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BACKGROUND & AIMS: A better understanding of prognostic factors in ulcerative colitis (UC) could improve patient management and reduce complications. We aimed to identify evidence-based predictors for outcomes in pediatric UC, which may be used to optimize treatment algorithms. METHODS: Potential outcomes worthy of prediction in UC were determined by surveying 202 experts in pediatric UC. A systematic review of the literature, with selected meta-analysis, was performed to identify studies that investigated predictors for these outcomes. Multiple national and international meetings were held to reach consensus on evidence-based statements. RESULTS: Consensus was reached on 31 statements regarding predictors of colectomy, acute severe colitis (ASC), chronically active pediatric UC, cancer and mortality. At diagnosis, disease extent (6 studies, N = 627; P = .035), Pediatric Ulcerative Colitis Activity Index score (4 studies, n = 318; P < .001), hemoglobin, hematocrit, and albumin may predict colectomy. In addition, family history of UC (2 studies, n = 557; P = .0004), extraintestinal manifestations (4 studies, n = 526; P = .048), and disease extension over time may predict colectomy, whereas primary sclerosing cholangitis (PSC) may be protective. Acute severe colitis may be predicted by disease severity at onset and hypoalbuminemia. Higher Pediatric Ulcerative Colitis Activity Index score and C-reactive protein on days 3 and 5 of hospital admission predict failure of intravenous steroids. Risk factors for malignancy included concomitant diagnosis of primary sclerosing cholangitis, longstanding colitis (>10 years), male sex, and younger age at diagnosis. CONCLUSIONS: These evidence-based consensus statements offer predictions to be considered for a personalized medicine approach in treating pediatric UC.
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Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/terapia , Adolescente , Niño , Preescolar , Colectomía , Consenso , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas , PronósticoRESUMEN
BACKGROUND & AIMS: A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. METHODS: A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. RESULTS: Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. CONCLUSIONS: These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.
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Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Adolescente , Niño , Preescolar , Consenso , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Pulmonary manifestation (PM) of inflammatory bowel disease (IBD) in children is a rare condition. The exact pathogenesis is still unclear, but several explanatory concepts were postulated and several case reports in children were published. We performed a systematic Medline search between April 1976 and April 2022. Different pathophysiological concepts were identified, including the shared embryological origin, "miss-homing" of intestinal based neutrophils and T lymphocytes, inflammatory triggering via certain molecules (tripeptide proline-glycine-proline, interleukin 25), genetic factors and alterations in the microbiome. Most pediatric IBD patients with PM are asymptomatic, but can show alterations in pulmonary function tests and breathing tests. In children, the pulmonary parenchyma is more affected than the airways, leading histologically mainly to organizing pneumonia. Medication-associated lung injury has to be considered in pulmonary symptomatic pediatric IBD patients treated with certain agents (i.e., mesalamine, sulfasalazine or infliximab). Furthermore, the risk of pulmonary embolism is generally increased in pediatric IBD patients. The initial treatment of PM is based on corticosteroids, either inhaled for the larger airways or systemic for smaller airways and parenchymal disease. In summary, this review article summarizes the current knowledge about PM in pediatric IBD patients, focusing on pathophysiological and clinical aspects.
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Enfermedades Inflamatorias del Intestino , Niño , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Infliximab/uso terapéutico , Pulmón , Mesalamina , ProlinaRESUMEN
BACKGROUND: The influenza season 2017-2018 of the northern hemisphere was the highest since 2001 and was caused predominantly by influenza B virus. METHODS: We performed a retrospective analysis of all patients in a university hospital in northern Germany with laboratory-confirmed influenza during the winter season 2017-2018 and analyzed underlying conditions, complications, and outcome. RESULTS: A total of 272 cases of influenza were diagnosed: 70 influenza A (25.7%), 201 influenza B (73.9%), and 1 co-infection. Of 182 adults, 145 were hospitalized, 73 developed pneumonia, 11 developed myocardial infarction, two a transient ischemic attack, one a stroke, and one perimyocarditis. Eleven of the 145 hospitalized adult patients (7.6%) died, ten of them because of pneumonia. All of them had preexisting diseases. Pneumonia was associated with a mortality of 13.7%. Underlying cardiac insufficiency was correlated with higher mortality (7/51 with versus 4/126 patients without cardiac insufficiency; pâ¯< 0.05). Ninety cases of influenza were diagnosed in 89 children (30 A, 60 B), one child had first influenza B, then influenza A. Twenty-eight children (31%) were hospitalized, 15 children developed one or more complications (lower respiratory tract infections, meningeal irritations, febrile seizures, otitis media, myositis). No child died. Influenza vaccination status was known in 149 adult patients, pneumonia occurred more frequently in non-vaccinated individuals (43/90; 47.8%) than in vaccinated patients (18/59; 30.5%, pâ¯< 0.05). CONCLUSION: Patients with influenza should be monitored for secondary pneumonia and myocardial infarction, and vaccination should be enforced especially in patients with coronary heart disease and cardiac insufficiency.
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Insuficiencia Cardíaca , Gripe Humana , Infarto del Miocardio , Neumonía , Adulto , Niño , Hospitalización , Hospitales Universitarios , Humanos , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Neumonía/complicaciones , Neumonía/epidemiología , Estudios Retrospectivos , Estaciones del AñoRESUMEN
Intramural duodenal hematoma (IDH) in children is a rare complication after esophagogastroduodenoscopy. It is commonly described in patients with additional disorders or risk factors, such as coagulopathy. We present a case of a previously healthy 6-year-old boy with a large obstructing intramural duodenal hematoma and concomitant pancreatitis after an elective esophagogastroduodenoscopy. The patient presented with typical symptoms of an IDH, such as abdominal pain and distension, nausea and vomiting. IDH was diagnosed using ultrasound and magnetic resonance imaging examination. Conservative management with gastric decompression using a nasogastric feeding tube, bowel rest, total parenteral nutrition and analgesia was performed. After three weeks, the patient was discharged from the hospital without any complaints. Interventional management of IDH in pediatric patients with a lack of response to conservative therapy or complicating IDH should be discussed in an interdisciplinary team.
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Enfermedades Duodenales , Ileus , Obstrucción Intestinal , Biopsia , Niño , Enfermedades Duodenales/diagnóstico por imagen , Enfermedades Duodenales/etiología , Hematoma/diagnóstico por imagen , Hematoma/etiología , Humanos , MasculinoRESUMEN
Objectives Measurement of birth length and birth head circumference is part of the newborn assessment. Both measurements aid in distinguishing between proportionate and disproportionate small and large for gestational age newborns. It had been shown that birth weight is related to maternal height and weight. This study aims to analyze birth length and birth head circumference percentiles based on maternal stature. Methods This observational study analyzed birth length and birth head circumference percentiles of 2.3 million newborns stratified by maternal height and weight from the first obstetric assessment. Percentiles were calculated for sex and 22-43 gestational weeks for all infants. Eighteen subgroups based on six maternal height and three weight strata were defined and percentiles calculated from 32 to 42 gestational weeks using GAMLSS package for R. Results Newborns of mothers with height <158 cm and weight <53 kg (short stature) had a rate of preterm birth of 9%, compared to 5% in the tall stature group (height >177 cm, weight >79 kg). Small stature mothers were 1.7 years younger. Birth length differed by several centimeters for the same percentiles between groups of short and tall stature mothers, whereas birth head circumference differed up to 1.2 cm. The largest deviation of birth length was between the 97th percentiles. For male newborns born at term, birth length at the 97th percentile differed by 3.2 cm, at the 50th percentile by 2.7 cm and at the third percentile by 2.5 cm. Conclusions Birth length and birth head circumference are related to maternal height and weight. To more completely assess newborns, the maternal size should be considered.
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Peso al Nacer/fisiología , Estatura/fisiología , Cefalometría/métodos , Tamizaje Neonatal/métodos , Adulto , Correlación de Datos , Femenino , Alemania/epidemiología , Edad Gestacional , Humanos , Recién Nacido , Masculino , Edad Materna , Herencia Materna , Madres , Perinatología/métodos , Perinatología/estadística & datos numéricos , EmbarazoRESUMEN
OBJECTIVES: The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. METHODS: This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. RESULTS: Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. CONCLUSIONS: There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight.
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Peso al Nacer , Estatura , Edad Gestacional , Estatura/etnología , Femenino , Alemania , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Embarazo , Valores de Referencia , Factores SexualesRESUMEN
Autoimmune pathology of acute disseminated encephalomyelitis (ADEM) is generally restricted to the brain. Our objective is to expand the phenotype of ADEM. A four-year-old girl was admitted to the pediatric emergency room of a university medical center five days after a common upper respiratory tract infection. Acute symptoms were fever, leg pain, and headaches. She developed meningeal signs, and her level of consciousness dropped rapidly. Epileptic seizure activity started, and she became comatose, requiring intubation and mechanical ventilation. Serial brain magnetic resonance imaging (MRI) illustrated the fulminant development of ADEM. Treatment escalation with high-dose corticosteroids, immunoglobulins, and plasma exchange did not lead to clinical improvement. On day ten, the patient developed treatment-refractory cardiogenic shock and passed away. The postmortem assessment confirmed ADEM and revealed acute lymphocytic myocarditis, likely explaining the acute cardiac failure. Human metapneumovirus and picornavirus were detected in the tracheal secrete by PCR. Data sources-medical chart of the patient. This case is consistent with evidence from experimental findings of an association of ADEM with myocarditis as a postinfectious systemic autoimmune response, with life-threatening involvement of the brain and heart.
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Encefalomielitis Aguda Diseminada/complicaciones , Miocarditis/etiología , Convulsiones/etiología , Encéfalo/patología , Preescolar , Encefalomielitis Aguda Diseminada/patología , Encefalomielitis Aguda Diseminada/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Infecciones del Sistema Respiratorio/complicacionesRESUMEN
BACKGROUND: We aimed to evaluate the long-term clinical and socioeconomic outcome of structured transition care in adolescents with inflammatory bowel disease (IBD). METHODS: We compared the clinical long-term course of 24 patients with and 11 patients without structured transition care within 24 months before and 24 months after transfer from paediatric to adult health care. Socio-economic parameters and quality of life were assessed by IBD Questionnaire (IBDQ-32) and additional items. Treatment costs were calculated for medication, surgery and hospitalisation. RESULTS: The percentage of transfer group patients with an IBD-related intestinal complication was higher compared to the transition group (64% vs. 21%, p = 0.022). We also found a tendency towards a higher number of IBD-related surgery in the transfer group compared to the transition group (46% vs. 13%, p = 0.077). Transfer group patients received higher mean cumulated doses of radiation compared with the transition group (4.2 ± 5.3 mSv vs. 0.01 ± 0.01 mSv, p = 0.036). Delayed puberty was only noted in the transfer group (27%, p = 0.025). Mean expenditures for surgeries and hospitalisation tended to be lower in the transition group compared to transfer group patients (744 ± 630 vs. 2,691 ± 4,150, p = 0.050). Sexual life satisfaction was significantly higher (p = 0.023) and rates of loose bowel movements tended to be lower (p = 0.053) in the transition group. CONCLUSIONS: Structured transition of adolescents with IBD from paediatric into adult health care can lead to important clinical and economic benefits.
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Procedimientos Quirúrgicos del Sistema Digestivo , Hospitalización/estadística & datos numéricos , Enfermedades Inflamatorias del Intestino , Pubertad Tardía/epidemiología , Calidad de Vida , Transición a la Atención de Adultos , Adolescente , Adulto , Procedimientos Quirúrgicos del Sistema Digestivo/economía , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Alemania/epidemiología , Gastos en Salud/estadística & datos numéricos , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/psicología , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Factores Socioeconómicos , Tiempo , Transición a la Atención de Adultos/economía , Transición a la Atención de Adultos/organización & administraciónRESUMEN
BACKGROUND: Racecadotril is a guideline-recommended option for the treatment of acute diarrhea in children but existing guidelines and previous reviews of the field are based on a small fraction of published evidence. Therefore, we have performed a systematic search for randomized controlled trials evaluating racecadotril as add-on or in comparison to other treatments. METHODS: A search was performed in PubMed, Scopus and Google Scholar without limits about country of origin or reporting language. A meta-analysis was conducted for the five most frequently used efficacy parameters. RESULTS: We have retrieved 58 trials, from nine countries including six in comparison to placebo, 15 in comparison to various active treatments and 41 as add-on to various standard treatments (some multi-armed studies allowing more than one comparison). Trials used 45 distinct efficacy parameters, most often time to cure, % of cured children after 3 days of treatment, global efficacy and number of stools on second day of treatment. Racecadotril was superior to comparator treatments in outpatients and hospitalized patients with a high degree of consistency as confirmed by meta-analysis for the five most frequently used outcome parameters. For instance, it reduced time to cure from 106.2 h to 78.2 h (mean reduction 28.0 h; P < 0.0001 in 24 studies reporting on this parameter). Tolerability of racecadotril was comparable to that of placebo (10.4% vs. 10.6% adverse events incidence) or that of active comparator treatments other than loperamide (2.4% in both groups). CONCLUSIONS: Based on a comprehensive review of the existing evidence, we conclude that racecadotril is more efficacious than other treatments except for loperamide and has a tolerability similar to placebo and better than loperamide. These findings support the use of racecadotril in the treatment of acute diarrhea in children.
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Antidiarreicos/uso terapéutico , Diarrea/tratamiento farmacológico , Tiorfan/análogos & derivados , Enfermedad Aguda , Antidiarreicos/efectos adversos , Niño , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiorfan/efectos adversos , Tiorfan/uso terapéuticoRESUMEN
Background Anthropometric parameters such as birth weight (BW) and adult body height vary between ethnic groups. Ethnic-specific percentile charts are currently being used for the assessment of newborns. However, due to globalization and interethnic families, it is unclear which charts should be used. A correlation between a mother's height and her child's BW (1 cm accounts for a 17 g increase in BW) has been observed. The study aims to test differences in small for gestational age (SGA) and large for gestational age (LGA) rates, employing BW percentile charts based on maternal height between ethnic groups. Methods This retrospective study of 2.3 million mother/newborn pairs analyzed BW, gestational age, sex, maternal height and ethnicity from the German perinatal survey (1995-2000). These data were stratified for maternal height (≤157, 158-163, 164-169, 170-175, ≥176 cm) and region of origin (Germany, Central and Northern Europe, North America, Mediterranean region, Eastern Europe, Middle East and North Africa, and Asia excluding Middle East). Percentile charts were calculated for each maternal height group. Results The average BW and maternal height differ significantly between ethnic groups. On current percentile charts, newborns of taller mothers (≥176 cm) have a low rate of SGA and a high rate of LGA, whereas newborns of shorter mothers (≤157 cm) have a high rate of SGA and a low rate of LGA. When the BW data are stratified based on the maternal height, mothers of similar height from different ethnic groups show similar average BWs, SGA and LGA rates. Conclusion Maternal body height has a greater influence on BW than maternal ethnicity. The use of BW percentile charts for maternal height should be considered.
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Peso al Nacer , Estatura , Parto/etnología , Adulto , Etnicidad , Femenino , Alemania/epidemiología , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Embarazo , Resultado del Embarazo/etnología , Estudios RetrospectivosRESUMEN
We investigated the effects of maternal age, body weight, body height, weight gain during pregnancy, smoking during pregnancy, previous live births and being a single mother on somatic development at birth. We analysed data from the German Perinatal Survey for the years 1998-2000 from eight German federal states. We had available data on 508,926 singleton pregnancies and neonates in total; for 508,893 of which we could classify the neonates as small, appropriate or large for gestational age (SGA, AGA or LGA) based on the 10th and 90th birth weight percentiles. Multivariable regression analyses found statistically significant effects of a clinically relevant magnitude for smoking during pregnancy [odds ratio (OR) 2.9 for SGA births for women smoking >10 cigarettes per day], maternal height (OR 1.4 for SGA births for women <162 cm; OR 1.4 for LGA births for women >172 cm), maternal weight (OR 1.5 for SGA births for women <59 kg; OR 1.9 for LGA births for women >69 kg), weight gain during pregnancy (OR 1.9 for SGA births for women with a weight gain <8 kg; OR 2.0 for LGA births for women with a weight gain >18 kg) and previous live births (OR 2.1 for LGA births for women with one or more previous live births). Maternal age and being a single mother also had significant effects but their magnitude was small. Our analysis confirms the clinically relevant effects of smoking, maternal anthropometric measures and weight gain during pregnancy on neonatal somatic development.
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Peso al Nacer , Desarrollo Fetal , Ganancia de Peso Gestacional , Edad Materna , Fumar , Adulto , Estatura , Femenino , Alemania , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Embarazo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
In patients with juvenile idiopathic arthritis (JIA), increased release of IFN-γ and GM-CSF in cells infiltrating synovial tissue can be a potent driver of monocyte activation. Given the fundamental role of monocyte activation in remodeling the early phases of inflammatory responses, here we analyze the GM-CSF/IFN-γ induced activity of human monocytes in such a situation in vitro and in vivo. Monocytes from healthy donors were isolated and stimulated with GM-CSF ± IFN-γ. Monocyte activation and death were analyzed by flow cytometry, immunofluorescence microscopy, ELISA, and qPCR. T-cell GM-CSF/IFN-γ expression and monocyte function were determined in synovial fluid and peripheral blood from 15 patients with active JIA and 21 healthy controls. Simultaneous treatment with GM-CSF and IFN-γ induces cell death of monocytes. This cell death is partly cathepsin B-associated and has morphological characteristics of necrosis. Monocytes responding to costimulation with strong proinflammatory activities are consequently eliminated. Monocytes surviving this form of hyperactivation retain normal cytokine production. Cathepsin B activity is increased in monocytes isolated from synovial fluid from patients with active arthritis. Our data suggest GM-CSF/IFN-γ induced cell death of monocytes as a novel mechanism to eliminate overactivated monocytes, thereby potentially balancing inflammation and autoimmunity in JIA.
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Artritis Juvenil/inmunología , Muerte Celular , Citocinas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Interferón gamma/farmacología , Monocitos/inmunología , Adolescente , Autoinmunidad , Estudios de Casos y Controles , Catepsina B/metabolismo , Femenino , Citometría de Flujo , Humanos , Activación de Linfocitos , Masculino , Líquido SinovialRESUMEN
Human and murine studies showed that GM-CSF exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF-activated monocytes (GMaMs) in vivo. We used microarray technology and functional assays to characterize GMaMs in vitro and used a mouse model of colitis to study GMaM functions in vivo. GM-CSF activates monocytes to increase adherence, migration, chemotaxis, and oxidative burst in vitro, and primes monocyte response to secondary microbial stimuli. In addition, GMaMs accelerate epithelial healing in vitro. Most important, in a mouse model of experimental T cell-induced colitis, GMaMs show therapeutic activity and protect mice from colitis. This is accompanied by increased production of IL-4, IL-10, and IL-13, and decreased production of IFN-γ in lamina propria mononuclear cells in vivo. Confirming this finding, GMaMs attract T cells and shape their differentiation toward Th2 by upregulating IL-4, IL-10, and IL-13 in T cells in vitro. Beneficial effects of GM-CSF in Crohn's disease may possibly be mediated through reprogramming of monocytes to simultaneously improved bacterial clearance and induction of wound healing, as well as regulation of adaptive immunity to limit excessive inflammation.
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Inmunidad Adaptativa/efectos de los fármacos , Colitis/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Intestino Grueso/efectos de los fármacos , Monocitos/efectos de los fármacos , Traslado Adoptivo , Animales , Adhesión Celular/efectos de los fármacos , Quimiotaxis/efectos de los fármacos , Colitis/inmunología , Colitis/patología , Regulación de la Expresión Génica , Humanos , Interferón gamma/farmacología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-4/farmacología , Intestino Grueso/inmunología , Intestino Grueso/patología , Ratones , Ratones Noqueados , Monocitos/citología , Monocitos/inmunología , Cultivo Primario de Células , Estallido Respiratorio/efectos de los fármacos , Factores de Transcripción SOXF/deficiencia , Factores de Transcripción SOXF/genética , Factores de Transcripción SOXF/inmunología , Transducción de Señal , Linfocitos T/inmunología , Linfocitos T/patología , Linfocitos T/trasplanteRESUMEN
The trefoil factor TFF2 is a member of a tripartite family of small proteins that is produced by the stomach and the colon. Recombinant TFF2, when applied intrarectally in a rodent model of hapten colitis, hastens mucosal healing and reduces inflammatory indexes. Additionally, TFF2 is expressed in immune organs, supporting a potential immunomodulatory and reparative role in the bowel. In this study we confirm that TFF2 is expressed in the colon and is specifically enriched in epithelial cells relative to colonic leukocytes. TFF2-deficient, but not TFF1-deficient, mice exhibit a more severe response to acute or chronic dextran sulfate (DSS)-induced colitis that correlates with a 50% loss of expression of TFF3, the principal colonic trefoil. In addition, the response to acute colitis is associated with altered expression of IL-6 and IL-33, but not other inflammatory cytokines. While TFF2 can reduce macrophage responsiveness and block inflammatory cell recruitment to the colon, the major role in limiting the susceptibility to acute colitis appears to be maintenance of barrier function. Bone marrow transfer experiments demonstrate that leukocyte expression of TFF2 is not sufficient for prevention of colitis induction but, rather, that the gastrointestinal epithelium is the primary source of TFF2. Together, these findings illustrate that epithelial TFF2 is an important endogenous regulator of gut mucosal homeostasis that can modulate immune and epithelial compartments. Because of its extreme stability, even in the corrosive gut lumen, TFF2 is an attractive candidate as an oral therapeutic scaffold for future drug development in the treatment of inflammatory bowel disease.
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Trasplante de Médula Ósea , Colitis/metabolismo , Colon/metabolismo , Citocinas/metabolismo , Sulfato de Dextran , Células Epiteliales/metabolismo , Mediadores de Inflamación/metabolismo , Mucinas/deficiencia , Proteínas Musculares/deficiencia , Péptidos/deficiencia , Pérdida de Peso , Animales , Células Cultivadas , Colitis/inducido químicamente , Colitis/genética , Colitis/inmunología , Colitis/patología , Colitis/prevención & control , Colon/inmunología , Colon/patología , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/patología , Femenino , Interleucina-33 , Interleucina-6/metabolismo , Interleucinas/metabolismo , Leucocitos/inmunología , Leucocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Mucinas/genética , Mucinas/metabolismo , Proteínas Musculares/genética , Péptidos/genética , Péptidos/metabolismo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Factor Trefoil-1 , Factor Trefoil-2 , Factor Trefoil-3RESUMEN
Current literature consolidates the view of Crohn's disease (CD) as a form of immunodeficiency highlighting dysregulation of intestinal innate immunity in the pathogenesis of CD. Intestinal macrophages derived from blood monocytes play a key role in sustaining the innate immune homeostasis in the intestine, suggesting that the monocyte/macrophage compartment might be an attractive therapeutic target for the management of CD. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that also promotes myeloid cell activation, proliferation, and differentiation. GM-CSF has a protective effect in human CD and mouse models of colitis. However, the role of GM-CSF in immune and inflammatory reactions in the intestine is not well defined. Beneficial effects exerted by GM-CSF during intestinal inflammation could relate to modulation of the mucosal barrier function in the intestine, including epithelial cell proliferation, survival, restitution, and immunomodulatory actions. The aim of this review is to summarize potential mechanistic roles of GM-CSF in intestinal innate immune cell homeostasis and to highlight its central role in maintenance of the intestinal immune barrier in the context of immunodeficiency in CD.
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Enfermedad de Crohn/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Inmunidad Innata/inmunología , Inflamación/inmunología , Intestinos/inmunología , Animales , Autoanticuerpos/inmunología , Colitis/patología , Colitis/fisiopatología , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Homeostasis , Humanos , Inmunidad Innata/genética , Inflamación/patología , Mucosa Intestinal/patología , Intestinos/patología , Macrófagos/inmunología , Ratones , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiologíaRESUMEN
BACKGROUND: Hydrogen breath tests are noninvasive procedures frequently applied in the diagnostic workup of functional gastrointestinal disorders. Here, we review hydrogen breath test results and the occurrence of lactose, fructose and sorbitol malabsorption in pediatric patients; and determine the significance of the findings and the outcome of patients with carbohydrate malabsorption. METHODS: We included 206 children (88 male, 118 female, median age 10.7 years, range 3-18 years) with a total of 449 hydrogen breath tests (lactose, n = 161; fructose, n = 142; sorbitol, n = 146) into a retrospective analysis. Apart from test results, we documented symptoms, the therapeutic consequences of the test, the outcome and the overall satisfaction of the patients and families. RESULTS: In total, 204 (46%) of all breath tests were positive. Long-term follow-up data could be collected from 118 patients. Of 79 patients (67%) who were put on a diet reduced in lactose, fructose and/or sorbitol, the majority (92%, n = 73) reported the diet to be strict and only 13% (n = 10) had no response to diet. Most families (96%, n = 113) were satisfied by the test and the therapy. There were only 21 tests (5%) with a borderline result because the criteria for a positive result were only partially met. CONCLUSIONS: Hydrogen breath tests can be helpful in the evaluation of children with gastrointestinal symptoms including functional intestinal disorders. If applied for a variety of carbohydrates but only where indicated, around two-third of all children have positive results. The therapeutic consequences are successfully relieving symptoms in the vast majority of patients.
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Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/metabolismo , Fructosa/metabolismo , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/metabolismo , Hidrógeno/análisis , Hidrógeno/metabolismo , Lactosa/metabolismo , Síndromes de Malabsorción/diagnóstico , Síndromes de Malabsorción/metabolismo , Sorbitol/metabolismo , Adolescente , Pruebas Respiratorias , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: The gut is an environment in which the immune system closely interacts with a vast number of foreign antigens, both inert such as food and alive, from the viral, bacterial, fungal and protozoal microbiota. Within this environment, germinal centres, which are microanatomical structures where B cells affinity-mature, are chronically present and active. MAIN BODY: The functional mechanism by which gut-associated germinal centres contribute to gut homeostasis is not well understood. Additionally, the role of T cells in class switching to immunoglobulin A and the importance of B cell affinity maturation in homeostasis remains elusive. Here, we provide a brief overview of the dynamics of gut-associated germinal centres, T cell dependency in Immunoglobulin A class switching, and the current state of research regarding the role of B cell selection in germinal centres in the gut under steady-state conditions in gnotobiotic mouse models and complex microbiota, as well as in response to immunization and microbial colonization. Furthermore, we briefly link those processes to immune system maturation and relevant diseases. CONCLUSION: B cell response at mucosal surfaces consists of a delicate interplay of many dynamic factors, including the microbiota and continuous B cell influx. The rapid turnover within gut-associated germinal centres and potential influences of an early-life window of immune system imprinting complicate B cell dynamics in the gut.
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BACKGROUND: The number of children and adolescents with inflammatory bowel disease (IBD) is increasing. Many chronically ill children and adolescents have low health literacy. Patient empowerment (PE) enables positive changes and control over one's disease through specific activities, information, and counseling. The CEDNA (IBD Needs Assessment) Survey aimed to provide the necessary data to improve PE in pediatric IBD (PIBD). METHODS: Questionnaires were distributed to adolescent IBD patients and parents of children and adolescents with IBD throughout Germany. The answers were given anonymously. Based on the available data, a subgroup analysis was conducted in relation to the age of the patients and the period since diagnosis. For the parents' responses, the same age groups were analyzed for comparison with the patients' responses. RESULTS: From October 2021 to April 2022, 2810 questionnaires were distributed and 1158 questionnaires were completed (n = 708 parents [61.1%], n = 450 patients [38.9%]). The results indicate that health literacy in children with IBD is low. Significant gaps in knowledge of important IBD topics were identified, and a comparison of responses regarding preferred methods and timing of obtaining information revealed differences between patient and parent preferences. The greatest need for knowledge on IBD topics was found in the group of 16-17-year-old patients on transition (n = 214, 31.8%) and in the group of patients diagnosed 1-2 years ago on the causes of IBD (n = 288, 17.4%). The willingness to seek advice was unexpectedly low. CONCLUSIONS: The analysis of all findings according to the patient's age structure and duration since diagnosis can be used to enable age-appropriate communication at certain stages of the disease. This tailored information should increase patients' health literacy, improve their management of the disease, and reduce the burden on their families.
RESUMEN
[This corrects the article DOI: 10.3389/fped.2023.1170563.].