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Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.
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Ácido Aspártico , Caspase 6 , Infecções por Coronavirus , Coronavirus , Cisteína , Interações Hospedeiro-Patógeno , Replicação Viral , Animais , Apoptose , Ácido Aspártico/metabolismo , Caspase 6/metabolismo , Coronavirus/crescimento & desenvolvimento , Coronavirus/patogenicidade , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/virologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Cricetinae , Cisteína/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Humanos , Interferons/antagonistas & inibidores , Interferons/imunologia , Pulmão/patologia , Mesocricetus , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , SARS-CoV-2 , Taxa de Sobrevida , Redução de PesoRESUMO
AIM: Laparoscopic gastrostomy is a frequently performed procedure in children requiring long-term enteral nutrition. The role of prophylactic anti-reflux surgery during gastrostomy placements is controversial. The current study aims to evaluate the role of prophylactic anti-reflux procedures during gastrostomy placement. METHODS: A retrospective single-center analysis of all children without reflux receiving laparoscopic gastrostomy from January 2005 through December 2021 was performed. Demographics and clinical outcomes were compared between patients receiving gastrostomy placement alone and patients receiving gastrostomy with prophylactic anti-reflux surgery. RESULTS: A total of 79 patients had a confirmed absence of reflux by a 24-h pH/impedance study before operation. Thirty-six of these patients underwent prophylactic anti-reflux surgery (PAR) while 43 received gastrostomy (PG) alone. The operative time and conversion rate were significantly higher in the PAR group (140.5 ± 67.5 vs. 80.2 ± 66.8 min, p = 0.0001 and 8.3% vs. 0%, p = 0.04). There were no major complications in either group. De novo reflux was detected in five patients (11.6%) in the PG group. None of these patients progressed to require anti-reflux surgery. CONCLUSION: The occurrence of de novo reflux after laparoscopic gastrostomy was low and could be managed without anti-reflux surgery. A routine pre-operative pH study is helpful for appropriate patient selection to avoid unnecessary anti-reflux surgery, which lengthens operative time and increases the conversion rate.
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Refluxo Gastroesofágico , Laparoscopia , Criança , Humanos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Estudos Retrospectivos , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/prevenção & controle , Refluxo Gastroesofágico/cirurgia , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Fundoplicatura/efeitos adversosRESUMO
PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.
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Antibacterianos , Antibioticoprofilaxia , Cistoscopia , Dextranos , Ácido Hialurônico , Refluxo Vesicoureteral , Humanos , Refluxo Vesicoureteral/terapia , Refluxo Vesicoureteral/tratamento farmacológico , Masculino , Feminino , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ácido Hialurônico/administração & dosagem , Dextranos/administração & dosagem , Pré-Escolar , Estudos Retrospectivos , Cistoscopia/métodos , Antibioticoprofilaxia/métodos , Lactente , Criança , Resultado do Tratamento , Injeções/métodosRESUMO
INTRODUCTION: Trauma is the leading cause of paediatric mortality and morbidity. Stay-home regulations for coronavirus disease 2019 (COVID-19) reportedly changed trauma severity, yet data from Hong Kong were lacking. This study examined Hong Kong's spectrum of paediatric trauma and addressed knowledge gaps concerning epidemiological changes during COVID-19. METHODS: Children with traumatic injuries who attended a tertiary trauma centre from January 2010 to March 2022 were included in this retrospective, cross-sectional study. We analysed demographic and clinical data and conducted unadjusted bivariate analyses of injury patterns before and after the pandemic. RESULTS: In total, 725 children attended the Accident and Emergency Department due to trauma, 585 before and 140 during COVID-19. The male-to-female ratio was 1.84:1. The 90-day trauma-related mortality was 0.7%. The overall Injury Severity Score was 3.52 ± 5.95. The paediatric trauma incidence was similar before and after social-distancing policies (both 5.8 cases monthly). Gender, ISS distribution, intensive care unit stay length, and hospital stay length values were similar (p > 0.05). Trauma call activation (8.4% vs. 5.7%, p = 0.002) and road traffic accidents (10.6% vs. 5.7%, p = 0.009) significantly decreased, yet younger-patient injuries (< 10 years old; 85.7% vs. 71%, p < 0.001), burns (28% vs. 45.7%, p < 0.001), and domestic injuries (65.5% vs. 85.7%, p < 0.001) significantly increased. No significant self-harm, assault, or abuse increases were found. CONCLUSIONS: The paediatric trauma incidences were similar before and during the pandemic. However, domestic and burn injuries significantly increased, highlighting the importance of injury prevention.
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COVID-19 , Serviço Hospitalar de Emergência , Escala de Gravidade do Ferimento , Ferimentos e Lesões , Humanos , COVID-19/epidemiologia , Hong Kong/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Criança , Ferimentos e Lesões/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Adolescente , Lactente , Incidência , Pandemias , Centros de Traumatologia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , SARS-CoV-2RESUMO
PURPOSE: We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism. METHODS: BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34. On day 34, their serum samples were collected for hormonal markers. Necrosis, fibrosis and CK 19 expression in the liver were evaluated. Liver organoids were developed and their morphology as well as bulk RNA sequencing data were analyzed. RESULTS: Twenty-four mice developed BA features after RRV injection and were equally divided into steroid and PBS groups. On day 34, the weight gain of steroid group increased significantly than PBS group (p < 0.0001). All mice in the PBS group developed liver fibrosis but only one mouse in the steroid group did. Serum bilirubin and liver parenchymal enzymes were significantly lower in steroid group. The morphology of liver organoids were different between the two groups. A total of 6359 differentially expressed genes were found between steroid group and PBS group. CONCLUSION: Based on our findings obtained from RRV-induced BA animal and organoid models, steroid has the potential to mitigate liver fibrosis in BA.
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Atresia Biliar , Modelos Animais de Doenças , Cirrose Hepática , Organoides , Animais , Camundongos , Organoides/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Fígado/patologia , Fígado/efeitos dos fármacosRESUMO
PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.
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Atresia Biliar , Colestase , Hipertensão Portal , Portoenterostomia Hepática , Humanos , Atresia Biliar/cirurgia , Atresia Biliar/complicações , Portoenterostomia Hepática/métodos , Masculino , Feminino , Hipertensão Portal/etiologia , Lactente , Colestase/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Seguimentos , Sobreviventes/estatística & dados numéricos , Recém-Nascido , Pré-EscolarRESUMO
BACKGROUND: Laparoscopic inguinal hernia repair is one of the procedures most commonly performed by paediatric surgeons. Current research on the learning curve for laparoscopic hernia repair in children is scarce. This study aims to evaluate the clinical outcome and learning curve of laparoscopic intra-corporeal inguinal hernia repair in children. METHODS: A retrospective single-centre analysis of all paediatric patients who underwent laparoscopic intra-corporeal inguinal hernia repair between 2010 and 2019 was performed. The clinical outcomes were analysed. The data on the achievement of the learning curve by surgical trainees were evaluated with the CUSUM technique, focusing on operative time. RESULTS: There were 719 patients with laparoscopic intra-corporeal inguinal hernia repair (comprising 1051 sides) performed during the study period. The overall ipsilateral recurrence rate was 1.8% without other complications detected. CUSUM analysis showed that there were 3 phases of training, for which the trainees underwent initial learning phase (Phase 1) for the first 7 cases. After mastering of the skills and extrapolating the skills to male patients with smaller body size (Phase 2), they then achieved performance comparable to that of the senior surgeons after 18 procedures (Phase 3). CONCLUSIONS: 18 procedures seem to be the number required to reach the learning curve plateau in terms of operative time by surgical trainees. The clinical outcomes show that laparoscopic intra-corporeal inguinal hernia repair is a safe and transferrable technique, even in the hands of trainees, with adequate supervision and careful case selection. It also provides skill acquisition for minimally invasive surgery.
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Hérnia Inguinal , Laparoscopia , Humanos , Masculino , Criança , Hérnia Inguinal/cirurgia , Curva de Aprendizado , Estudos Retrospectivos , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Herniorrafia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: To evaluate factors affecting length of stay (LOS) after choledochal cyst resection in paediatric patients. METHODS: This was a retrospective study on patients operated between 2004 and 2021. Associations between clinical factors and LOS were evaluated by bivariate analysis, multiple regression, and equivalence test. RESULTS: Sixty-two patients were included. Twenty-four underwent hepaticoduodenostomy as biliary reconstruction. Five suffered from major complications. The median (25th-75th percentile) operation time was 279 (182-378) min. Median LOS, time to enteral feeding, and time to abdominal drain removal were 8(6-10), 2(1-3), and 5(4-7) days, respectively. Seven factors were found significantly associated with a shorter LOS in bivariate analysis and were included in multiple regression. It revealed that early abdominal drain removal (p < 0.001), early enteral feeding (p = 0.042), and the absence of major complications (p < 0.001) were significantly associated with shorter LOS. Equivalence test suggested that age and preoperative cholangitis had no practical effect on LOS. CONCLUSIONS: Early enteral feeding, early drain removal, and avoidance of major complications are associated with a shorter LOS.
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Cisto do Colédoco , Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Humanos , Criança , Cisto do Colédoco/cirurgia , Tempo de Internação , Estudos Retrospectivos , Ducto Colédoco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
PURPOSE: This aim of this study was to identify the pre-operative risk factors for conversion during laparoscopic excision of choledochal cyst in paediatric patients. METHODS: A retrospective single-centre study was carried out. All paediatric patients (< 18 years) who had undergone laparoscopic excision of choledochal cyst between 2004 and 2021 were reviewed. The outcome was conversion to open surgery and pre-operative factors that affected the conversion rate were analyzed. RESULTS: Sixty-one patients were included. Conversion was required in 24 cases (39.3%). There was no difference in the conversion rate between the first (before 2012, n = 30) and second (after 2012, n = 31) half of the series (36.7% vs. 42.0%, p = 0.674). Majority was type 1 cyst (86.8%) and the median cyst size was 4.6 cm (IQR: 2.2-6.4 cm). Antenatal diagnosis was available in 18 patients (29.5%). The median age at operation was 23.0 months (IQR: 8.0-72.0 months). Pre-operatively, 19 patients (31.1%) suffered from cholangitis and 5 (8.2%) of them required cholecystostomy. Comparing patients with successful laparoscopic surgery (L) and converted cases (C), there were no differences in the age at operation (p = 0.74), cyst size (p = 0.35), availability of antenatal diagnosis (p = 0.23) and cholangitic episodes (p = 0.40). However, a higher percentage of patients required cholecystostomy in the converted group (L vs. C = 2.7% vs. 16.7%, p = 0.05). Using logistic regression analysis, it was also a risk factor for conversion (OR = 3.5 [1.37-5.21], p = 0.05). CONCLUSION: Pre-operative cholecystostomy is a potential risk factor for conversion during laparoscopic excision of choledochal cyst in children.
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Colangite , Colecistostomia , Cisto do Colédoco , Laparoscopia , Criança , Humanos , Feminino , Gravidez , Lactente , Pré-Escolar , Estudos Retrospectivos , Cisto do Colédoco/cirurgia , Cisto do Colédoco/diagnóstico , Resultado do Tratamento , Laparoscopia/efeitos adversos , Colangite/etiologiaRESUMO
PURPOSE: We aimed to compare the outcomes of primary anastomosis (PA) and enterostomy as treatments for intestinal atresia in neonates to identify the factors influencing the choice of modality. METHODS: We conducted a retrospective single-centre analysis of all neonates with intestinal atresia between 2000 and 2020 and measured the clinical outcomes. We performed logistic regression to identify factors that influenced the choice of surgical approach. RESULTS: Of 62 intestinal atresia neonates, 71% received PA. There were no significant differences in gestation, gender, age at operation, birth weight, or body weight at operation between the PA and enterostomy groups. PA reoperation was not required for 78% of patients, and the PA group had shorter hospital stays. Complications, operative time, duration on parenteral nutrition, time to full enteral feeding were comparable in both groups. Upon multivariate regression analysis, surgeons favoured PA in proximal atresia [Odds ratio (OR) 38.5, 95% Confidence Interval (CI) 2.558-579] while enterostomy in smaller body size [OR 2.75, CI 0.538-14.02] and lower Apgar score [OR 1.1, CI 0.07-17.8]. Subgroup analysis in these patient groups demonstrated comparable outcomes with both surgical approaches. CONCLUSION: Both surgical approaches achieved comparable outcomes, but PA was associated with short hospital stays and the avoidance of stoma-related complications, and reoperation was generally not required. This surgical approach was suitable for patients with proximal atresia, but enterostomy remained a sensible choice for patients with smaller body sizes and lower Apgar scores.
Assuntos
Enterostomia , Atresia Intestinal , Recém-Nascido , Humanos , Atresia Intestinal/cirurgia , Atresia Intestinal/complicações , Estudos Retrospectivos , Resultado do Tratamento , Anastomose CirúrgicaRESUMO
Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA.
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AIM: This study reviewed the experience of a tertiary paediatric surgery and obstetric centre on prenatal counselling of congenital surgical anomalies and to explore the role of paediatric surgeons on perinatal outcomes of antenatally detected anomalies. METHODS: A retrospective analysis of all antenatal consultations and subsequent medical records after birth were performed between 2009 and 2018. Data including timing of consultations, gestations at birth, birthweight, impact on obstetrics management, neonatal mortality and need of surgery were included. RESULTS: A total of 256 fetuses were diagnosed to have congenital surgical anomalies on antenatal ultrasound. The most common were urogenital (31%) and thoracic (30%) anomalies. Twelve of the 256 (4.7%) had multiple anomalies. The mean gestation at referral was 23 ± 5 weeks. The majority (85.4%) were born at term. Mode and timing of delivery was altered in 7% of patients. Four received fetal intervention after surgical consultation. Termination of pregnancy rate was 5.4% (n = 14). Neonatal death was reported in 7.8% of the cohort. CONCLUSION: Congenital surgical anomalies had a significant impact on perinatal outcome as well as morbidity in later infancy and childhood. A multidisciplinary approach in managing pregnancy with these anomalies should be implemented. Combined-specialty consultations and counselling deliver valuable information for parents.
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Anormalidades Múltiplas , Mortalidade Infantil , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Encaminhamento e Consulta , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid. In addition, the differentiation conditions induce elevated levels of serine proteases, which are essential for productive infection of human influenza viruses and low-pathogenic avian influenza viruses. We also established improved 2D monolayer culture conditions for the differentiated airway organoids. To demonstrate the ability of differentiated airway organoids to identify human-infective virus, 3D and 2D differentiated airway organoids are applied to evaluate two pairs of viruses with known distinct infectivity in humans, H7N9/Ah versus H7N2 and H1N1pdm versus an H1N1 strain isolated from swine (H1N1sw). The human-infective H7N9/Ah virus replicated more robustly than the poorly human-infective H7N2 virus; the highly human-infective H1N1pdm virus replicated to a higher titer than the counterpart H1N1sw. Collectively, we developed differentiated human airway organoids which can morphologically and functionally simulate human airway epithelium. These differentiated airway organoids can be applied for rapid assessment of the infectivity of emerging respiratory viruses to human.
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Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H7N2/patogenicidade , Influenza Humana , Organoides/virologia , Sistema Respiratório/virologia , Humanos , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H7N2/crescimento & desenvolvimento , Organoides/patologia , Sistema Respiratório/patologiaRESUMO
BACKGROUND AND AIMS: Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA. METHODS: We combined organoid and transcriptomic analysis to gain new insights into BA pathobiology using patient samples and a mouse model of BA. RESULTS: Liver organoids derived from patients with BA and a rhesus rotavirus A-infected mouse model of BA, exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures and altered beta-amyloid-related gene expression. Beta-amyloid accumulation was observed around the bile ducts in BA livers and exposure to beta-amyloid induced the aberrant morphology in control organoids. CONCLUSION: The novel observation that beta-amyloid accumulates around bile ducts in the livers of patients with BA has important pathobiological implications, as well as diagnostic potential. LAY SUMMARY: Biliary atresia is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. Using human and mouse 'liver mini-organs in the dish', we unexpectedly identified beta-amyloid deposition - the main pathological feature of Alzheimer's disease and cerebral amyloid angiopathy - around bile ducts in livers from patients with biliary atresia. This finding reveals a novel pathogenic mechanism that could have important diagnostic and therapeutic implications.
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Peptídeos beta-Amiloides , Ductos Biliares , Atresia Biliar , Hepatócitos/metabolismo , Fragmentos de Peptídeos , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Ductos Biliares/metabolismo , Ductos Biliares/patologia , Atresia Biliar/genética , Atresia Biliar/metabolismo , Atresia Biliar/patologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Organoides , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , TranscriptomaRESUMO
AIM OF THE STUDY: The objective of this study is to identify risk factors associated with the development of post-operative enterocolitis (HAEC), in short segment Hirschsprung's disease (HSCR-S). METHODS: A retrospective study was carried out for post-operative patients with HSCR-S from 1997 to 2017. HSCR-S was defined as the most proximal extension of aganglionosis limited to the sigmoid colon. An episode of HAEC was defined as the presence of (1) vomiting or explosive diarrhea; (2) abdominal distension; (3) fever and (4) leukocytosis. Risk factors for the development of HACE were determined using multivariate logistic regression. MAIN RESULTS: The medical records of 96 patients were reviewed. The overall incidence of HAEC was 20.8% (n = 20) and 65.0% (n = 13) of HAEC occurred within the first year of operation. After a univariate logistic regression analysis, three risk factors for HAEC were identified: (1) presence of other major anomalies [OR: 1.43 (1.12-2.32), p = 0.041]; (2) creation of pre-operative defunctioning stoma [OR: 2.28 (1.47-3.23), p = 0.035]; (3) extension of aganglionosis to the sigmoid colon [OR: 1.89 (1.05-3.19), p = 0.049]. After multivariate logistic regression analysis, a significant association was demonstrated for creation of pre-operative defunctioning stoma [OR: 1.81 (1.08-3.22), p = 0.045] and extension of aganglionosis to the sigmoid colon [OR: 1.91 (1.37-2.98), p = 0.038]. CONCLUSIONS: The requirement of pre-operative defunctioning stoma and a more proximal extension of aganglionosis are risk factors for the development of post-operative HAEC in HSCR-S. Patients with these risk factors should be closely followed up especially during the first year after the operation.
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Enterocolite/etiologia , Doença de Hirschsprung/cirurgia , Complicações Pós-Operatórias , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Estomas Cirúrgicos/efeitos adversosRESUMO
OBJECTIVES: To review long-term transplant-free survival and quality of life (QOL) of patients with biliary atresia (BA). METHODS: A retrospective study reviewing all patients with Kasai operation between January 1, 1980 and December 31, 2015 was performed to evaluate the transplant-free survival. Subgroup analysis of patients older than 20 years was carried out to assess the QOL using the Short Form-36 Health Survey and incidences of disease-related complications. Comparison between patients with native and transplanted liver was performed using two-tailed independent samples t-test (P valueâ<â0.05, significant). RESULTS: The 20-year Kaplan-Meier transplant-free survival of the 141 patients in our study was 51%. The subgroup analysis of long-term survivors revealed a trend of increased prevalence of complications like esophageal varices, portal hypertension, and recurrent admissions in the patient groups with raised serum bilirubin (SB).Thirty-one patients were successfully contacted for QOL assessment, 26 (16 with native liver and 10 with transplanted liver) responded (76.5%). BA patients who were documented to have active complications have a significantly lower vitality score (50.7 vs 57.5, Pâ=â0.015). There was no statistically significant difference in the scores between the transplanted group and the disease-free control group. However, the native liver group achieved a lower score in both the general health section (42.9 vs 49.6, Pâ=â0.029) and the overall physical component (49.6 vs 54.4, Pâ=â0.037). CONCLUSIONS: A significant proportion of our patients survive with their native liver for more than 20 years. These long-term survivors may suffer from complications that impair their QOL. They require continuous life-long care.
Assuntos
Atresia Biliar/cirurgia , Transplante de Fígado/métodos , Portoenterostomia Hepática/métodos , Qualidade de Vida , Adolescente , Adulto , Atresia Biliar/complicações , Atresia Biliar/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Transplante de Fígado/efeitos adversos , Masculino , Portoenterostomia Hepática/efeitos adversos , Prevalência , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/PURPOSE: Short segment Hirschsprung's disease (HSCR) carries a better prognosis than long segment disease, but the definition of short is controversial. The objective of this study is to determine anatomically the extent of disease involvement that would be associated with a better functional outcome. METHODS: This is a retrospective multicenter (n = 3) study with patients (≥ 3 years) who had transanal pullthrough operation done for aganglionosis limited to the recto-sigmoid colon were reviewed. The extent of disease involvement and bowel resection was retrieved by reviewing the operative records as well as histopathological reports of the resected specimens. Clinical assessment was performed according to the criteria of a seven-itemed bowel function score (BFS) (maximum score = 20). Manometric assessment was performed with anorectal manometry. RESULTS: The study period started from 2003 to 45 patients were studied with median age at assessment = 52.0 months and operation = 3.0 months. The disease involvement was categorized into upper sigmoid-descending colon (DC) (n = 8), sigmoid colon (SC) (n = 12), upper rectum (UR) (n = 14) and lower rectum (LR) (n = 11) according to the level of normal biopsy result. There was no significant difference in the age of assessment between the four groups. The median BFSs in the DC, SC, UR and LR were 13, 15, 17 and 17, respectively (p = 0.01). Nine patients from the DC and SC groups reported soiling for more than twice per week. Sub-group analysis comparing patients with and without the entire sigmoid colon resected revealed worse functional outcomes in terms of the incidence of soiling (40.7 vs 22.2%, p = 0.05) and the BFS (14 vs 18, p = 0.04) in the former group. Anorectal manometry did not reveal any significant difference between the four groups, but a higher proportion of patients in the UR and LR groups appeared to have a normal sphincter resting pressure (DC vs SC vs UR vs LR = 62.5 vs 75.0 vs 85.7 vs 80.0%, p = 0.10). CONCLUSION: Patients with short segment HSCR are not equal at all. HSCR patients with aganglionosis limited to the rectum without the need of removing the entire sigmoid colon have a better bowel control and overall functional score. Less bowel loss and colonic dissection maybe the underlying reasons. Although future studies with a larger sample size and a longer follow-up period are required to validate the results of this study, it has provided a new insight to the current understanding of short segment disease in HSCR.