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BACKGROUND: The indications for hip arthroscopy have been increasing, as have been the number of patients undergoing total hip arthroplasty (THA) after hip arthroscopy. Several matched cohort studies have assessed the impact of prior hip arthroscopy on THA, but conflicting results have been observed. The purpose of this study was to evaluate the influence of prior arthroscopy on subsequent THA. METHODS: This systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 checklist. PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library were searched to identify relevant studies. Dichotomous variables were summarized qualitatively as a meta-analysis of pooled odds ratios (ORs) and 95% confidence intervals (CIs), and continuous variables were summarized as standardized mean differences and 95% CIs. P-values <0.05 were considered statistically significant. The risk of bias was evaluated for each study, as was publication bias. RESULTS: In patients who underwent hip arthroscopy prior to THA, the ORs for dislocation, reoperation, and revision were 2.02 (P = 0.01), 1.66 (P = 0.01), and 2.15 (P = 0.001), respectively. There were no significant between-group differences in the Harris Hip Score (HHS; P = 0.40), WOMAC (P = 0.069), FJS-12 (P = 0.77), estimated blood loss (P = 0.48), and surgical time (P = 0.16). CONCLUSIONS: Prior hip arthroscopy is a risk for postoperative dislocation, reoperation, or revision after conversion THA. However, prior hip arthroscopy has no effect on patient-reported outcomes, or operative factors such as surgical time and blood loss.
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Artroplastia de Reemplazo de Cadera , Luxación de la Cadera , Luxaciones Articulares , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Reoperación , Artroscopía/efectos adversos , Artroscopía/métodos , Luxaciones Articulares/cirugía , Estudios de Cohortes , Articulación de la Cadera/cirugía , Resultado del Tratamiento , Luxación de la Cadera/etiología , Luxación de la Cadera/cirugíaRESUMEN
The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.
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Enfermedades Transmisibles , Infecciones del Sistema Respiratorio , Niño , Humanos , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/terapia , Japón/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI-H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real-time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP-AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2-induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild-type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.
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BACKGROUND: Oral allergy syndrome (OAS) is characterized by an immediate allergic reaction that mainly or partially affects the oral mucosa, pharynx, or lips, and it is usually caused by ingesting fresh fruits or vegetables. Most patients with OAS also have allergic rhinitis due to pollen. As allergic rhinitis is increasingly prevalent in the Japanese population and the age at disease development is decreasing, morbidity associated with OAS among the younger population is likely to increase. However, there is little information about the prevalence of this disease among Japanese children, specifically the influences of residency in regions with different environments. OBJECTIVE: To investigate the prevalence of OAS and seasonal allergic rhinitis (SAR) among Japanese children and evaluate the relationship between OAS and SAR. METHODS: We administered a questionnaire-based survey among children aged 7-15 years, living in 4 cities in central Japan. RESULTS: The questionnaires were administered to 4103 children and completed by 3365 (82.0%). Overall, 524 children (15.6%) reported OAS-like symptoms after ingesting fruits or vegetables. The prevalence of seasonal SAR and oral symptoms significantly differed among the 4 cities. The total prevalence of oral symptoms co-occurring with SAR was 24.4%, which was significantly higher than the prevalence of symptoms occurring without SAR (10.2%, p < 0.001). CONCLUSIONS: Herein, oral symptoms were more likely to occur in patients with SAR than in those without SAR. The prevalence of SAR and food-induced oral symptoms significantly differed among the regions, suggesting they might be affected by regional differences in lifestyles and flora.
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Hipersensibilidad a los Alimentos , Rinitis Alérgica Estacional , Rinitis Alérgica , Adolescente , Niño , Humanos , Pueblos del Este de Asia , Hipersensibilidad a los Alimentos/complicaciones , Prevalencia , Rinitis Alérgica/complicaciones , Rinitis Alérgica Estacional/diagnóstico , Encuestas y Cuestionarios , Boca , FaringeRESUMEN
This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.
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Dermatitis Atópica , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Emolientes/uso terapéutico , Glucocorticoides , Humanos , Japón , Pomadas/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.
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Dermatitis Atópica , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Emolientes/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Pomadas/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
Background: Thrombotic microangiopathy (TMA) is a syndrome associated with hemolytic anemia, thrombocytopenia, and various organ disorders. Thrombotic thrombocytopenic purpura (TTP) is a disease that develops when a disintegrin-like and metalloproteinase with thrombospondin type l motif 13 (ADAMTS13) activity decreases to < 10% of that in normal plasma, causing platelet thrombosis in microvessels throughout the body. Currently, ADAMTS13-deficient TMA is diagnosed as TTP. Systemic lupus erythematosus (SLE)-related TMA includes both acquired TTP, in which ADAMTS13 activity is significantly reduced, and secondary TMA, in which ADAMTS13 activity is not reduced. Both diseases have different prognoses. Case Presentation: An 11-year-old girl was admitted to our hospital on suspicion of TMA with thrombocytopenia and hemolytic anemia. Because the patient had hypocomplementemia, SLE-related TMA or complement-related TMA was considered. Therefore, we initiated plasma exchange (PE) for the patient. Subsequently, she fulfilled the pediatric SLE diagnostic criteria, and ADAMTS13 activity was shown to be decreased and the anti-ADAMTS13 antibody titer increased. She was thus diagnosed with acquired TTP caused by SLE. Treatment response was good as a platelet count and ADAMTS13 activity improved with three times of PE, followed by methylprednisolone pulse therapy and administration of mycophenolate mofetil. Renal pathology showed thrombus formation in glomerular arterioles and lupus nephritis categorized as Class III (A) of the International Society of Nephrology and the Renal Pathology Society classification. Because the patient was thought to be in the high-risk group of SLE, three courses of intravenous cyclophosphamide pulse therapy were administered as an additional induction therapy. No recurrence of TTP was observed. Conclusion: In SLE-related TMA, measurement of ADAMTS13 activity and the anti-ADAMTS13 antibody titer are necessary for diagnosis, and for predicting prognosis and recurrence of the disease; however, in the acute phase of immune-mediated TMA, it is important to initiate proper treatments even before knowing the results to improve prognosis.
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We investigated genome-wide DNA methylation patterns in 64 pediatric patients with acute myeloid leukemia (AML). Based on unsupervised clustering with the 567 most variably methylated cytosine guanine dinucleotide (CpG) sites, patients were categorized into 4 clusters associated with genetic alterations. Clusters 1 and 3 were characterized by the presence of known favorable prognostic factors, such as RUNX1-RUNX1T1 fusion and KMT2A rearrangement with low MECOM expression, and biallelic CEBPA mutations (all 8 patients), respectively. Clusters 2 and 4 comprised patients exhibiting molecular features associated with adverse outcomes, namely internal tandem duplication of FLT3 (FLT3-ITD), partial tandem duplication of KMT2A, and high PRDM16 expression. Depending on the methylation values of the 1243 CpG sites that were significantly different between FLT3-ITD+ and FLT3-ITD- AML, patients were categorized into 3 clusters: A, B, and C. The STAT5-binding motif was most frequently found close to the 1243 CpG sites. All 8 patients with FLT3-ITD in cluster A harbored high PRDM16 expression and experienced adverse events, whereas only 1 of 7 patients with FLT3-ITD in the other clusters experienced adverse events. PRDM16 expression levels were also related to DNA methylation patterns, which were drastically changed at the cutoff value of PRDM16/ABL1 = 0.10. The assay for transposase-accessible chromatin sequencing of AMLs supported enhanced chromatin accessibility around genomic regions, such as HOXB cluster genes, SCHIP1, and PRDM16, which were associated with DNA methylation changes in AMLs with FLT3-ITD and high PRDM16 expression. Our results suggest that DNA methylation levels at specific CpG sites are useful to support genetic alterations and gene expression patterns of patients with pediatric AML.
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Metilación de ADN , Leucemia Mieloide Aguda , Niño , Cromatina , Humanos , Leucemia Mieloide Aguda/genética , MutaciónRESUMEN
RAS pathway alterations have been implicated in the pathogenesis of various hematological malignancies. However, their clinical relevance in pediatric acute myeloid leukemia (AML) is not well characterized. We analyzed the frequency, clinical significance, and prognostic relevance of RAS pathway alterations in 328 pediatric patients with de novo AML. RAS pathway alterations were detected in 80 (24.4%) of 328 patients: NF1 (n=7, 2.1%), PTPN11 (n=15, 4.6%), CBL (n=6, 1.8%), NRAS (n=44, 13.4%), KRAS (n=12, 3.7%). Most of these alterations in the RAS pathway were mutually exclusive also together with other aberrations of signal transduction pathways such as FLT3-ITD (P=0.001) and KIT mutation (P=0.004). NF1 alterations were frequently detected in patients with complex karyotype (P=0.031) and were found to be independent predictors of poor overall survival (OS) in multivariate analysis (P=0.007). At least four of seven patients with NF1 alterations had biallelic inactivation. NRAS mutations were frequently observed in patients with CBFB-MYH11 and were independent predictors of favorable outcomes in multivariate analysis (OS, P=0.023; event-free survival [EFS], P=0.037). Patients with PTPN11 mutations more frequently received stem cell transplantation (P=0.035) and showed poor EFS than patients without PTPN11 mutations (P=0.013). Detailed analysis of RAS pathway alterations may enable a more accurate prognostic stratification of pediatric AML and may provide novel therapeutic molecular targets related to this signal transduction pathway.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Niño , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , PronósticoRESUMEN
Gene expression programs and concomitant chromatin regulation change dramatically during the maturation of postmitotic neurons. Subnuclear positioning of gene loci is relevant to transcriptional regulation. However, little is known about subnuclear genome positioning in neuronal maturation. Using cultured murine hippocampal neurons, we found genomic locus 14qD2 to be enriched with genes that are upregulated during neuronal maturation. Reportedly, the locus is homologous to human 8p21.3, which has been extensively studied in neuropsychiatry and neurodegenerative diseases. Mapping of the 14qD2 locus in the nucleus revealed that it was relocated from the nuclear periphery to the interior. Moreover, we found a concomitant decrease in lamin B1 expression. Overexpression of lamin B1 in neurons using a lentiviral vector prevented the relocation of the 14qD2 locus and repressed the transcription of the Egr3 gene on this locus. Taken together, our results suggest that reduced lamin B1 expression during the maturation of neurons is important for appropriate subnuclear positioning of the genome and transcriptional programs.
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Lamina Tipo B , Neuronas , Animales , Núcleo Celular , Humanos , Lamina Tipo B/genética , Ratones , NeurogénesisRESUMEN
Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.
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Tos/etiología , Tos/terapia , Guías de Práctica Clínica como Asunto , Neumología/organización & administración , Sociedades Médicas/organización & administración , Esputo , Enfermedad Aguda , Asma , Enfermedad Crónica , Tos/clasificación , Femenino , Reflujo Gastroesofágico , Humanos , Hipersensibilidad , Japón , Masculino , Enfermedades Respiratorias/complicaciones , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/terapiaRESUMEN
Whipple disease is a systemic chronic infection caused by Tropheryma whipplei. Although chronic diarrhea is a common gastrointestinal symptom, diagnosis is often difficult because there are no specific endoscopic findings, and the pathogen is not detectable by stool culture. We present a female patient with Whipple disease who developed chronic bloody diarrhea and growth retardation at the age of 4 years. Colonoscopy showed a mildly edematous terminal ileum and marked erythema without vascular patterns throughout the sigmoid colon and rectum. Subsequently, a primary diagnosis of ulcerative colitis was made. Histopathological analysis of the terminal ileum showed the presence of foamy macrophages filled with periodic acidSchiff-positive particles. Polymerase chain reaction using DNA from a terminal ileum biopsy sample amplified a fragment of 16S rRNA from T. whipplei. Antibiotic treatment relieved the patient's symptoms. There was no evidence of immunodeficiency in the present case. Since Whipple disease worsens after anti-tumor necrosis factor inhibitor therapy, considering this infection in the differential diagnosis may be important in patients with inflammatory bowel disease, especially before initiation of immunotherapy.
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The lymphocyte stimulation test (LST) facilitates the diagnosis of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs). However, LSTs require large volumes of blood and prolonged culture durations. Recently, we found that IL2RA mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with non-IgE-GI-FAs increased after a 24 h stimulation with milk proteins. We designated this gene expression test as the instant peripheral blood allergen stimulation test (iPAST). In this study, we investigated whether other activated T cell-associated genes are superior to IL2RA in the iPAST for the supplementary diagnosis of non-IgE-GI-FAs. After incubating PBMCs with milk proteins for 24 h, the mRNA levels of three genes, LRRC32, TNFRSF4, and CD69, were assessed using quantitative RT-PCR. The diagnostic significance of the mRNA expression was evaluated by analyzing the receiver operating characteristic (ROC) curve. Upon stimulation with α-casein, κ-casein, α-lactalbumin, or a mixture of four milk protein components (Pmix), LRRC32 expression in the PBMCs of 16 patients with non-IgE-GI-FAs was found to be higher than that in their 17 control counterparts, whereas TNFRSF4 and CD69 levels remained unaltered. Except for ß-lactoglobulin and cow's milk (CM), the area under the ROC curve (AUC) for LRRC32 mRNA expression upon stimulation was >0.7, which validated the diagnostic ability of this test. Notably, α-casein and Pmix had higher AUC scores of 0.820 and 0.842, respectively, than other antigens. iPAST assessed by LRRC32 as well as IL2RA may be useful for the supplementary diagnosis of non-IgE-GI-FAs as an alternative to LSTs and provide insight into the pathogenesis of non-IgE-GI-FAs.
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Hipersensibilidad a los Alimentos , Activación de Linfocitos , Proteínas de la Membrana , Animales , Bovinos , Células Cultivadas , Femenino , Humanos , Inmunoglobulina E , Lactante , Leucina , Leucocitos Mononucleares , Proteínas de la Membrana/metabolismoRESUMEN
The Japanese Guideline for Childhood Asthma (JGCA) 2020 is a translation of the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL) 2017 into English, which was published by the Japanese Society of Pediatric Allergy and Clinical Immunology. It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. These guidelines will be of interest to non-specialist physicians involved in the care of children with asthma. In JPGL, JPGL2017 is the first evidence-based guidelines updated according to the GRADE system and Minds approach, and it addresses eight clinical questions about the treatment of childhood asthma. In children aged ≤5 years, infant and preschool asthma is diagnosed according to the response to short acting beta2 agonists or the effect of a therapeutic trial during 1 month with controller treatment and worsening after treatment cessation. Long-term management both promotes pharmacological therapy and measures against risk factors that induce exacerbation, better patient education and a partnership with trinity. In addition, long-term management should not be carried out without review but rather be based on a cycle of evaluation, adjustment and treatment. In JPGL2017, the transdermal patch and oral beta2 agonists are positioned as drugs within the concept of "short-term additional treatment" to be used until the symptoms are stabilized when the control state transiently deteriorates.
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Asma/diagnóstico , Asma/terapia , Factores de Edad , Asma/etiología , Niño , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Japón , PediatríaRESUMEN
Endoscopy is a central tool for diagnosing and evaluating paediatric inflammatory bowel diseases (PIBD), but is too invasive to be frequently repeated in young children. Furthermore, it is challenging to distinguish Crohn's disease (CD) from ulcerative colitis (UC) endoscopically. This study aimed to determine biomarkers useful for the diagnosis of PIBD. Cytokines, chemokines, and growth factors were quantified in the sera of 15 patients with CD or UC, at disease onset prior to treatment, and 26 age-matched controls. Correlation of cytokine levels with the paediatric CD activity index (PCDAI) and the paediatric UC activity index (PUCAI) was analysed. Interleukin (IL)-6, IL-13, IL-7, and vascular endothelial growth factor were higher in the CD group than in the UC group. The receiver operating characteristic curve analysis showed that IL-7 was a putative biomarker for distinguishing CD from UC (area under the curve: 0.94). Granulocyte-macrophage colony-stimulating factor was associated with PCDAI, and an IL-1 receptor antagonist, IL-6, and macrophage inflammatory protein-1ß were associated with PUCAI. These findings indicate significant differences in cytokine signatures among patients with new-onset PIBD, which may improve accuracy in diagnosing PIBD.
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Citocinas/sangre , Enfermedades Inflamatorias del Intestino/diagnóstico , Interleucinas/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adolescente , Biomarcadores/sangre , Niño , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Masculino , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is not well yet investigate. METHODS: We performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment. RESULTS: Of the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their intelligence quotient. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00-14.37, OR = 4.65; 95% CI: 1.11-19.37). There was no significant difference in physical development (P = 0.64). CONCLUSIONS: The best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.
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Apnea Central del Sueño , Niño , Estudios de Cohortes , Humanos , Hipoventilación/congénito , Lactante , Japón , Estudios Retrospectivos , Apnea Central del Sueño/diagnóstico , Apnea Central del Sueño/etiología , Apnea Central del Sueño/terapiaRESUMEN
Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic ß-cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8+ regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the intestinal microbiota and increases the abundance of Ruminococcus spp., resulting in the induction of CD8+ Treg cells. Furthermore, trehalose has therapeutic effects on both streptozotocin-induced diabetes and in the NOD mouse model of T1D. In addition, compared with healthy volunteers, patients with T1D have fewer CD8+ Treg cells, and the abundance of intestinal Ruminococcus positively correlates with the number of CD8+ Treg cells in humans.
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Linfocitos T CD8-positivos/inmunología , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/inmunología , Células Secretoras de Insulina/inmunología , Linfocitos T Reguladores/inmunología , Animales , Clostridiales , Diabetes Mellitus Experimental/prevención & control , Diabetes Mellitus Tipo 1/prevención & control , Modelos Animales de Enfermedad , Faecalibacterium prausnitzii , Femenino , Microbioma Gastrointestinal , Humanos , Inmunosupresores , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , ARN Ribosómico 16S/metabolismo , Ruminococcus , Trehalosa/farmacologíaRESUMEN
BACKGROUND: Escherichia coli causes neonatal early-onset sepsis (EOS) that is associated with high mortality and increasing antibiotic resistance. Thus, we estimated the prevalence, antibiotic susceptibility and risk factors for colonization of E. coli in premature infants at birth and characterized the pathogenicity of the isolates. METHODS: A prospective surveillance study was conducted at three Japanese perinatal centers between August 2014 and February 2017. Infants weighing <2 kg and/or at gestational age <35 weeks at birth were enrolled. We screened the mothers and neonates for E. coli colonization. Pulsed-field gel electrophoresis was used to analyze the relatedness between the maternal and neonatal isolates. Virulence factors for the isolates were determined using polymerase chain reaction. RESULTS: We enrolled 421 premature infants born to 382 mothers. The rate of colonization in mothers was 47.6%, comprising 5.9% extended-spectrum beta-lactamase-producing E. coli (ESBL-E) and 20.0% ampicillin-resistant strains. Ten (2.4%) infants exhibited colonization; ESBL-E and ampicillin-resistant strains colonized three and four infants, respectively. Three antibiotic-resistant, strain-positive infants developed EOS. Pulsed-field gel electrophoresis revealed vertical transmission of bacteria in four infants. Multivariate logistic regression analysis revealed that ESBL-E-positive mothers [odds ratio (OR), 19.2; 95% confidence interval (CI), 2.5-145.7)] and vaginal delivery (OR, 9.4; 95% CI, 1.7-50.7) were risk factors for neonatal colonization. The infant isolates possessed numerous virulence factors. CONCLUSIONS: Although the prevalence of E. coli-colonized premature infants at birth was low, the rate of antibiotic resistance and the attack rate for EOS were high. Infants with ESBL-E positive mothers should be closely monitored for EOS.