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1.
Front Cardiovasc Med ; 11: 1399659, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988666

RESUMO

Objective: This study investigates the impact of mild pulmonary vein obstruction, detected via echocardiography before hospital discharge, on the likelihood of reoperation in patients who have undergone repair for Total Anomalous Pulmonary Venous Connection (TAPVC). Method: Utilizing a single-center, retrospective cohort approach, we analyzed 38 cases from October 2017 to December 2023, excluding patients with functionally univentricular circulations or atrial isomerism. Our primary outcome was the necessity for reoperation within one year due to anatomical issues related to the initial TAPVC repair. Mild obstruction was defined as a pulmonary vein flow velocity ≥1.2 m/s. Result: Our findings revealed that 31.6% of patients exhibited pre-discharge mild obstruction. During the median follow-up of 10 months, reoperations were notably higher in the mild obstruction group compared to the normal group, with a significant association between pre-discharge mild obstruction and increased risk of reoperation. Specifically, in the fully adjusted model, mild obstruction was linked to a 13.9-fold increased risk of reoperation. Conclusion: Our results suggest that a pre-discharge echocardiography Doppler velocity threshold of 1.2 m/s could serve as a critical predictor for reoperation, emphasizing the need for targeted follow-up strategies for at-risk patients.

2.
Immunotargets Ther ; 13: 349-366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050484

RESUMO

Background: The heterogeneity and dynamic changes of endometrial cells have a significant impact on health as they determine the normal function of the endometrium during the menstrual cycle. Dysfunction of the endometrium can lead to the occurrence of various gynecological diseases. Therefore, deconvolution of immune microenvironment that drives transcriptional programs throughout the menstrual cycle is key to understand regulatory biology of endometrium. Methods: Herein, we comprehensively analyzed single-cell transcriptome of 59,397 cells across ten human endometrium samples and revealed the dynamic cellular heterogeneity throughout the menstrual cycle. Results: We identified two perivascular cell subtypes, four epithelial subtypes and four fibroblast cell types in endometrium. Moreover, we inferred the cell type-specific transcription factor (TF) activities and linked critical TFs to transcriptional output of diverse immune cell types, highlighting the importance of transcriptional regulation in endometrium. Dynamic interactions between various types of cells in endometrium contribute to a range of biological pathways regulating differentiation of secretory. Integration of the molecular biomarkers identified in endometrium and bulk transcriptome of 535 endometrial cancers (EC), we revealed five RNA-based molecular subtypes of EC with highly intratumoral heterogeneity and different clinical manifestations. Mechanism analysis uncovered clinically relevant pathways for pathogenesis of EC. Conclusion: In summary, our results revealed the dynamic immune microenvironment of endometrium and provided novel insights into future development of RNA-based treatments for endometriosis and endometrial carcinoma.

3.
PLoS One ; 19(7): e0307833, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39047007

RESUMO

The fungal pathogen Batrachochytrium dendrobatidis (Bd) causes the disease amphibian chytridiomycosis, which has contributed to population declines in many species of amphibians throughout the world. Previous observational studies have shown that nematodes, waterfowl, lizards, other dipterans, and crayfish have properties which may allow them to harbor and spread Bd; therefore, we sought to determine the carrier capabilities of invertebrates to a further extent in a laboratory setting. We use the insect Drosophila melanogaster as a model organism to quantify the potential relationship between insects and Bd. Our findings show that D. melanogaster can test positive for Bd for up to five days post-exposure and can transmit Bd to conspecifics without suffering mortality. Insects of various types interact with the amphibian habitat and amphibians themselves, making this a potentially important route of transmission between amphibians and of dispersal across the environment.


Assuntos
Batrachochytrium , Drosophila melanogaster , Animais , Drosophila melanogaster/microbiologia , Batrachochytrium/patogenicidade , Anfíbios/microbiologia , Micoses/veterinária , Micoses/microbiologia , Quitridiomicetos/patogenicidade , Quitridiomicetos/fisiologia
4.
Front Pediatr ; 12: 1274913, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357504

RESUMO

Objective: This study aimed to investigate the relationship between technical performance scores (TPS) and the early prognosis of tetralogy of Fallot repair (TOF). Methods: A retrospective study was conducted on TOF repair patients at our center from Oct 2017 to Oct 2022. Patients were classified into Class 1 (no residua), Class 2 (minor residua), or Class 3 (major residua) based on TPS derived from predischarge echocardiograms and need for reintervention. Statistical methods were used to assess the association between TPS and early prognosis. Results: A total of 75 TOF repair patients (40% female, 60% male) were analyzed and categorized into TPS1 (24%), TPS2 (53.3%), and TPS3 (22.6%) based on pre-discharge echocardiographic findings. The median follow-up time was 7.0 months. The multivariable Cox regression analysis indicated that TPS3 scores are associated with a 12.68-fold increase in risk compared to TPS1 and TPS2 scores [95% CI = 12.68 (0.9∼179.28), P = 0.06]. The Spearman rank correlation analysis revealed a weak positive correlation between TPS classification and low cardiac output syndrome (r = 0.26, P = 0.03). However, there were no significant differences in ICU stay or duration of mechanical ventilation among the groups. Conclusion: TPS3 after intracardiac TOF repair is associated with higher risk of early re-intervention, highlighting the importance of close follow-up and monitoring in this patient population. Patients who develop low cardiac output syndrome in the early postoperative period may have residual defects that require prompt identification.

5.
IEEE Trans Biomed Eng ; 71(8): 2278-2286, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38194403

RESUMO

Congenital heart disease (CHD) is a common birth defect in children. Intelligent auscultation algorithms have been proven to reduce the subjectivity of diagnoses and alleviate the workload of doctors. However, the development of this algorithm has been limited by the lack of reliable, standardized, and publicly available pediatric heart sound databases. Therefore, the objective of this research is to develop a large-scale, high-standard, high-quality, and accurately labeled pediatric CHD heart sound database. METHOD: From 2020 to 2022, we collaborated with experienced cardiac surgeons from three general children's hospitals to collect heart sound signals from 1259 participants using electronic stethoscopes. To ensure the accuracy of the labels, the labels for all data were confirmed by two cardiac experts. To establish the baseline of ZCHsound, we extracted 84 features and used machine learning models to evaluate the performance of the classification task. RESULTS: The ZCHSound database was divided into two datasets: one is a high-quality, filtered clean heart sound dataset, and the other is a low-quality, noisy heart sound dataset. In the evaluation of the high-quality dataset, our random forest ensemble model achieved an F1 score of 90.3% in the classification task of normal and pathological heart sounds. CONCLUSION: This study has successfully established a large-scale, high-quality, rigorously standardized pediatric CHD sound database with precise disease diagnosis. This database not only provides important learning resources for clinical doctors in auscultation knowledge but also offers valuable data support for algorithm engineers in developing intelligent auscultation algorithms.


Assuntos
Bases de Dados Factuais , Cardiopatias Congênitas , Ruídos Cardíacos , Processamento de Sinais Assistido por Computador , Humanos , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/diagnóstico por imagem , Ruídos Cardíacos/fisiologia , Criança , Pré-Escolar , Lactente , Algoritmos , Masculino , Aprendizado de Máquina , Feminino , Recém-Nascido , Adolescente
6.
Front Cardiovasc Med ; 10: 1172104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215548

RESUMO

Background: In this case report, we utilized a three-dimensional printing model to replicate the complex anatomy of a criss-cross heart with double outlet right ventricle-an extremely rare congenital cardiac abnormality. This approach facilitated our understanding of the patient's unique condition and enabled us to plan the surgical procedure with greater precision. Case presentation: Our department received a 13-year-old female patient who presented with a pronounced heart murmur and a decrease in exercise capacity. Subsequent two-dimensional imaging revealed the presence of a criss-cross heart with double outlet right ventricle-an intricate and uncommon cardiac malformation that poses challenges for accurate visualization through conventional two-dimensional modalities. To address this challenge, we constructed and printed a three-dimensional model using computed tomography data, which enabled us to visualize and understand the complex intracardiac structures and plan surgical interventions with greater precision. Using this approach, we successfully performed a right ventricular double outlet repair, and the patient made a full recovery following the procedure. Conclusion: The criss-cross heart with double outlet right ventricle constitutes a complex and uncommon cardiac anomaly that poses considerable challenges in terms of diagnosis and surgical intervention. Employing three-dimensional modeling and printing represents a promising approach, given its potential to enhance the precision and comprehensiveness of the anatomical evaluation of the heart. As a result, this method holds significant promise in facilitating accurate diagnosis, meticulous surgical planning, and ultimately improving clinical outcomes for patients affected by this condition.

7.
Front Pediatr ; 11: 1128947, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36994434

RESUMO

Prenatal anterior mediastinal teratomas are rare. Anterior mediastinal teratomas can cause edema during the perinatal period. Color Doppler ultrasonography and chest computed tomography (CT) are of great value in diagnosing neonatal anterior mediastinal teratomas. Here, we report a case of prenatally diagnosed neonatal anterior mediastinal teratoma. After birth, transthoracic echocardiography and chest enhanced CT showed a large solid mass in the pericardial cavity. Owing to compression of the heart, the tumor was completely removed 1 day after birth, and cardiopulmonary bypass was performed. Pathology results indicated an immature teratoma (Grade I). At 9-month follow-up, the patient remained in good overall condition without observed recurrences.

8.
China Tropical Medicine ; (12): 704-2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-979790

RESUMO

@#Abstract: Objective To establish a screening-diagnosis-evaluation system of neonatal congenital heart disease (CHD) suitable for Hainan Province based on the application of percutaneous blood oxygen saturation measurement and cardiac auscultation screening, and to provide a basis for further promotion of the evaluation effect. Methods Screening agencies (all midwifery institutions) used the "double index method" to screen newborns for congenital heart disease. Those who were screened positive for any index were transferred to diagnostic institutions (the people's hospitals of all cities and counties and some tertiary hospitals) for echocardiography examination within 1 week. Those with abnormal results were transferred to the treatment institution (two tertiary hospitals) for reconfirmation and evaluation. All data were managed online. Results In this study, 96 913 newborns born in midwifery institutions in 19 cities and counties were screened, with a response rate of 99.44%. The ratio of male infants (50 836) to female infants (46 077) was 1.10∶1. A total of 2 284 positive patients were screened by dual index method, and ultrasound diagnosis was performed, with the rate of cardiac ultrasonography of 98.07% (2 240/2 284) and a high response rate. A total of 238 cases of congenital heart disease were diagnosed (incidence rate of 0.25%), with the top three main types were ventricular septal defect, atrial septal defect, and patent ductus arteriosus. The sensitivity (88.24%) and Youden index (0.86) of dual-indicator screening for CHD detection were significantly higher than the other separate indicators. Through Kappa consistency test analysis, the consistency of dual-indicator screening with simple heart murmur screening results was excellent, with a Kappa coefficient value of 0.835 (>0.75); the consistency of dual-indicator screening and simple POX screening results was good, with a Kappa coefficient value of 0.429 (between 0.40-0.75), and the differences were statistically significant (P<0.001). By the end of the study, 136 children had undergone open-chest/occlusion surgery, with good postoperative recovery, and the rest were followed up. Conclusions The neonatal CHD screening-diagnosis-assessment technology system established in this study, with close connections between various blocks, high screening response rate and echocardiography examination rate, is beneficial for the early diagnosis and treatment of CHD children, and has certain application value in institutions at all levels in Hainan Province, and is worth further promotion.

9.
Medicine (Baltimore) ; 101(47): e32070, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451474

RESUMO

RATIONALE: Double-outlet left ventricle (DOLV) is a rare congenital cardiac malformation in which both great arteries arise entirely or predominantly from the left ventricle. An extracardiac conduit is the first surgical option for repairing DOLV, specifically because its placement of the extracardiac conduit can be customized to accommodate all possible anatomical variations. The bovine jugular veins and homograft valves are often used as conduits. There have been no reports on the use of handmade trileaflet-valved conduits for correcting DORV. PATIENT CONCERNS: A 1-year old male was admitted for significant heart murmur and cyanosis, according to the results of transthoracic echocardiography, computed tomography angiography, and cardioangiography, and was diagnosed with DOLV and pulmonary stenosis. DIAGNOSIS AND INTERVENTIONS: The patient underwent biventricular repair with a handmade trileaflet-valved extracardiac conduit. The postoperative course was uneventful. OUTCOME: Three months after the surgery, TTF indicated mild right ventricular outflow obstruction and pulmonary valve regurgitation. LESSONS: Correction of the left ventricular double outlet with a handmade trileaflet-valved conduit has been shown to have excellent performance, and long-term outcomes should be followed over time.


Assuntos
Ventrículos do Coração , Estenose da Valva Pulmonar , Masculino , Animais , Bovinos , Humanos , Lactente , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Próteses e Implantes , Ecocardiografia , Cianose
10.
J Thorac Dis ; 14(10): 3706-3718, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36389321

RESUMO

Background: The exact incidence and predictors of mortality and left atrioventricular valve (LAVV) re-operation in congenital atrioventricular septal defect (AVSD) repair are still unclear. This study analyzed the middle to long-term outcomes of surgical repair for AVSD. Methods: A total of 150 patients (69 males and 81 females) who underwent AVSD repair at Children's Hospital of Fudan University from January 2013 to December 2021 were divided into complete defect group (C-group, 67 cases), transitional defect group (T-group, 26 cases), and partial defect group (P-group, 57 cases). Outcomes during the peri-operative and 10-year follow-up periods were evaluated. Results: The total mortality was 5.33% (8/150), including seven early deaths (10.4%) and no late deaths in the C-group, no early deaths (0%) and one late death (1.8%) in the P-group, and no early or late deaths in the T-group. Up to the last follow-up, severe LAVV regurgitation had occurred in 27 patients, including 16 in the C-group, four in the T-group, and seven in the P-group. In total, 12 (12/150, 8.0%) patients received LAVV re-operation, including seven in the C-group, three in the T-group, and two in the P-group. Cox regression analysis showed that pre-operative severe pulmonary hypertension (P=0.006) and severe LAVV regurgitation within 24 hours after the first surgery (P=0.023) were independent risk factors for mortality. ≥ Moderate LAVV regurgitation within the first 24 hours after surgery (P=0.014) was an independent risk factor for LAVV re-operation. Conclusions: Complete AVSD repair increased the risk of early death, severe LAVV regurgitation and re-operation. Pre-operative severe pulmonary hypertension and residual severe LAVV regurgitation indicated high risk for mortality. ≥ Moderate LAVV regurgitation within 24 hours after the first surgery predicted a high probability of LAVV re-operation.

11.
Int J Bioprint ; 8(3): 550, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105130

RESUMO

Age-related macular degeneration (AMD) is the leading cause of visual loss and affects millions of people worldwide. Dysfunction of the retinal pigment epithelium (RPE) is associated with the pathogenesis of AMD. The purpose of this work is to build and evaluate the performance of ultrathin scaffolds with an electrohydrodynamic jet (EHDJ) printing method for RPE cell culture. We printed two types of ultrathin (around 7 µm) polycaprolactone scaffolds with 20 µm and 50 µm pores, which possess mechanical properties resembling that of native human Bruch's membrane and are biodegradable. Light microscopy and cell proliferation assay showed that adult human retinal pigment epithelial (ARPE-19) cells adhered and proliferated to form a monolayer on the scaffolds. The progress of culture matured on the scaffolds was demonstrated by immunofluorescence (actin, ZO-1, and Na+/K+-ATPase) and Western blot analysis of the respective proteins. The RPE cells cultured on EHDJ-printed scaffolds with 20 µm pores presented higher permeability, higher transepithelial potential difference, and higher expression level of Na+/K+-ATPase than those cultured on Transwell inserts. These findings suggest that the EHDJ printing can fabricate scaffolds that mimic Bruch's membrane by promoting maturation of RPE cells to form a polarized and functional monolayered epithelium with potential as an in vitro model for studying retinal diseases and treatment methods.

12.
Sci Total Environ ; 850: 158013, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35970467

RESUMO

Potato production plays an important role in safeguarding food security in China since the central government implemented the 'Potato-as-Staple-Food' policy in 2015. However, a key challenge facing China's potato production is to realize a tradeoff between economic return and environmental impact. Effective strategies for reducing carbon emission without compromising potato yield remain to be developed. This study conducted a comprehensive assessment by integrating climate, soil, crop, and agricultural input data, crop model and life cycle impact assessment model to quantify potato yields, GHG emission amounts and intensities (GHGI), and economic benefits under the conventional planting pattern (CPP), the lowest GHG emission pattern (LEP), and the highest yield pattern (HYP) across China's potato planting regions including four sub-regions, i.e., North Single planting region (NS), Central Double planting region (CD), South Winter planting region (SW), and Southwest Mixed planting region (SWM). Averaged fresh potato yield, GHG emission amount, and GHGI under the CPP were 21.7 t ha-1, 2815.1 kg CO2eq ha-1, and 137.3 kg CO2eq t-1, respectively, in China's potato planting region. Compared with the CPP, averaged GHG emission amount and GHGI under the LEP could be decreased by 48.2 % and 51.5 % respectively while the fresh potato yield and economic benefit could be enhanced by 8.1 % and 18.5 %, respectively. For the HYP, averaged GHG emission amount and GHGI could be decreased by 24.2 % and 39.8 % respectively while the fresh potato yield and economic benefit could be enhanced by 18.7 % and 39.6 %, respectively, compared with the CPP. Across the four potato planting regions, SW had the largest potential in reducing GHG emissions owing to a high reduction amount of nitrogen application rate. Our study demonstrates that optimizing agronomic management could reduce environmental impact without compromising economic benefit and provides a scientific method for assessing crop potential to realize the climate-smart planting.


Assuntos
Solanum tuberosum , Agricultura/métodos , Carbono , China , Fertilizantes , Nitrogênio , Solo
13.
Nucleic Acids Res ; 50(9): e49, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35061901

RESUMO

Large-scale cancer genome sequencing has enabled the catalogs of somatic mutations; however, the mutational impact on intrinsically disordered protein regions (IDRs) has not been systematically investigated to date. Here, we comprehensively characterized the mutational landscapes of IDRs and found that IDRs have higher mutation frequencies across diverse cancers. We thus developed a computational method, ROI-Driver, to identify putative driver genes enriching IDR and domain hotspots in cancer. Numerous well-known cancer-related oncogenes or tumor suppressors that play important roles in cancer signaling regulation, development and immune response were identified at a higher resolution. In particular, the incorporation of IDR structures helps in the identification of novel potential driver genes that play central roles in human protein-protein interaction networks. Interestingly, we found that the putative driver genes with IDR hotspots were significantly enriched with predicted phase separation propensities, suggesting that IDR mutations disrupt phase separation in key cellular pathways. We also identified an appreciable number of clinically relevant genes enriching IDR mutational hotspots that exhibited differential expression patterns and are associated with cancer patient survival. In summary, combinations of mutational effects on IDRs significantly increase the sensitivity of driver detection and are likely to open new therapeutic avenues for various cancers.


Assuntos
Biologia Computacional/métodos , Proteínas Intrinsicamente Desordenadas , Neoplasias , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Intrinsicamente Desordenadas/química , Mutação , Neoplasias/genética , Neoplasias/metabolismo , Oncogenes , Mapas de Interação de Proteínas
14.
PLoS One ; 15(4): e0231811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302369

RESUMO

The disease chytridiomycosis, caused by the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd), has contributed to global amphibian declines. Bd infects the keratinized epidermal tissue in amphibians and causes hyperkeratosis and excessive skin shedding. In individuals of susceptible species, the regulatory function of the amphibian's skin is disrupted resulting in an electrolyte depletion, osmotic imbalance, and eventually death. Safe and effective treatments for chytridiomycosis are urgently needed to control chytrid fungal infections and stabilize populations of endangered amphibian species in captivity and in the wild. Currently, the most widely used anti-Bd treatment is itraconazole. Preparations of itraconazole formulated for amphibian use has proved effective, but treatment involves short baths over seven to ten days, a process which is logistically challenging, stressful, and causes long-term health effects. Here, we explore a novel anti-fungal therapeutic using a single application of the ionic liquid, 1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP-NTf2), for the treatment of chytridiomycosis. BMP-NTf2 was found be effective at killing Bd in vitro at low concentrations (1:1000 dilution). We tested BMP-NTf2 in vivo on two amphibian species, one that is relatively tolerant of chytridiomycosis (Pseudacris regilla) and one that is highly susceptible (Dendrobates tinctorius). A toxicity trial revealed a surprising interaction between Bd infection status and the impact of BMP-NTf2 on D. tinctorius survival. Uninfected D. tinctorius tolerated BMP-NTf2 (mean ± SE; 96.01 ± 9.00 µl/g), such that only 1 out of 30 frogs died following treatment (at a dose of 156.95 µL/g), whereas, a lower dose (mean ± SE; 97.45 ± 3.52 µL/g) was not tolerated by Bd-infected D. tinctorius, where 15 of 23 frogs died shortly upon BMP-NTf2 application. Those that tolerated the BMP-NTf2 application did not exhibit Bd clearance. Thus, BMP-NTf2 application, under the conditions tested here, is not a suitable option for clearing Bd infection in D. tinctorius. However, different results were obtained for P. regilla. Two topical applications of BMP-NTf2 on Bd-infected P. regilla (using a lower BMP-NTf2 dose than on D. tinctorius, mean ± SE; 9.42 ± 1.43 µL/g) reduced Bd growth, although the effect was lower than that obtained by daily doses of itracanozole (50% frogs exhibited complete clearance on day 16 vs. 100% for itracanozole). Our findings suggest that BMP-NTf2 has the potential to treat Bd infection, however the effect depends on several parameters. Further optimization of dose and schedule are needed before BMP-NTf2 can be considered as a safe and effective alternative to more conventional antifungal agents, such as itraconazole.


Assuntos
Antifúngicos/farmacologia , Anuros/microbiologia , Quitridiomicetos/efeitos dos fármacos , Imidas/farmacologia , Líquidos Iônicos/farmacologia , Pirrolidinas/farmacologia , Animais , Antifúngicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Imidas/uso terapêutico , Líquidos Iônicos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/microbiologia , Pirrolidinas/uso terapêutico , Pele/microbiologia , Esporos Fúngicos/efeitos dos fármacos
15.
Pediatr Cardiol ; 41(1): 38-45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650215

RESUMO

Although isolated congenital ventricular septal defects (VSD) can be repaired with a high degree of success, residual shunts (RS) are commonplace postoperatively. Small RS are relatively innocuous and tend to spontaneously close with time, despite the emotional burden it poses for the patient and family. A large RS, however, needs ongoing surveillance and may necessitate reintervention. Factors influencing the incidence of RS as well as the likelihood and expected timing of its spontaneous closure are discussed in this study. The patient records and relevant data of 362 consecutive patients undergoing cardiac operation with isolated congenital VSD closure as primary procedure between January 2017 and December 2017 were included in the study. Postoperative transthoracic echocardiograms were performed at hospital discharge, and during follow-up, at 1 month, 3 months, 6 months and 1 year postoperatively. Residual defects were measured under echocardiogram at every follow-up. Factors expected to be associated with RS occurrence and spontaneous closure were included for logistic and Cox regression statistical analysis. There were 113 cases where RS occurred according to the first postoperative echocardiograms that were performed at discharge, of which 80 were confirmed closed during subsequent follow-up, with a median follow-up of 96 days. A cutoff of 1.25 mm for the initial RS was found to be the best predictor of spontaneous closure at 6-month follow-up. Small shunts had higher closure rate than larger ones by a follow-up duration of 300 days, at which the two groups tended to reach a similar spontaneous closure rate. Longer surgical bypass time distinguished small from larger residual shunts measured upon discharge. Following repair of isolated congenital VSDs, the incidence of a residual shunt is high. The majority spontaneously close within 300 days following surgery. Longer bypass time predicted a larger residual shunt upon discharge. Larger than 1.25 mm shunts had lower short-term closure rate but seemed not to differ from smaller shunts beyond 300 days postoperatively.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Comunicação Interventricular/cirurgia , Complicações Pós-Operatórias/terapia , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Período Pós-Operatório , Fatores de Risco
16.
J Control Release ; 297: 71-78, 2019 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-30707901

RESUMO

Biologics have limited permeability across the intestine and are prone to degradation in the acidic-proteolytic milieu of the gastrointestinal tract, leading to poor oral bioavailability. Iontophoresis is a promising technology that can substantially improve transport of drugs across biological barriers and has been particularly explored for skin. In this study, we investigated whether iontophoresis across the intestine can be utilized to improve oral insulin transport. Application of electric current to intestinal cells resulted in opening of the tight junctions in vitro and a consequent about 3-fold improvement in paracellular transport of insulin. When evaluated in vivo using insulin-loaded mucoadhesive patches, iontophoresis produced profound hypoglycemia (63% blood glucose drop in 3 h) without damaging the intestinal tissue and the efficacy depended on insulin dose and current density. This study presents a proof of principle for intestinal iontophoresis as a novel method for oral protein delivery.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Insulina/administração & dosagem , Mucosa Intestinal/metabolismo , Iontoforese/métodos , Adesividade , Administração Oral , Animais , Transporte Biológico , Glicemia/efeitos dos fármacos , Células CACO-2 , Química Farmacêutica/métodos , Corantes Fluorescentes/química , Humanos , Insulina/química , Imagem Óptica , Permeabilidade , Ratos , Pele/metabolismo
18.
Medicine (Baltimore) ; 97(27): e11327, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29979405

RESUMO

RATIONALE: Ventricular septal defects are the most common congenital heart defect in children. As this method avoids sternotomy, the post-procedural morbidity is lower. However, transcatheter closure of perimembranous ventricular septal defects are still associated with complications such as arrhythmia (particularly, Atrioventricular Block), device embolization, atrioventricularvalve and/or aortic valves regurgitation, residual shunts. Some complications can be life threatening and require urgent surgical intervention. PATIENT CONCERNS: An 32-months-old boy was admitted for a significant precordial systolic murmur. The patient underwent transcatheter perimembranous ventricular septal defects closure. 12 months later, Transthoracic echocardiography revealed the device displaced, 4 mm shunt acrocss the ventricular septum and moderate tricuspid regurgitation detected. DIAGNOSIS: According to the echocardiography result, the patient was diagnosed with displacement of the ventricular septal defect occluder and tricuspid regurgitation. INTERVENTIONS: After the diagnosis, the patient underwent removal of the ventricular septal defect occluder and closure of the perimembranous ventricular septal defect. OUTCOMES: The post-operative recovery was uneventful. One year post-procedural follow-up transthoracic echocardiography showed there was no residual shunt and no tricuspid regurgitation. LESSONS: Transcatheter closure of Ventricular septal defects is an attractive alternative to surgery in simple perimembranous ventricular septal defects. Proper follow-up should be emphasized to the patient.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Comunicação Interventricular/cirurgia , Dispositivo para Oclusão Septal/efeitos adversos , Cateterismo Cardíaco/métodos , Pré-Escolar , Remoção de Dispositivo , Ecocardiografia , Falha de Equipamento , Humanos , Masculino
19.
Proc Natl Acad Sci U S A ; 115(28): 7296-7301, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29941553

RESUMO

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.


Assuntos
Glicemia/metabolismo , Insulina , Líquidos Iônicos , Administração Oral , Animais , Cápsulas , Colina/farmacocinética , Colina/farmacologia , Relação Dose-Resposta a Droga , Humanos , Insulina/farmacocinética , Insulina/farmacologia , Líquidos Iônicos/farmacocinética , Líquidos Iônicos/farmacologia , Masculino , Ratos , Ratos Wistar , Terpenos/farmacocinética , Terpenos/farmacologia
20.
Medicine (Baltimore) ; 97(25): e11073, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924000

RESUMO

INTRODUCTION: Cardiac myxomas are the most frequent primary cardiac tumor in adults. The incidence in pediatric patients is extremely low. Heavy calcification of an atrial myxoma is uncommon in children. CASE PRESENTATION: An 18-month-old boy was admitted for a significant precordial systolic murmur. Transthoracic echocardiography revealed a cardiac mass extending from the inferior vena cava across the right atrium and tricuspid valve into the right ventricle with severe tricuspid regurgitation. According to the echocardiography result, the patient was diagnosed with an inferior vena cava and right atrial tumor with tricuspid regurgitation. After the diagnosis, the patient underwent removal of the tumor via median sternotomy. The mass was removed under cardiopulmonary bypass with deep hypothermia circulatory arrest. The tricuspid valve was repaired by valvuloplasty and annuloplasty. The postoperative recovery was unremarkable. Follow-up echocardiogram at 1 month revealed moderate tricuspid regurgitation without myxoma recurrence. CONCLUSION: Heavy calcification of an atrial myxoma is uncommon especially in children. Definitive therapy for myxomas requires prompt surgical excision and long-term follow-up is recommended in children although recurrence after excision is rare.


Assuntos
Calcinose/patologia , Neoplasias Cardíacas/patologia , Mixoma/patologia , Veia Cava Inferior/patologia , Calcinose/diagnóstico por imagem , Ecocardiografia , Sopros Cardíacos/etiologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Humanos , Lactente , Masculino , Mixoma/complicações , Mixoma/diagnóstico por imagem , Mixoma/cirurgia , Esternotomia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/cirurgia , Veia Cava Inferior/diagnóstico por imagem
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