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1.
Nature ; 623(7989): 956-963, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38030784

RESUMEN

Monolayer graphene with nanometre-scale pores, atomically thin thickness and remarkable mechanical properties provides wide-ranging opportunities for applications in ion and molecular separations1, energy storage2 and electronics3. Because the performance of these applications relies heavily on the size of the nanopores, it is desirable to design and engineer with precision a suitable nanopore size with narrow size distributions. However, conventional top-down processes often yield log-normal distributions with long tails, particularly at the sub-nanometre scale4. Moreover, the size distribution and density of the nanopores are often intrinsically intercorrelated, leading to a trade-off between the two that substantially limits their applications5-9. Here we report a cascaded compression approach to narrowing the size distribution of nanopores with left skewness and ultrasmall tail deviation, while keeping the density of nanopores increasing at each compression cycle. The formation of nanopores is split into many small steps, in each of which the size distribution of all the existing nanopores is compressed by a combination of shrinkage and expansion and, at the same time as expansion, a new batch of nanopores is created, leading to increased nanopore density by each cycle. As a result, high-density nanopores in monolayer graphene with a left-skewed, short-tail size distribution are obtained that show ultrafast and ångström-size-tunable selective transport of ions and molecules, breaking the limitation of the conventional log-normal size distribution9,10. This method allows for independent control of several metrics of the generated nanopores, including the density, mean diameter, standard deviation and skewness of the size distribution, which will lead to the next leap in nanotechnology.

2.
Mol Cell ; 81(22): 4663-4676.e8, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34637754

RESUMEN

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin.


Asunto(s)
Encéfalo/metabolismo , Proteína de Unión a CREB/genética , Proteínas del Citoesqueleto/metabolismo , Proteína p300 Asociada a E1A/genética , Células Madre Embrionarias/metabolismo , Factor Nuclear 1 de Respiración/metabolismo , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular , Cromatina/química , Femenino , Genómica , Células HEK293 , Heterocigoto , Humanos , Masculino , Ratones , Neuronas/metabolismo , Unión Proteica , Dominios Proteicos , Proteómica , Activación Transcripcional
3.
J Cell Sci ; 136(12)2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37232206

RESUMEN

Mitochondrial dynamics regulate the quality and morphology of mitochondria. Calcium (Ca2+) plays an important role in regulating mitochondrial function. Here, we investigated the effects of optogenetically engineered Ca2+ signaling on mitochondrial dynamics. More specifically, customized illumination conditions could trigger unique Ca2+ oscillation waves to trigger specific signaling pathways. In this study, we found that modulating Ca2+ oscillations by increasing the light frequency, intensity and exposure time could drive mitochondria toward the fission state, mitochondrial dysfunction, autophagy and cell death. Moreover, illumination triggered phosphorylation at the Ser616 residue but not the Ser637 residue of the mitochondrial fission protein, dynamin-related protein 1 (DRP1, encoded by DNM1L), via the activation of Ca2+-dependent kinases CaMKII, ERK and CDK1. However, optogenetically engineered Ca2+ signaling did not activate calcineurin phosphatase to dephosphorylate DRP1 at Ser637. In addition, light illumination had no effect on the expression levels of the mitochondrial fusion proteins mitofusin 1 (MFN1) and 2 (MFN2). Overall, this study provides an effective and innovative approach to altering Ca2+ signaling for controlling mitochondrial fission with a more precise resolution than pharmacological approaches in the temporal dimension.


Asunto(s)
Calcio , Dinámicas Mitocondriales , Dinámicas Mitocondriales/fisiología , Calcio/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Mitocondrias/metabolismo , Fosforilación , Muerte Celular , Proteínas Mitocondriales/metabolismo
4.
Circulation ; 147(11): 867-876, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36597886

RESUMEN

BACKGROUND: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. METHODS: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects. RESULTS: Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001). CONCLUSIONS: Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause.


Asunto(s)
COVID-19 , Miocarditis , Adolescente , Niño , Adulto Joven , Humanos , Vacunas contra la COVID-19/efectos adversos , Miocarditis/etiología , Glicoproteína de la Espiga del Coronavirus , COVID-19/prevención & control , SARS-CoV-2 , Citocinas , Autoanticuerpos , Anticuerpos Antivirales
5.
J Gen Virol ; 105(1)2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38189334

RESUMEN

Phosphorylation and dephosphorylation of viral movement proteins plays a crucial role in regulating virus movement. Our study focused on investigating the movement protein TGBp1 of Bamboo mosaic virus (BaMV), which is a single-stranded positive-sense RNA virus. Specifically, we examined four potential phosphorylation sites (S15, S18, T58, and S247) within the TGBp1 protein. To study the impact of phosphorylation, we introduced amino acid substitutions at the selected sites. Alanine substitutions were used to prevent phosphorylation, while aspartate substitutions were employed to mimic phosphorylation. Our findings suggest that mimicking phosphorylation at S15, S18 and T58 of TGBp1 might be linked to silencing suppressor activities. The phosphorylated form at these sites exhibits a loss of silencing suppressor activity, leading to reduced viral accumulation in the inoculated leaves. Furthermore, mimicking phosphorylation at residues S15 and S18 could diminish viral accumulation at the single-cell level, while doing so at residue T58 could influence virus movement. However, mimicking phosphorylation at residue S247 does not appear to be relevant to both functions of TGBp1. Overall, our study provides insights into the functional significance of specific phosphorylation sites in BaMV TGBp1, illuminating the regulatory mechanisms involved in virus movement and silencing suppression.


Asunto(s)
Potexvirus , Fosforilación , Potexvirus/genética , Alanina , Sustitución de Aminoácidos
6.
Breast Cancer Res Treat ; 203(2): 291-306, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37851288

RESUMEN

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.


Asunto(s)
Neoplasias de la Mama , Estudio de Asociación del Genoma Completo , Femenino , Humanos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Pronóstico , Factores de Riesgo , Pueblos del Este de Asia/genética
7.
Mol Pharm ; 21(6): 2625-2636, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38771015

RESUMEN

Extracellular vesicle (EV) research is rapidly advancing from fundamental science to translational applications in EV-based personalized therapeutics and diagnostics. Yet, fundamental questions persist regarding EV biology and mechanisms, particularly concerning the heterogeneous interactions between EVs and cells. While we have made strides in understanding virus delivery and intracellular vesicle transport, our comprehension of EV trafficking remains limited. EVs are believed to mediate intercellular communication through cargo transfer, but uncertainties persist regarding the occurrence and quantification of EV-cargo delivery within acceptor cells. This ambiguity is crucial to address, given the significant translational impact of EVs on therapeutics and diagnostics. This perspective article does not seek to provide exhaustive recommendations and guidance on EV-related studies, as these are well-articulated in position papers and statements by the International Society for Extracellular Vesicles (ISEV), including the 'Minimum Information for Studies of Extracellular Vesicles' (MISEV) 2014, MISEV2018, and the recent MISEV2023. Instead, recognizing the multilayered heterogeneity of EVs as both a challenge and an opportunity, this perspective emphasizes novel approaches to facilitate our understanding of diverse EV biology, address uncertainties, and leverage this knowledge to advance EV-based personalized diagnostics and therapeutics. Specifically, this perspective synthesizes current insights, identifies opportunities, and highlights exciting technological advancements in ultrasensitive single EV or "digital" profiling developed within the author's multidisciplinary group. These newly developed technologies address technical gaps in dissecting the molecular contents of EV subsets, contributing to the evolution of EVs as next-generation liquid biopsies for diagnostics and providing better quality control for EV-based therapeutics.


Asunto(s)
Vesículas Extracelulares , Medicina de Precisión , Vesículas Extracelulares/metabolismo , Humanos , Medicina de Precisión/métodos , Comunicación Celular , Animales
8.
World J Urol ; 42(1): 15, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38189994

RESUMEN

PURPOSE: This study aimed to identify the characteristics associated with the need for urinary intervention for a blunt renal injury with collection system involvement using a computed tomography (CT) protocol for trauma. MATERIALS AND METHODS: Abdominal CT images of patients with blunt renal injuries from 2016 to 2020 were reviewed. Patients with low-grade renal trauma, non-collecting system involvement, American Association for the Surgery of Trauma grade V shattered kidney, and emergent nephrectomy were excluded. The largest perinephric mass thickness was measured in the axial view using CT, and a cutoff value was obtained using a receiver-operating characteristic curve analysis. Risk factors for further urinary intervention were analyzed. RESULTS: Among the 70 patients included in this study, those with perinephric mass thicknesses < 25 mm (n = 36) had a significantly lower rate of urinary intervention than those with perinephric mass thicknesses ≥ 25 mm (0 vs. 5; p = 0.023). There was no significant difference in the follow-up durations of the groups (19 days vs. 38 days; p = 0.198). More than 90% of the perinephric mass in the < 25 mm group resolved within a median follow-up duration of 38 days, whereas nearly half of the ≥ 25 mm group had a residual perinephric mass during a median follow-up duration of 19 days. CONCLUSION: The initial CT protocol for trauma was useful for predicting the need for further urinary interventions for collecting system injuries. A perinephric mass thickness < 25 mm is predictive of a low likelihood of requiring urinary intervention.


Asunto(s)
Heridas no Penetrantes , Humanos , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/terapia , Riñón/diagnóstico por imagen , Nefrectomía , Procedimientos Quirúrgicos Urológicos , Factores de Riesgo
10.
Am J Emerg Med ; 77: 39-45, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38096638

RESUMEN

OBJECTIVE: Patients with dizziness commonly present to Emergency Departments (ED) and 6% of these patients will be diagnosed with acute stroke. The TriAGe+ score comprises of eight clinical parameters and stratifies patients into four risk groups. The Japanese authors reported that the tool performed well, so our aim was to validate this diagnostic tool in our ED in Hong Kong. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in the ED of our university hospital in Hong Kong. The primary outcome was the diagnosis of an acute cerebrovascular event. Receiver operator characteristic (ROC) analysis was performed to determine the best cut-off score. Secondary outcomes included univariable and multivariable analyses of stroke predictors. RESULTS: 455 patients aged 18 years or above with dizziness or vertigo at ED triage were recruited between 19 July and 30 September 2021. The overall prevalence of stroke was 11.9%. The median TriAGe+ score was 7 (IQR = 4-9). The AUC was 0.9. At a cut-off >5, sensitivity was 96.4% (95%CI: 87.3-99.5) and the negative likelihood ratio was 0.09 (95%CI: 0.02-0.3). At a cut-off >10, specificity was 99.8% (95%CI: 98.6-100.0), and the positive likelihood ratio was 237.6 (95%CI: 33.1-1704). On multivariable analyses, atrial fibrillation, blood pressure, gender, dizziness (not vertigo) and no history of dizziness, vertigo or labyrinth/vestibular disease were found to be positively associated with stroke outcomes significantly. CONCLUSION: The TriAGe+ score is an efficient stroke prediction score for patients presenting to the ED with dizziness.


Asunto(s)
Mareo , Accidente Cerebrovascular , Humanos , Mareo/diagnóstico , Mareo/epidemiología , Servicio de Urgencia en Hospital , Hong Kong/epidemiología , Hospitales Universitarios , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Triaje , Vértigo/diagnóstico , Vértigo/epidemiología , Estudios Retrospectivos
11.
Postgrad Med J ; 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38679808

RESUMEN

BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 128-134, 2024 Feb.
Artículo en Zh | MEDLINE | ID: mdl-38433642

RESUMEN

The sympathetic nervous system(SNS)plays a pivotal role in maintaining organ homeostasis and the pathogenesis of various ailments.Studies have unveiled a profound interconnection between sympathetic nerves and the development of liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome.Therefore,researchers have proposed SNS as a candidate therapeutic target for liver-related disorders.This article reviewed the research progress of sympathetic nerves in liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome,aiming to enrich the knowledge about the roles of sympathetic nerves in cirrhosis and its complications and provide new ideas for the treatment of liver cirrhosis and its complications.


Asunto(s)
Cardiomiopatías , Síndrome Hepatorrenal , Humanos , Cirrosis Hepática , Sistema Nervioso Simpático , Homeostasis
13.
Acta Cardiol Sin ; 40(2): 191-199, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38532820

RESUMEN

Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.

14.
Cancer Sci ; 114(10): 4063-4072, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37489252

RESUMEN

The study used clinical data to develop a prediction model for breast cancer survival. Breast cancer prognostic factors were explored using machine learning techniques. We conducted a retrospective study using data from the Taipei Medical University Clinical Research Database, which contains electronic medical records from three affiliated hospitals in Taiwan. The study included female patients aged over 20 years who were diagnosed with primary breast cancer and had medical records in hospitals between January 1, 2009 and December 31, 2020. The data were divided into training and external testing datasets. Nine different machine learning algorithms were applied to develop the models. The performances of the algorithms were measured using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1-score. A total of 3914 patients were included in the study. The highest AUC of 0.95 was observed with the artificial neural network model (accuracy, 0.90; sensitivity, 0.71; specificity, 0.73; PPV, 0.28; NPV, 0.94; and F1-score, 0.37). Other models showed relatively high AUC, ranging from 0.75 to 0.83. According to the optimal model results, cancer stage, tumor size, diagnosis age, surgery, and body mass index were the most critical factors for predicting breast cancer survival. The study successfully established accurate 5-year survival predictive models for breast cancer. Furthermore, the study found key factors that could affect breast cancer survival in Taiwanese women. Its results might be used as a reference for the clinical practice of breast cancer treatment.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Adulto , Estudios Retrospectivos , Aprendizaje Automático , Valor Predictivo de las Pruebas , Curva ROC
15.
Strahlenther Onkol ; 199(8): 718-726, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36326857

RESUMEN

BACKGROUND: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. MATERIALS AND METHODS: In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. RESULTS: Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5 cm3 had a lower incidence of initial enlargement (p = 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8 ± 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (p = 0.045). No correlation was noted between initial enlargement and tumor control. CONCLUSION: Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5 cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.


Asunto(s)
Neuroma Acústico , Radiocirugia , Humanos , Radiocirugia/métodos , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Estudios Retrospectivos , Imagen por Resonancia Magnética , Aceleradores de Partículas , Estudios de Seguimiento , Resultado del Tratamiento
16.
J Neurooncol ; 165(3): 535-545, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38060066

RESUMEN

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.


Asunto(s)
Neoplasias Encefálicas , Glioma , Ratones , Animales , Humanos , Estudios Prospectivos , Proyectos Piloto , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamiento farmacológico , Barrera Hematoencefálica/metabolismo , Glioma/diagnóstico por imagen , Glioma/radioterapia , Microambiente Tumoral
17.
Dig Dis Sci ; 68(1): 259-267, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35790704

RESUMEN

BACKGROUND: Current postpolypectomy guidelines treat 1-9 mm nonadvanced adenomas (NAAs) as carrying the same level of risk for metachronous advanced colorectal neoplasia (ACRN). AIMS: To evaluate whether small (6-9 mm) NAAs are associated with a greater risk of metachronous ACRN than diminutive (1-5 mm) NAAs. METHODS: We retrospectively evaluated 10,060 index colonoscopies performed from July 2011 to June 2019. A total of 1369 patients aged ≥ 40 years with index NAAs and having follow-up examinations were categorized into 5 groups based on size and number of index findings: Group 1, ≤ 2 diminutive NAAs (n = 655); Group 2, ≤ 2 small NAAs (n = 529); Group 3, 3-4 diminutive NAAs (n = 78); Group 4, 3-4 small NAAs (n = 65); and Group 5, 5-10 NAAs (n = 42). Size was classified based on the largest NAA. ACRN was defined as finding an advanced adenoma or colorectal cancer at follow-up. RESULTS: The absolute risk of metachronous ACRN increased from 7.2% in patients with all diminutive NAAs to 12.2% in patients with at least 1 small NAA (P = 0.002). Patients in Group 2 (adjusted odds ratio [AOR] 1.89; 95% confidence interval [CI], 1.21-2.95), Group 3 (AOR 2.40; 95% CI 1.78-4.90), Group 4 (AOR 2.77; 95% CI 1.35-5.66), and Group 5 (AOR 3.71; 95% CI 1.65-8.37) were associated with an increased risk of metachronous ACRN compared with Group 1. CONCLUSIONS: Patients with small NAAs have an increased risk of metachronous ACRN. Postpolypectomy guidelines should consider including risk stratification between small and diminutive adenomas.


Asunto(s)
Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Neoplasias Primarias Secundarias , Humanos , Estudios Retrospectivos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Colonoscopía , Adenoma/epidemiología , Adenoma/cirugía , Neoplasias Primarias Secundarias/epidemiología , Factores de Riesgo
18.
World J Surg ; 47(10): 2357-2366, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37433919

RESUMEN

PURPOSE: We aimed to identify factors related to delayed intervention in abdominal trauma patients who underwent diagnostic laparoscopy using a nationwide databank. METHODS: From 2017 to 2019, abdominal trauma patients who underwent diagnostic laparoscopy were retrospectively evaluated using the Trauma Quality Improvement Program. Patients who underwent delayed interventions after a primary diagnostic laparoscopy were compared with those who did not. Factors associated with poor outcomes that are usually correlated with overlooked injuries and delayed interventions were also analyzed. RESULTS: Of the 5221 studied patients, 4682 (89.7%) underwent inspection without any intervention. Only 48 (0.9%) patients underwent delayed interventions after primary laparoscopy. Compared with patients receiving immediate interventions during primary diagnostic laparoscopy, patients receiving delayed interventions were more likely to have small intestine injuries (58.3% vs. 28.3%, p < 0.001). Among patients with hollow viscus injuries, a significantly higher probability of overlooked injuries that required delayed intervention was observed in patients with small intestine injuries (small intestine injury: 16.8%; gastric injury: 2.5%; large intestine injury: 5.2%). However, delayed small intestine repair did not significantly affect the risk of surgical site infection (SSI) (p = 0.249), acute kidney injury (AKI) (p = 0.998), or hospital length of stay (LOS) (p = 0.053). In contrast, significantly positive relationships between delayed large intestine repair and poor outcomes were observed (SSI, odds ratio = 19.544, p = 0.021; AKI, odds ratio = 27.368, p < 0.001; LOS, ß = 13.541, p < 0.001). CONCLUSIONS: Most examinations and interventions (near 90%) were successful during primary laparoscopy for abdominal trauma patients. Small intestine injuries were easily overlooked. Delayed small intestine repair-related poor outcomes were not observed.


Asunto(s)
Traumatismos Abdominales , Laparoscopía , Humanos , Estudios Retrospectivos , Mejoramiento de la Calidad , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/cirugía , Infección de la Herida Quirúrgica/cirugía
19.
J Thromb Thrombolysis ; 56(4): 518-528, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37452906

RESUMEN

BACKGROUND: The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully established. OBJECTIVES: To determine the effectiveness and safety related to pooled or specific DOACs to that with warfarin in patients with AF and AKD. METHODS: Patients with AF and AKD (estimated glomerular filtration rate < 30 mL/min) who received DOAC or warfarin from July 2011 to December 2020 were retrospectively identified in a medical center in Taiwan. Primary outcomes were hospitalized for stroke/systemic embolism and major bleeding. Secondary outcomes included any ischemia and any bleeding. RESULTS: A total of 1,011 patients were recruited, of whom 809 (80.0%) were in the DOACs group (15.3% dabigatran, 25.4% rivaroxaban, 25.2% apixaban, and 14.1% edoxaban), and 202 (20.0%) in the warfarin group. DOACs had considerably lower risks of stroke/systemic embolism (adjusted hazard ratio [aHR] 0.29; 95% CI, 0.09-0.97) and any ischemia (aHR, 0.42; 95% CI, 0.22-0.79), but had comparable risks of major bleeding (aHR, 0.99; 95% CI, 0.34-2.92) and any bleeding (aHR, 0.74; 95% CI, 0.50-1.09) than warfarin. Apixaban was linked to considerably lower risks of any ischemia (aHR, 0.13; 95% CI, 0.04-0.48) and any bleeding (aHR, 0.53; 95% CI, 0.28-0.99) than warfarin. CONCLUSION: Among patients with AF and AKD, DOACs were linked to a lower risk of ischemic events, and apixaban was linked to a lower risk of any ischemia and any bleeding than warfarin.

20.
Am J Emerg Med ; 72: 170-177, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37536089

RESUMEN

INTRODUCTION: Contrast-enhanced computed tomography (CT) scans are usually needed in the emergency department (ED) to evaluate intra-abdominal injuries associated with pelvic fractures. Three-dimensional (3-D) images for pelvis reconstruction are also needed for planning surgical fixation after admission. This study investigates the advantages integrating a one-stage computed tomography (CT) scan with these two diagnostic modalities simultaneously to reduce the time to surgery and improve the outcomes of pelvic fracture fixation. METHODS: A retrospective cohort study (2018-2021) of patients with pelvic fractures was performed. Patients were categorized into the one-stage CT group or the two-stage CT group, and propensity score matching was used to address biases. The outcome measures included time to surgical fixation, time to CT scan for 3-D pelvis reconstruction, and overall length of hospital stay. RESULTS: Four hundred forty-four pelvic fracture patients who underwent definite surgical fixation were identified. Of those, 320 underwent a one-stage CT scan, while the remaining 124 underwent a two-stage CT scan. After well-balanced matching, those in the one-stage CT group had a significantly shorter time to surgical fixation than those in the two-stage CT group (4.6 vs. 6.8 days, p < 0.001). Even among critically ill patients necessitating intensive care unit (ICU) admission, the one-stage CT scan group had a shorter time to definitive surgical fixation (5.5 vs. 7.2 days, p = 0.002) and a shorter hospital stay (19.0 vs. 32.7 days, p = 0.006). CONCLUSION: A one-stage contrast-enhanced CT scan combined with simultaneous 3-D pelvis reconstruction is promising for expediting surgical fixation in pelvic fracture patients. This innovative strategy may improve patient outcomes by facilitating timely surgical interventions and minimizing delays associated with additional CT scans.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Humanos , Fijación Interna de Fracturas/métodos , Estudios Retrospectivos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones , Fijación de Fractura , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , Huesos Pélvicos/lesiones , Tomografía Computarizada por Rayos X/métodos , Pelvis , Servicio de Urgencia en Hospital
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