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A number of synthetic cannabinoids have been appearing in the recreational drug market for more than a decade. Recent additions are so-called semi-synthetic cannabinoids, and they structurally closely resemble the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol. Knowledge of new (semi-)synthetic cannabinoids is essential to help identify them in authentic forensic case samples. Therefore, the aim of the study was to examine two commercially available electronic cigarette liquid products claiming to contain cannabinoids and characterize the structures of the main compounds. The liquid products were analyzed by gas chromatography-mass spectrometry (GC-MS), GC-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), and liquid chromatography-high-resolution mass spectrometry (LC-HRMS). In product A, typical cannabinoids (cannabidiol, cannabigerol, and cannabinol) and terpenes (α-caryophyllene and ß-caryophyllene) were identified by comparison with reference materials. An unknown peak was isolated by semi-preparative high-performance LC, analyzed by nuclear magnetic resonance (NMR) spectroscopy, and identified to be Δ9-tetrahydrocannabihexol acetate (Δ9-THCH-O). To the authors' knowledge, this is the first report of the identification of Δ9-THCH-O in commercially available products. Another compound estimated as cannabihexol acetate was also detected. In product B, cannabidiol, cannabinol, α-caryophyllene, and ß-caryophyllene were identified, while two unknown peaks were estimated as tetrahydrocannabidiol isomers. Despite products A and B being labeled to contain "60% HHCPM" and "80% 10-OH-HHC," respectively, no such compounds were detected. The findings of this study could help detect Δ9-THCH-O in case samples and highlight the need to keep monitoring commercial products to identify new drugs, while warning that the package labels cannot be trusted.
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BACKGROUND: Peripheral pulmonary stenosis (PPS) is a condition characterized by the narrowing of the pulmonary arteries, which impairs blood flow to the lung. The mechanisms underlying PPS pathogenesis remain unclear. Thus, the aim of this study was to investigate the genetic background of patients with severe PPS to elucidate the pathogenesis of this condition. METHODS AND RESULTS: We performed genetic testing and functional analyses on a pediatric patient with PPS and Williams syndrome (WS), followed by genetic testing on 12 patients with WS and mild-to-severe PPS, 50 patients with WS but not PPS, and 21 patients with severe PPS but not WS. Whole-exome sequencing identified a rare PTGIS nonsense variant (p.E314X) in a patient with WS and severe PPS. Prostaglandin I2 synthase (PTGIS) expression was significantly downregulated and cell proliferation and migration rates were significantly increased in cells transfected with the PTGIS p.E314X variant-encoding construct when compared with that in cells transfected with the wild-type PTGIS-encoding construct. p.E314X reduced the tube formation ability in human pulmonary artery endothelial cells and caspase 3/7 activity in both human pulmonary artery endothelial cells and human pulmonary artery smooth muscle cells. Compared with healthy controls, patients with PPS exhibited downregulated pulmonary artery endothelial prostaglandin I2 synthase levels and urinary prostaglandin I metabolite levels. We identified another PTGIS rare splice-site variant (c.1358+2T>C) in another pediatric patient with WS and severe PPS. CONCLUSIONS: In total, 2 rare nonsense/splice-site PTGIS variants were identified in 2 pediatric patients with WS and severe PPS. PTGIS variants may be involved in PPS pathogenesis, and PTGIS represents an effective therapeutic target.
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Sistema Enzimático do Citocromo P-450 , Oxirredutases Intramoleculares , Estenose da Valva Pulmonar , Síndrome de Williams , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Movimento Celular , Proliferação de Células , Células Cultivadas , Códon sem Sentido , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Sequenciamento do Exoma , Predisposição Genética para Doença , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Fenótipo , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/enzimologia , Estenose da Valva Pulmonar/genética , Estenose da Valva Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Síndrome de Williams/genética , Síndrome de Williams/fisiopatologia , Síndrome de Williams/enzimologiaRESUMO
A new class of synthetic cannabinoids termed OXIZIDs has recently emerged on the recreational drug market. In order to continue the detection of new drugs in biological specimens, the identification of metabolites is essential. The aim of this study was to elucidate the metabolites of BZO-4en-POXIZID produced in human liver microsomes (HLMs) and human hepatocyte incubations and to compare the results with closely related analogs using the same experimental setup. Each drug was incubated for 1 h in HLM and BZO-4en-POXIZID was also incubated in human hepatocytes for up to 3 h. Subsequently, the incubates were analyzed by liquid chromatography-high-resolution mass spectrometry. BZO-4en-POXIZID metabolites were obtained in the incubation with HLMs and human hepatocytes, via the metabolic pathways of dihydrodiol formation, hydroxylation, reduction of the alkene bond and glucuronidation. The major metabolic pathway was found to be dihydrodiol formation at the pentenyl tail moiety. BZO-POXIZID, 5 F-BZO-POXIZID, BZO-HEXOXIZID and BZO-CHMOXIZID underwent similar metabolism to those reported in the literature, via the metabolic pathways of N-dealkylation, hydroxylation, ketone formation and oxidative defluorination (to alcohol or carboxylic acid). The results suggest that OXIZIDs are mainly metabolized at the N-alkyl moiety and the major metabolic pathways are hydroxylation when the N-alkyl moiety is a simple hydrocarbon, whereas functional-group-specific pathways (dihydrodiol formation and oxidative defluorination) are preferred when the moiety contains specific functional groups (alkene or fluoro), as has been observed for other synthetic cannabinoids. The major metabolites generated via these major metabolic pathways should serve as useful analytical targets for urine analysis. Furthermore, the higher abundance of glucuronidated metabolite suggests that enzymatic hydrolysis of glucuronides may be necessary for urine analysis to increase phase I metabolite concentration and improve detection.
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Canabinoides , Naftalenos , Humanos , Espectrometria de Massas/métodos , Naftalenos/metabolismo , Canabinoides/análise , Alcenos/metabolismo , Microssomos Hepáticos/metabolismoRESUMO
Currently, zebrafish, rodents, canines, and pigs are the primary disease models used in cardiovascular research. In general, larger animals have more physiological similarities to humans, making better disease models. However, they can have restricted or limited use because they are difficult to handle and maintain. Moreover, animal welfare laws regulate the use of experimental animals. Different species have different mechanisms of disease onset. Organs in each animal species have different characteristics depending on their evolutionary history and living environment. For example, mice have higher heart rates than humans. Nonetheless, preclinical studies have used animals to evaluate the safety and efficacy of human drugs because no other complementary method exists. Hence, we need to evaluate the similarities and differences in disease mechanisms between humans and experimental animals. The translation of animal data to humans contributes to eliminating the gap between these two. In vitro disease models have been used as another alternative for human disease models since the discovery of induced pluripotent stem cells (iPSCs). Human cardiomyocytes have been generated from patient-derived iPSCs, which are genetically identical to the derived patients. Researchers have attempted to develop in vivo mimicking 3D culture systems. In this review, we explore the possible uses of animal disease models, iPSC-derived in vitro disease models, humanized animals, and the recent challenges of machine learning. The combination of these methods will make disease models more similar to human disease.
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The quantitative evaluation of the drug mixing condition was conducted for application in the forensic discrimination of drug powders using micro Fourier transform infrared (FT-IR) spectroscopy. Bromhexine hydrochloride (BHCl) and p-hydroxybenzoic acid (PHBA) were used as the simulated drug and additive, respectively. Equal masses of two chemicals were (1) simply mixed, (2) homogenized using agate mortar, or (3) dissolved in methanol and dried, and then (4) homogenized using agate mortar. The mixed powders dispersed on BaF2 plates were subjected to mapping analysis of micro FT-IR spectroscopy using synchrotron radiation (SR) or globar light in transmission mode with aperture sizes of 2.5 x 2.5 and 10 x 10µm2, and x-y scanning steps of 2.5 and 10 µm, respectively. The areas of the vibration bands specific to BHCl (C-N bending) and PHBA (C=O stretching) were converted to the molar contents (CBHCl, CPHBA), and the relative content ratio (RCR: CPHBA/[CBHCl + CPHBA]) was used as one mixing parameter. The resulting two-dimensional distribution map provided the relative spatial localizations of the two species, and frequency histograms with a horizontal axis of RCR were plotted to evaluate the RCR distribution. The percentage frequency of the extreme value in which RCR was 0 or 1 (%EV) was used as one mixing index. After excluding the extreme values, the coefficient of variation (CV) of the RCR distribution was used as another mixing index. The differentiation among four mixing modes could be evaluated from the standpoint of %EV and CV, and the discrimination capacity by SR instrument was superior to that by globe light instrument.
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OBJECTIVE: Fontan-associated liver disease (FALD) is widely recognised as a common complication in patients long after the Fontan operation. However, data on the predictors of FALD that can guide its screening and management are lacking. The present study aimed to identify the predictors of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in post-Fontan patients. METHODS: This was a multi-institutional retrospective cohort study. Clinical data of all perioperative survivors of Fontan operation before 2011 who underwent postoperative catheterisation were collected through a retrospective chart review. RESULTS: A total of 1117 patients (538 women, 48.2%) underwent their first Fontan operation at a median age of 3.4 years. Postoperative cardiac catheterisation was conducted at a median of 1.0 year. During a median follow-up period of 10.3 years, 67 patients (6.0%) died; 181 (16.2%) were diagnosed with liver fibrosis, 67 (6.0%) with LC, 54 (4.8%) with focal nodular hyperplasia and 7 (0.6%) with HCC. On multivariable analysis, high central venous pressure (CVP) (HR, 1.28 (95% CI 1.01 to 1.63) per 3 mm Hg; p=0.042) and severe atrioventricular valve regurgitation (HR, 6.02 (95% CI 1.53 to 23.77); p=0.010) at the postoperative catheterisation were identified as independent predictors of LC/HCC. CONCLUSIONS: Patients with high CVP and/or severe atrioventricular valve regurgitation approximately 1 year after the Fontan operation are at increased risk of developing advanced liver disease in the long term. Whether therapeutic interventions to reduce CVP and atrioventricular valve regurgitation decrease the incidence of advanced liver disease requires further elucidation.
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Carcinoma Hepatocelular , Técnica de Fontan , Cardiopatias Congênitas , Neoplasias Hepáticas , Humanos , Feminino , Pré-Escolar , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Estudos Retrospectivos , Técnica de Fontan/efeitos adversos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/complicações , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: JWH-424, (8-bromo-1-naphthyl)(1-pentyl-1H-indol-3-yl)methanone, is a synthetic cannabinoid, which is a brominated analogue of JWH-018, one of the best-known synthetic cannabinoids. Despite the structural similarity to JWH-018, little is known about JWH-424 including its metabolism. The aim of the study was to compare human liver microsomes (HLM) and the fungus Cunninghamella elegans as the metabolism catalysts for JWH-424 to better understand the characteristic actions of the fungus in the synthetic cannabinoid metabolism. METHODS: JWH-424 was incubated with HLM for 1 h and Cunninghamella elegans for up to 72 h. The HLM incubation mixtures were diluted with methanol and fungal incubation mixtures were extracted with dichloromethane and reconstituted in methanol before analyses by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). RESULTS: HLM incubation resulted in production of ten metabolites through dihydrodiol formation, hydroxylation, and/or ipso substitution of the bromine with a hydroxy group. Fungal incubation led to production of 23 metabolites through carboxylation, dihydrodiol formation, hydroxylation, ketone formation, glucosidation and/or sulfation. CONCLUSIONS: Generally, HLM models give good predictions of human metabolites and structural analogues are metabolised in a similar fashion. However, major hydroxy metabolites produced by HLM were those hydroxylated at naphthalene instead of pentyl moiety, the major site of hydroxylation for JWH-018. Fungal metabolites, on the other hand, had undergone hydroxylation mainly at pentyl moiety. The metabolic disagreement suggests the necessity to verify the human metabolites in authentic urine samples, while H9 and H10 (hydroxynaphthalene), H8 (ipso substitution), F22 (hydroxypentyl), and F17 (dihydroxypentyl) are recommended for monitoring of JWH-424 in urinalysis.
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Canabinoides , Cunninghamella , Humanos , Microssomos Hepáticos , Metanol , Biotransformação , Espectrometria de MassasRESUMO
Perceived discrimination and work impairment are commonly observed in COVID-19 survivors, but their relationship has not been well understood. We aimed to evaluate the role of discrimination in the development of psychological distress and work impairment in COVID-19 survivors. From April 2020 to November 2021, 309 patients were recruited at two designated COVID-19 hospitals in Japan. Participants completed a standardized questionnaire including COVID-19 sequelae, psychological distress, impairments in work performance and perceived discrimination. The majority of participants (62.5%) experienced one or more COVID-19 sequelae. Psychological distress was observed in 36.9% and work impairment in 37.9%. In multivariate logistic regression analyses, COVID-19 sequelae and discrimination were associated with both psychological distress and work impairment. Mediation analysis demonstrated that the direct effect of sequelae on work impairment was non-significant after accounting for psychological distress, suggesting that the effect of sequelae on work impairment was mainly mediated through psychological distress. These findings were replicated in a subgroup analysis limited to patients with mild COVID-19. We conclude that discrimination plays an important role in the development of psychological distress and work impairment, and that both discrimination and psychological distress should be targets of intervention in COVID-19 survivors.
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COVID-19 , Angústia Psicológica , Humanos , COVID-19/complicações , Sobreviventes/psicologia , Japão/epidemiologia , Estresse Psicológico/psicologiaRESUMO
Fiber examination is frequently performed in forensics, and gel permeation chromatography (GPC) is one candidate method for discriminating polyester fibers. Here, the effects of machine washing on weight-average molecular weight (M w), polydispersity index (PDI), and the percentage peak area of cyclic ethylene terephthalate trimer (PPAL) of commercial polyester shirts and manufactured poly(ethylene terephthalate) (PET) yarns were investigated using GPC. GPC was performed using a 1,1,1,3,3,3-hexafluoro-propan-2-ol polymer solubilizer, styrene-divinylbenzene copolymer GPC columns, a chloroform mobile phase, and a 254 nm absorbance monitor. The statistical change in the polyester fibers during machine washing was evaluated by comparing three GPC parameters of the same fiber samples before and after machine washing. Among the commercial polyester shirts examined, the GPC parameters changed significantly after machine washing with a considerable PPAL decrease. In contrast, the GPC parameters of manufactured PET yarns changed significantly with a moderate increase in M w. This work elucidates the change on GPC parameters of polyester fibers by machine washing.
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[This corrects the article DOI: 10.1297/cpe.26.153.].
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BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease, with approximately 10% of cases associated with genetic variants. Recent genetic studies have reported pathogenic variants in the TBX4 gene in patients with PAH, especially in patients with childhood-onset of the disease, but the pathogenesis of PAH caused by TBX4 variant has not been fully uncovered. METHODS: We analysed the TBX4 gene in 75 Japanese patients with sporadic or familial PAH using a PCR-based bidirectional sequencing method. Detected variants were evaluated using in silico analyses as well as in vitro analyses including luciferase assay, immunocytochemistry and chromatin immunoprecipitation (ChIP) whether they have altered function. We also analysed the function of TBX4 using mouse embryonic lung explants with inhibition of Tbx4 expression. RESULTS: Putative pathogenic variants were detected in three cases (4.0%). Our in vitro functional analyses revealed that TBX4 directly regulates the transcriptional activity of fibroblast growth factor 10 (FGF10), whereas the identified TBX4 variant proteins failed to activate the FGF10 gene because of disruption of nuclear localisation signal or poor DNA-binding affinity. Furthermore, ex vivo inhibition of Tbx4 resulted in insufficiency of lung morphogenesis along with specific downregulation of Tie2 and Kruppel-like factor 4 expression. CONCLUSION: Our results implicate variants in TBX4 as a genetic cause of PAH in a subset of the Japanese population. Variants in TBX4 may lead to PAH through insufficient lung morphogenesis by disrupting the TBX4-mediated direct regulation of FGF10 signalling and pulmonary vascular endothelial dysfunction involving PAH-related molecules.
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Hipertensão Arterial Pulmonar , Proteínas com Domínio T , Animais , DNA , Hipertensão Pulmonar Primária Familiar/genética , Fator 10 de Crescimento de Fibroblastos , Camundongos , Sinais de Localização Nuclear , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Fatores de TranscriçãoRESUMO
Automotive glasses are important forensic evidence often recovered from crime scenes. Black ceramic prints on automotive glasses contains various elements in high concentrations. A portable X-ray fluorescence spectrometer (pXRF) allows an instant and nondestructive analysis of various elements. In this study, the Bruker Tracer 5 g was used as the pXRF equipment. The NIST SRM612 glass standard was used to determine the limit of detection (LODs) of a pXRF and its optimal conditions. The acceleration voltages of 15, 30, and 50 kV were appropriate for measuring Si Kα (1.740 keV)-Ni Kα (7.473 keV), Cu Kα (8.042 keV)-Pb Lα (10.552 keV), and after Bi Kα (10.839 keV), respectively. The pXRF was used to compare 37 black ceramic prints on automotive glasses from the known source. The samples were divided into two groups: the Pb type and the Bi type. The samples were compared in pairs. The most appropriate and effective indicators for discriminating between the Pb and Bi type of black ceramic prints on automotive glasses were Zr Kα /Pb Lα and Cu Kα /Cr Kα for the Pb type, and Zr Kα /Bi Lα and Cu Kα /Crα for the Bi type, respectively. The samples were compared with other elements detected by pXRF to further discriminate them. 98.9% of all pairs were successfully discriminated. Results showed that black ceramic prints on automotive glasses are able to be discriminated by pXRF.
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This cross-sectional study aimed to investigate the post-acute consequences of COVID-19. We conducted a self-administered questionnaire survey on sequelae, psychological distress (K6), impairments in work performance (WFun), and COVID-19-related experiences of stigma and discrimination in two designated COVID-19 hospitals in Hiroshima Prefecture, Japan, between August 2020 and March 2021. The prevalence of sequelae was calculated by age and COVID-19 severity. Factors independently associated with sequelae or psychological distress were identified using logistic regression analysis. Among 127 patients who had recovered from COVID-19, 52.0% had persistent symptoms at a median of 29 days [IQR 23-128] after COVID-19 onset. Among patients with mild COVID-19, 49.5% had sequelae. The most frequent symptoms were olfactory disorders (15.0%), taste disorders (14.2%), and cough (14.2%). Multivariate analysis showed that age was an independent risk factor for sequelae (adjusted odds ratios [AOR] for ≥ 60 years vs. < 40 years 3.63, p = 0.0165). Possible psychological distress was noted in 30.7% (17.9% of males and 45.0% of females). Female sex and the presence of sequelae were independent risk factors for psychological distress. Of all participants, 29.1% had possible impairments in work performance. Experiences of stigma and discrimination were reported by 43.3% of participants. This study revealed the significant impacts of Long COVID on health in local communities. A large-scale, long-term cohort study is desired.
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COVID-19 , COVID-19/complicações , COVID-19/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Sobreviventes , Síndrome de COVID-19 Pós-AgudaRESUMO
Dilated cardiomyopathy (DCM) is caused by various gene variants and characterized by systolic dysfunction. Lamin variants have been reported to have a poor prognosis. Medical and device therapies are not sufficient to improve the prognosis of DCM with the lamin variants. Recently, induced pluripotent stem (iPS) cells have been used for research on genetic disorders. However, few studies have evaluated the contractile function of cardiac tissue with lamin variants. The aim of this study was to elucidate the function of cardiac cell sheet tissue derived from patients with lamin variant DCM. iPS cells were generated from a patient with lamin A/C (LMNA) -mutant DCM (LMNA p.R225X mutation). After cardiac differentiation and purification, cardiac cell sheets that were fabricated through cultivation on a temperature-responsive culture dish were transferred to the surface of the fibrin gel, and the contractile force was measured. The contractile force and maximum contraction velocity, but not the maximum relaxation velocity, were significantly decreased in cardiac cell sheet tissue with the lamin variant. A qRT-PCR analysis revealed that mRNA expression of some contractile proteins, cardiac transcription factors, Ca2+-handling genes, and ion channels were downregulated in cardiac tissue with the lamin variant.Human iPS-derived bioengineered cardiac tissue with the LMNA p.R225X mutation has the functional properties of systolic dysfunction and may be a promising tissue model for understanding the underlying mechanisms of DCM.
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Cardiomiopatias , Cardiomiopatia Dilatada , Células-Tronco Pluripotentes Induzidas , Cardiomiopatias/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação , Miócitos Cardíacos/metabolismoRESUMO
Stem cells are used in cardiovascular biology and biomedicine, and research in this field is expanding. Two types of stem cells have been used in research: induced pluripotent and somatic stem cells. Stem cell research in cardiovascular medicine has developed rapidly following the discovery of different types of stem cells. Induced pluripotent stem cells (iPSCs) possess potent differentiation ability, unlike somatic stem cells, and have been postulated for a long time. However, differentiating into adult-type mature and functional cardiac myocytes (CMs) remains difficult. Bone marrow stem/stromal cells (BMSCs), adipose-derived stem cells (ASCs), and cardiac stem cells (CSCs) are somatic stem cells used for cardiac regeneration. Among somatic stem cells, bone marrow stem/stromal cells (BMSCs) were the first to be discovered and are relatively well-characterized. BMSCs were once thought to have differentiation ability in infarcted areas of the heart, but it has been identified that paracrine cytokines and micro-RNAs derived from BMSCs contributed to that effect. Moreover, vesicles and exosomes from these cells have similar effects and are effective in cardiac repair. The molecular signature of exosomes can also be used for diagnostics because exosomes have the characteristics of their origin cells. Cardiac stem cells (CSCs) differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells, and supply cardiomyocytes during myocardial infarction by differentiating into newly formed cardiomyocytes. Stem cell niches and inflammatory cells play important roles in stem cell regulation and the recovery of damaged tissues. In particular, chemokines can contribute to the communication between inflammatory cells and stem cells. In this review, we present the current status of this exciting and promising research field.
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AIMS: The criteria for 'good' Fontan haemodynamics have been poorly defined in relation to long-term outcomes. The aim of this study was to identify the risk factors for mortality among haemodynamic parameters obtained early after the Fontan operation. METHODS AND RESULTS: Clinical data of all perioperative survivors of the Fontan operation performed before 2011, from nine institutions, were collected through a retrospective chart review. In total, 1260 patients were included. The median age at the time of Fontan operation was 3.6 years. Post-operative cardiac catheterization was conducted in 1117 patients at a median period of 1.0 years after the operation. During the median follow-up period of 10.2 years, 107 patients died. The mortality rates at 10, 20, and 25 years after the operation were 5%, 12%, and 22%, respectively. On multivariable analysis, older age at the time of the operation {≥15 years, hazard ratio (HR) [95% confidence interval (CI)]: 3.2 (1.7-5.9)} and haemodynamic parameters obtained at post-operative catheterization, such as low ejection fraction [<30%, HR (95% CI): 7.5 (3.2-18)], low systemic oxygen saturation [<80%, HR (95% CI): 3.8 (1.6-9.1)], high central venous pressure [≥16 mmHg, HR (95% CI): 2.3 (1.3-3.9)], and low mean systemic arterial pressure [<60 mmHg, HR (95% CI): 3.0 (1.4-6.2)] were identified as independent predictors of mortality. The predictive model based on these parameters had a c-index of 0.75 at 10 years. CONCLUSIONS: Haemodynamic parameters obtained at a median period of 1.0 years, post-operatively, can accurately identify patients with a high mortality risk, who may need intensive management to improve long-term outcomes.
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Técnica de Fontan , Técnica de Fontan/efeitos adversos , Hemodinâmica , Humanos , Estudos Retrospectivos , Fatores de Risco , SobreviventesRESUMO
There has been no multicenter study on the prognosis of pediatric hypertrophic cardiomyopathy (HCM) in Japan. Therefore, we conducted a retrospective multicenter observational study on the long-term survival rate in patients diagnosed with HCM under the age of 18 between 1990 and 2014. Twenty institutions participated. A total of 180 patients were identified. The median age at diagnosis was 5.8 years old and median duration of observation was 8.3 years. Although six patients (3%) deteriorated into the dilated phase of HCM, no patient received heart transplantation. Freedom from death at 1, 5, 10, and 20 years were 97%, 92%, 84%, and 80%, respectively. There were 26 deaths. Among them, 11 patients died suddenly, presumably due to arrhythmia, and 15 patients died of heart failure. The presence of heart failure symptoms and a greater cardiothoracic ratio were significant risk factors for heart failure-related death. There were no significant risk factors identified for arrhythmia-related death. In conclusion, the prognosis of pediatric HCM in Japan is good and similar to those reported in population-based studies in the United States and Australia. Significant risk factors for heart failure-related death were identified in pediatric patients with HCM in Japan.