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BACKGROUND: The development of graft fibrosis after pediatric liver transplantation (PLT) remains a major concern as it can lead to graft failure and ultimately graft loss. Elastography is a non-invasive method to assess liver fibrosis, but its role in the posttransplant setting is unclear. The aim of our study was to evaluate shear wave elastography (SWE) in the assessment of liver fibrosis after PLT, including split-liver recipients. METHODS: We retrospectively analyzed data from PLT recipients who underwent surveillance liver biopsy and concurrent 2D-SWE during the study period from April 2018 to July 2021. Spearman's correlation was used to compare histologic fibrosis stages with liver stiffness measurements (LSM) by 2D-SWE. AUROC analysis was performed to evaluate the performance. One sample t-test was used to compare results with reference values of healthy children. RESULTS: 62 cases were included. 29% showed histologic fibrosis. LSM by 2D-SWE were feasible in all children regardless of age or graft type. There was a significant correlation between LSM and fibrosis stage for all three scoring systems used (Ishak, p = 0.003; METAVIR, p = 0.005; LAF Score, p = 0.003). Patients with a history of biliary complications had increased liver stiffness (p = 0.015). The AUROC of 2D-SWE for predicting significant liver graft fibrosis was 0.81. Liver stiffness after PLT without graft fibrosis was higher than in healthy subjects, but comparable to that in children with chronic liver disease without fibrosis. CONCLUSION: 2D-SWE can reliably detect children with significant liver graft fibrosis, even in split-liver recipients. This study demonstrates the value of a non-invasive tool for fibrosis staging after PLT. 2D-SWE has the potential to improve long-term outcomes after PLT and to reduce the number of surveillance liver biopsies. But elastography is not a substitute for liver biopsy.
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Técnicas de Imagem por Elasticidade , Cirrose Hepática , Transplante de Fígado , Humanos , Técnicas de Imagem por Elasticidade/métodos , Estudos Retrospectivos , Criança , Feminino , Masculino , Cirrose Hepática/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Pré-Escolar , Adolescente , Lactente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/diagnóstico por imagem , Biópsia , Fígado/patologia , Fígado/diagnóstico por imagemRESUMO
BACKGROUND: Pediatric liver transplantations generally represent advanced surgery for selected patients. In case of acute or chronic graft failure, biliary or vessel complications, a retransplantation (reLT) can be necessary. In these situations massive adhesions, critical patient condition or lack of good vessels for anastomosis often are problematic. METHODS: Between 2008 and 2021, 208 pediatric patients received a liver transplantation at our center. Retrospectively, all cases with at least one retransplantation were identified and stored in a database. Indication, intra- and postoperative course and overall survival (OS) were analyzed. RESULTS: Altogether 31 patients (14.9%) received a reLT. In 22 cases only one reLT was done, 8 patients received 2 reLTs and 1 patient needed a fourth graft. Median age for primary transplantation, first, second and third reLT was 14 (range: 1-192 months), 60.5 (range: 1-215 months), 58.5 (range: 14-131 months) and 67 months, respectively. Although biliary atresia (42%) and acute liver failure (23%) represented the main indications for the primary liver transplantation, acute and chronic graft failure (1st reLT: 36%, 2nd reLT: 38%), hepatic artery thrombosis (1st reLT: 29%, 2nd reLT: 25%, 3rd reLT: 100%) and biliary complications (1st reLT: 26%, 2nd reLT: 37%) were the most frequent indications for reLT. OS was 81.8% for patients with 1 reLT, 87.5% with 2 reLTs and 100% with 3 reLTs. CONCLUSION: Pediatric liver retransplantation is possible with a good outcome even after multiple retransplantations in specialized centers. Nevertheless, careful patient and graft selection, as well as good preoperative conditioning, are essential.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Criança , Reoperação , Estudos Retrospectivos , FígadoRESUMO
BACKGROUND: After pediatric split liver transplantation, intra-abdominal loss of domain due to large-for-size left lateral grafts is a frequent problem for fascial closure and potentially leads to reduced liver perfusion and abdominal compartment syndrome. Therefore, delayed fascial closure with the use of temporary silastic meshes and reoperation or alternative fascial bridging procedures are necessary. METHODS: Between March 2019 and October 2021, biologic meshes were used for abdominal wall expansion in 6 cases of pediatric split liver transplantation. These cases were analyzed retrospectively. RESULTS: One male and 5 female children with median age of 6 months (range: 0-57 months) and weight of 6 kg (range: 3.5-22 kg) received a large-for-size left lateral graft. Graft-to-recipient weight ratio (GRWR) was 4.8% (range: 1.5%-8.5%) in median. Biologic mesh implantation for abdominal wall expansion was done in median 7 days (range: 3-11 days) after transplantation when signs of abdominal compartment syndrome with portal vein thrombosis in 3 and of the liver artery in 1 case occurred. In 2 cases, bovine acellular collagen matrix and 4 cases ovine reinforced tissue matrix was used. Median follow-up was 12.5 months (range: 4-28 months) and showed good liver perfusion by sonography and normal corporal development without signs of ventral hernia. One patient died because of fulminant graft rejection and emergency re-transplantation 11 months after the initial transplantation. CONCLUSIONS: Biologic meshes can be used as safe method for abdominal wall expansion to achieve fascial closure in large-for-size liver transplant recipients. Usage for primary fascial closure can be considered in selected patients.
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Parede Abdominal , Produtos Biológicos , Hipertensão Intra-Abdominal , Humanos , Criança , Masculino , Animais , Feminino , Bovinos , Ovinos , Recém-Nascido , Lactente , Pré-Escolar , Parede Abdominal/cirurgia , Estudos Retrospectivos , Fígado/cirurgiaRESUMO
BACKGROUND: Infants can present in the first year of life with excessive, recurrent crying without an apparent illness or failure to thrive. The excessive crying results in a wide variety of problems for infants, parents and health care service. OBJECTIVES: This study aimed at evaluating how often parents of children with excessive crying seek help in the medical and paramedical health care system and which therapies are prescribed. MATERIALS AND METHODS: This study uses data collected within KUNO Kids health study. Families who participated completed questionnaires 4 weeks after birth and answered questions which screened for excessive crying. Families whose child was screened positive completed an additional questionnaire on symptoms, parental management and health care utilization. Data were analysed using descriptive statistics. RESULTS: We received 238 questionnaires from children with excessive crying, 105 fulfilled the modified Wessel criteria. Of these 37 children (36%) were seen by a pediatrician because of crying. 57 (55%) received medications by the pediatrician. 51 (49%) of the parents specified that they also used paramedical therapies due to crying or whining, most often osteopathy. 45 (43%) adapted their own nutrition or their child's nutrition. CONCLUSIONS: Our study shows that parents experience problems in dealing excessive crying. Frequent consultations with pediatricians or use of paramedical therapies are common, demanding additional resources. The parents received different diagnoses for excessive crying. Available drugs like Simeticon, homeopathy or manual therapy are recommended and applied despite largely missing evidence.
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OBJECTIVES: Despite major advances in prevention, sudden infant death syndrome (SIDS) remains an important cause of infant mortality. The aim of our study was to determine actual knowledge and intentions to implement SIDS prevention measures among new mothers and to identify potential knowledge gaps for improved postpartum counselling strategies. METHODS: Data was collected in a standardized interview from participants of the KUNO-Kids birth cohort study before discharge from maternity ward. The mothers did not receive any specific teaching prior to the interview. RESULTS: The majority of 2,526 interviewed mothers were able to actively report important recommendations for safe infant sleep, including the exclusive face-up position. However, 154 mothers (9%) intended to position the newborn face-down sometimes or often. The most frequently envisaged sleeping furniture was a bedside sleeper (n=1,144, 47%), but 2.2% of mothers indicated that the intended default sleeping place for the newborn would be the parents' bed (which is discouraged by the recommendations). For 43% of the infants (n=1,079), mothers planned to have loose objects in the bed and 189 mothers (7%) intended to use a loose blanket. 22% of infants (n=554) will live in a household with a smoker. Multivariate regression showed a significant association of "good knowledge" with maternal age and with not being a single parent, whereas the household size was negatively associated. CONCLUSION: Although the majority of mothers in our birth cohort were aware of many recommendations for safe infant sleep, our data also uncovered weaknesses in SIDS prevention knowledge and point to specific areas with potential for improved counselling.
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Morte Súbita do Lactente , Gravidez , Recém-Nascido , Lactente , Humanos , Feminino , Criança , Estudos Transversais , Estudos de Coortes , Morte Súbita do Lactente/prevenção & controle , Morte Súbita do Lactente/etiologia , Intenção , Sono , Fatores de Risco , Cuidado do Lactente , Decúbito DorsalRESUMO
Inflammasomes and innate immune cells have been shown to contribute to liver injury, thereby activating Kupffer cells, which release several cytokines, including IL-6, IL-1ß, and TNFα. Augmenter of liver regeneration (ALR) is a hepatotropic co-mitogen that was found to have anti-oxidative and anti-apoptotic properties and to attenuate experimental non-alcoholic fatty liver disease (NAFLD) and cholestasis. Additionally, hepatic ALR expression is diminished in patients with NAFLD or cholestasis, but less is known about the mechanisms of its regulation under these conditions. Therefore, we aimed to investigate the role of IL-1ß in ALR expression and to elucidate the molecular mechanism of this regulation in vitro. We found that ALR promoter activity and mRNA and protein expression were reduced upon treatment with IL-1ß. Early growth response protein-1 (Egr-1), an ALR inducer, was induced by IL-1ß but could not activate ALR expression, which may be attributed to reduced Egr-1 binding to the ALR promoter. The expression and nuclear localization of hepatocyte nuclear factor 4 α (HNF4α), another ALR-inducing transcription factor, was reduced by IL-1ß. Interestingly, c-Jun, a potential regulator of ALR and HNF4α, showed increased nuclear phosphorylation levels upon IL-1ß treatment but did not change the expression of ALR or HNF4α. In conclusion, this study offers evidence regarding the regulation of anti-apoptotic and anti-oxidative ALR by IL-1ß through reduced Egr-1 promoter binding and diminished HNF4α expression independent of c-Jun activation. Low ALR tissue levels in NAFLD and cholestatic liver injury may be caused by IL-1ß and contribute to disease progression.
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Colestase , Hepatopatia Gordurosa não Alcoólica , Humanos , Colestase/metabolismo , Citocinas/metabolismo , Interleucinas/metabolismo , Fígado/metabolismo , Regeneração Hepática , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases, ranging from liver steatosis to metabolic dysfunction-associated steatohepatitis (MASH), increasing the risk of developing cirrhosis and hepatocellular carcinoma (HCC). Fibrosis within MASLD is critical for disease development; therefore, the identification of fibrosis-driving factors is indispensable. We analyzed the expression of interleukin 32 (IL-32) and chemokine CC ligand 20 (CCL20), which are known to be linked with inflammation and fibrosis, and for their expression in MASLD and hepatoma cells. RT-PCR, ELISA and Western blotting analyses were performed in both human liver samples and an in vitro steatosis model. IL-32 and CCL20 mRNA expression was increased in tissues of patients with NASH compared to normal liver tissue. Stratification for patatin-like phospholipase domain-containing protein 3 (PNPLA3) status revealed significance for IL-32 only in patients with I148M (rs738409, CG/GG) carrier status. Furthermore, a positive correlation was observed between IL-32 expression and steatosis grade, and between IL-32 as well as CCL20 expression and fibrosis grade. Treatment with the saturated fatty acid palmitic acid (PA) induced mRNA and protein expression of IL-32 and CCL20 in hepatoma cells. This induction was mitigated by the substitution of PA with monounsaturated oleic acid (OA), suggesting the involvement of oxidative stress. Consequently, analysis of stress-induced signaling pathways showed the activation of Erk1/2 and p38 MAPK, which led to an enhanced expression of IL-32 and CCL20. In conclusion, cellular stress in liver epithelial cells induced by PA enhances the expression of IL-32 and CCL20, both known to trigger inflammation and fibrosis.
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Fígado Gorduroso , Hepatócitos , Doenças Metabólicas , Humanos , Carcinoma Hepatocelular/genética , Quimiocina CCL20/genética , Quimiocinas , Hepatócitos/metabolismo , Ligantes , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Ácido Palmítico , Regulação para Cima , Gorduras Insaturadas/metabolismoRESUMO
BACKGROUND: The prevalence of food allergies (FA) in children increased rapidly at the turn of the century. The EuroPrevall study identified Germany as a country with very high prevalence of FA at that time. Using two large German birth cohorts, we provide an update of the status quo 10 years later. METHODS: KUNO Kids and Ulm SPATZ Health studies are two ongoing prospective birth cohorts. Information on FA was obtained by questionnaires at birth and after 6, 12, and 24 months. Univariable and multivariable logistic regression analyses were performed to investigate risk factors during pregnancy, birth, and early childhood. RESULTS: In 1139 and 1006 children from KUNO Kids and SPATZ, the point prevalence of parent-reported FA symptoms at the ages of 1 and 2 years was 13.2% (95% CI: 11.2-15.2) and 13.9% (95% CI: 11.5-17.2) in KUNO Kids. Doctor's diagnosed FA at 1 and 2 years was 2.4% (95% CI: 1.6-3.4) and 2.7% (95% CI: 1.2-4.3) in KUNO Kids and 2.3% (95% CI: 1.3-3.6) and 3% (95% CI: 2.0-4.5) in SPATZ. Cow's milk and citrus fruits were most frequently suspected by parents to cause FA symptoms. Atopy in the child was associated with a higher frequency of FA at any time, whereas atopy in first-degree relatives was only associated with FA at year 1. Smoke exposure during pregnancy was a risk for FA at age 2. CONCLUSION: The prevalence of food allergy seems to have plateaued in the last 10 years in Germany. FA is often suspected by parents but only rarely diagnosed by oral food challenge. Risk factor analysis may help to establish personalized health approaches.
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Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Alérgenos , Animais , Coorte de Nascimento , Bovinos , Pré-Escolar , Feminino , Hipersensibilidade Alimentar/diagnóstico , Humanos , Lactente , Gravidez , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND: Portal vein complications (PVCs) after pediatric liver transplantation (LT) are sometimes asymptomatic, especially in the early phase, and can threaten both the graft and patient's survival. Therefore, the purpose of this study is to analyze the risk factors for portal vein thrombosis (PVT) and portal vein stenosis (PVS) after pediatric LT. METHODS: All pediatric patients (n = 115) who underwent primary LT at Regensburg University Hospital between January 2010 and April 2017 were included in this study. The pre-, intra-, and postoperative parameters of all patients were retrospectively reviewed and risk factors for both PVT and PVS were analyzed. RESULTS: Of the 115 patients, living donor LT was performed on 57 (49.5%) patients, and biliary atresia was the primary diagnosis in 65 patients (56%). After pediatric LT, 9% of patients developed PVT, and 16.5% developed PVS. Patient weight ≤7 kg [odds ratio (OR) 9.35, 95% confidence interval (CI) 1.03-84.9, p = .04] and GRWR >3% (OR 15.4, 95% CI 1.98-129.5, p = .01) were the independent risk factors for the development of PVT and PVS, respectively upon multivariate analysis. The overall patient survival rates at 1, 3, and 5 years were 91%, 90%, and 89%, respectively, and there was no difference in patient survival among those with and without PVCs. CONCLUSIONS: Pediatric patients with body weight <7 kg and/or receiving a graft with GRWR >3% may develop PVCs and so require certain surgical modifications, close follow-up, and prophylactic anticoagulant therapy following transplant.
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Transplante de Fígado , Trombose Venosa , Criança , Constrição Patológica/complicações , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Veia Porta/cirurgia , Estudos Retrospectivos , Trombose Venosa/complicações , Trombose Venosa/etiologiaRESUMO
BACKGROUND: Studies show that parents significantly impact their children's health through their cardiometabolic risk profile and health behavior. There is only little information about the prevalence of cardiometabolic risk factors and lifestyle factors among new parents yet. The aims of this study are therefore to evaluate the prevalences of cardiometabolic risk factors in parents of infants in Germany and to examine their lifestyle and health behavior. METHODS: In the KUNO-Kids health study, an ongoing birth cohort, parents (n = 930 mothers and 769 fathers) were asked about cardiometabolic risk factors (obesity/hypertension/type 2 diabetes mellitus) and lifestyle factors (dietary/sports/smoking habits/alcohol consumption) during the first year after the birth of their children via questionnaires. Chi-square as well as fisher exact tests were conducted to analyse associations between lifestyle factors and cardiometabolic risk factors. RESULTS: 34.2% of mothers and 58.5% of fathers were overweight or obese. In 11.8% of the families, at least one parent suffered from hypertension, in 2.4% from type 2 diabetes mellitus. One year after delivery, 8.5% of mothers were smoking, 6.9% showed a risky alcohol consumption (> 10 g/d). 16.0% of fathers were smoking 4 weeks after childbirth, 10.7% showed risky alcohol consumption (> 20 g/d). 21.6% of mothers carried out sports activity for more than 2 h a week then. Parental hypertension was linked to a higher prevalence of risky alcohol consumption, obesity to a lower prevalence of daily fruits consumption. CONCLUSIONS: Cardiometabolic risk factors were widespread among new parents with obesity and overweight having the highest prevalences. A considerable number of parents also practiced an unhealthy lifestyle showing that there is potential for improvement to promote the healthy development of their children.
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Diabetes Mellitus Tipo 2 , Hipertensão , Criança , Lactente , Feminino , Humanos , Prevalência , Estudos de Coortes , Sobrepeso/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Coorte de Nascimento , Fatores de Risco , Estilo de Vida , Pais , Obesidade/epidemiologia , Hipertensão/epidemiologia , Índice de Massa CorporalRESUMO
BACKGROUND: Appropriate health system utilisation during pregnancy is fundamental for maintaining maternal and child's health. To study the use and determinants of supplementary prenatal screening and diagnostics in Germany this study provides comprehensive data. METHODS: We obtained data from a recently established prospective German birth cohort study, the KUNO Kids Health Study. Analyses are based on Andersen's Behavioural Model of health system use, which distinguishes between predisposing (e.g. country of birth), enabling (e.g. health insurance) and need factors (e.g. at-risk pregnancy). We examined bi- and multivariate association with the use of supplementary prenatal screening and diagnostics using logistic regression. RESULTS: The study has a sample size of 1886 participating mothers. One fifth of the mothers investigated did not use any supplementary prenatal screening or diagnostics. Notably, the chance of using supplementary prenatal screening and diagnostics more than doubled if the pregnant woman had a private health insurance (OR 2.336; 95% CI 1.527-3.573). Higher maternal age (OR 1.038; 95% CI 1.006-1.071) and environmental tobacco smoke exposure (OR 1.465 95% CI 1.071-2.004) increased the use of supplementary prenatal screening and diagnostics. However, regarding need factors only having an at-risk-pregnancy (OR 1.688; 95% CI 1.271-2.241) showed an independent association. CONCLUSION: The important role of the type of health insurance and the relatively small influence of need factors was surprising. Especially with respect to equity in accessing health care, this needs further attention.
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Mães , Diagnóstico Pré-Natal , Estudos Transversais , Feminino , Humanos , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Progressive enlargement of the coronary artery (CA) diameters on serial echocardiography can support diagnosis of Kawasaki's disease (KD) even CA dimensions are within the normal range. METHODS: A single-center, retrospective study compared mean Z-scores of the proximal CA internal diameters in children hospitalized with non-KD febrile illnesses (FCs) with those of KD patients. RESULTS: A total of 223 patients with suspicion of KD have been admitted over a period of 16 years and data were evaluable for 176 children. Distributions for age, sex, and body surface area were similar for both groups. FC had a significantly shorter duration of hospitalization, higher levels of hemoglobin, lower levels of liver transaminases, and segmented neutrophils, respectively. The majority of FC patients (75/82, 91.5%) had normal CA Z-scores (p < 0.001) and only 3 (3.7%) had CA Z-score ≥2.5 standard deviation (SD). In KD, subjects (46/94, 49.5%) had a CA dilation (Z-score ≥2.5 SD) and the maximum CA Z-score (Zmax) was significantly higher compared with FC patients (p < 0.001). On serial echocardiograms, FC patients showed a mild decrease, whereas KD patients developed a significant increase of CA Zmax (p < 0.001). Seven KD patients had a segmental dilation of a CA which has been confirmed by cardiac catheter. In FC, no segmental dilation of any CA was documented by echocardiography. CONCLUSION: This study found that mean CA dimensions in FCs were smaller and did not increase in serial echocardiograms compared with KD patients.
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Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Criança , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/diagnóstico por imagem , Dilatação Patológica , Ecocardiografia , Humanos , Lactente , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: With the start of the vaccination campaign, a new phase in the management of the coronavirus pandemic has begun. Approval and recommendation for COVID-19 vaccination of children followed gradually; to date (4 October 2022), vaccination for children under five years of age has not been approved in Germany. AIM OF THE STUDY: The aim was to investigate how parents' intention to vaccinate their children against COVID-19 developed from May 2020 to February 2021 (from the first to the second wave of the COVID-19 pandemic) and to analyse the determinants of the intention to vaccinate. METHODS: In May 2020, 612 families participating with their children aged 1.5-6 years in the KUNO Kids Health Study completed an online survey (participation rate 51%), and 507 completed the second survey in February 2021. Determinants of the intention to vaccinate were analysed for both time points using univariable and multivariable logistic regression models. RESULTS: While 51% of parents reported wanting their children vaccinated against COVID-19 in May 2020, this proportion decreased to 41% by February 2021. At least at one of the two time points, health literacy and perceived competence regarding protective measures against the virus were significantly positively associated with higher vaccination intentions, while belonging to a risk group and the perception that the political measures were exaggerated were associated with lower vaccination intentions. DISCUSSION: Parents' intention to have their children vaccinated against COVID-19 was low and decreased further from the first to the second wave of the coronavirus pandemic. Attitudinal and competence-related determinants were important at both time points and could be targeted in a future vaccination campaign addressing parents of younger children.
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COVID-19 , Intenção , Criança , Humanos , Pré-Escolar , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Alemanha/epidemiologia , Pais , Vacinação , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Data on cognitive function after pLT are rare, particularly regarding children with cognitive impairment. From 2016 to 2018, we evaluated cognitive function in 36 patients after pLT aged 6-17 years with the WISC IV (at least 1 year after transplantation) and analyzed potential risk factors for cognitive impairment (IQ < 70) by means of retrospective medical data (peri-, intra-, and post-operative factors, and donor and specific organ data of the primary liver transplant) on an exploratory base. At a median age of 9.6 years (range = 6-16.9), 22% of patients were cognitive impaired (IQ < 70; including five untestable patients with severe cognitive impairment). Children tested with the WISC IV scored within the lower normal range but differed significantly from normal population. Strongest associations showed infections at pLT, development of severe sepsis requiring intensive care within the first 6 months after pLT, neurological complications within the first 10 days and the occurrence of CPR during or after pLT, and as early laboratory variables pH value on day 0 after pLT. In our analysis, neither intraoperative factors nor donor-specific factors seemed to influence cognitive outcome. In our small cohort, medical complications before and after pLT but not transplantation itself had an influence on cognitive outcome. As such, children experiencing medical problems before and in the early post-operative phase after pLT should be closely evaluated in larger samples regarding their neurological and psychomotor development during vulnerable phases and should receive early educational support to improve long-term cognitive function.
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Disfunção Cognitiva/etiologia , Transplante de Fígado , Complicações Pós-Operatórias/etiologia , Adolescente , Criança , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Período Perioperatório , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Bile acid synthesis is restricted to hepatocytes and is rate-limited by CYP7A1 (cholesterol 7α hydroxylase). CYP7A1 expression undergoes tight regulation and is repressed after partial hepatectomy to prevent the accumulation of toxic bile acids. Augmenter of Liver Regeneration (ALR) is a hepatotrophic factor shown to support liver regeneration by augmenting cell proliferation and reducing apoptosis. Nevertheless, less is known about ALR's role in protecting hepatocytes from bile acid accumulation and bile acid-induced apoptosis. Therefore, HepG2 and Huh-7 cells were incubated with recombinant human ALR (rALR) and the expression of CYP7A1, bile acid-induced apoptosis as well as potential molecular mechanisms were analyzed. We found that rALR reduces CYP7A1 expression by increasing nuclear NFκB levels. Moreover, rALR reduced glycochenodeoxycholate (GCDC)-induced-apoptosis by decreased expression of pro-apoptotic Bax and enhanced expression of anti-apoptotic Mcl-1, which is regulated by phosphatidylinositol-3-kinase (PI3K)/Akt activation and glycogen synthase kinase-3ß (GSK3ß) phosphorylation. Inhibitors for PI3K/Akt (GSK690693) and GSK3ß (SB415286) confirmed the specificity of rALR treatment for this pathway. In addition, rALR reduces pro-death signaling by decreasing GCDC-induced JNK phosphorylation. Taken all together, rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3ß pathway and inhibition of JNK signaling. Thereby this suggests a new role of ALR in augmenting the process of liver regeneration.
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Apoptose , Ácidos e Sais Biliares/biossíntese , Carcinoma Hepatocelular/terapia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Hepatócitos/citologia , Neoplasias Hepáticas/terapia , Regeneração Hepática , Ácidos e Sais Biliares/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Colesterol 7-alfa-Hidroxilase , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
A COVID-19 vaccine can be an important key for mitigating the spread of the pandemic, provided that it is accepted by a sufficient proportion of the population. This study investigated parents' intention to get vaccinated and to have one's child vaccinated against COVID-19. In May 2020, 612 parents participating with their child in the KUNO-Kids health study completed an online survey. Multivariable logistic regression models were calculated to analyze predictors of intention to vaccinate. Fifty-eight percent of parents intended to get vaccinated against COVID-19, and 51% intended to have their child vaccinated. Significant predictors for the intention to get vaccinated and for having the child vaccinated included stronger parental confidence in one's knowledge about prevention measures and lower beliefs that policy measures were exaggerated.Conclusion: COVID-19 vaccination hesitancy was considerable in our sample of parents in Germany. However, our study revealed some potentially modifiable factors which should be addressed by a comprehensive and tailored communication and education strategy. What is Known? ⢠A COVID-19 vaccine can mitigate the spread of the pandemic. ⢠Many parents are skeptical about vaccinations in general. What is New? ⢠COVID-19 vaccination hesitancy was considerable in our sample of parents from Germany, not only for getting vaccinated but also for having the child vaccinated. ⢠Negative parental attitudes regarding policy measures to contain the pandemic were associated with a lower intention to vaccinate.
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Vacinas contra COVID-19 , COVID-19 , Criança , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Intenção , Pais , SARS-CoV-2 , Inquéritos e Questionários , VacinaçãoRESUMO
Kawasaki disease (KD) is an acute vasculitis predominantly affecting the small arteries of young children. Up to 25% of untreated patients suffer from coronary artery (CA) complications. Early diagnosis and treatment is mandatory in incomplete KD to reduce the risk of coronary involvement. Between 2002 and 2018, 124 patients have been diagnosed suffering from KD at the University Children's Hospital Regensburg (KUNO). We assessed luminal diameters of both CAs normalized as Z-scores by 2D-echocardiography. A total of 94 patients were analyzed. Of them, 31 (33%) were affected by an incomplete form of KD. In 24 children (26%), serial echocardiography was necessary in order to confirm diagnosis. Mean Z-scores for the left main coronary artery (LMCA), right main coronary artery (RMCA), and left anterior descending artery increased significantly between the initial (LMCA 0.79z, RMCA 0.15z, LAD 0.49z) and second (LMCA 1.69z, RMCA 0.99z, LAD 1.69z) examination (p < 0.05).Conclusion:To confirm diagnosis of KD, it might not be necessary to detect dilation or aneurysms. Our observation suggests that patients suspected having KD should be monitored with serial echocardiography in order to detect a possible enlargement of the CA diameters, even if Z-scores are within the normal range. What is Known: ⢠Kawasaki disease (KD) is an acute vasculitis predominantly affecting the small arteries of young children. Up to 25% of untreated patients suffer from coronary artery (CA) complications. ⢠Due to less classic clinical criteria in patients with incomplete KD, the risk for CA pathology is even higher. What is New: ⢠A significant progression of patients' CA Z-scores in serial echocardiographic measurements may be helpful to ensure diagnosis of KD early even if Z-scores are within the normal range. ⢠Twenty-seven patients (90%) with incomplete KD could be diagnosed within 10 days of fever, early enough to prevent significantly higher rates of CA aneurysm.
Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Criança , Pré-Escolar , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Vasos Coronários/diagnóstico por imagem , Dilatação Patológica , Ecocardiografia , Humanos , Lactente , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagemRESUMO
Recent studies showed contrasting findings in morphological changes due to competitive soccer in adolescent players (SP). We present a prospective study in 315 consecutive adolescent (10-14 years) male elite SP and 53 healthy matched active controls (CON). All participants underwent a complete transthoracic two-dimensional echocardiography (TTE). The mean age in SP was 12.8 ± 0.65 years compared to 12.6 ± 0.8 years in CON. For all left ventricular (LV) dimensions, mean Z-score values were higher in SP. There was a significant Z-score increase in interventricular septum diastolic diameter (2.47z vs. 1.62z, p < 0.05), left ventricular posterior wall diastolic and systolic diameter (1.15z vs. 0.47z, p < 0.05 and 1.05z vs. - 0.4z, p < 0.05). Athletes had significant greater LV mass indexed for BSA (94 ± 12 g/m2 vs. 81 ± 13 g/m2, p < 0.05). There was no significant difference in LV function or diameters. Conclusion: Our findings suggest that elite soccer training in adolescent male is a type of sport predominantly related to cardiac resistance remodeling. Adolescent SP may develop supernormal left ventricular wall dimensions (+ 2.0 to + 2.5z). If in SP Z-scores, any LV dimension above + 2.5 is measured, primary or secondary cardiomyopathies should be excluded. What is Known: ⢠Morphological cardiac adaptation in response to exercise depends on the type, duration, and intensity of training. ⢠Morphological and functional changes due to competitive sports (athlete's heart) occur even in pre-adolescent athletes. What is New: ⢠Our findings point out that German elite soccer training in adolescent male (10-14 years of age) is a type of sport predominantly related to cardiac resistance remodeling. ⢠If in an adolescent competitive soccer player any LV dimension Z-score value above + 2.5 is measured, a primary or secondary cardiomyopathy should be excluded.
Assuntos
Futebol , Adolescente , Criança , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Estudos Prospectivos , Função Ventricular EsquerdaRESUMO
BACKGROUND: Seasonal influenza vaccination has been recommended for pregnant women in Germany since 2010. The aim of this study was to examine prevalence and determinants of receipt of provider recommendation for influenza vaccination as well as influenza vaccination uptake during pregnancy. METHODS: We analysed data from the "KUNO Kids Health Study", a prospective birth cohort. During the study period (5th July 2015 to 27th June 2018) data were collected from participating mothers by interview and questionnaire. According to Andersen's behavioural model of health services use potential influencing factors describing the circumstances and characteristics of the mothers and their pregnancies which are potentially affecting whether women receive a recommendation for a vaccination or whether they utilize influenza vaccination were classified into three domains: 'predisposing characteristics', 'enabling resources' and 'need'. Using multivariable logistic regression models odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: As a combined result across three flu seasons, 368 of 1814 (20.3%) women received an influenza vaccination recommendation during pregnancy. Having had a high-risk pregnancy increased the odds of receiving a vaccination recommendation (OR = 1.3; 95% CI = 1.0-1.6; p = 0.045). In contrast, pregnancy onset in summer (OR = 0.7; 95% CI = 0.5-1.0; p = 0.027), autumn (OR = 0.4; 95% CI = 0.3-0.5; p < =0.001) or winter (OR = 0.5; 95% CI = 0.3-0.6; p < =0.001) (compared to spring) as well as mother's birthplace outside Germany (OR = 0.6; 95% CI = 0.4-0.9; p = 0.023) reduced the chance of getting a vaccination recommendation. Two hundred forty-two of one thousand eight hundred sixty-five (13%) women were vaccinated against influenza during pregnancy. Having received a vaccination recommendation was strongly associated with vaccination uptake (OR = 37.8; 95% CI = 25.5-55.9; p < =0.001). Higher health literacy status was also associated with a higher chance of vaccination uptake (OR = 1.7; 95% CI = 1.2-2.6; p = 0.008), whereas pregnancy onset in autumn (compared to spring) reduced the chance (OR = 0.5; 95% CI = 0.3-0.8; p = 0.008). CONCLUSIONS: At 13% the uptake rate of influenza vaccination is low. Having received a recommendation to vaccinate was strongly associated with uptake but only one fifth of all mothers report such a recommendation. Raising awareness in physicians regarding vaccinating during pregnancy seems to be of essential importance to increase vaccine uptake and to prevent influenza-related complications in pregnant women.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Complicações Infecciosas na Gravidez/prevenção & controle , Encaminhamento e Consulta , Vacinação/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Alemanha , Humanos , Gravidez , Cuidado Pré-Natal , Estações do AnoRESUMO
BACKGROUND: The aim of this study was to examine the interaction of a multitude of socio-economic, lifestyle, environmental, psychosocial and birth related determinants and their effect on maternal health four weeks after delivery. METHODS: We used data from a German birth cohort study, the KUNO-Kids health study. Social determinants, as well as the self-rated maternal health and the physical and mental health status of mothers (indicated by means of the SF-12-questionnaire) were assessed through standardized questionnaires and personal interviews right after delivery and four weeks later. Linear regression models were calculated to determine the relationship between influencing factors and health outcomes. RESULTS: 1428 women were included in the analysis. Maternal self-rated health showed significant positive associations with breastfeeding (B (regression coefficient) 2.67; 0.86-4.48 (95% Confidence interval)) and estimating one's child as rather healthy (B 0.27; 0.19-0.34) and negative associations with social and emotional strains (B -3.50; -5.11- -1.88), obesity (B -2.56; -4.69- -0.42), having experienced a C-section (B -1.73; -3.23- -0.23), a positive history of somatic diseases (B -2.14; -3.53- -0.74), parental stress (B -0.39; -0.66- -0.11) and education of more than ten years (B -2.42; -3.95- -0.90). Maternal physical health status showed significant negative associations with age (B -0.13; -0.25- -0.01), employment before maternity leave (B -1.90; -3.59- -0.21), social and emotional strains (B -1.50; -2.67- -0.34), parental stress (B -0.28; -0.45- -0.12), C-section (B -4.06; -5.12- -2.99), having the first child (B -2.03; -3.09- -0.97) and a history of somatic diseases (B -2.00; -2.99- -1.01). Maternal mental health status showed significant positive associations with education of more than 10 years (B 2.27; 0.98-3.56) and a high level of social support (B 1.20; 0.06-2.34), while social and emotional strains (B -4.16; -5.48- -2.84) and parental stress (B -0.70; -0.92- -0.47) were negatively associated. CONCLUSIONS: We identified important protective factors for maternal health four weeks after delivery, such as a high level of social support. However, parental stress and social and emotional strains in particular seem to have a negative influence on maternal health. These findings have public health relevance.