Serum proteomic profiling for autism using magnetic bead-assisted matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a pilot study

Background

The pathogenesis of autism spectrum disorders remains elusive and currently there are no diagnostic or predictive biomarkers in autism available. Proteomic profiling has been used in a wide range of neurodevelopmental disorder studies, which could produce deeper perceptions of the molecular bases behind certain disease and potentially becomes useful in discovering biomarkers in autism spectrum disorders.

Methods

Serum samples were collected from autistic children about 3 years old in age (n = 32) and healthy controls (n = 20) in similar age and gender. The samples were identified specific proteins that are differentially expressed by magnetic bead-based pre-fractionation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS).

Results

Eight protein peaks were significantly different in autistic children from the healthy controls (P < 0.0001). The two peaks with the most significant differences were 6428 and 7758 Da in size.

Conclusion

According to differences in serum protein profiles between the autistic children and healthy controls, this study identified a set of differentially expressed proteins those are significant for further evaluation and might function as biomarkers in autism.

     

Conservative antibiotic treatment for acute uncomplicated appendicitis is feasible

Purpose

Appendectomy versus conservative antibiotic treatment (CAT) for children with acute uncomplicated appendicitis (AUA) remains unresolved, with concerns regarding the practicality of CAT. We analyzed our center’s experience with CAT for AUA, using a protocol with strict inclusion, exclusion and treatment criteria.

Methods

Non-randomized, prospective cohort study included all children admitted betwee 2014 and 2016, with clinical and laboratory tests suspicious for AUA. Data collected included clinical signs and symptoms; laboratory, ultrasound and pathology results. Follow-up was conducted through clinic visits, telephone conversations and national registry analysis.

Results

Included in CAT: 362 children, 19 underwent appendectomy within 1–2 days. Overall, 75 were readmitted for recurrent acute appendicitis during 22 months (6–43) follow-up. Thirty were treated successfully with antibiotics a second time. The remaining 45 had appendectomy. Overall, 86.8% underwent CAT with no surgery. Histology of all recurrent AUA revealed no perforations.

Conclusion

We confirm the feasibility of conservative management of AUA in children. A rigorous diagnostic plan with strict inclusion and exclusion criteria will lead to high success rate of CAT with a strong safety profile. CAT does not compete with surgery or render appendectomy unnecessary. It is a safe alternative to surgery in selected cases.

     

Staged imaging pathway for the evaluation of pediatric appendicitis

Purpose

Despite significant radiation exposure involved with computed tomography (CT) in evaluation of pediatric appendicitis, its use is still widespread. The goal of this study was to assess the effect of a staged imaging pathway for appendicitis to significantly decrease CT use while maintaining diagnostic accuracy.

Methods

Chart review was performed for patients evaluated for appendicitis over a 12-month period prior to and after pathway implementation.

Results

There was a significant decrease in CT use as initial imaging after implementation of the pathway; 87.1–13.4 % for evaluations positive for appendicitis (decrease 84.6 %, p < 0.0001) and 82.6–9.2 % for evaluations negative for appendicitis (decrease 88.9 %, p < 0.0001). Use of CT during any point in the evaluation decreased from 91.7 to 25.1 % (decrease 72.6 %, p < 0.0001). The negative appendectomy rate was similar; 5.4 % prior, 4.9 % post (p = 0.955). The missed appendicitis rate did not statistically change; 1.1 % prior, 3.7 % post (p = 0.523). The perforation rate was not statistically altered; 6.5 % prior; 9.8 % post (p = 0.421). 350 less patients underwent CT during the year following the pathway.

Conclusions

The staged imaging pathway resulted in a marked decrease in children exposed to CT without compromising diagnostic accuracy.

     

Pediatric appendicitis with appendicolith often presents with prolonged abdominal pain and a high risk of perforation

Background

Appendicolith can cause appendiceal obstruction and acute appendicitis. Its high prevalence may be related to the high perforation rate in pediatric appendicitis. This study assessed the characteristics of appendicolith and its clinical significance in pediatric appendicitis.

Methods

A retrospective study was performed among children and adolescents younger than 17 years who were preoperatively diagnosed with appendicitis in the pediatric emergency department (ED). A total of 269 patients with a mean age of 9.98 ± 3.37 years were enrolled. Clinical features and contrast-enhanced computed tomography findings were analyzed.

Results

Among the 269 patients, 147 (54.6%) had appendicoliths, with a mean maximal diameter of 5.21 ± 2.34 mm. Compared to the no appendicolith group, the appendicolith group demonstrated more prolonged abdominal pain (≥ 48 hours) before the ED visit (23.1% vs. 11.5%; P = 0.013), clinical features of severe appendicitis (presence of fever, vomiting, positive urine ketone, and increased C-reactive protein), and higher rate of perforation (43.5% vs. 9.8%; P < 0.001). Multivariate risk factor analysis for perforated appendicitis in the appendicolith group revealed that maximal diameter of 5 mm or more in the appendicolith (adjusted odds ratio [aOR] 2.919; 95% CI 1.325–6.428, P = 0.008) and proximal collapse adjacent to the appendicolith (aOR 2.943; 95% CI 1.344–6.443, P = 0.007) were significant.

Conclusions

Pediatric appendicitis with appendicolith often presents with prolonged abdominal pain and severe clinical conditions with a high risk of perforation.

     

A systematic review and individual patient data meta-analysis of published randomized clinical trials comparing early versus interval appendectomy for children with perforated appendicitis

Purpose

Our objective was to perform a meta-analysis on RCTs that compared outcomes in children with perforated appendicitis (PA) who underwent either early appendectomy (EA) or interval appendectomy (IA). We also sought to determine if the presence of an intra-abdominal abscess (IAA) at admission impacted treatment strategy and outcomes.

Methods

We identified two RCTs comparing EA versus IA in children with PA. A meta-analysis was performed using regression models and the overall adverse event rate was analyzed. The treatment effect variation depending on the presence of IAA at admission was also evaluated.

Results

EA significantly reduced the odds of an adverse event (OR 0.28, 95 % CI 0.1–0.77) and an unplanned readmission (OR 0.08, 95 % CI 0.01–0.67), as well as the total charges (79 % of the IA, 95 % CI 63–100) for those who did not have an IAA at admission. In children with an IAA, there was no difference between EA and IA. However, heterogeneity of treatment effect was present regarding IAA at presentation.

Conclusions

While EA appears to improve outcomes in patients without an abscess, the published data support no significant difference in outcomes between EA and IA in patients with an abscess.

     

The non-visualized appendix and secondary signs on ultrasound for pediatric appendicitis in the community hospital setting

Background

Secondary signs of appendicitis on ultrasound may aid with diagnosis in the setting of a non-visualized appendix (NVA). This role has not been shown in the community hospital setting.

Materials and methods

All right lower quadrant ultrasounds performed in children for clinical suspicion of appendicitis over a 5-year period in a single community hospital were evaluated. Secondary signs of inflammation including free fluid, ileus, fat stranding, abscess, and lymphadenopathy were documented. Patients were followed for 1 year for the primary outcome of appendicitis. These data were analyzed to determine the utility of secondary signs in the diagnosis of acute appendicitis when an NVA is reported.

Results

Six hundred and seventeen ultrasounds were reviewed; 470 of these had an NVA. Of NVAs, 47 (10%) of patients were diagnosed with appendicitis. Sensitivity and specificity of having at least one secondary were 38.3% and 80%, respectively. The positive and negative predictive values of having at least one secondary sign were 17.3% and 92%, respectively.

Conclusion

These data suggest that the absence of secondary signs has a strong negative predictive value for appendicitis in the community hospital setting; however, the full utility of secondary signs may be limited in this setting.

     

Imaging in pediatric appendicitis is key to a low normal appendix percentage: a national audit on the outcome of appendectomy for appendicitis in children

Purpose

A laparoscopic approach for emergency appendectomy is increasingly used, in pediatric patients as well. The objective of this study is to audit the current state of diagnostic work-up, surgical techniques and its outcome in children with acute appendicitis.

Methods

A prospective consecutive observational cohort study was carried out in a 2-month study period. All patients under 18 years that were operated for suspected acute appendicitis were included. Primary outcome was the infectious complication rate after open and laparoscopic approach; secondary outcomes were preoperative use of imaging and post-operative predictive value of imaging, normal appendix rate and children with a postoperative ileus.

Results

A total of 541 children were operated for suspected acute appendicitis in 62 Dutch hospitals. Preoperative imaging was used in 98.9% of children. The normal appendix rate was 3.1%. In 523 children an appendectomy was performed. Laparoscopy was used in 61% of the patients and conversion rate was 1.7%. Complicated appendicitis was diagnosed in 29.4% of children. Overall 30-day complication rate was 11.9% and similar after open and laparoscopic. No difference was found in superficial surgical site infections, nor in intra-abdominal abscesses between the open and laparoscopic approach. Complicated appendicitis is an independent risk factor for infectious complications.

Conclusion

The laparoscopic approach is most frequently used, except for young children. Superficial surgical site infections are more frequent after open surgery only in patients with complicated appendicitis. The normal appendix rate is low, most likely because of routine preoperative imaging.

     

Can common serum biomarkers predict complicated appendicitis in children?

Purpose

As appendicitis in children can be managed differently according to the severity of the disease, we investigated whether commonly used serum biomarkers on admission could distinguish between simple and complicated appendicitis.

Methods

Admission white blood cell (WBC), neutrophil (NEU), and C-reactive protein (CRP) levels were analysed by ROC curve, and Kruskal–Wallis and contingency tests. Patients were divided according to age and histology [normal appendix (NA), simple appendicitis (SA), complicated appendicitis (CA)].

Results

Of 1197 children (NA = 186, SA = 685, CA = 326), 7% were <5 years, 55% 5–12, 38% 13–17. CA patients had higher CRP and WBC levels than NA and SA (p < 0.0001). NEU levels were lower in NA compared to SA or CA (p < 0.0001), but were similar between SA and CA (p = 0.6). CA patients had higher CRP and WBC levels than SA patients in 5–12- (p < 0.0001) and 13–17-year groups (p = 0.0075, p = 0.005), but not in <5-year group (p = 0.72, p = 0.81). We found CRP >40 mg/L in 58% CA and 37% SA (p < 0.0001), and WBC >15 × 10⁹/L in 58% CA and 43% SA (p < 0.0001).

Conclusions

Admission CRP and WBC levels may help the clinician predict complicated appendicitis in children older than 5 years of age. Early distinction of appendicitis severity using these tests may guide caregivers in the preoperative decision-making process.

     

Empyema Due to Thoracic Migrating Appendicolith

Background

Retained appendicolith following appendicectomy, and can cause recurrent abscess in the abdomen and retroperitoneum.

Case characteristics

11-yr-old boy who presented with subpulmonic abscess and pneumonia following appendicectomy for perforated appendicitis.

Observations

Thoracotomy revealed a thick walled subpulmonic abscess surrounding an appendicolith along with a rent in the posterolateral aspect of the diaphragm.

Message

In children presenting with pus collections and a history of recent appendicectomy, the possibility of a migrating appendicolith should be considered.

     

Long-term outcome and need of re-operation in gastro-esophageal reflux surgery in children

Background

Fundoplication is considered a mainstay in the treatment of gastro-esophageal reflux. However, the literature reports significant recurrences and limited data on long-term outcome.

Aims

To evaluate our long-term outcomes of antireflux surgery in children and to assess the results of redo surgery.

Methods

We retrospectively analyzed all patients who underwent Nissen fundoplication in 8 consecutive years. Reiterative surgery was indicated only in case of symptoms and anatomical alterations. A follow-up study was carried out to analyzed outcome and patients’ Visick score assessed parents’ perspective.

Results

Overall 162 children were included for 179 procedures in total. Median age at first intervention was 43 months. Comorbidities were 119 (73 %), particularly neurological impairments (73 %). Redo surgery is equal to 14 % (25/179). Comorbidities were risk factors to Nissen failure (p = 0.04), especially children suffering neurological impairment with seizures (p = 0.034). Follow-up datasets were obtained for 111/162 = 69 % (median time: 51 months). Parents’ perspectives were excellent or good in 85 %.

Conclusions

A significant positive impact of redo Nissen intervention on the patient’s outcome was highlighted; antireflux surgery is useful and advantageous in children and their caregivers. Children with neurological impairment affected by seizures represent significant risk factors.

     

Utility of PAS and β-catenin staining in histological categorisation and prediction of prognosis of hepatoblastomas

Aims

The aim of this study was to assess the usefulness of PAS, β-catenin and Ki-67 in categorising hepatoblastomas (HBs) and their significance in predicting prognosis. In addition, we have also documented the various chemotherapy induced histologic changes in HBs.

Method

In this retrospective observational study of 29 cases of hepatoblastomas, 27 cases were considered for statistical analysis, excluding two cases of diagnostic core biopsies. All clinicopathological parameters and follow up data were collected. All HB cases including the mixed epithelial and mesenchymal HBs were classified into two groups: fetal predominant and embryonal predominant type according to the predominant epithelial component. PAS, β-catenin and Ki-67 staining were done and their correlation with histologic subtypes was assessed. Kaplan–Meier survival analysis was performed in relation to histology, PAS, β-catenin and Ki-67 staining characteristics.

Result

Diffuse nuclear staining of β-catenin was significantly more common in embryonal predominant type (p = 0.036), whereas strong PAS positivity was significantly associated with fetal predominant type (p = 0.002). But no significant correlation was seen between histologic type and Ki-67 staining (p = 0.42). Survival analysis showed cases with diffuse PAS positivity, focal nuclear β-catenin staining and low Ki-67 LI had better survival.

Conclusion

PAS is a simple stain and can be utilised in histological categorisation of HB and also predicting its outcome. Nuclear β-catenin staining which is significantly common in embryonal elements in HB predicts shorter survival.

     

Hämorrhagischer Schock im frühen Kindesalter – Besonderheiten der Kreislaufregulation

Background

Acute hemorrhages in neonates and young children can be compensated for a long period of time until a decrease in blood pressure and manifest shock occur.

Objective

To determine the characteristics of the pathophysiology of the circulation in children and to recognize critical signs and symptoms of hemorrhage.

Material and methods

Pathophysiology and discussion of the literature

Results

Shock in neonates and children can be present long before a decrease in blood pressure occurs. It is characterized by tachycardia, tachy(dys)pnea, prolonged capillary refilling time, disorders of consciousness (apathy), disturbance of temperature regulation and reduced urine output. Laboratory markers are metabolic acidosis and elevated lactate and a normocytic anemia earlier than in adults.

Conclusion

In contrast to adults a decrease in blood pressure in neonates and young children is a late sign of shock, whereas normocytic anemia occurs earlier than in adults.

     

Phlegmonous appendicitis in children is characterized by eosinophilia in white blood cell counts

Background

Phlegmonous and complicated appendicitis represent independent entities depending on hereditary immunological mechanisms. However, clinically there are no means to distinguish uncomplicated phlegmonous from complicated appendicitis. The ability to distinguish these two forms of appendicitis is relevant as current attempts are to treat both forms of the disease differently. The aim of the present study was to investigate differences in white blood cell counts (WBCs) in these conditions to identify areas of interest for future molecular studies.

Methods

White blood cell counts of patients aged between 7 and 14 years who underwent appendectomy from January 2008 to June 2016 were investigated with special reference to particular cellular subpopulations.

Results

A total of 647 children were included in the study. Within distinct inflammatory patterns, significant eosinophilia and basophilia were found in phlegmonous inflammation compared with complicated inflammation (0.11?±?0.19?×?10⁹/L vs. 0.046?±?0.104?×?10⁹/L, P?<?0.0001, and 0.033?±?0.031?×?10⁹/L vs. 0.028?±?0.024?×?10⁹/L, P?<?0.001).

Conclusions

Compared with complicated disease, phlegmonous appendicitis seems to depend primarily on eosinophil inflammation. This observation is stable over time and indicates a direction for investigation of underlying genetic prerequisites.

     

Understanding parental refusal of permission for child participation in surgical prospective trials

Purpose

The success of prospective randomized trials relies on voluntary participation, which has been perceived as a barrier for successful trials in children who rely on parental permission. We sought to identify the reasons parents decline child participation to understand potential limitations in the consent process.

Methods

A prospective observational study was conducted in 92 patients asked to participate in prospective randomized trials between 2012 and 2015. Parental reasons for refusal were documented.

Results

The 92 refusals were distributed between studies investigating the management of circumcision, gastroschisis, pectus excavatum, appendicitis, pyloric stenosis, undescended testicles, abdominal abscess and gastroesophageal reflux. Reasons for refusal included preference of treatment path (37 %), inability to follow up (21 %), unspecified resistance to participate in research (18 %), preference to maintain independent surgeon decision (16 %), and desire for historically standard treatment (8 %). Of the families who opted to pursue a specific treatment arm rather than randomization, 35 % had prior experience with that treatment, 32 % had researched the procedure, 18 % wished to pursue the minimal intervention and 15 % did not specify.

Conclusions

Parental preference of therapy is the most common reason for refusal of study participation. This variable could be influenced with more effective explanation of study rationale and existing equipoise.

     

Pediatric Asthma and Food Allergy

Objective

To quantitatively summarize the evidence from observational studies on the relation between pediatric asthma and food allergy.

Methods

A literature search was conducted in Medline and EMBASE (August 2016). Two independent reviewers appraised the studies and extracted the estimates of interest. Methodological quality of the included studies was assessed using National Heart Lung and Blood Institute (NHLBI) Quality Assessment Tools. Data were pooled using random-effects meta-analysis.

Results

A total of 32 relevant studies were identified but only 8 studies met the inclusion criteria. Using random-effect model, food allergy showed strong association with asthma in children (OR = 2.87 [95% CI: 2.05–4.00]; P < 0.0001).

Conclusions

This study suggested that food allergy is associated with an increased risk of asthma in children.

     

Creating diagnostic criteria for perforated appendicitis using cross-sectional imaging

Introduction

Preoperative determination of perforated versus acute appendicitis can be difficult. We compared CT and MRI performance in diagnosing perforated appendicitis, and created diagnostic criteria.

Methods

We retrospectively reviewed all pediatric patients who underwent appendectomy within one day of CT or MRI between 1/1/2013 and 1/16/2016. True diagnosis was determined by pathology report. Findings on CT/MRI were grouped into “hard” findings (abscess, pneumoperitoneum, extruded fecalith, appendiceal wall with visible hole) and “soft” findings (extensive/diffuse inflammation/free fluid, phlegmon). Correlation of white blood cell count (WBC), temperature, peritoneal signs, and symptom duration >72 h with perforation was assessed using logistic regression. Significant correlates were incorporated in clinical criteria.

Results

135 patients underwent appendectomy after CT/MRI. Fifty patients underwent MRI and 85 CT. Using hard and/or soft findings, MRI was 86.7% sensitive and 74.3% specific, compared to 68.4% (p = 0.19) and 92.4% (p = 0.025) for CT. WBC > 15, temperature >38.0 °C, and peritoneal signs predicted perforation. Diagnostic accuracy of MRI was highest using imaging findings alone. Accuracy of CT was improved by mandating at least one of the previous three clinical correlates, resulting in 68.4% sensitivity and 93.9% specificity.

Conclusions

MRI trended toward more sensitive and CT was more specific for complicated appendicitis. CT specificity is improved by our algorithm.

     

Radiation dose associated with CT-guided drain placement for pediatric patients

Background

To date, there are limited radiation dose data on CT-guided procedures in pediatric patients.

Objective

Our goal was to quantify the radiation dose associated with pediatric CT-guided drain placement and follow-up drain evaluations in order to estimate effective dose.

Materials and methods

We searched the electronic medical record and picture archiving and communication system (PACS) to identify all pediatric (<18 years old) CT-guided drain placements performed between January 2008 and December 2013 at our institution. We compiled patient data and radiation dose information from CT-guided drain placements as well as pre-procedural diagnostic CTs and post-procedural follow-up fluoroscopic abscess catheter injections (sinograms). Then we converted dose–length product, fluoroscopy time and number of acquisitions to effective doses using Monte Carlo simulations and age-appropriate conversion factors based on annual quality-control testing.

Results

Fifty-two drainages were identified with mean patient age of 11.0 years (5 weeks to 17 years). Most children had diagnoses of appendicitis (n=23) or inflammatory bowel disease (n=11). Forty-seven patients had diagnostic CTs, with a mean effective dose of 7.3 mSv (range 1.1–25.5 mSv). Drains remained in place for an average of 16.9 days (range 0–75 days), with an average of 0.9 (0–5) sinograms per patient in follow-up. The mean effective dose for all drainages and follow-up exams was 5.3 mSv (0.7–17.1) and 62% (32/52) of the children had effective doses less than 5 mSv.

Conclusion

The majority of pediatric patients who have undergone CT-guided drain placements at our institution have received total radiation doses on par with diagnostic ranges. This information could be useful when describing the dose of radiation to parents and providers when CT-guided drain placement is necessary.

     

Clinical Features and Peripheral Blood T Lymphocyte Subsets in Hand,Foot, and Mouth Disease According to Different Pathogens

Objective

To investigate the changes in lymphocyte subsets that are caused by infection with different pathogens in children with hand, foot, and mouth disease.

Methods

T lymphocyte subsets were measured in the patients’ peripheral blood, and serum, throat swab, and fecal samples were tested for enterovirus.

Results

Fecal and throat swab samples exhibited similar positive detection rates, and were significantly more likely to be positive, compared to serum samples (P < 0.01). The EV71-positive group exhibited significantly lower CD4 + TM cell counts (QR: 1.058), compared to the CD4 + TM cell counts in the CoxA16-positive group (QR: 1.391; P < 0.05).

Conclusions

Throat swab and fecal samples exhibited significantly higher positive detection rates, compared to serum samples. In addition, EV71-infected children exhibited significantly lower CD4+ T-cell counts, compared to CoxA16-infected children, which suggests that EV71 infection may be associated with a poorer prognosis.

     

Age Specific Peak Expiratory Flow Nomogram in Children

Objective

To determine peak flow rate nomogram in children between 5 to 12 y of age in suburban population.

Methods

This was a cross-sectional study randomly done on 5000 healthy school children. Mini-Wright flow meter was used for measurement of peak expiratory flow rate (PEFR). The range of age, weight and height were defined and linear and multiple regression analysis were performed.

Results

Correlation between PEFR and height was more significant and between PEFR and weight was lower. On the basis of height, the regression equation for both sexes were drawn; Boys: PEFR = 3.29 (Height in cm) - 218.38; Girls: PEFR = 3.25 (Height in cm) - 216.49.

Conclusions

Thus, region specific nomograms for PEFR for assessing the severity and monitoring of airway obstruction in relation to age, sex, weight and height of children can be determined.

     

Measuring Brand Awareness as a Component of Eating Habits in Indian Children: The Development of the IBAI Questionnaire

Objective

To develop an instrument that allows one to estimate the Indian children’s brand awareness of alimentary products.

Methods

The IBAI (International Brand Awareness Instrument), an age specific tool composed of 12 sheets with images reporting brand logos of alimentary products, has been adjusted for the Indian context in order to investigate on infants’ cognitive skills of recalling and recognizing. The IBAI was piloted in a sample of 100 children aged from 3 to 10 y and enrolled in New Delhi schools.

Results

Children aged 7–10 y showed an higher brand awareness as compared to those of 3–6 y.

Conclusions

The IBAI instrument may be a component for further analysis of the influence of food marketing on child’s diet, foods’ choices and preferences within the Indian social and cultural macro-context. Findings suggest that children over 6 y are particularly gullible by brands and TV promoted advertising. Prevention through information should, therefore be offered to school aged children and their parents, involving teachers, nutritionists and experts in developmental psychology also.