RESUMO
PURPOSE: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity. METHODS: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL. RESULTS: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL. CONCLUSION: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.
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Células Dendríticas , Linfadenite Histiocítica Necrosante , Interferon-alfa , Linfonodos , Humanos , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/sangue , Linfadenite Histiocítica Necrosante/imunologia , Masculino , Interferon-alfa/sangue , Feminino , Criança , Adolescente , Adulto , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Pré-Escolar , Linfonodos/patologia , Proteínas de Resistência a Myxovirus/genética , Proteínas de Resistência a Myxovirus/metabolismo , Proteínas de Resistência a Myxovirus/sangue , Adulto Jovem , Pessoa de Meia-Idade , Linfoma/diagnóstico , Linfoma/imunologia , Linfoma/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/sangue , Biomarcadores/sangue , Citocinas/sangue , Citocinas/metabolismoRESUMO
Surveillance videos of operating rooms have potential to benefit post-operative analysis and study. However, there is currently no effective method to extract useful information from the long and massive videos. As a step towards tackling this issue, we propose a novel method to recognize and evaluate individual activities using an anomaly estimation model based on time-sequential prediction. We verified the effectiveness of our method by comparing two time-sequential features: individual bounding boxes and body key points. Experiment results using actual surgery videos show that the bounding boxes are suitable for predicting and detecting regional movements, while the anomaly scores using key points can hardly be used to detect activities. As future work, we will be proceeding with extending our activity prediction for detecting unexpected and urgent events.
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Movimento , Salas Cirúrgicas , Humanos , Período Pós-Operatório , Gravação de VideoteipeRESUMO
BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited and neurodegenerative disorder. Approximately 10% of NPC patients have acute liver failure and sometimes need liver transplantation (LT), and 7% reportedly develop inflammatory bowel disease (IBD). We report the case of a girl with NPC who had a re- accumulation of cholesterol in the transplanted liver and NPC-related IBD. CASE REPORT: The patient underwent living donor liver transplantation (LDLT) due to severe acute liver failure caused by an unknown etiology inherited from her father. At 1 year and 6 months (1Y6M), she developed neurological delay, catalepsy, and vertical supranuclear gaze palsy. The foam cells were found in her skin, and fibroblast Filipin staining was positive; hence, she was diagnosed with NPC. It was identified that her father had NPC heterozygous pathogenic variant. At 2 years, she had anal fissure, skin tag and diarrhea. She was diagnosed with NPC-related IBD, using a gastrointestinal endoscopy. Three years after LT, liver biopsy revealed foam cells and numerous fatty droplets. At 8 years, broken hepatocytes and substantial fibrosis were observed. She died from circulation failure due to hypoalbuminemia at 8Y2M. CONCLUSIONS: In NPC, load of cholesterol metabolism is suggested to persist even after LT. LDLT from NPC heterozygous variant donor was insufficient to metabolize cholesterol overload. In NPC patients, the possibility of cholesterol re-accumulation should be considered when LT is performed. NPC-related IBD should be considered when NPC patients have anorectal lesions or diarrhea.
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Doenças Inflamatórias Intestinais , Falência Hepática Aguda , Transplante de Fígado , Doença de Niemann-Pick Tipo C , Humanos , Recém-Nascido , Feminino , Doença de Niemann-Pick Tipo C/complicações , Doença de Niemann-Pick Tipo C/diagnóstico , Doadores Vivos , Colesterol/metabolismo , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.
Assuntos
Citocinas , Síndrome de Linfonodos Mucocutâneos , Choque Séptico , Síndrome de Resposta Inflamatória Sistêmica , Infecções por Yersinia pseudotuberculosis , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Citocinas/sangue , Humanos , Interleucina-6/sangue , Quimiocina CXCL9/sangue , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Choque Séptico/sangue , Choque Séptico/diagnóstico , Infecções por Yersinia pseudotuberculosis/sangue , Infecções por Yersinia pseudotuberculosis/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition.
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Sinalização do Cálcio , Peixe-Zebra , Animais , Cálcio/metabolismo , Movimento Celular , Cães , Células Epiteliais/metabolismo , Células Madin Darby de Rim Canino , Peixe-Zebra/metabolismoRESUMO
BACKGROUND: Schaaf-Yang syndrome (SYS) is a rare hereditary disease caused by truncating point mutations of the paternal allele of melanoma antigen L2 (MAGEL2), one of five protein-coding genes within the Prader-Willi syndrome (PWS) critical domain. SYS shares many clinical and molecular characteristics with PWS but has some distinct features, such as joint contractures and autism. Patients with PWS show abnormal electroencephalography (EEG) patterns. However, there are very few reports on EEG findings in patients with SYS. METHODS: A SYS patient was included in this study. Detailed neurological examinations and EEG were performed from neonate to infant ages. Sanger sequencing was performed. RESULTS: Our patient presented abnormal EEG findings and had diffuse brain dysfunction symptoms including a reduced level of consciousness, diminished spontaneous movements, hypotonia, feeding difficulties, and hypoventilation from early after birth. As she grew older and her background activity of EEG normalized, her neurodevelopmental symptoms remained but improved. Sanger sequencing of this patient revealed a novel, heterozygous c.2005C > T, truncating mutation in the MEGAL2 gene. CONCLUSIONS: We described an SYS-associated, time-dependent, EEG pattern in a patient with SYS. Our findings of longitudinal EEG changes in a patient with SYS revealed a specific pattern of how affected individuals develop brain function.
Assuntos
Eletroencefalografia , Mutação , Síndrome de Prader-Willi , Artrogripose , Anormalidades Craniofaciais , Feminino , Humanos , Hipopituitarismo , Lactente , Recém-Nascido , Deficiência Intelectual , Síndrome de Prader-Willi/genética , Proteínas/genéticaRESUMO
When performing endoscopic reduction in patients with gastric volvulus, it is important to maintain a low level of intragastric pressure and to fix the endoscope in the duodenum. Gel immersion endoscopy is a new method for securing the visual field by injecting clear gel. The balloon-attached endoscope makes it easier to fix the tip in the duodenum without mucosal damage. We report successful reduction of a mesenteroaxial gastric volvulus using an endoscope with a balloon in combination with gel immersion endoscopy. A 3-year-old Japanese male developed gastric volvulus. Since gastric decompression using a nasogastric tube failed to reduce the volvulus, endoscopic reduction was performed under general anesthesia. After aspiration of intragastric gas, clear gel was injected through the accessory channel which secured the visual field in the stomach even with residue while maintaining low intragastric pressure. After reaching the descending portion of the duodenum, the balloon attached to the tip of the endoscope was inflated and fixed in the duodenum. The volvulus was successfully reduced by pulling back the endoscope with clockwise torque. Acute mesenteroaxial gastric volvulus has the potential to cause ischemia and perforation which can be life-threatening, so most patients are treated with surgical intervention. Gel immersion endoscopy is safe and effective to secure the visual field, even in children. Endoscopic reduction may be a viable treatment option for reducing gastric volvulus in non-emergent patients.
Assuntos
Volvo Intestinal , Volvo Gástrico , Criança , Pré-Escolar , Endoscópios , Endoscopia/métodos , Endoscopia Gastrointestinal/métodos , Humanos , Imersão , Masculino , Volvo Gástrico/etiologia , Volvo Gástrico/cirurgiaRESUMO
Juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT) are both relatively rare hereditary disorders. Some patients with the SMAD4 gene mutation develop both JPS and HHT, a condition termed JPS-HHT. We herein report a case of childhood-onset JPS-HHT. At nine years old, the patient underwent colonoscopy under suspicion of Crohn's disease, which revealed multiple polyps. A genetic analysis for familial adenomatous polyposis and Peutz-Jeghers syndrome found no mutations. After several years, extraintestinal manifestations, such as repeated epistaxis and several telangiectasias in the upper palate and stomach, were identified, which led to the performance of gene mutation analysis for SMAD4. As a result, a missense mutation in exon 8, codon 361 from arginine to cysteine (c.1081 C>T) was found. Based on this finding, the patient underwent cerebral magnetic resonance angiography, pulmonary perfusion scintigraphy and thoracoabdominal contrast computed tomography. The examination revealed that she had pulmonary arteriovenous fistulas and arteriovenous malformations in both the liver and right mammary gland. Thus, continuous surveillance for vascular lesions and gastrointestinal cancer is scheduled. Making a precise diagnosis of JPS-HHT can lead to the detection of asymptomatic complications and enable appropriate future disease management.
Assuntos
Polipose Intestinal , Síndromes Neoplásicas Hereditárias , Telangiectasia Hemorrágica Hereditária , Criança , Feminino , Humanos , Polipose Intestinal/congênito , Polipose Intestinal/genética , Mutação , Síndromes Neoplásicas Hereditárias/genética , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genéticaRESUMO
INTRODUCTION: Pulmonary Langerhans cell histiocytosis (PLCH) is a well known entity in adults but is exceedingly rare in children. The main complication of PLCH is the occurrence of pneumothorax (PTX) and tension bullae with subsequent recurrence and persistence despite conservative management. CASE PRESENTATION: A 3-year-old child was diagnosed with PLCH with thyroid involvement. Chemotherapy was immediately initiated and continued with chest tube drainage for repeated bilateral PTX. Tension bullae developed in the right lung 1 month after initiating treatment. Emergency resection of the bullae and ligation of pulmonary cysts were performed. On the tenth postoperative day, she developed a tension bulla in the left lung. Emergency thoracotomy was performed. On the tenth postoperative day, chest X-ray and CT suggested return of the right bulla and mediastinal shift, and reoperation was performed. Repeated lung biopsy showed no sign of active LCH. Although her condition improved after the operation, subsequent repeated PTXs occurred and were difficult to treat. She was discharged home after four months. Currently, she is receiving maintenance therapy as an outpatient. During the 12-month follow-up, the pulmonary lesions also showed a tendency for improvement. DISCUSSION: Although it is difficult to treat recurrent PTX and tension bullae in advanced PLCH, continuous treatment of the primary disease (LCH) and the complications of pulmonary lesions can improve prognosis. CONCLUSION: Treatment of PLCH accompanied by recurrent PTX and tension bullae is challenging. The condition can be resolved by treating the primary disease in parallel with combined modality treatment, including surgical operation for complications.
RESUMO
Duodenocolic fistula (DCF) is a rare disorder defined by the presence of an internal fistula between the duodenum and colon. Colon cancer, Crohn's disease, diverticulum and duodenal ulcer are common causes of DCF, and vomiting and diarrhea are its main symptoms. We report a 14-year-old boy with DCF who had been treated for a functional gastrointestinal disorder (FGID). The boy had often experienced episodes of vomiting and diarrhea since infancy, and had been diagnosed with FGID. He was referred to our hospital because of a 2-month exacerbation of persistent vomiting and diarrhea. Upper gastrointestinal contrast revealed no abnormalities. Eventually, esophagogastroduodenoscopy detected a duodenal fistula, and DCF was diagnosed by endoscopic fistulography. Colonoscopy showed a diverticulum in the ascending colon near the fistula. In addition, a C13 urea breath test for Helicobacter pylori infection was positive. One hypothetical pathogenesis of his DCF was perforated colonic diverticulitis. Adhesion between the fistula wall and colonic diverticulum near the fistula strongly suggested a relationship between the fistula and the diverticulum. However, he never presented with symptoms of colonic diverticulitis. Thus, a congenital origin was also suspected. After confirming temporary relief from the symptoms by endoscopic closure, surgical closure was performed.
Assuntos
Doenças do Colo/diagnóstico , Duodenopatias/diagnóstico , Gastroenteropatias/diagnóstico , Fístula Intestinal/diagnóstico , Adolescente , Doença Crônica , Doenças do Colo/complicações , Diagnóstico Diferencial , Diarreia/etiologia , Duodenopatias/complicações , Endoscopia do Sistema Digestório , Humanos , Fístula Intestinal/complicações , Masculino , Vômito/etiologiaRESUMO
OBJECTIVES: The benefit of balloon-assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan. METHODS: This was a prospective, multi-institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double-balloon or single-balloon enteroscopy. Data were collected prospectively using a standardized questionnaire. RESULTS: We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1-17 years). Antegrade (oral-route) BAE was performed in 20 procedures (lowest body weight 12.9âkg, youngest age 3.7 years), and retrograde (anal-route) BAE in 76 (lowest body weight 10.8âkg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double-balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral-route BAE for diagnosis was significantly longer than anal-route for diagnosis (Pâ<â0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE. CONCLUSIONS: This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.
Assuntos
Enteroscopia de Duplo Balão/métodos , Enteroscopia de Balão Único/métodos , Adolescente , Criança , Pré-Escolar , Enteroscopia de Duplo Balão/efeitos adversos , Feminino , Humanos , Lactente , Enteropatias/diagnóstico , Intestino Delgado/cirurgia , Japão , Masculino , Duração da Cirurgia , Estudos Prospectivos , Enteroscopia de Balão Único/efeitos adversosAssuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encéfalo/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite (Inflamação)/etiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Criança , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurite (Inflamação)/diagnóstico , Neurite (Inflamação)/imunologiaRESUMO
5-Aminosalicylic acid preparations have been used as first-line drugs for treatment of ulcerative colitis (UC). However, some patients with UC present with exacerbation of symptoms because of allergy to mesalazine. Diagnosis of mesalazine allergy in active UC may be challenging because its symptoms mimic those of UC. Here we describe a 13-year-old boy with mesalazine allergy who achieved remission when his medication was changed from mesalazine to salazosulfapyridine. During his clinical course mesalazine was prescribed twice, and on each occasion exacerbation of the symptoms occurred. We considered a diagnosis of mesalazine allergy, and this was confirmed by a drug lymphocyte stimulation test; the result for salazosulfapyridine was negative. On the basis of criteria involving simple mucosal biopsy combined with endoscopy for predicting patients with UC who would ultimately require surgery, we considered that the UC in this case might be susceptible to steroid treatment, and we therefore treated the patient with salazosulfapyridine and prednisolone. Shortly afterwards, remission was achieved and the patient has remained in good condition on salazosulfapyridine alone. When treating patients with mesalazine, the possibility of allergy should always be borne in mind, especially when the clinical course is inconsistent with the results of biopsy.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Mucosa Intestinal/patologia , Mesalamina/efeitos adversos , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia , Colite Ulcerativa/patologia , Colo/patologia , Colonoscopia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/patologia , Substituição de Medicamentos , Humanos , Masculino , Mesalamina/uso terapêutico , Sulfassalazina/uso terapêuticoAssuntos
DNA Bacteriano/análise , Mycobacterium bovis/genética , Parede Torácica/diagnóstico por imagem , Tuberculose/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Humanos , Masculino , Reação em Cadeia da Polimerase , Parede Torácica/microbiologia , Tomografia Computadorizada por Raios X , Tuberculose/microbiologiaRESUMO
Reports of cow's milk allergy (CMA) after neonatal gastrointestinal surgery have recently increased. In recent years it has been suggested that the development of CMA after gastrointestinal surgery in newborn infants is due to an immune function. In addition, the development of CMA might be synergistically exacerbated by congenital abnormalities of the intestinal mucosa, general conditional changes and local damage to the intestine by invasive surgery, and poor pre- or post-surgical nutrition. CMA manifests as a variety of symptoms, such as mild vomiting and bloody stool, decreased activity, poor oral intake, and ileus. CMA may also rarely cause gastrointestinal perforation. Here, we report the case of a newborn infant who developed CMA following repair of focal small intestinal perforation, in which eosinophilic enteritis was suspected to be a possible cause of anastomosis leakage.
RESUMO
BACKGROUND: Only a handful of studies have investigated children with functional dyspepsia (FD) and irritable bowel syndrome (IBS) classified according to the Rome III criteria, and limited information is available on the lifestyle of affected patients. METHODS: We conducted an Internet questionnaire survey of 2060 parents among the general public in Japan who lived with their children aged 10-15, who were screened for FD and IBS. RESULTS: The prevalence of FD and IBS was 2.8% and 6.1%, respectively, and 1.4% of the subjects met the criteria for both FD and IBS. The lifestyles of 155 subjects who met the criteria for FD, IBS, or both were compared with those of 1745 control subjects. In comparison with the controls, a significantly higher percentage of subjects with FD, IBS, or both thought that their sleep was insufficient, ate meals irregularly, were susceptible to stress and to dizziness on standing, had difficulty in getting out of bed or felt sluggish in the morning, had a tendency to faint when standing, and had migraine/chronic headache. CONCLUSIONS: Children with FD and IBS are susceptible to stress, have impaired sleep and eating habits, and have more frequent symptoms of comorbid orthostatic dysregulation and headache.
Assuntos
Dispepsia/epidemiologia , Internet , Síndrome do Intestino Irritável/epidemiologia , Programas de Rastreamento/métodos , Inquéritos e Questionários , Adolescente , Criança , Dispepsia/diagnóstico , Feminino , Humanos , Síndrome do Intestino Irritável/diagnóstico , Japão/epidemiologia , Masculino , Prevalência , Fatores de RiscoRESUMO
OBJECTIVES: The safety and efficacy of double-balloon enteroscopy (DBE) in pediatric patients has not been well documented. We aimed to evaluate the clinical efficacy and safety of DBE in children, especially those under 10. METHODS: We retrospectively analyzed our database of DBE procedures performed between September 2000 and September 2013. Procedures performed in pediatric patients (under 18) were selected from a total of 3980, including double-balloon endoscopic retrograde cholangioscopy (DBERC). RESULTS: Two hundred fifty-seven DBE procedures were performed in 117 pediatric patients (median age 12.5 years). Antegrade (oral-route) DBE was performed in 166 procedures including 104 DBERC procedures (lowest body weight 13.5 kg, youngest age 3 years), and retrograde (anal-route) DBE in 91 (lowest body weight 12.0 kg, youngest age 2 years). The overall diagnostic yield for obscure gastrointestinal bleeding and abdominal pain was 58.8%. The purpose of DBERC was achieved in 76.9% of procedures. The overall complication rate in our series was 5.4% (1.9% with the DBERC cases removed); in patients under 10, it was 10.4% (7/67). No severe complications associated with enteroscope insertion and sedation were observed. Serum amylase levels tended to be elevated in patients who underwent oral-route DBE. CONCLUSIONS: DBE is safe and feasible for diagnostic evaluation of small bowel disorders in pediatric patients, even those younger than 10 years. Special attention for possible complications must, however, be paid during therapeutic DBE procedures, including DBERC, especially for patients under 10.
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Endoscopia Gastrointestinal/efeitos adversos , Gastroenteropatias/cirurgia , Cápsulas Endoscópicas , Criança , Serviços de Saúde da Criança , Pré-Escolar , Bases de Dados Factuais , Endoscopia Gastrointestinal/instrumentação , Feminino , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Segurança do Paciente , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the sensitivity and specificity of a stool color card used for a mass screening of biliary atresia conducted over 19 years. In addition, the age at Kasai procedure and the long-term probabilities of native liver survival were investigated. STUDY DESIGN: From 1994 to 2011, the stool color card was distributed to all pregnant women in Tochigi Prefecture, Japan. Before or during the postnatal 1-month health checkup, the mothers returned the completed stool color card to the attending pediatrician or obstetrician. All suspected cases of biliary atresia were referred for further examination. Diagnosis was confirmed by laparotomy or operative cholangiography for high-risk cases before the Kasai procedure. Patients with biliary atresia were followed from the date of their Kasai procedure until liver transplantation, death, or October 31, 2013, whichever comes sooner. RESULTS: A total of 313,230 live born infants were screened; 34 patients with biliary atresia were diagnosed. The sensitivity and specificity of stool color card screening at the 1-month check-up was 76.5% (95% CI 62.2-90.7) and 99.9% (95% CI 99.9-100.0), respectively. Mean age at the time of Kasai procedure was 59.7 days. According to Kaplan-Meier analysis, the native liver survival probability at 5, 10, and 15 years was 87.6%, 76.9%, and 48.5%, respectively. CONCLUSIONS: The sensitivity and specificity of the stool color card have been demonstrated by our 19-year cohort study. We found that the timing of Kasai procedure and long-term native liver survival probabilities were improved, suggesting the beneficial effect of stool color card screening.
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Atresia Biliar/diagnóstico , Diagnóstico Precoce , Fezes/química , Previsões , Programas de Rastreamento/métodos , Atresia Biliar/mortalidade , Atresia Biliar/cirurgia , Feminino , Seguimentos , Humanos , Recém-Nascido , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Portoenterostomia Hepática/métodos , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVE: Neonatal-onset multisystem inflammatory disease (NOMID) is a dominantly inherited autoinflammatory disease caused by NLRP3 mutations. NOMID pathophysiology is explained by the NLRP3 inflammasome, which produces interleukin-1ß (IL-1ß). However, epiphyseal overgrowth in NOMID is resistant to anti-IL-1 therapy and may therefore occur independently of the NLRP3 inflammasome. This study was undertaken to investigate the effect of mutated NLRP3 on chondrocytes using induced pluripotent stem cells (iPSCs) from patients with NOMID. METHODS: We established isogenic iPSCs with wild-type or mutant NLRP3 from 2 NOMID patients with NLRP3 somatic mosaicism. The iPSCs were differentiated into chondrocytes in vitro and in vivo. The phenotypes of chondrocytes with wild-type and mutant NLRP3 were compared, particularly the size of the chondrocyte tissue produced. RESULTS: Mutant iPSCs produced larger chondrocyte masses than wild-type iPSCs owing to glycosaminoglycan overproduction, which correlated with increased expression of the chondrocyte master regulator SOX9. In addition, in vivo transplantation of mutant cartilaginous pellets into immunodeficient mice caused disorganized endochondral ossification. Enhanced chondrogenesis was independent of caspase 1 and IL-1, and thus the NLRP3 inflammasome. Investigation of the human SOX9 promoter in chondroprogenitor cells revealed that the CREB/ATF-binding site was critical for SOX9 overexpression caused by mutated NLRP3. This was supported by increased levels of cAMP and phosphorylated CREB in mutant chondroprogenitor cells. CONCLUSION: Our findings indicate that the intrinsic hyperplastic capacity of NOMID chondrocytes is dependent on the cAMP/PKA/CREB pathway, independent of the NLRP3 inflammasome.