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Adolescents with complex congenital heart disease (CHD) are at risk of experiencing complications later in life. The purpose of this study was to develop an online health management program for adolescents with complex CHD and to evaluate its effects on self-efficacy, health behavior, and health-related quality of life. A randomized controlled trial design was used. A total of 29 adolescents with complex CHD were divided into an experimental group of 15 and a control group of 14. Participants in the intervention group took part in the 4-week online health management program (weekly online group sessions, 1:1 phone coaching, dietary diary feedback, and provision of health information) developed based on self-efficacy theory, while those in the control group received standard medical follow-up. Data were collected from August 2021 to March 2022 using a questionnaire-including the Korean Self-Rated Abilities for Health Practices: Health Self-Efficacy Measure (K-SRAHP) and Pediatric Cardiac Quality of Life Inventory (PCQLI)-and an ActiGraph accelerometer to track physical activity and sleep. The intervention group showed significant improvements in health self-efficacy (p = 0.003), psychosocial impact (p = 0.013), daily step counts (p = 0.011), and moderate to vigorous-intensity physical activity (p = 0.027). Additionally, a decrease in weekend leisure time sedentary behavior (p = 0.035) was observed. However, there were no significant differences in sleep behavior between two groups. The online health management program significantly enhanced self-efficacy, health behavior, and psychosocial impact in adolescents with complex CHD. These findings will inform the development of policies for transitional medical care tailored to adolescents with complex CHD.
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BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. METHODS: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). RESULTS: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. CONCLUSIONS: A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
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BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.
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Vasos Coronários , Humanos , Feminino , Masculino , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/anatomia & histologia , Criança , Adolescente , República da Coreia , Pré-Escolar , Fatores Sexuais , Superfície Corporal , LactenteRESUMO
BACKGROUND: Coronary artery complications (CACs) in patients who undergoing prosthetic pulmonary valve implantation for congenital heart disease can lead to fetal outcomes. However, the incidence of and risk factors for CACs in these patients remain unknown. METHODSâANDâRESULTS: A retrospective cohort study was conducted on patients who underwent cardiac computed tomography or invasive coronary angiography after prosthetic pulmonary valve implantation at Seoul National University Hospital from June 1986 to May 2021. Among 341 patients, 25 (7.3%) were identified with CACs, and 2 of them died. Among the patients with CACs, congenital coronary anomalies and an interarterial course of the coronary artery were identified in 11 (44%) and 18 (72%) patients, respectively. Interarterial and intramural courses of the coronary artery were associated with a 4.4- and 10.6-fold increased risk of CACs, respectively. Among patients with tetralogy of Fallot and pulmonary atresia, the aortic root was rotated further clockwise in patients with coronary artery compression compared to those without it (mean [±SD] 128.0±19.9° vs. 113.5±23.7°; P=0.024). The cut-off rotation angle of the aorta for predicting the occurrence of coronary artery compression was 133°. CONCLUSIONS: Perioperative coronary artery evaluation and prevention of CACs are required in patients undergoing prosthetic pulmonary valve implantation, particularly in those with coronary artery anomalies or severe clockwise rotation of the aortic root.
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Valva Pulmonar , Humanos , Estudos Retrospectivos , Feminino , Masculino , Fatores de Risco , Adulto , Valva Pulmonar/cirurgia , Valva Pulmonar/diagnóstico por imagem , Implante de Prótese de Valva Cardíaca/efeitos adversos , Cardiopatias Congênitas/cirurgia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária , Adolescente , Adulto Jovem , Próteses Valvulares Cardíacas/efeitos adversos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Incidência , Criança , Pessoa de Meia-Idade , Tetralogia de Fallot/cirurgiaRESUMO
Background and Objectives: The purpose of this study was to compare sex differences in the incidence of sarcopenia, demographic characteristics, and preoperative sarcopenic parameters in patients undergoing TKA for advanced knee osteoarthritis (OA). Moreover, we sought to compare patient-reported outcome measures (PROMs) and the predisposing factors after TKA in patients with sarcopenia by sex through subgroup analysis. Materials and Methods: From May 2020 to September 2022, a total of 892 patients who were evaluable for sarcopenia before primary TKA were enrolled. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Patients were assessed according to the presence or absence of sarcopenia. After a two-to-one matched-pair analysis for subgroup analysis, 21 knees in men were matched with a corresponding number of knees in women (42), resulting in a total of 63 knees. PROMs were investigated using the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and the Short Form-12 physical and mental component summary scores. Moreover, the postoperative complications and predisposing factors for male sarcopenia were investigated. Results: The prevalence of sarcopenia was 10.9% (97/892), and the prevalence was higher in men (19.6%, 21/107) than in women (9.7%, 76/785). In subgroup analyses, male patients had significantly inferior PROMs up to 12 months after index surgery. Moreover, there was no significant difference in the systemic complications between the two groups. Multivariate binary logistic regression analysis indicated that alcohol consumption, smoking, and higher modified Charlson Comorbidity Index (mCCI) were predisposing factors for male patients with sarcopenia. The prevalence of sarcopenia was higher in male patients undergoing primary TKA. Conclusions: When compared with the propensity-matched female group, male patients had inferior PROMs up to 12 months postoperatively. Alcohol consumption, current smoker status, and higher mCCI were predisposing factors for sarcopenia in male patients with advanced knee OA.
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Artroplastia do Joelho , Osteoartrite do Joelho , Sarcopenia , Humanos , Feminino , Masculino , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/cirurgia , Sarcopenia/complicações , Sarcopenia/epidemiologia , Caracteres Sexuais , Resultado do Tratamento , Articulação do Joelho/cirurgia , Estudos RetrospectivosRESUMO
Isosorbide, an environmentally friendly and renewable substance, finds extensive application in diverse fields, such as a bisphenol A substitute, polymers, functional materials, organic solvents, fuels, and pharmaceuticals. Despite its increasing interest and widespread usage, there remains a notable absence of available reports regarding its absorption, distribution, metabolism, and excretion (ADME) properties. This study endeavors to investigate the ADME characteristics of isosorbide in rats. Isosorbide levels in biological samples were quantified based on the analytical method using gas chromatography-mass spectrometry (GC-MS). Following administration, isosorbide exhibited rapid absorption and elimination, with a bioavailability of 96.1%. The metabolic stability assay indicated that isosorbide remained stable during metabolism. The majority of absorbed isosorbide was promptly excreted, with urinary excretion as the primary route. This study furnishes valuable insights into the ADME of isosorbide, contributing to its safety assessment and fostering its continued application across various domains.
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Isossorbida , Ratos , Animais , Disponibilidade BiológicaRESUMO
BACKGROUND: Pulsta valve is increasingly used for percutaneous pulmonary valve implantation (PPVI) in patients with a large native right ventricular outflow tract (RVOT). This study aims to elucidate the outcomes of Pulsta valve implantation within the native RVOT and assess its adaptability to various native main pulmonary artery (PA) anatomies. METHODS: A multicenter retrospective study included 182 patients with moderate to severe pulmonary regurgitation in the native RVOT who underwent PPVI with Pulsta valves® between February 2016 and August 2023 at five Korean and Taiwanese tertiary referral centers. RESULTS: Pulsta valve implantation was successful in 179 out of 182 patients (98.4%) with an average age of 26.7 ± 11.0 years. The median follow-up duration was 29 months. Baseline assessments revealed enlarged right ventricle (RV) volume (mean indexed RV end-diastolic volume: 163.1 (interquartile range, IQR: 152.0-180.3 mL/m²), which significantly decreased to 123.6(IQR: 106.6-137.5 mL/m2 after 1 year. The main PA types were classified as pyramidal (3.8%), straight (38.5%), reverse pyramidal (13.2%), convex (26.4%), and concave (18.1%) shapes. Pulsta valve placement was adapted, with distal main PA for pyramidal shapes and proximal or mid-PA for reverse pyramidal shapes. Two patients experienced Pulsta valve embolization to RV, requiring surgical removal, and one patient encountered valve migration to the distal main PA, necessitating surgical fixation. CONCLUSIONS: Customized valve insertion sites are pivotal in self-expandable PPVI considering diverse native RVOT shape. The rather soft and compact structure of the Pulsta valve has characteristics to are adaptable to diverse native RVOT geometries.
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Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Pulmonar , Valva Pulmonar , Humanos , Adolescente , Adulto Jovem , Adulto , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Ventrículos do Coração , Estudos Retrospectivos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Resultado do Tratamento , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/cirurgia , Cateterismo CardíacoRESUMO
Midaortic syndrome (MAS) presents challenges in diagnosis due to the absence of well-defined diagnostic criteria in pediatric patients. This retrospective study aimed to aid in the diagnosis of MAS by employing computed tomography (CT) to measure the z-score of the aorta as well as to identify and understand its clinical features. CT images, echocardiography findings, and medical records of 17 patients diagnosed with MAS between 1997 and 2023 were reviewed, and z-scores were calculated. Aortic size on follow-up CT, blood pressure, and left ventricular function and hypertrophy at the last follow-up were analyzed, and possible prognostic factors were examined. Except for one patient, all individuals exhibited a z-score below - 2 at the level corresponding to stenosis. Left ventricular dysfunction occurred more frequently in patients aged < 5 years (p = 0.024). Patients with idiopathic MAS showed a better prognosis in terms of blood pressure and follow-up aortic size (p = 0.051 and 0.048, respectively). CT-measured aortic z-scores may be useful for the diagnosis and follow-up of MAS.
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BACKGROUND: About 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features. METHODS: Data were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation. RESULTS: Five machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort. CONCLUSIONS: Using commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility. IMPACT: We demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.
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Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Lactente , Biomarcadores , Resistência a Medicamentos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Retrospectivos , População do Leste AsiáticoRESUMO
The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n = 200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p = 0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.
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Técnica de Fontan , Criança , Humanos , Adolescente , Pressão Sanguínea , Frequência Cardíaca , Sulfonamidas/efeitos adversos , Método Duplo-CegoRESUMO
OBJECTIVE: Intra-atrial reentrant tachycardia is an important late-onset complication in patients undergoing the Fontan procedure. However, the protective effects of prophylactic cryoablation against late-onset intra-atrial reentrant tachycardia are unclear. This study investigated the late development of intra-atrial reentrant tachycardia in patients undergoing the lateral tunnel Fontan procedure and the role of prophylactic cryoablation. METHODS: This was a single-center retrospective cohort study of patients who underwent the lateral tunnel Fontan procedure between 1988 and 2003. Univariate and multivariable competing risks regression models were used to determine the associations of prophylactic cryoablation and covariates with the outcomes of interest: late-onset intra-atrial reentrant tachycardia, all-cause mortality, and cardiovascular mortality. RESULTS: In total, 130 patients who underwent the lateral tunnel Fontan procedure, 30 of whom had undergone prophylactic cryoablation, were included in this study and followed up for a median of 23.6 years (interquartile range, 17.7-26.5). Intra-atrial reentrant tachycardia was identified in 14 patients (10.8%), none of whom underwent prophylactic cryoablation. The median Fontan-to-intra-atrial reentrant tachycardia time was 17.2 years (interquartile range, 11.1-23.1). Prophylactic cryoablation was protective against late-onset intra-atrial reentrant tachycardia (P < .0001) and cardiovascular mortality (P < .0001) in the type 3 test. CONCLUSIONS: None of the patients who underwent prophylactic cryoablation developed late-onset intra-atrial reentrant tachycardia during a median follow-up time of 22.9 years. Our study demonstrated that prophylactic cryoablation was effective in preventing late-onset intra-atrial reentrant tachycardia and cardiovascular mortality in patients undergoing the lateral tunnel Fontan.
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Despite advances in microfabrication, compact spectrometers still face challenges in shrinking their size without sacrificing optical performance. Here, the solid immersion grating microspectrometer (SIG-µSPEC) for high spectral resolution in a broad operational wavelength range is reported. The spectroscopic module incorporates a silicon microslit, index-matched lens, plane mirrors, solid immersion grating (SIG), and a CMOS line sensor within a small form factor. The SIG facilitates high angular dispersion of light on a planar focal plane, resulting in an average spectral resolution of 5.8 nm, with over 76% maximum sensitivity from 400 to 800 nm. SIG-µSPEC measures the spectral reflectance of fruits at different ripening stages, clearly revealing changes in the chlorophyll absorption band. The measured spectrum is further utilized for the precise prediction of the soluble solid content (SSC) levels, achieving a high correlation (R2 = 0.91) and a ratio of prediction-to-deviation of 2.36. This compact microspectrometer holds the potential for precise and non-invasive spectral analysis across point-of-care fields.
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Sarcopenia is a condition in which muscle mass and strength are decreased and muscle function is impaired. It is an indicator of frailty and loss of independence in older adults. It is also associated with increased physical disability, which increases the risk of falls. As a multifactorial disease, sarcopenia is caused by a combination of factors including aging, hormonal changes, nutritional deficiencies, and physical inactivity. Understanding the underlying pathophysiology of sarcopenia and identifying its different causes is critical to developing effective prevention and treatment strategies. This review summarizes the pathophysiology, consequences, diagnostic methods, and multidisciplinary approaches to sarcopenia.
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Background: The rate of the prenatal diagnosis of congenital heart disease is increasing along with advances in fetal echocardiography techniques. Here, we aimed to investigate the trend of the use of fetal echocardiography over time and to compare the medical costs of congenital heart disease treatment according to whether fetal echocardiography was performed. Methods: We reviewed our hospital's database, and patients who underwent the first surgery for congenital heart disease within 30 days of birth during 2005-2007, 2011-2013, and 2017-2019 were included. The severity of congenital heart disease diagnosed in each case was evaluated according to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Scores (STS-EACTS Mortality Scores) and Mortality Categories (STAT Mortality Categories). Results: In total, 375 patients were analyzed, and fetal echocardiography use increased significantly after the 2010s compared with in 2005-2007 (19.1% vs. 39%, p = 0.032 in Mortality Category 1-3; 15.5% vs. 69.5%, p = 0.000 in Mortality Category 4-5). Additionally, the mean STS-EACTS Mortality Score was higher in prenatally diagnosed patients than in postnatally diagnosed patients (2.287 vs. 1.787, p = 0.001). In the recent period, there was no significant difference in hospitalization durations and medical costs according to whether or not fetal echocardiography was performed. Conclusions: This single center study showed the use of fetal echocardiography is increasing. Further, prenatal diagnosis with fetal echocardiography causing no differences in medical costs in recent years. Therefore, we suggest that fetal echocardiography can be applied more widely without increasing the economic burden.
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BACKGROUND: The purpose of this study was to introduce the surgical technique using long locking plate and locking attachment plate (LAP) in patient with periprosthetic femoral fracture around ipsilateral stem after total knee arthroplasty (TKA). Moreover, we sought to investigate the outcomes of this fixation technique and to propose a new subtype in the existing classification of periprosthetic femoral fractures. METHODS: From January 2013 to January 2022, thirty-four consecutive periprosthetic femoral fractures around ipsilateral stem following TKA with minimum 1-year follow-up were enrolled in this study. Most cases were fixed with long-locking plate and LAP using the MIPO technique. For subgroup analysis, we classified patients with stemmed hip implant (group H) and stemmed knee implant (group K). Bone union, American Knee Society Score (AKSS) scale, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, the Western Ontario and McMaster Universities Osteoarthritis Index for pain and function, and range of motion were investigated. RESULTS: The number of group H and K were 24 patients (70.6%) and 10 patients (29.4%), respectively. The mean age at operation was 71.5 years (range, 65â85 years), and the mean follow-up period was 27.5 months (range, 12â72 months). Bone union was confirmed radiographically in all patients, and the mean union time was 4.9 months (range, 3.5â6 months). There were no significant differences in radiographic and clinical outcomes between the groups. CONCLUSIONS: Long-locking plate combined with LAP showed favorable radiographic and clinical outcomes in patients with periprosthetic femoral fracture around ipsilateral stem after TKA. LEVEL OF EVIDENCE: Level IV, Retrospective Case Series.
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Artroplastia de Quadril , Artroplastia do Joelho , Fraturas do Fêmur , Osteoartrite , Fraturas Periprotéticas , Humanos , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/cirurgia , Fraturas Periprotéticas/diagnóstico por imagem , Fraturas Periprotéticas/etiologia , Fraturas Periprotéticas/cirurgia , Placas Ósseas , Osteoartrite/cirurgia , Resultado do Tratamento , Consolidação da FraturaRESUMO
Effective tumor regression has been observed with chimeric antigen receptor (CAR) T cells; however, the development of an affordable, safe, and effective CAR-T cell treatment remains a challenge. One of the major obstacles is that the suboptimal genetic modification of T cells reduces their yield and antitumor activity, necessitating the development of a next-generation T cell engineering approach. In this study, we developed a nonviral T cell nanoengineering system that allows highly efficient delivery of diverse functional nanomaterials into primary human T cells in a genetically stable and scalable manner. Our platform leverages the unique cell deformation and restoration process induced by the intrinsic inertial flow in a microchannel to create nanopores in the cellular membrane for macromolecule internalization, leading to effective transfection with high scalability and viability. The proposed approach demonstrates considerable potential as a practical alternative technique for improving the current CAR-T cell manufacturing process.
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Imunoterapia Adotiva , Linfócitos T , Humanos , Imunoterapia Adotiva/métodos , Transfecção , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
Kawasaki disease (KD) is an acute pediatric vasculitis that predominantly affects children under the age of 5 years. To date, genome-wide association studies (GWAS) have identified several KD susceptibility genes (e.g., BLK, CD40, FCGR2A, BCL2L11, and IGHV), which are mainly involved in B cell immunity. In this study, we aimed to identify additional KD susceptibility genes mainly involved in B cell development and functions by analyzing our previous GWAS data and conducting a replication study using new sample. Initially, we selected 30 single nucleotide polymorphisms (SNPs) in B-cell-related genes that were significantly (P < 0.01) associated with KD in our previous GWAS analysis of 247 KD cases with complete type and 1,000 healthy controls. Replication study was performed by genotyping the new 837 KD case samples with Fluidigm system and comparing them with 3,553 control genotypes. Among the 30 candidate SNPs, two were significantly associated with KD (P < 0.001) in the replication study. An even greater association between these SNPs and KD was observed in the combined analysis of GWAS and replication samples: odds ratio (OR) = 1.97 (P = 8.61 × 10-6) for rs2270699 (nonsynonymous SNP: c.10588C > T, p.Arg3530Trp) in the heparan sulfate proteoglycan 2 (HSPG2) gene and OR = 1.28 (P = 1.34 × 10-6) for rs3130992 (intronic SNP) in both the corneodesmosin (CDSN) and psoriasis susceptibility 1 candidate 1 (PSORS1C1) genes. These results suggest that the B-cell-related genes, HSPG2 and CDSN or PSORS1C1, play a role in the development of KD.
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Predisposição Genética para Doença , Síndrome de Linfonodos Mucocutâneos , Pré-Escolar , Humanos , Estudo de Associação Genômica Ampla , Genótipo , Peptídeos e Proteínas de Sinalização Intercelular , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background and Objectives: This study aimed to investigate the prevalence of sarcopenia in patients undergoing total knee arthroplasty (TKA) for advanced knee osteoarthritis (OA), and to assess whether sarcopenia accompanying OA affects patient-reported outcome measures (PROMs) after TKA. We evaluated which predisposing factors could influence the development of sarcopenia in patients with advanced knee OA. Material and Methods: A total of 445 patients whose body composition, muscle strength, and physical performance could be measured before primary TKA were enrolled. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Patients were categorized into sarcopenia (S, n = 42) and non-sarcopenia groups (NS, n = 403). PROMs were investigated using the Knee Injury and Osteoarthritis Outcome Score and Western Ontario and McMaster Universities Osteoarthritis Index. Additionally, postoperative complications and predisposing factors for sarcopenia were evaluated. Results: The incidence of sarcopenia in the entire sample was 9.4%; the prevalence was higher in men (15.4%) than in women (8.7%), and significantly increased with advancing age (p < 0.001). At the six-month follow-up, PROMs in group S were significantly inferior to those in group NS, except for the pain score; however, at the 12-month follow-up, no significant difference was observed between the groups. Multivariate logistic regression indicated that age, body mass index (BMI), and a higher modified Charlson Comorbidity Index (mCCI) were predisposing factors for sarcopenia. Conclusions: A higher prevalence of sarcopenia was observed in men with progressive knee OA. Up to six months after primary TKA, PROMs in group S were inferior to those in group NS, except for the pain score; however, no significant difference was observed between the groups at 12 months. Age, BMI, and higher mCCI were predisposing factors for sarcopenia in patients with OA.
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Artroplastia do Joelho , Osteoartrite do Joelho , Masculino , Humanos , Feminino , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/cirurgia , Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Dor , Resultado do TratamentoRESUMO
The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.