The role of rapid syndromic diagnostic testing of gastrointestinal pathogens as a clinical decision support tool in a pediatric emergency department.

PURPOSE: This study aimed to investigate the role of rapid syndromic diagnostic testing of gastrointestinal pathogens as a clinical decision support tool in a pediatric emergency department (ED) by comparing clinical decision and patient outcome parameters pre- and post-implementation. METHODS: This was a big data analytical study of children < 18 years old without any underlying diseases, that visited the ED with acute moderate to severe diarrhea during a 34-month period from 2018 to 2022 using Seoul St. Mary's hospital's healthcare corporate data warehouse to retrieve demographic, clinical, and laboratory parameters. Outcome measures pre- and post-implementation of a rapid syndromic multiplex gastrointestinal panel (GI panel) were compared. RESULTS: A total of 4,184 patients' data were included in the analyses. Broad spectrum antibiotics were prescribed at a significantly lower rate to patients presenting with acute infectious diarrhea at discharge from the ED (9.9% vs 15.8%, P < 0.001) as well as upon admission (52.2% vs 66.0%, P < 0.001) during the post-implementation period compared to the pre-implementation period. Although the duration of ED stay was found to be significantly longer (6.5 vs 5.5 h, P < 0.0001), the rate of ED revisit due to persistent or aggravated symptoms was significantly lower (Δ in intercept, ß = -0.027; SE = 0.013; P = 0.041), and the admission rate at follow up after being discharged from the ED shown to be significantly lower during the post-implementation period compared to the pre-implementation period (0.8% vs. 2.1%, P = 0.001, respectively). No significant difference in disease progression was observed (P = 1.000). CONCLUSION: Using the GI panel in the ED was shown to decrease broad spectrum antibiotic prescribing practices and reduce revisits or admission at follow up by aiding clinical decisions and improving patient outcome.

Changes in the Incidence of Intussusception and Infectious Diseases After the COVID-19 Pandemic in Korea.

BACKGROUND: Intussusception refers to the invagination of a part of the intestine into itself. The exact cause for this condition is unknown in most cases. The active implementation of coronavirus disease 2019 (COVID-19) infection control guidelines has reduced the spread of COVID-19 and the incidence of other infectious diseases in children. The current study aimed to identify changes in pediatric intussusception and infectious diseases after the implementation of infection control guidelines and confirm the association between intussusception and contagious diseases. METHODS: We analyzed the electronic medical records of pediatric patients diagnosed with intussusception from seven hospitals in Korea between January 2017 and December 2020. We used open data from the Korea Disease Control and Prevention Agency to investigate changes in infectious diseases over the same period. RESULTS: Altogether, we evaluated 390 children with intussusception. There was a statistically significant decrease in the incidence of monthly visits with intussusception in the COVID-19 period group (9.0 vs. 3.5, P < 0.001). When the monthly incidence of infectious diseases was compared between the pre-COVID-19 and the COVID-19 periods, a statistically significant decrease in respiratory viruses (7979.0 vs. 815.2, P < 0.001), enterovirus infection (262.2 vs. 6.6, P < 0.001), and viral enteritis (916.2 vs. 197.8, P < 0.001) were confirmed in the COVID-19 period. Through interrupted time series analysis, it was confirmed that the incidence of intussusception and viral infectious diseases have drastically decreased since March 2020, when COVID-19 infection control guidelines were actively implemented. CONCLUSION: We confirmed that implementing infection control guidelines during the COVID-19 pandemic resulted in a decrease in intussusception and viral infectious diseases. Through this result, it was possible to indirectly confirm the existing hypothesis that viral infections play a significant role in the pathophysiologic mechanism of intussusception.

Eosinophilic gastroenteritis as a cause of non-Helicobacter pylori, non-gastrotoxic drug ulcers in children.

BACKGROUND: While Helicobacter pylori (H. pylori) ulcers has declined recently, H. pylori-negative and/or gastrotoxic drug-negative peptic ulcers (HNGN-PU) has increased. This study aimed to analyze the etiology of peptic ulcers in children and the differences in clinical, laboratory, endoscopic, and histopathologic findings of peptic ulcers according to etiology, including eosinophilic gastroenteritis (EoGE). METHODS: In total, 255 children (157 boys and 98 girls) with peptic ulcers were recruited. The subjects were categorized into 5 groups according to the etiology of the ulcer: 1) H. pylori infection (n = 51); 2) gastrotoxic drugs (n = 18); 3) idiopathic (n = 144); 4) systemic disease (n = 23); 5) EoGE (n = 19). Clinical data were reviewed and analyzed retrospectively. RESULTS: Age at diagnosis, ulcer recurrence, atopic dermatitis history, white blood cell count, blood eosinophil count, platelet count, serum albumin level, iron level, erythrocyte sedimentation rate, and C-reactive protein level differed significantly among the 5 groups (all p < 0.05). Regarding endoscopic findings, multiple ulcers and gastric mucosal nodularity differed among the 5 groups (all p < 0.05). When comparing the EoGE ulcer group with the others, EoGE group revealed older ages (p = 0.022), higher rates of ulcer recurrence (p = 0.018), atopic dermatitis history (p = 0.001), and both blood and tissue eosinophilia (both p = 0.001). CONCLUSIONS: EoGE ulcers constituted 10.2% of HNGN-PU in pediatric patients. In children with HNGN-PU, peripheral eosinophilia, ulcer recurrence, and atopic dermatitis history might imply EoGE, necessitating thorough investigation of tissue eosinophils during endoscopic biopsy. TRIAL REGISTRATION: A total of 255 children was retrospectively registered between between July 2003 and April 2017.

Fecal Calprotectin as a Useful Non-Invasive Screening Marker for Eosinophilic Gastrointestinal Disorder in Korean Children.

BACKGROUND: Eosinophilic gastrointestinal disorder (EoGID) is an emerging disease condition in Korean children, but its diagnosis requires invasive endoscopic biopsies. Fecal calprotectin (FCal) is a noninvasive biomarker for intestinal inflammation to differentiate organic gastrointestinal diseases from functional abdominal pain disorder. This study aimed to evaluate the diagnostic accuracy of FCal and to determine the optimal cutoff to differentiate EoGID from functional abdominal pain disorder. METHODS: A total of 253 children (122 boys, 131 girls; mean age 12.2 ± 3.6, range 2.9-17.8 years) who underwent endoscopy with biopsies for chronic gastrointestinal symptoms were recruited, except for 38 children diagnosed with inflammatory bowel disease, and divided into EoGID (n = 67) and functional abdominal pain disorder (n = 186). FCal, white blood cell (WBC) counts, eosinophil counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured in all subjects at initial diagnosis. RESULTS: FCal levels weakly correlated with WBC (r = 0.127, P = 0.044) and CRP (r = 0.126, P = 0.040) but not with ESR and eosinophil count. FCal levels were significantly higher in the EoGID group than in the functional abdominal pain disorder group (mean 179.5 ± 242.9 mg/kg vs. 44.3 ± 68.1 mg/kg; P < 0.001), while WBC, ESR, CRP, and eosinophil count did not differ between the two groups (all P > 0.05). An optimal cutoff of FCal 73.2 mg/kg distinguished EoGID from functional abdominal pain disorder with a sensitivity of 50.7% and a specificity of 84.6%. CONCLUSION: FCal is a useful and reliable noninvasive marker for differentiating EoGID from functional abdominal pain disorder in Korean children with chronic gastrointestinal symptoms when optimal cutoffs are applied.

Melanotic neuroectodermal tumor of infancy disseminated by a ventriculoperitoneal shunt and diagnosed from the inguinal sac.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare congenital neoplasm that originates from the neural crest cells, which give rise to the melanocytes of the skin and leptomeninges. We report a case of MNTI with neurocutaneous melanosis of a 28-month-old girl. She was born with hydrocephalus and several large congenital giant nevi. There were no findings except for hydrocephalus, after a ventriculoperitoneal (VP) shunt operation performed when she was 6 months old. She was operated on for a growing inguinal mass at 8 months. The specimen from the inguinal sac was positive for HMB45, vimentin, chromogranin, and neuron-specific enolase. Brain magnetic resonance imaging showed an extensive enhancing extra-axial mass with high signal intensity, along the cerebral spinal fluid space. We report a rare case of MNTI, diagnosed from an inguinal hernia sac, with a disseminated clinical manifestation.

Recurrent lymphadenopathy in children with Kikuchi-Fujimoto disease.

UNLABELLED: Kikuchi-Fujimoto disease (KFD) is characterized by self-limiting regional lymphadenopathy with prolonged fever. Although the reported recurrence rate of KFD is known to be 3-4 %, this rate appears to be higher in our clinical experience, and rates up to 38.5 % have been previously reported. In this retrospective study, we reviewed medical records of children with pathologically confirmed KFD to investigate the factors associated with recurrent KFD. Enrolled children were divided into two groups according to the recurrence of KFD, and clinical and laboratory factors were compared between the two groups. The recurrence of KFD was determined based not on repeated pathologic confirmation but on the presence of clinical febrile lymphadenopathy. A total of 33 children with KFD, 26 boys (78.8 %) and 7 girls (21.2 %), with a median age of 12 years (9 months to 19 years), were enrolled. Thirty-one children (93.9 %) complained of fever, and most of the children (90.9 %) complained of cervical lymphadenopathy. Neutropenia (<1,500/µL) or lymphopenia (<1,500/µL) was observed in 51.5 %. Lactate dehydrogenase level, erythrocyte sedimentation rate, and C-reactive protein level were elevated in 90.9, 96.9, and 54.5 % of children, respectively. Fourteen children (42.4 %) experienced recurrent KFD, including ten children after biopsy and four children before and after biopsy. In a multivariate analysis, a past history of other systemic illnesses (p = 0.013) and a higher absolute lymphocyte count (p = 0.023) were significantly associated with recurrent KFD. These systemic illnesses were chronic idiopathic thrombocytopenic purpura, autoimmune thyroiditis, nephrotic syndrome, perinatal cytomegalovirus infection, and hemophagocytic lymphohistiocytosis. CONCLUSION: Our results suggest that recurrent KFD is more frequent than reported, and recurrent KFD should be considered in children with a history of other systemic illnesses such as immune disorders.

Macrophage activation syndrome in neonatal lupus presenting with fever and rash.

Neonatal lupus can occur in infants born to mother with autoimmune disorders through transplacental auto-antibodies. Clinical manifestations in neonatal lupus include cutaneous lesions and hematologic or hepatobiliary findings resembling those seen in systemic lupus erythematosus. In autoimmune state, macrophage activation syndrome (MAS) represent a critical and potentially fatal complication that can result in mortality if not immediately identified and managed with the appropriate care. Here we present a 33-day-old girl diagnosed with neonatal lupus and serious MAS. She was delivered by a primipara mother who did not exhibit any autoimmune symptoms. The patient visited the hospital due to fever and pancytopenia. Laboratory data were compatible with MAS, including pancytopenia, high level of ferritin, soluble interleukin-2, and decreased natural killer cell activity. In addition, autoimmune study showed positive results for anti-nuclear antibody (ANA), anti-Sjogren syndrome antigen A (SSA), and SSB, The autoimmune study for mother also showed positive results for ANA, anti-SSA, and SSB. The patient recovered after she received high dose steroid and supportive care. Our case indicates that neonatal lupus should be taken into consideration when fever, erythematous skin rash, and pancytopenia are observed in infants, even if their mothers have no prior history of autoimmune conditions.

Life-threatening scrub typhus with hemophagocytosis and acute respiratory distress syndrome in an infant.

Scrub typhus is a rickettsial disease, caused by Orientia tsutsugamushi, which is transmitted via the bite of a chigger. This disease is one of the most important infectious diseases in the Asia-Pacific area; however, a severe infant case has not yet been reported. Here, we present the case of an 8-month-old boy with scrub typhus accompanied by hemophagocytic lymphohistiocytosis (HLH). His rapid course was complicated by acute respiratory distress syndrome (ARDS), status epilepticus and disseminated intravascular coagulation (DIC). He recovered after clarithromycin therapy and intensive supportive care. Although being extremely rare, scrub typhus can be life-threatening in an infant; therefore, physicians in endemic countries should be aware of the necessity for early recognition and prompt treatment of suspected cases.

Risk Factors of Low Bone Mineral Density in Newly Diagnosed Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing worldwide incidence. IBD is frequently diagnosed during childhood in the adolescent period of ongoing growth and development, and it can affect patients' linear growth, puberty, nutrition, and bone health. Therefore, its treatment and monitoring are critical to prevent secondary outcomes. However, few studies have highlighted the association between pediatric IBD and skeletal outcomes in Asian populations. We aimed to identify the prevalence and risk factors for low bone mineral density (BMD) in Korean children and adolescents with newly diagnosed IBD. Patients aged 10-18 years diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) who underwent lumbar spine bone mineral density (LSBMD) and femoral bone mineral density (FBMD) analyses via dual-energy X-ray absorptiometry at the time of IBD diagnosis were included. Low BMD was considered when the age- and sex-matched BMD Z-score was <-1.0. The LSBMD and FBMD Z-scores were correlated with clinical parameters, including general characteristics, anthropometry, and IBD-associated laboratory markers. Regression analyses were performed to identify the risk factors for low BMD. Although the general characteristics between CD (n = 42) and UC (n = 9) groups did not differ, the mean Z-scores of LSBMD and FBMD of the 51 subjects were -0.11 ± 1.24 and -0.58 ± 1.38, respectively. Furthermore, 7.8% and 18% of the study subjects had LSBMD and FBMD Z-scores < -2.0, whereas more than 50% had scores of 0--1.0. Among the clinical factors, body mass index (BMI) Z-score, duration of clinical manifestations, and serum alanine aminotransferase and selenium levels were associated with LSBMD Z-scores in the final multivariate regression analyses. Odds ratios of BMI < -2.0 standard deviation for low LSBMD and FBMD Z-scores were 31.97 and 41.45, respectively. A BMI Z-score < -0.93 was determined as the best cut-off for predicting low BMD. In newly diagnosed pediatric IBD, a substantial number of children are likely to have low BMD in prior to initial treatment while lower BMI, longer duration of clinical manifestation, and higher selenium concentration could affect initial BMD status. Routine bone health surveillance from initial IBD diagnosis throughout the treatment's completion is recommended for preventing the early development of secondary osteoporosis.

Proven Cytomegalovirus Colitis Associated with Dasatinib Administration in Two Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Gastrointestinal (GI) bleeding is a rare adverse event of dasatinib, which is known to be caused by dasatinib-induced colitis, severe thrombocytopenia, and platelet dysfunction. We present two cases of pediatric patients who developed hematochezia during treatment with dasatinib after hematopoietic stem cell transplantation (HSCT). A colonic tissue biopsy was performed to differentiate the cause of GI bleeding. Both patients were diagnosed with proven cytomegalovirus (CMV) colitis, but only one was treated with ganciclovir. The patient who did not receive antiviral therapy experienced recurrent GI bleeding during dasatinib administration, leading to multiple treatment interruptions. During dasatinib therapy after HSCT, patients with GI bleeding and confirmed CMV colitis may benefit from antiviral therapy to reduce interruptions in dasatinib therapy.

Factors associated with hiatal hernia in neurologically impaired children.

BACKGROUND: Hiatal hernia is clinically important because it impairs the protective mechanism that prevents gastroesophageal reflux-induced injury. Diagnosing hiatal hernia is more important in neurologically impaired children because hiatal hernia-induced gastroesophageal reflux often causes severe complications such as aspiration pneumonia or malnutrition. We aimed to evaluate the patient characteristics and early predictors of hiatal hernia in neurologically impaired children. METHODS: We retrospectively investigated 97 neurologically impaired children who underwent esophagogastroduodenoscopy and upper gastrointestinal series between March 2004 and June 2019. Demographic and clinical characteristics, as well as endoscopic and radiological findings, were statistically analyzed. RESULTS: Of the 97 children recruited, 22 (22.7%) had hiatal hernia. When comparing the non-hiatal hernia group with the hiatal hernia group, neurological disease longer than 6 months (odds ratio 10.9, 95% confidence interval 1.2-96.5), wasting (odds ratio 4.6, 95% confidence interval 1.3-16.3), enteral tube feeding (odds ratio 9.2, 95% confidence interval 1.6-53.0), and history of aspiration pneumonia (odds ratio 6.5, 95% confidence interval 1.2-34.5) were identified as early predictors of hiatal hernia. CONCLUSIONS: Timely identification of predictors of developing hiatal hernia in neurologically impaired children is important for early diagnostic confirmation to initiate optimal medical or surgical treatment of hiatal hernia to avoid serious complications such as aspiration pneumonia and malnutrition.

Pelvic radiography as a non-invasive screening tool for hiatal hernia in children with cerebral palsy.

The diagnosis of hiatal hernia (HH), causing severe gastroesophageal reflux disease and complications in children with cerebral palsy (CP) is cumbersome because invasive investigations are required for diagnosis. Hip displacement, one of the most common complications in children with CP, can be diagnosed with a simple pelvic radiograph. This study aimed to evaluate the association between the severity of hip displacement and HH and the diagnostic accuracy of Reimers' hip migration percentage (MP) on pelvic radiography in assessing the presence of HH. A total of 52 children with CP (27 boys, 25 girls; mean age, 6.3 years; range, 0.6-17.4 years) who underwent esophagogastroduodenoscopy, upper gastrointestinal series and pelvic radiography between March 2013 and February 2020 were recruited. Demographic and clinical characteristics, as well as endoscopic and radiological findings, were evaluated and statistically analyzed. HH was defined as ≥ 2 cm proximal displacement of the gastroesophageal junction identified in esophagogastroduodenoscopy or upper gastrointestinal series, and MP was calculated by evaluating the pelvic radiograph. Of the 52 children enrolled in this study, HH was diagnosed in 18 children (34.6%). When the patients were classified and analyzed according to the MP result, HH was observed in 10%, 26.7%, and 70.6% in MP <33%, MP 33%-39%, and MP > 40% groups, respectively (P < .001). The optimal MP cutoff of 36.5% distinguished pediatric CP patients with HH from those without HH with a sensitivity of 78%, specificity of 68%, a positive predictive value of 56.0%, and a negative predictive value of 85.2%, respectively. The application of MP and the severity of hip displacement, which can be easily measured by simple radiography, may be useful and reliable in screening for detecting HH in children with CP. Retrospectively registered. This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-2007-627-106).

Compositional Differences of Meconium Microbiomes of Preterm and Term Infants, and Infants That Developed Necrotizing Enterocolitis or Feeding Intolerance.

The primary aim of this study was to investigate the compositional differences of the first passed meconium microbiome in preterm and term infants, and the secondary aim was to compare the meconium microbiomes of preterm and term infants that later developed necrotizing enterocolitis (NEC)/Feeding intolerance (FI) compared to those that did not develop NEC/FI. During the study period, a total of 108 preterm and term newborns' first passed meconium occurring within 72 hours of birth were collected and microbiome analyzed. Meconium microbiomes showed a disruption in the percentages of the core microbiome constituents in both the phylum and genus levels in infants born < 30 weeks of gestational age (GA) compared to those born ≥ 30 weeks of GA. In the phylum level, Bacteroidetes and Firmicutes, and in the genus level, Prevotella and Bacteroides, were predominant, with Prevotella accounting for 20−30% of the relative abundance. As GA increased, a significant increase in the relative abundance of Bacteroidetes (P for trend < 0.001) and decrease in Proteobacteria (P for trend = 0.049) was observed in the phylum level. In the genus level, as GA increased, Prevotella (P for trend < 0.001) and Bacteroides (P for trend = 0.002) increased significantly, whereas Enterococcus (P for trend = 0.020) decreased. Compared to the control group, the meconium of infants that later developed NEC/FI had significantly lower alpha diversities but similar beta-diversities. Furthermore, the NEC/FI group showed a significantly lower abundance of Bacteroidetes (P < 0.001), and higher abundance of Firmicutes (P = 0.034). To conclude, differences were observed in the composition of the first passed meconium in preterm and term infants that later develop NEC/FI compared to those that did not.

Usefulness of Endoscopic Hill Grade in Evaluating Children Suspected of Having Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: This study aim to evaluate the relationship between the Hill grade confirmed by esophagogastroduodenoscopy (EGD) and the degree of gastroesophageal reflux (GER) by 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH) in children suspected of having gastroesophageal reflux disease (GERD). METHODS: A retrospective review of 105 children and adolescents who underwent EGD and MII-pH for the evaluation of GERD from March 2013 to July 2019 was performed. Clinical features and results of EGD and 24-hour MII-pH were collected and statistically analyzed. RESULTS: Hill grades 1, 2, 3, and 4 were identified using EGD in 56 (53.3%), 22 (22.0%), 16 (15.2%), and 11 (10.5%) patients, respectively. As the Hill grade increased, the proportion of neurological diseases (P < 0.001) and endoscopic erosive esophagitis (P < 0.001) increased significantly. The acid exposure index, bolus exposure index, number of reflux episodes, and number of GER reaching proximal extent on MII-pH increased significantly as the endoscopic Hill grade increased (all P < 0.001). Linear regression analysis revealed an increase in the Hill grade by 1 increased the acid exposure index by 2.0%, bolus exposure index by 0.7%, number of reflux episodes by 18.9 episodes, and the number of GER reaching the proximal esophagus increased by 10.5 episodes on average (all P < 0.001). CONCLUSIONS: Hill grade on EGD was associated with GER in children. Estimating the degree of GER by applying Hill grade in the retroflexion view may be useful in practice when evaluating children suspected with GERD.

Quality Improvements in Management of Children with Acute Diarrhea Using a Multiplex-PCR-Based Gastrointestinal Pathogen Panel.

Conventional methods for etiologic diagnoses of acute gastroenteritis (AGE) are time consuming and have low positive yield leading to limited clinical value. This study aimed to investigate quality improvements in patient management, antibiotic stewardship, and in-hospital infection transmission prevention using BioFire® FilmArray® Gastrointestinal Panel (GI Panel) in children with acute diarrhea. This was a prospective study recruiting children < 19 years old with new onset diarrhea during the study period, and a matched historical cohort study of children diagnosed with AGE during the 4 years prior. Patients in the prospective cohort underwent stool testing with GI Panel and conventional methods. A total of 182 patients were included in the prospective cohort, of which 85.7% (n = 156) had community-onset and 14.3% (n = 26) had hospital-onset diarrhea. A higher pathogen positivity rate for community-onset diarrhea was observed by the GI Panel (58.3%, n = 91) compared to conventional studies (42.3%, n = 66) (p = 0.005) and historical cohort (31.4%, n = 49) (p < 0.001). The stool tests reporting time after admission was 25 (interquartile range, IQR 17-46) hours for the GI Panel, and 72 (IQR 48-96) hours for the historical cohort (p < 0.001). A significant reduction in antibiotic use was observed in the prospective cohort compared to historical cohort, 35.3% vs. 71.8%; p < 0.001), respectively. Compared to the GI Panel, norovirus ICT was only able to detect 4/11 (36.4%) patients with hospital-onset and 14/27 (51.8%) patients with community-onset diarrhea. The high positivity rate and rapid reporting time of the GI Panel had clinical benefits for children admitted for acute diarrhea, especially by reducing antibiotic use and enabling early adequate infection precaution and isolation.