In the epidemiologic context of maternal obesity and type 2 diabetes(T2D),the incidence of gestational diabetes has significantly increased in the last decades.Infants of diabetic mothers are prone to various neonatal...In the epidemiologic context of maternal obesity and type 2 diabetes(T2D),the incidence of gestational diabetes has significantly increased in the last decades.Infants of diabetic mothers are prone to various neonatal adverse outcomes,including metabolic and hematologic disorders,respiratory distress,cardiac disorders and neurologic impairment due to perinatal asphyxia and birth traumas,among others.Macrosomia is the most constant consequence of diabetes and its severity is mainly influenced by maternal blood glucose level.Neonatal hypoglycemia is the main metabolic disorder that should be prevented as soon as possible after birth.The severity of macrosomia and the maternal health condition have a strong impact on the frequency and the severity of adverse neonatal outcomes.Pregestational T2 D and maternal obesity significantly increase the risk of perinatal death and birth defects.The high incidence of maternal hyperglycemia in developing countries,associated with the scarcity of maternal and neonatal care,seriously increase the burden of neonatal complications in these countries.展开更多
AIM:To present our experience with tuberculous peritonitis treated in our hospital from 2002-2007. METHODS: We reviewed the medical records of 9 children with tuberculous peritonitis. RESULTS: Nine patients (5 boys, 4...AIM:To present our experience with tuberculous peritonitis treated in our hospital from 2002-2007. METHODS: We reviewed the medical records of 9 children with tuberculous peritonitis. RESULTS: Nine patients (5 boys, 4 girls) of mean age 14.2 years were diagnosed with peritoneal tuberculosis. All patients presented with abdominal distention. Abdominal pain was seen in 55.5% and fever in 44.4% of the patients. Four cases had coexisting pleural effusion and two had pulmonary tuberculosis with parenchymal consolidation. Ultrasonography found ascites with septation in 7 patients. Two patients had only ascites without septation. Ascitic fluid analysis of 8 patients yielded serum-ascite albumin gradients of less than 1.1 gr/dL. Laparoscopy and laparotomy showed that whitish tuberculi were the most common appearance. Adhesions were also seen in three cases. The diagnosis of peritoneal tuberculosis was confirmed histo-pathologically in 7 patients and microbiologically in two. Two patients had been diagnosed by ascitic fluid diagnostic features and a positive response to antituberculous treatment. All patients completed the antituberculous therapy without any complications. CONCLUSION: Tuberculous peritonitis has to be clinically suspected in all patients with slowly progressive abdominal distension, particularly when it is accompanied by fever and pain. Laparoscopy and peritoneal biopsy are still the most reliable, quick and safe methods for the diagnosis of tuberculous peritonitis.展开更多
The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction...The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.展开更多
AIM:To optimize a xeno-free cryopreservation protocol for primary human hepatocytes.METHODS:The demand for cryopreserved hepatocytes is increasing for both clinical and research purposes.Despite several hepatocyte cry...AIM:To optimize a xeno-free cryopreservation protocol for primary human hepatocytes.METHODS:The demand for cryopreserved hepatocytes is increasing for both clinical and research purposes.Despite several hepatocyte cryopreservation protocols being available,improvements are urgently needed.We first compared controlled rate freezing to polystyrene box freezing and did not find any significant change between the groups.Using the polystyrene box freezing,we compared two xeno-free freezing solutions for freezing of primary human hepatocytes:a new medium(STEM-CELLBANKER,CB),which contains dimethylsulphoxide(DMSO) and anhydrous dextrose,both permeating and non-permeating cryoprotectants,and the frequently used DMSO-University of Wisconsin(DMSOUW) medium.The viability of the hepatocytes was assessed by the trypan blue exclusion method as well as a calcein-esterase based live-dead assay before and after cryopreservation.The function of the hepatocytes was evaluated before and after cryopreservation by assessing enzymatic activity of 6 major cytochrome P450 isoforms(CYPs):CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP3A4 and CYP3A7.RESULTS:The new cryoprotectant combination preserved hepatocyte viability significantly better than the standard DMSO-UW protocol(P < 0.01).There was no significant difference in viability estimation between both the trypan blue(TB) and the Live-Dead Assay methods.There was a correlation between viability of fresh hepatocytes and the difference in cell viability between CB and DMSO protocols(r 2 = 0.69) using the TB method.However,due to high within-group variability in the activities of the major CYPs,any statistical between-group differences were precluded.Cryopreservation of human hepatocytes using the cryoprotectant combination was a simple and xeno-free procedure yielding better hepatocyte viability.Thus,it may be a better alternative to the standard DMSO-UW protocol.Estimating CYP activities did not seem to be a relevant way to compare hepatocyte function between different groups due to high normal variability between different liver samples.CONCLUSION:The cryoprotectant combination may be a better alternative to the standard DMSO-UW protocol in primary human hepatocyte cryopreservation.展开更多
This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma(HCC) tissues and its relationship with α-fetoprotein(AFP) in HCC.Immunohistochemistry was used to determine the expression ...This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma(HCC) tissues and its relationship with α-fetoprotein(AFP) in HCC.Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues(n=10),liver cirrhosis tissues(n=20),and primary HCC tissues(n=60).The relationship between β-catenin expression and clinical parameters of HCC was investigated.Real-time PCR and Western blotting were used to detect the m RNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP,and also the m RNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP sh RNA plasmids.The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues.Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues,and such ectopic expression of β-catenin was predominant in HCC tissues.The abnormal expression of β-catenin was correlated with serum AFP levels,cancer cell differentiation and vascular invasion(P〈0.05).Additionally,the increased expression of AFP resulted in the upregulation of β-catenin m RNA and protein levels,while knockdown of AFP with AFP sh RNA led to significantly decreased β-catenin m RNA and protein levels(P〈0.05).It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development.AFP can lead to increased expression of β-catenin,which may account for the poor prognosis of AFP-associated HCC patients.展开更多
Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role o...Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods:FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples.Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4^+T cells.Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4^+T cells.Furthermore,we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T(Tfh)cell polarization and function.Results:Patients with low FOXO1 protein levels were prone to have an advanced tumor stage(P=0.049),higher ECOG ps(P=0.024),the presence of bone marrow invasion(P=0.000),and higher IPI(P=0.035).Additionally,the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group(χ^2=5.346,P=0.021).We also observed that inactivation of FOXO1 increased CD4^+T cell proliferation and altered the survival and cell-cycle progression of CD4^+T cells.Finally,we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.Conclusions:Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL.We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival,and to design appropriate therapeutic strategies.展开更多
In the published article1,an error appeared in Acknowledgments on page 753.We omitted Natural Science Foundation of Guangdong Province from Acknowledgments,and we updated it as below.We apologize for the errors and fo...In the published article1,an error appeared in Acknowledgments on page 753.We omitted Natural Science Foundation of Guangdong Province from Acknowledgments,and we updated it as below.We apologize for the errors and for any confusion it may have caused.展开更多
The coronavirus disease pandemic caught many pediatric hospitals unpreparedand has forced pediatric healthcare systems to scramble as they examine and planfor the optimal allocation of medical resources for the highes...The coronavirus disease pandemic caught many pediatric hospitals unpreparedand has forced pediatric healthcare systems to scramble as they examine and planfor the optimal allocation of medical resources for the highest priority patients.There is limited data describing pediatric intensive care unit (PICU) preparednessand their health worker protections.AIMTo describe the current coronavirus disease 2019 (COVID-19) preparedness effortsamong a set of PICUs within a simulation-based network nationwide.METHODS A cross-sectional multi-center national survey of PICU medical director(s) fromchildren’s hospitals across the United States. The questionnaire was developedand reviewed by physicians with expertise in pediatric critical care, disasterreadiness, human factors, and survey development. Thirty-five children’shospitals were identified for recruitment through a long-established nationalresearch network. The questions focused on six themes: (1) PICU and medicaldirector demographics;(2) Pediatric patient flow during the pandemic;(3)Changes to the staffing models related to the pandemic;(4) Use of personalprotective equipment (PPE);(5) Changes in clinical practice and innovations;and(6) Current modalities of training including simulation.RESULTSWe report on survey responses from 22 of 35 PICUs (63%). The majority of PICUswere located within children’s hospitals (87%). All PICUs cared for pediatricpatients with COVID-19 at the time of the survey. The majority of PICUs (83.4%)witnessed decreases in non-COVID-19 patients, 43% had COVID-19 dedicatedunits, and 74.6% pivoted to accept adult COVID-19 patients. All PICUsimplemented changes to their staffing models with the most common changesbeing changes in COVID-19 patient room assignment in 50% of surveyed PICUsand introducing remote patient monitoring in 36% of the PICU units. Ninety-fivepercent of PICUs conducted training for donning and doffing of enhanced PPE.Even 6 months into the pandemic, one-third of PICUs across the United Statesreported shortages in PPE. The most common training formats for PPE werehands-on training (73%) and video-based content (82%). The most commonconcerns related to COVID-19 practice were changes in clinical protocols andguidelines (50%). The majority of PICUs implemented significant changes in theirairway management (82%) and cardiac arrest management protocols in COVID-19patients (68%). Simulation-based training was the most commonly utilizedtraining modality (82%), whereas team training (73%) and team dynamics (77%)were the most common training objectives.CONCLUSIONSA substantial proportion of surveyed PICUs reported on large changes in theirpreparedness and training efforts before and during the pandemic. PICUsimplemented broad strategies including modifications to staffing, PPE usage,workflow, and clinical practice, while using simulation as the preferred trainingmodality. Further research is needed to advance the level of preparedness,support staff assuredness, and support deep learning about which preparednessactions were effective and what lessons are needed to improve PICU care andstaff protection for the next COVID-19 patient waves.展开更多
CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as wel...CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4+CD25hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4+CD25hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3+ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4+CD25hi FOXP3+ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4+CD25hi cells could contribute to the development of type 1 diabetes.展开更多
Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was cond...Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.展开更多
Bowel preparation is a core issue in colonoscopy,as it is closely related to the quality of the procedure.Patients often find that bowel preparation is the most unpleasant part of the examination.It is widely accepted...Bowel preparation is a core issue in colonoscopy,as it is closely related to the quality of the procedure.Patients often find that bowel preparation is the most unpleasant part of the examination.It is widely accepted that the quality of cleansing must be excellent to facilitate detecting neoplastic lesions.In spite of its importance and potential implications,until recently,bowel preparation has not been the subject of much study.The most commonly used agents are high-volume polyethylene glycol(PEG)electrolyte solution and sodium phosphate.There has been some confusion,even in published meta-analyses,regarding which of the two agents provides better cleansing.It is clear now that both PEG and sodium phosphate are effectivewhen administered with proper timing.Consequently,the timing of administration is recognized as one of the central factors to the quality of cleansing.The bowel preparation agent should be administered,at least in part,a few hours in advance of the colonoscopy.Several low volume agents are available,and either new or modified schedules with PEG that usually improve tolerance.Certain adjuvants can also be used to reduce the volume of PEG,or to improve the efficacy of other agents.Other factors apart from the choice of agent can improve the quality of bowel cleansing.For instance,the effect of diet before colonoscopy has not been completely clarified,but an exclusively liquid diet is probably not required,and a low-fiber diet may be preferable because it improves patient satisfaction and the quality of the procedure.Some patients,such as diabetics and persons with heart or kidney disease,require modified procedures and certain precautions.Bowel preparation for pediatric patients is also reviewed here.In such cases,PEG remains the most commonly used agent.As detecting neoplasia is not the main objective with these patients,less intensive preparation may suffice.Special considerations must be made for patients with inflammatory bowel disease,including safety and diagnostic issues,so that the most adequate agent is chosen.Identifying neoplasia is one of the main objectives of colonoscopy with these patients,and the target lesions are often almost invisible with white light endoscopy.Therefore excellent quality preparation is required to find these lesions and to apply advanced methods such as chromoendoscopy.Bowel preparation for patients with lower gastrointestinal bleeding represents a challenge,and the strategies available are also reviewed here.展开更多
BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive asse...BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.展开更多
Type 1 diabetes mellitus(T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than...Type 1 diabetes mellitus(T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1 DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1 DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1 DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1 DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction.展开更多
BACKGROUND:The Pediatric Infectious Disease Society(PIDS)and Infectious Disease Society of America(IDSA)published an evidence-based guideline for the treatment of uncomplicated communityacquired pneumonia(CAP)in child...BACKGROUND:The Pediatric Infectious Disease Society(PIDS)and Infectious Disease Society of America(IDSA)published an evidence-based guideline for the treatment of uncomplicated communityacquired pneumonia(CAP)in children,recommending aminopenicillins as the first-line therapy.Poor guideline compliance with 10%–50%of patients admitted to the hospital receiving narrow-spectrum antibiotics has been reported.A new clinical practice guideline(CPG)was implemented in our emergency department(ED)for uncomplicated CAP.The aim of this study was to examine baseline knowledge and ED provider prescribing patterns pre-and post-CPG implementation.METHODS:Prior to CPG-implementation,an anonymous case-based survey was distributed to evaluate knowledge of the current PIDS/IDSA guideline.A retrospective chart review of patients treated in the ED for CAP from January 2015 to February 2017 was performed to assess prescribing patterns for intravenous(IV)antibiotics in the ED at Children’s National Health System pre-and post-CPG implementation.RESULTS:ED providers were aware of the PIDS/IDSA guideline recommendations,with 86.4%of survey responders selecting ampicillin as the initial antibiotic of choice.However,only 41.2%of patients admitted to the hospital with uncomplicated CAP pre-CPG received ampicillin(P<0.01).There was no statistically signifi cant increase in ampicillin prescribing post-CPG(P=0.40).CONCLUSIONS:Providers in the ED are aware of the PIDS/IDSA guideline regarding the first-line therapy for uncomplicated CAP;however,this knowledge does not translate into clinical practice.Implementation of a CPG in isolation did not significantly change prescribing patterns for uncomplicated CAP.展开更多
Forkhead box protein P1(FOXP1)is a transcription factor belonging to the forkhead box(FOX)proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain(Bacon and Rappold,2...Forkhead box protein P1(FOXP1)is a transcription factor belonging to the forkhead box(FOX)proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain(Bacon and Rappold,2012).Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system(CNS),while mutations in FOXP1 have been implicated in cognitive abnormalities(Bacon and Rappold, 2012).展开更多
Viral infection is one of the most important causes of myocarditis both in adult and pediatric age. We describe acute myocarditis due to SARS-CoV-2 infection in an otherwise healthy 12-years-old Caucasian boy. He was ...Viral infection is one of the most important causes of myocarditis both in adult and pediatric age. We describe acute myocarditis due to SARS-CoV-2 infection in an otherwise healthy 12-years-old Caucasian boy. He was admitted because of a history of 2 days of fever, dry cough, diarrhea, abdominal pain and fatigue. In spite of a family history of COVID-19 patient strict contact, a first nasopharyngeal swab for SARS-CoV-2 RNA resulted negative. After 4 days, his clinical condition evolved, with the onset of interstitial pneumonia, as documented by chest tomography and tachycardia. Blood analysis showed an NTproBNP and TnT increasing, transthoracic echocardiography revealed normal left ventricle (LV) dimension, altered myocardial texture, diffuse hypokinesis and impaired left ventricular function. A nasopharyngeal swab tested positive for SARS-CoV-2 infection at day 6 after admission. Heart failure conventional treatment associated with heparin, glucocorticoids and Remdesivir were administered with progressive improvement of clinical and instrumental conditions. No residual heart damage was documented during the following 3 monthes cardiological outpatient follow-up. Although COVID-19 infection has a milder course of disease in children than in adults, severe forms of the disease may occur and myocarditis should be carefully considered in the pediatric age.展开更多
Photopheresis has been claimed to have immune-modulat-ing effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on...Photopheresis has been claimed to have immune-modulat-ing effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1-and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-γ and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-γ , IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-γ /IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD 65 was reduced after treatment in the photopheresis group. The IFN-γ /IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation.展开更多
Background Personal genetic predisposition and early life environmental factors are important for the development of childhood asthma.We aimed to search whether egg,milk and mite sensitizations at 0–2 years old are r...Background Personal genetic predisposition and early life environmental factors are important for the development of childhood asthma.We aimed to search whether egg,milk and mite sensitizations at 0–2 years old are risk factors for asthma symptoms at 9–11 years old.Methods A total of 210 wheezer children who had specific immunoglobulin(Ig)E in 2010–2012 were included in the study(followed by pediatric allergy).Patients were divided into non-atopic(group 1,n=157)and atopic patients[groups 2–7,n=53(5 patients were in both group 4 and group 5)]based on sensitizations.Using the International Study of Asthma and Allergy in Childhood questionnaire,current wheeze(CW,2nd question),exercise wheezing(EW,7th question),and dry cough(DC,8th question)were surveyed.Also,parental allergies,eczema at 0–2 years,current eosinophil percentage and total IgE were recorded.Results Eczema was observed as an important risk factor[CW:odds ratio(OR)=2.83,95%confidence interval(CI)=1.54–5.23,P≤0.001;EW:OR=2.71,95%CI=1.33–5.54,P=0.006;DC:OR=3.03,95%CI=1.47–6.25,P=0.003],whereas having no atopic sensitization at 0–2-year-old(group 1)was found as a significant protective factor for asthma at 9–11 years old(CW:OR=0.32,95%CI=0.15–0.70,P=0.004;EW:OR=0.21,95%CI 0.10–0.44,P≤0.001;DC:OR=0.25,95%CI=0.10–0.59,P=0.002).Conclusion Early personal eczema is a significant risk factor for the development of asthma symptoms at 9–11 years old,whereas not having an allergic sensitization at 0–2 years old(group 1)is an important protective factor.展开更多
The composition and the diversity of the gut microbiome play a major role in the health and well-being of humans beginning at birth.The impact of the diet on the structure and the function of the gut microbiome is evi...The composition and the diversity of the gut microbiome play a major role in the health and well-being of humans beginning at birth.The impact of the diet on the structure and the function of the gut microbiome is evident by the changes in the gut microbiome concurrent with the transition from human milk to solid food.Complex oligosaccharides contained in milk are essential nutrients for commensal microbes in the infant gut.The most important commensal bacterium in the infant gut,bifidobacterium,requires a1,2 fucosylated oligosaccharides for growth.Because not all humans are able to secrete a1,2 fucosylated oligosaccharides into milk,the gut microbiome of infants and bifidobacteria,in particular,vary considerably between‘secretors’and‘non-secretors’.A paucity of a1,2 fucosylated oligosaccharides and bifidobacteria in the gut of infants may be associated with poor health.展开更多
文摘In the epidemiologic context of maternal obesity and type 2 diabetes(T2D),the incidence of gestational diabetes has significantly increased in the last decades.Infants of diabetic mothers are prone to various neonatal adverse outcomes,including metabolic and hematologic disorders,respiratory distress,cardiac disorders and neurologic impairment due to perinatal asphyxia and birth traumas,among others.Macrosomia is the most constant consequence of diabetes and its severity is mainly influenced by maternal blood glucose level.Neonatal hypoglycemia is the main metabolic disorder that should be prevented as soon as possible after birth.The severity of macrosomia and the maternal health condition have a strong impact on the frequency and the severity of adverse neonatal outcomes.Pregestational T2 D and maternal obesity significantly increase the risk of perinatal death and birth defects.The high incidence of maternal hyperglycemia in developing countries,associated with the scarcity of maternal and neonatal care,seriously increase the burden of neonatal complications in these countries.
文摘AIM:To present our experience with tuberculous peritonitis treated in our hospital from 2002-2007. METHODS: We reviewed the medical records of 9 children with tuberculous peritonitis. RESULTS: Nine patients (5 boys, 4 girls) of mean age 14.2 years were diagnosed with peritoneal tuberculosis. All patients presented with abdominal distention. Abdominal pain was seen in 55.5% and fever in 44.4% of the patients. Four cases had coexisting pleural effusion and two had pulmonary tuberculosis with parenchymal consolidation. Ultrasonography found ascites with septation in 7 patients. Two patients had only ascites without septation. Ascitic fluid analysis of 8 patients yielded serum-ascite albumin gradients of less than 1.1 gr/dL. Laparoscopy and laparotomy showed that whitish tuberculi were the most common appearance. Adhesions were also seen in three cases. The diagnosis of peritoneal tuberculosis was confirmed histo-pathologically in 7 patients and microbiologically in two. Two patients had been diagnosed by ascitic fluid diagnostic features and a positive response to antituberculous treatment. All patients completed the antituberculous therapy without any complications. CONCLUSION: Tuberculous peritonitis has to be clinically suspected in all patients with slowly progressive abdominal distension, particularly when it is accompanied by fever and pain. Laparoscopy and peritoneal biopsy are still the most reliable, quick and safe methods for the diagnosis of tuberculous peritonitis.
文摘The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.
基金Supported by Grants from VINNMER,Lundin foundation, R&D Funds from Stockholm County and Karolinska Institutet (ALF),and the Swedish Research Council
文摘AIM:To optimize a xeno-free cryopreservation protocol for primary human hepatocytes.METHODS:The demand for cryopreserved hepatocytes is increasing for both clinical and research purposes.Despite several hepatocyte cryopreservation protocols being available,improvements are urgently needed.We first compared controlled rate freezing to polystyrene box freezing and did not find any significant change between the groups.Using the polystyrene box freezing,we compared two xeno-free freezing solutions for freezing of primary human hepatocytes:a new medium(STEM-CELLBANKER,CB),which contains dimethylsulphoxide(DMSO) and anhydrous dextrose,both permeating and non-permeating cryoprotectants,and the frequently used DMSO-University of Wisconsin(DMSOUW) medium.The viability of the hepatocytes was assessed by the trypan blue exclusion method as well as a calcein-esterase based live-dead assay before and after cryopreservation.The function of the hepatocytes was evaluated before and after cryopreservation by assessing enzymatic activity of 6 major cytochrome P450 isoforms(CYPs):CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP3A4 and CYP3A7.RESULTS:The new cryoprotectant combination preserved hepatocyte viability significantly better than the standard DMSO-UW protocol(P < 0.01).There was no significant difference in viability estimation between both the trypan blue(TB) and the Live-Dead Assay methods.There was a correlation between viability of fresh hepatocytes and the difference in cell viability between CB and DMSO protocols(r 2 = 0.69) using the TB method.However,due to high within-group variability in the activities of the major CYPs,any statistical between-group differences were precluded.Cryopreservation of human hepatocytes using the cryoprotectant combination was a simple and xeno-free procedure yielding better hepatocyte viability.Thus,it may be a better alternative to the standard DMSO-UW protocol.Estimating CYP activities did not seem to be a relevant way to compare hepatocyte function between different groups due to high normal variability between different liver samples.CONCLUSION:The cryoprotectant combination may be a better alternative to the standard DMSO-UW protocol in primary human hepatocyte cryopreservation.
文摘This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma(HCC) tissues and its relationship with α-fetoprotein(AFP) in HCC.Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues(n=10),liver cirrhosis tissues(n=20),and primary HCC tissues(n=60).The relationship between β-catenin expression and clinical parameters of HCC was investigated.Real-time PCR and Western blotting were used to detect the m RNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP,and also the m RNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP sh RNA plasmids.The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues.Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues,and such ectopic expression of β-catenin was predominant in HCC tissues.The abnormal expression of β-catenin was correlated with serum AFP levels,cancer cell differentiation and vascular invasion(P〈0.05).Additionally,the increased expression of AFP resulted in the upregulation of β-catenin m RNA and protein levels,while knockdown of AFP with AFP sh RNA led to significantly decreased β-catenin m RNA and protein levels(P〈0.05).It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development.AFP can lead to increased expression of β-catenin,which may account for the poor prognosis of AFP-associated HCC patients.
基金supported by Natural Science Foundation of Fujian Province (Grant No. 2015J01314)
文摘Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods:FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples.Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4^+T cells.Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4^+T cells.Furthermore,we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T(Tfh)cell polarization and function.Results:Patients with low FOXO1 protein levels were prone to have an advanced tumor stage(P=0.049),higher ECOG ps(P=0.024),the presence of bone marrow invasion(P=0.000),and higher IPI(P=0.035).Additionally,the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group(χ^2=5.346,P=0.021).We also observed that inactivation of FOXO1 increased CD4^+T cell proliferation and altered the survival and cell-cycle progression of CD4^+T cells.Finally,we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.Conclusions:Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL.We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival,and to design appropriate therapeutic strategies.
文摘In the published article1,an error appeared in Acknowledgments on page 753.We omitted Natural Science Foundation of Guangdong Province from Acknowledgments,and we updated it as below.We apologize for the errors and for any confusion it may have caused.
文摘The coronavirus disease pandemic caught many pediatric hospitals unpreparedand has forced pediatric healthcare systems to scramble as they examine and planfor the optimal allocation of medical resources for the highest priority patients.There is limited data describing pediatric intensive care unit (PICU) preparednessand their health worker protections.AIMTo describe the current coronavirus disease 2019 (COVID-19) preparedness effortsamong a set of PICUs within a simulation-based network nationwide.METHODS A cross-sectional multi-center national survey of PICU medical director(s) fromchildren’s hospitals across the United States. The questionnaire was developedand reviewed by physicians with expertise in pediatric critical care, disasterreadiness, human factors, and survey development. Thirty-five children’shospitals were identified for recruitment through a long-established nationalresearch network. The questions focused on six themes: (1) PICU and medicaldirector demographics;(2) Pediatric patient flow during the pandemic;(3)Changes to the staffing models related to the pandemic;(4) Use of personalprotective equipment (PPE);(5) Changes in clinical practice and innovations;and(6) Current modalities of training including simulation.RESULTSWe report on survey responses from 22 of 35 PICUs (63%). The majority of PICUswere located within children’s hospitals (87%). All PICUs cared for pediatricpatients with COVID-19 at the time of the survey. The majority of PICUs (83.4%)witnessed decreases in non-COVID-19 patients, 43% had COVID-19 dedicatedunits, and 74.6% pivoted to accept adult COVID-19 patients. All PICUsimplemented changes to their staffing models with the most common changesbeing changes in COVID-19 patient room assignment in 50% of surveyed PICUsand introducing remote patient monitoring in 36% of the PICU units. Ninety-fivepercent of PICUs conducted training for donning and doffing of enhanced PPE.Even 6 months into the pandemic, one-third of PICUs across the United Statesreported shortages in PPE. The most common training formats for PPE werehands-on training (73%) and video-based content (82%). The most commonconcerns related to COVID-19 practice were changes in clinical protocols andguidelines (50%). The majority of PICUs implemented significant changes in theirairway management (82%) and cardiac arrest management protocols in COVID-19patients (68%). Simulation-based training was the most commonly utilizedtraining modality (82%), whereas team training (73%) and team dynamics (77%)were the most common training objectives.CONCLUSIONSA substantial proportion of surveyed PICUs reported on large changes in theirpreparedness and training efforts before and during the pandemic. PICUsimplemented broad strategies including modifications to staffing, PPE usage,workflow, and clinical practice, while using simulation as the preferred trainingmodality. Further research is needed to advance the level of preparedness,support staff assuredness, and support deep learning about which preparednessactions were effective and what lessons are needed to improve PICU care andstaff protection for the next COVID-19 patient waves.
基金supported by the Swedish Child Diabetes Foundationthe Medical Research Council of Southeast Sweden(FORSS-8847).
文摘CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4+CD25hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4+CD25hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3+ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4+CD25hi FOXP3+ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4+CD25hi cells could contribute to the development of type 1 diabetes.
文摘Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.
文摘Bowel preparation is a core issue in colonoscopy,as it is closely related to the quality of the procedure.Patients often find that bowel preparation is the most unpleasant part of the examination.It is widely accepted that the quality of cleansing must be excellent to facilitate detecting neoplastic lesions.In spite of its importance and potential implications,until recently,bowel preparation has not been the subject of much study.The most commonly used agents are high-volume polyethylene glycol(PEG)electrolyte solution and sodium phosphate.There has been some confusion,even in published meta-analyses,regarding which of the two agents provides better cleansing.It is clear now that both PEG and sodium phosphate are effectivewhen administered with proper timing.Consequently,the timing of administration is recognized as one of the central factors to the quality of cleansing.The bowel preparation agent should be administered,at least in part,a few hours in advance of the colonoscopy.Several low volume agents are available,and either new or modified schedules with PEG that usually improve tolerance.Certain adjuvants can also be used to reduce the volume of PEG,or to improve the efficacy of other agents.Other factors apart from the choice of agent can improve the quality of bowel cleansing.For instance,the effect of diet before colonoscopy has not been completely clarified,but an exclusively liquid diet is probably not required,and a low-fiber diet may be preferable because it improves patient satisfaction and the quality of the procedure.Some patients,such as diabetics and persons with heart or kidney disease,require modified procedures and certain precautions.Bowel preparation for pediatric patients is also reviewed here.In such cases,PEG remains the most commonly used agent.As detecting neoplasia is not the main objective with these patients,less intensive preparation may suffice.Special considerations must be made for patients with inflammatory bowel disease,including safety and diagnostic issues,so that the most adequate agent is chosen.Identifying neoplasia is one of the main objectives of colonoscopy with these patients,and the target lesions are often almost invisible with white light endoscopy.Therefore excellent quality preparation is required to find these lesions and to apply advanced methods such as chromoendoscopy.Bowel preparation for patients with lower gastrointestinal bleeding represents a challenge,and the strategies available are also reviewed here.
文摘BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.
文摘Type 1 diabetes mellitus(T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1 DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1 DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1 DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1 DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction.
基金Drs.Rebekah Shaw and Erica Popovsky received protected time for research during their pediatric residency through the Research,Education,Advocacy,and Child Health Care(REACH)program at Children’s National Health System.During the study period,Dr.Andrea Hahn was also funded in part by the National Institute of Health(NIH)National Heart,Lung,and Blood Institute(K12 HL119994).Biostatical support was provided by the Clinical and Translational Science Institute at Children’s National Health System(UL1TR000075)through the NIH National Center for Advancing Translational Sciences.Its contents are solely the responsibility of the authors and do not necessarily represent the offi cial views of the National Center for Advancing Translational Sciences or the National Institutes of Health.
文摘BACKGROUND:The Pediatric Infectious Disease Society(PIDS)and Infectious Disease Society of America(IDSA)published an evidence-based guideline for the treatment of uncomplicated communityacquired pneumonia(CAP)in children,recommending aminopenicillins as the first-line therapy.Poor guideline compliance with 10%–50%of patients admitted to the hospital receiving narrow-spectrum antibiotics has been reported.A new clinical practice guideline(CPG)was implemented in our emergency department(ED)for uncomplicated CAP.The aim of this study was to examine baseline knowledge and ED provider prescribing patterns pre-and post-CPG implementation.METHODS:Prior to CPG-implementation,an anonymous case-based survey was distributed to evaluate knowledge of the current PIDS/IDSA guideline.A retrospective chart review of patients treated in the ED for CAP from January 2015 to February 2017 was performed to assess prescribing patterns for intravenous(IV)antibiotics in the ED at Children’s National Health System pre-and post-CPG implementation.RESULTS:ED providers were aware of the PIDS/IDSA guideline recommendations,with 86.4%of survey responders selecting ampicillin as the initial antibiotic of choice.However,only 41.2%of patients admitted to the hospital with uncomplicated CAP pre-CPG received ampicillin(P<0.01).There was no statistically signifi cant increase in ampicillin prescribing post-CPG(P=0.40).CONCLUSIONS:Providers in the ED are aware of the PIDS/IDSA guideline regarding the first-line therapy for uncomplicated CAP;however,this knowledge does not translate into clinical practice.Implementation of a CPG in isolation did not significantly change prescribing patterns for uncomplicated CAP.
文摘Forkhead box protein P1(FOXP1)is a transcription factor belonging to the forkhead box(FOX)proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain(Bacon and Rappold,2012).Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system(CNS),while mutations in FOXP1 have been implicated in cognitive abnormalities(Bacon and Rappold, 2012).
文摘Viral infection is one of the most important causes of myocarditis both in adult and pediatric age. We describe acute myocarditis due to SARS-CoV-2 infection in an otherwise healthy 12-years-old Caucasian boy. He was admitted because of a history of 2 days of fever, dry cough, diarrhea, abdominal pain and fatigue. In spite of a family history of COVID-19 patient strict contact, a first nasopharyngeal swab for SARS-CoV-2 RNA resulted negative. After 4 days, his clinical condition evolved, with the onset of interstitial pneumonia, as documented by chest tomography and tachycardia. Blood analysis showed an NTproBNP and TnT increasing, transthoracic echocardiography revealed normal left ventricle (LV) dimension, altered myocardial texture, diffuse hypokinesis and impaired left ventricular function. A nasopharyngeal swab tested positive for SARS-CoV-2 infection at day 6 after admission. Heart failure conventional treatment associated with heparin, glucocorticoids and Remdesivir were administered with progressive improvement of clinical and instrumental conditions. No residual heart damage was documented during the following 3 monthes cardiological outpatient follow-up. Although COVID-19 infection has a milder course of disease in children than in adults, severe forms of the disease may occur and myocarditis should be carefully considered in the pediatric age.
文摘Photopheresis has been claimed to have immune-modulat-ing effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1-and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-γ and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-γ , IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-γ /IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD 65 was reduced after treatment in the photopheresis group. The IFN-γ /IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation.
文摘Background Personal genetic predisposition and early life environmental factors are important for the development of childhood asthma.We aimed to search whether egg,milk and mite sensitizations at 0–2 years old are risk factors for asthma symptoms at 9–11 years old.Methods A total of 210 wheezer children who had specific immunoglobulin(Ig)E in 2010–2012 were included in the study(followed by pediatric allergy).Patients were divided into non-atopic(group 1,n=157)and atopic patients[groups 2–7,n=53(5 patients were in both group 4 and group 5)]based on sensitizations.Using the International Study of Asthma and Allergy in Childhood questionnaire,current wheeze(CW,2nd question),exercise wheezing(EW,7th question),and dry cough(DC,8th question)were surveyed.Also,parental allergies,eczema at 0–2 years,current eosinophil percentage and total IgE were recorded.Results Eczema was observed as an important risk factor[CW:odds ratio(OR)=2.83,95%confidence interval(CI)=1.54–5.23,P≤0.001;EW:OR=2.71,95%CI=1.33–5.54,P=0.006;DC:OR=3.03,95%CI=1.47–6.25,P=0.003],whereas having no atopic sensitization at 0–2-year-old(group 1)was found as a significant protective factor for asthma at 9–11 years old(CW:OR=0.32,95%CI=0.15–0.70,P=0.004;EW:OR=0.21,95%CI 0.10–0.44,P≤0.001;DC:OR=0.25,95%CI=0.10–0.59,P=0.002).Conclusion Early personal eczema is a significant risk factor for the development of asthma symptoms at 9–11 years old,whereas not having an allergic sensitization at 0–2 years old(group 1)is an important protective factor.
文摘The composition and the diversity of the gut microbiome play a major role in the health and well-being of humans beginning at birth.The impact of the diet on the structure and the function of the gut microbiome is evident by the changes in the gut microbiome concurrent with the transition from human milk to solid food.Complex oligosaccharides contained in milk are essential nutrients for commensal microbes in the infant gut.The most important commensal bacterium in the infant gut,bifidobacterium,requires a1,2 fucosylated oligosaccharides for growth.Because not all humans are able to secrete a1,2 fucosylated oligosaccharides into milk,the gut microbiome of infants and bifidobacteria,in particular,vary considerably between‘secretors’and‘non-secretors’.A paucity of a1,2 fucosylated oligosaccharides and bifidobacteria in the gut of infants may be associated with poor health.