ABSTRACT
Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn's disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.
Subject(s)
Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/therapy , Intestinal Mucosa/pathology , Antigens, CD/metabolism , Apyrase/metabolism , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Cell Death/drug effects , Cellular Microenvironment/drug effects , Child , Cohort Studies , Colon/pathology , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Dipyridamole/pharmacology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression Regulation/drug effects , Genetic Predisposition to Disease , Homeostasis/drug effects , Humans , Immunoglobulin G/blood , Immunologic Memory , Inflammation/pathology , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/genetics , Interferon Type I/metabolism , Macrophages/drug effects , Macrophages/metabolism , Methylprednisolone/pharmacology , Myeloid Cells/drug effects , Myeloid Cells/metabolismABSTRACT
The aim of this study was to improve clinical decision-making for the identification of persistent ectopic pregnancy after linear salpingostomy. The study identified 854 laparoscopic salpingostomies performed between 2011 and 2016; 794 had a human chorionic gonadotrophin (HCG) <10 mIU/ml documented in the electronic medical record within 1 month after surgery ('successes'). Sixty (7%) received either methotrexate or repeat surgery for persistent ectopic pregnancy ('failures'). Five hundred and seventeen, including 46 'failures', had two or more immediate post-operative HCG measurements available. The most clinically useful prediction rule was calculated by dividing the difference between the first and second post-operative HCG values by the first post-operative HCG value (i.e. [HCG1 - HCG2]/HCG1). When this ratio exceeded 0.75, it reliably ruled out persistent ectopic with a negative predictive value = 99%. When this ratio was less than 0.2, it identified persistent ectopics with a positive predictive value = 88%. It appears that this simple arithmetic calculation involving two early post-operative HCG values may allow for efficient triage of patients before post-operative day 5. If validated in prospective studies, this could help minimize the risk, inconvenience and expense of requiring several weeks of frequent follow up to rule in/rule out persistent ectopic pregnancy.
Subject(s)
Biomarkers/blood , Chorionic Gonadotropin/blood , Laparoscopy/adverse effects , Pregnancy, Ectopic/diagnosis , Salpingostomy/adverse effects , Adult , Clinical Decision-Making , Female , Humans , Pregnancy , Pregnancy, Ectopic/blood , Pregnancy, Ectopic/etiology , Retrospective StudiesABSTRACT
Objective We aimed to assess the optimal frequency for changing single-use enteral delivery sets during postoperative enteral feeding in infants with congenital heart disease (CHD).Methods We enrolled 120 CHD infants who were fed using an enteral nutrition pump directly connected to a milk bottle with a single-use enteral delivery set in a four-arm randomized controlled trial (ChiCTR2000039544). Patients were randomized into four groups based on the replacement frequency of the enteral delivery set (6 h, 12 h, 18 h, and 24 h groups). The primary outcome was the percentage of contaminated enteral delivery sets (overgrowth of microbiota and colonization of pathogenic bacteria). Secondary outcomes included evidence of infection, gastrointestinal tolerance, intestinal microflora dysbiosis, and healthcare costs.Results The percentages of microbial overgrowth detected in the 6 h, 12 h, 18 h, and 24 h groups were 6.7%, 30.0%, 46.7%, and 80%, respectively (P < 0.001). Significant differences were observed between the 6 h and 18 h groups (P < 0.001), the 6 h and 24 h groups (P < 0.001), and the 18 h and 24 h groups (P = 0.007). Meanwhile, pathogenic bacterial colonization was detected in 0, 4, 6, and 11 delivery sets in the 6 h, 12 h, 18 h, and 24 h groups, respectively (P = 0.002). No difference in clinical symptoms was found among the four groups. The total cost per patient in the 12 h group and the 18 h group was 340.2 RMB and 226.8 RMB, respectively.Conclusion Taking into consideration both microbial overgrowth and cost-effectiveness, the results of this study indicate that for children receiving continuous enteral feeding following CHD surgery, the optimal frequency for changing the single-use enteral delivery set when formula reconstituted from powder is used is 18 hours.
Subject(s)
Enteral Nutrition , Heart Defects, Congenital , Child , Enteral Nutrition/methods , Gastrointestinal Tract , Heart Defects, Congenital/surgery , Humans , InfantABSTRACT
BACKGROUND: The surface topography index (STI) has great potential in both routine computed tomography (CT) scan and emerging optical imaging systems. However, the diagnostic accuracy and stability of the STI as a deformity severity assessment index has not been fully confirmed. Therefore, the aim of the present study was to determine the diagnostic performance of the STI as a novel deformity severity assessment index for pectus excavatum. METHODS: The present study consisted of 722 chest CT images from a single center. The standard CT index (CTI) and STI were calculated for all patients. The between-group difference and the level of compliance between the CTI and STI was analyzed by t-test and Pearson correlation. The diagnostic value and optimum discriminatory values of the CTI and STI were calculated by a receiver-operating characteristic (ROC) curve and DeLong's test. RESULTS: The distributions of the CTI and STI were similar and showed a slight overlap between the pectus excavatum (PE) and non-PE groups. Both the CTI and STI significantly differed between the 2 groups (P<0.001). The STI demonstrated a strong Pearson correlation with the CTI (r=0.91, 95% confidence interval: 0.88-0.91, P<0.001). The ROC curves showed that STI =1.58 (sensitivity: 0.93, specificity: 0.95) could be considered equivalent to CTI =2.72 (sensitivity: 0.93, specificity: 0.97) as the optimum discriminatory values. DeLong's test showed no significant difference in the ROC curve results between the CTI and STI (Z=0.90, P=0.37). CONCLUSIONS: The STI has comparative discrimination ability in PE diagnosis and deformity severity assessment when used with the standard CTI. The STI as a novel index is not only an ideal evaluation metric of PE deformity but also an objective trait for PE patients just as weight and height for everyone.
ABSTRACT
INTRODUCTION: Hand-foot-and-mouth disease (HFMD) is a paediatric infectious disease that is particularly prevalent in China. Severe HFMDs characterised by neurological involvement are fatal and survivors who have apparently fully recovered might still be afflicted later in life with neurocognitive impairments. Only when a well-designed, prospective cohort study is in place can we develop clinical tools for early warning of neurological involvement and can we obtain epidemiological evidence regarding the lingering effects of the sequelea. METHODS AND ANALYSIS: A prospective, hospital-based cohort study is underway in Guangzhou, China. Clinical data and biosamples from hospitalised children (<14 years of age) with an admission diagnosis of HFMD will be collected to determine risk factors for subsequent neurological involvement. Clinical tools for early detection of severe HFMDs will be developed by integrating clinical and biological information. Questionnaire surveys and neurocognitive assessments will be conducted at discharge and each year in the first 2 years of follow-up and every 2 years afterwards until study participants turn 16 years of age or show no evidence of neurocognitive deficits. The association between childhood enterovirus infection and neurocognitive impairment later in life will be examined. ETHICS AND DISSEMINATION: A written informed consent from parents/guardians is a prerequisite for study entry. The protocol of this study has been approved by the hospital's ethics committee. Data usage follows the rules of the hospital's data oversight committee. Findings of this study will be disseminated through publications in international peer-reviewed journals and will be presented in academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR-EOC-17013293; Pre-results.
Subject(s)
Hand, Foot and Mouth Disease/complications , Neurocognitive Disorders/epidemiology , Adolescent , Animals , Child , Child, Preschool , China/epidemiology , Disease Progression , Female , Humans , Infant , Male , Prevalence , Prospective Studies , Research Design , Risk Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND: Pediatric patients undergoing invasive operations bear extra risk of developing nosocomial infections (NIs). However, epidemiological evidence of the underlying risk factors, which is needed for early prevention, remains limited. METHODS: Using data from the electronic medical records and the NI reporting system of a tertiary pediatric hospital, we conducted a retrospective analysis to identify preoperative and operation-related risk factors for postoperative NIs. Multivariable accelerated failure time models were fitted to select independent risk factors. The performance of these factors in risk stratification was examined by comparing the empirical risks between the model-defined low- and high-risk groups. RESULTS: A total of 18,314 children undergoing invasive operations were included for analysis. After a follow-up period of 154,700 patient-days, 847 postoperative NIs were diagnosed. The highest postoperative NI rate was observed for operations on hemic and lymphatic system. Surgical site infections were the NI type showing the highest overall risk; however, patients were more likely to develop urinary tract infections in the first postoperative week. Older age, higher weight-for-height z-score, longer preoperative ICU stay, preoperative enteral nutrition, same-day antibiotic prophylaxis, and higher hemoglobin level were associated with delayed occurrence of postoperative NIs, while longer preoperative hospitalization, longer operative duration, and higher American Society of Anesthesiologists score showed acceleration effects. Risk stratification based on these factors in an independent patient population was moderate, resulting in a high-risk group in which 72% of the postoperative NIs were included. CONCLUSIONS: Our findings suggest that pediatric patients undergoing invasive operations and at high risk of developing postoperative NIs are likely to be identified using basic preoperative and operation-related risk factors, which together might lead to moderately accurate risk stratification but still provide valuable information to guide early and judicious prevention.
Subject(s)
Cross Infection/epidemiology , Surgical Procedures, Operative/adverse effects , Surgical Wound Infection/epidemiology , Urinary Tract Infections/epidemiology , Child, Preschool , China/epidemiology , Cross Infection/etiology , Female , Follow-Up Studies , Hospitals, Pediatric/statistics & numerical data , Humans , Infant , Male , Models, Biological , Preoperative Period , Retrospective Studies , Risk Assessment/methods , Risk Factors , Surgical Wound Infection/etiology , Tertiary Care Centers/statistics & numerical data , Urinary Tract Infections/etiologyABSTRACT
INTRODUCTION: Successful surgical treatment of congenital heart disease improves neonates' long-term survival and leads to catch-up growth, which however does not occur in part of the patient population for largely undetermined reasons. METHODS AND ANALYSIS: A multicentre, prospective cohort study is being conducted in four paediatric medical institutions in China to collect detailed nutritional, anthropometric and clinical data at perioperative phases and during a 1-year period of follow-up after surgery. The study is expected to recruit approximately 5000 patients by the year of 2023 when the cohort is fully established. The primary endpoint of this study is the occurrence of postoperative catch-up growth, which will be determined in both absolute and relative terms (ie, reduced anthropometric deficits from the reference measures and improved z-scores that have passed the -2 SD cut-offs). Multivariable regression analyses will be performed to identify factors that are statistically significantly associated with the absence of postoperative catch-up growth. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the individual ethics committees of the participating centres (Guangzhou Women and Children's Medical Centre (2008071601), the Children's Hospital of Zhejiang University School of Medicine (2018-IRB-094), Gansu Provincial Maternity and Child-Care Hospital (2019-IRB-01) and Zhengzhou Cardiovascular Hospital (2019012001)). Written informed consent from parents will be obtained before study entry. Findings of this study will be disseminated through publications in international peer-reviewed journals and will be presented in academic conferences.
Subject(s)
Child Development , Heart Defects, Congenital/surgery , China/epidemiology , Clinical Protocols , Female , Heart Defects, Congenital/physiopathology , Humans , Infant , Infant, Newborn , Male , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Severe pectus excavatum (PE) may be concomitant with congenital cystic lung lesions (CCLLs) that also require surgery. It is ideal to correct these two deformities concurrently, but the safety and efficacy of a simultaneous surgical technique remain unknown. METHODS: Between 2007 and 2017, 635 patients with severe PE were admitted at our medical center. Eight patients underwent minimally invasive repair of PE and lobectomy simultaneously. The patient characteristics and operative data were analyzed and compared with another group of patients who underwent lobectomy alone for contemporaneous CCLLs. RESULTS: The severity of PE (mean Haller index 5.70) and CCLLs were confirmed by computed tomography (CT). Simultaneous minimally invasive repair and lobectomy were performed successfully. There were no significant differences in the mean blood loss (14 mL/kg), the mean weaning time from mechanical ventilation (900 minutes) and the mean hospital stay (16 days) (P>0.05). The mean operative time (170 minutes) was extended, as expected (P=0.02). With a mean follow-up of 22 months, the overall cosmetic results were good. CONCLUSIONS: Simultaneous minimally invasive repair and lobectomy appears to be a technically safe and reliable method for the treatment of concurrent PE and CCLLs, although further studies are needed in the long-term follow-up.