemorragia/terapia , Hemostasis , Hemostáticos/uso terapéutico , Modelos Biológicos , Corazón Auxiliar , Humanos , Flujo Pulsátil , Injerto VascularRESUMEN
We performed a 2-stage procedure combining balloon pulmonary angioplasty and pulmonary endarterectomy for a high-risk chronic thromboembolic pulmonary hypertension patient with high pulmonary vascular resistance. First, balloon pulmonary angioplasty was performed for distal lesions to improve hemodynamics and decrease the surgical risk. Subsequently, pulmonary endarterectomy was performed for proximal lesions, and the hemodynamics and symptoms improved dramatically. Our strategy was therefore found to be useful for treating a high-risk chronic thromboembolic pulmonary hypertension patient.
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Angioplastia de Balón , Endarterectomía , Hipertensión Pulmonar/terapia , Arteria Pulmonar/cirugía , Embolia Pulmonar/terapia , Anciano , Angiografía , Presión Arterial , Terapia Combinada , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/fisiopatología , Resultado del Tratamiento , Resistencia VascularRESUMEN
A triphosphasumanene trisulfide was designed and synthesized as an out-of-plane anisotropic π-conjugated molecule. Incorporating three anisotropic phosphine sulfide moieties into a sumanene skeleton induced a cumulative anisotropy with a large dipole moment (12.0 D), which is aligned in perpendicular direction with respect to the π-framework and more than twice as large as those of conventional out-of-plane anisotropic molecules. In the crystal, the molecules align to form columnar structures, in which electron-rich and electron-deficient sides of the π-framework face each other. The interactions between the electron-rich surfaces, which contain three sulfur atoms, and Au(111) were examined by X-ray photoelectron spectroscopy.
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Our studies on the synthesis of heterasumanenes, where benzylic carbon atoms of the sumanene are replaced by heteroatom functionalities, are summarized. Starting from triphenylene, repetitive lithiation at a bay position followed by introduction of silylene or germylene units provided the first trisila- and trigermasumanenes with no substituents on the skeletal carbon atoms. The synthesis of a trisilasumanene bearing six butoxy groups on the skeletal carbon atoms was also accomplished by our original sila-Friedel-Crafts reaction. A heterasumanene bearing three different heteroatom functionalities was also prepared from triphenylenothiophene by a sequential lithiation method, even though protecting groups were necessary to prevent lithiation at the α-carbon atoms of the dibenzothiophene unit. Structural analysis and optical properties of the novel heterasumanenes are also described.
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Treatment of dialkylbenzylsilanes (1) with trityl tetrakis(pentafluorophenyl)borate (TPFPB) afforded the corresponding silylium ions in equilibrium with their intra- or intermolecular π-complexes, which underwent dehydrogenative annulation with various alkenes to form 1,2,3,4-tetrahydro-2-silanaphthalenes (4) in up to 82% isolated yield. Sterically bulkier substituents on the silicon atom tended to increase the yield of cyclic products 4. The annulation products retained the stereochemistry in cases of the reactions using internal alkenes. The use of diisopropyl(1-naphthyl)silane (2) instead of 1 also resulted in annulation to obtain the 2,3-dihydro-1-sila-1H-phenalene derivatives 6. Electrophilic aromatic substitution at the 8-position was predominant, despite the two potentially reactive positions on the naphthyl group. The steric hindrance of the naphthyl group prevented addition of the cis-alkene to the silylium ion, which would considerably decrease yields of the desired products from 2 compared to those from 1.
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Diorganyl[2-(trimethylsilylethynyl)phenyl]silanes 1a-c and methyl-substituted phenylsilanes 1d and 1e were treated with a small amount of trityl tetrakis(pentafluorophenyl)borate (TPFPB) as an initiator in benzene to afford the corresponding benzosiloles (2a-e) in moderate to good yields. However, no reaction was observed for the reaction using [2-(1-hexynyl)phenyl]diisopropylsilane lf. The methyl substituent was tolerated under the reaction conditions and increased the yield of the corresponding benzosilole depending on the substitution position. From the result using 1f, the current reaction was found to require the trimethylsilyl group, which can stabilize intermediary alkenyl carbocations by the ß-silyl effect. The current reaction can be considered an intramolecular chain hydrosilylation of alkynylarylsilanes involving silyl cations as chain carriers. Therefore, the silyl cations generated by hydride abstraction from hydrosilanes 1 with the trityl cation causes intramolecular electrophilic addition to the C-C triple bond to form ethenyl cations, which abstract a hydride from 1 to afford benzosiloles 2 with the regeneration of the silyl cations.