Rapid Diagnosis of Hemophagocytic Lymphohistiocytosis Triggered by Disseminated BCG Infection in Infants With Severe Combined Immunodeficiency: Case Report.

Hemophagocytic lymphohistiocytosis triggered by disseminated Bacillus Calmette-Guerin infection is rare. Targeted next-generation sequencing for tuberculosis can rapidly identify different strains of Mycobacterium tuberculosis complex as well as drug resistance genes. Herein we report 2 cases of hemophagocytic lymphohistiocytosis in whom targeted next-generation sequencing rapidly identified Bacillus Calmette-Guerin as the infectious trigger.

Consensus for criteria of running a pediatric inflammatory bowel disease center using a modified Delphi approach.

BACKGROUND: Good quality of care for inflammatory bowel disease (IBD) depends on high-standard management and facility in the IBD center. Yet, there are no clear measures or criteria for evaluating pediatric IBD (PIBD) center in China. The aim of this study was to develop a comprehensive set of quality indicators (QIs) for evaluating PIBD center in China. METHODS: A modified Delphi consensus-based approach was used to identify a set of QIs of structure, process, and outcomes for defining the criteria. The process included an exhaustive search using complementary approaches to identify potential QIs, and two web-based voting rounds to select the QIs defining the criteria for PIBD center. RESULTS: A total of 101 QIs (35 structures, 48 processes and 18 outcomes) were included in this consensus. Structure QIs focused on the composition of multidisciplinary team, facilities and services that PIBD center should provide. Process QIs highlight core requirements in diagnosing, evaluating, treating PIBD, and disease follow-up. Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers. CONCLUSION: The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center. Video Abstract.

Invasive Bordetella pertussis Infection in Infants: A Case Report.

Infants are more likely to develop severe pertussis. We report a malignant pertussis case in a 2-month-old boy with respiratory failure, severe pneumonia, septic shock, and encephalopathy. Bordetella pertussis was detected from nasopharyngeal secretions by polymerase chain reaction, as well as both blood and cerebrospinal fluid samples via metagenomics next-generation sequencing.

Fish oil-containing lipid emulsions prevention on parenteral nutrition-associated cholestasis in very low birth weight infants: a meta-analysis.

BACKGROUND: The effect of fish oil-containing lipid emulsions on preventing parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants is not known. Thus, we conducted a meta-analysis to identify any prevention effect. METHODS: PubMed, EMBASE, and CENTRAL were searched up to 26 January 2021 for studies related to the preventive effect of fish oil-containing lipid emulsions and fish oil-free lipid emulsions on cholestasis in VLBW infants. Revman 5.3 was used to synthesize the results. A fixed-effect model was used to summarize the data when the heterogeneity was non-significant (I2 < 50%), and a random-effects model was used when the heterogeneity was significant (I2 > 50%). RESULTS: Of 728 articles, 11 randomized controlled trials met the inclusion criteria. The meta-analysis indicated that fish oil-containing lipid emulsion reduced the occurrence of PNAC significantly with risk ratio (RR) = 0.53, 95% confidence interval (CI) 0.36-0.80, P = 0.002. The heterogeneity was non-significant with I2 = 23%. Subgroup analysis based on parenteral nutrition duration and median birth weight was performed. The synthesis results for patients with parenteral nutrition duration exceeding 14 days revealed I2 = 35% (P = 0.15) and pooled RR = 0.47, 95% CI 0.30-0.73, P = 0.0008; and for patients with duration less than 14 days revealed I2 = 0% (P = 0.72) and pooled RR = 1.14, 95% CI 0.39-3.35, P = 0.81. The synthesis for patients with birth weight more than 1000 g revealed I2 = 0% (P = 0.41) and pooled RR = 0.55, 95% CI 0.26-1.18, P = 0.12; and for patients with birth weight below 1000 g revealed I2 = 44% (P = 0.11) and pooled RR = 0.53, 95% CI 0.33-0.85, P = 0.009. CONCLUSIONS: The fish oil-containing lipid emulsion can reduce the occurrence of PNAC in VLBW infants based on the available original randomized controlled trial studies, especially for patients with parenteral nutrition duration exceeding 14 days and extremely low birth weight infants. Future studies should be performed before a definitive conclusion can be established.

Clinical features of sodium-taurocholate cotransporting polypeptide deficiency in pediatric patients: case series and literature review.

Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency is a newly reported hereditary bile acid metabolic disease. Here we describe the clinical characteristics of 12 cases of pediatric NTCP deficiency, as well as review 60 previously reported cases in the literature in order to provide better guidance for pediatricians. The clinical records, laboratory and imaging data were collected of 12 cases who were treated at the pediatric infectious disease department of the West China Second University Hospital of Sichuan University, China, from December 2018 to July 2020. PubMed and Wanfang databases were searched and 11 studies including 60 pediatric NTCP deficiency patients from January 2015 to November 2020 were retrieved. In our center, there were 4 girls and 8 boys, with a median age at admission of 9.9 months (range, 2.2 to 70 months). Six patients (50%) had prolonged neonatal jaundice. All of the patients (12/12; 100%) had normal growth and development. The reason for the first visit was prolonged neonatal jaundice (4/12, 33.3%), non-liver related diseases (6/12, 50%) and routine checkup (2/12, 16.7%). Hypercholanemia was documented in 12/12 (100%), elevated aspartate aminotransferase (AST) in 6/12 (50%), and elevated alanine aminotransferase (ALT) in 1/12 (8.3%). All of the patients (12/12; 100%) had homozygous mutations of c.800C>T in SLC10A1. Sixty patients (22 girls and 38 boys) were included in the literature review; 36 (60%) had hyperbilirubinemia after 1 month. The reasons for testing for hypercholanemia were identified in 47/60 cases, and included prolonged neonatal jaundice and neonatal transient cholestasis in 26 (26/47, 55.3%); non-liver related diseases in 14 (14/47, 29.8%); routine medical examination in 3 (3/14, 6.4%); volunteer recruitment in 1 (1/14, 7.1%); dark urine in 1 (1/47, 2.1%). Hypercholanemia was confirmed in 60/60 (100%); 31 (51.7%) had elevated AST, and 10 (16.7%) had elevated ALT. Among 59 Chinese patients, 52 (88.1%) had homozygous mutations of c.800C>T in SLC10A1. The most common symptom of pediatric NTCP deficiency is jaundice. NTCP deficiency can also be detected during routine check-ups. The common biochemical features are hypercholanemia and elevated AST. Screening for c.800C>T mutation in SLC10A1 is useful for primary genetic screening in Chinese infants with persistent hypercholanemia after infectious, structural, and immunological factors are excluded.

Collagenous colitis in a child induced by chronic respiratory allergy: A case report.

INTRODUCTION: Collagen colitis (CC) is a microscopic colitis diagnosed by mucosal biopsy and is extremely rare in children. PATIENT CONCERNS: We reported a child with severe persistent diarrhea that could not be relieved with traditional diarrheal treatment. No abnormalities were found after multiple colonoscopies. DIAGNOSES: A significant increase in total IgE levels was found in the patient's blood. He had a history of mild chronic allergic rhinitis and slightly intermittent wheezing. However, we found that the child had a hyperallergic reaction to multiple respiratory antigens and had mild pulmonary dysfunction. Finally, colonoscopy with biopsy identified the diagnosis of CC. INTERVENTION: Considering that a respiratory allergic reaction was one of the causes of diarrhea, anti-allergic treatment was given to the child, and his severe diarrhea was soon relieved. Corticosteroid treatment was suggested to the patient, but his parents firmly refused steroid therapy. According to the patient's specific allergic reaction to mites, desensitization treatment was finally chosen for him. OUTCOMES: After 1 year of desensitization for dust mites, the patient's respiratory symptoms improved, total IgE levels decreased, autoantibodies declined, and diarrhea did not reoccur. Colonoscopy with biopsy showed a significant improvement in pathology. CONCLUSION: CC in children is rare, and childhood CC induced by a respiratory allergic reaction has not been previously reported. Therefore, this is a special case of CC in a patient who was cured with anti-allergy treatments and desensitization instead of steroid therapy.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Effect of Clostridium butyricum supplementation on the development of intestinal flora and the immune system of neonatal mice.

The objective of the present study was to examine whether Clostridium butyricum supplementation has a role in the regulation of the intestinal flora and the development of the immune system of neonatal mice. A total of 30 pregnant BALB/c mice, including their offspring, were randomly divided into three groups: In the maternal intervention group (Ba), maternal mice were treated with Clostridium butyricum from birth until weaning at postnatal day 21 (PD21) followed by administration of saline to the offspring at PD21-28; in the offspring intervention group (Ab), breast-feeding maternal mice were supplemented with saline and offspring were directly supplemented with Clostridium butyricum from PD21-28; in the both maternal and offspring intervention group (Bb), both maternal mice and offspring were supplemented with Clostridium butyricum at PD 0-21 and at PD21-28. While mice in the control group were given the same volume of normal saline. Stool samples from the offspring were collected at PD14, -21 and -28 to observe the intestinal flora by colony counts of Enterococcus spp., Enterobacter spp., Bifidobacterium spp. and Lactobacillus spp. Detection of intestinal secreted immunoglobulin A (sIgA) levels and serum cytokine (interferon-γ, and interleukin-12, -4 and -10) levels in offspring was performed to evaluate the effect on their immune system. The results revealed that compared with the control group, offspring in the Ba group displayed significantly decreased stool colony counts of Enterococcus spp. (t=3.123, P<0.01) at PD14 and significantly decreased counts of Enterobacter spp. at PD14 and -21 (t=2.563, P<0.05 and t=2.292, P<0.05, respectively). Compared with the control group, the stool colony counts of Bifidobacterium spp. and Lactobacillus spp. were significantly increased in the Ba group at PD21 (t=3.085, P<0.01 and t=2.8508, P<0.05, respectively). The Ab group had significantly higher stool colony counts of Bifidobacterium spp. and Lactobacillus spp. at PD28, compared with the control group (Q=7.679, P<0.01 and Q=6.149, P<0.01, respectively). There were no significant differences identified in the sIgA levels of the intestinal fluid and serum cytokine levels between the control group and the intervention groups. In conclusion, Clostridium butyricum administered to breast-feeding maternal mice was able to regulate the intestinal flora balance in their offspring. However, due to insignificant effects on sIgA level and the associated cytokines, Clostridium butyricum had a limited influence on the balance of type 1 vs. type 2 T-helper cells. However, using Clostridium butyricum as an invention may be a safe method for improving the balance of intestinal flora and associated processes in offspring.

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies.

BACKGROUND: To review the available evidence from prospective studies on the safety and tolerability of the ketogenic diet (KD) for the treatment of refractory childhood epilepsy. METHODS: A comprehensive bibliographic search was performed with the aim of retrieving prospective studies that monitored adverse effects (AEs) in children after receiving the classic or medium-chain triglyceride KD therapy for refractory epilepsy. RESULTS: A total of 45 studies were retrieved, including 7 randomized controlled trials. More than 40 categories of AEs were reported. The most common AEs included gastrointestinal disturbances (40.6%), hyperlipidemia (12.8%), hyperuricemia (4.4%), lethargy (4.1%), infectious diseases (3.8%) and hypoproteinemia (3.8%). Severe AEs, such as respiratory failure and pancreatitis, occurred in no more than 0.5% of children. Specifically, patients receiving KD therapy should be monitored for osteopenia, urological stones, right ventricular diastolic dysfunction, and growth disturbance. The total retention rates of the diet for 1 year and 2 years were 45.7% and 29.2%, respectively. Nearly half of the patients discontinued the diet because of lack of efficacy. AEs were not the main reason for the KD discontinuation. None of the 24 deaths reported after initiation of the diet was attributed to the KD. CONCLUSIONS: KD is a relatively safe dietary therapy. However, because the KD can cause various AEs, it should be implemented under careful medical supervision. Continuous follow-up is needed to address the long-term impact of the diet on the overall health of children.

[Current status of research on infantile cholestatic liver disease in China: a visualization analysis].

OBJECTIVE: To investigate the current status of research on infantile cholestatic liver disease in China and future research trends. METHODS: A co-word analysis was performed in October 2016. Document retrieval and screening were performed in the Chinese databases CNKI and Wanfang Data using "cholestasis" and "infant" as key words. Excel 2010 was used to establish a co-occurrence matrix of high-frequency key words, and Ucinet 6.0 and Netdraw were used to develop a visualized network of these high-frequency key words. RESULTS: A total of 383 articles were included. The co-occurrence analysis showed that "infant" and "cholestasis" were the core of research in this field, and "infantile hepatitis syndrome", "neonate", "intrahepatic", "biliary atresia", "heredity and metabolism", "hepatitis", "cytomegalovirus", "jaundice", and "conjugated bilirubin" were main research topics. Most of the other articles focused on "parenteral nutrition", "hepatobiliary imaging", "gene mutation", and "liver biopsy". There were relatively few articles on surgical diagnostic techniques and treatment for this disease. CONCLUSIONS: The research on infantile cholestatic liver disease in China focuses on etiology and differential diagnosis, and genetic diagnosis has become a hot topic in recent years. The research on treatment should be enhanced, and new diagnostic techniques are the research interest in future.

[Research advances in nutritional assessment methods in children with chronic liver diseases].

Malnutrition is commonly seen in children with chronic liver diseases, and there are interactions between them. Chronic liver diseases can cause malnutrition and this can affect the prognosis of children with chronic liver diseases. Due to the complexity of nutritional assessment in children with chronic liver diseases, there are still no unified standards for the diagnosis of malnutrition. Early identification of malnutrition and related intervention helps to improve the prognosis of children with chronic liver diseases. This article reviews the features of nutrition in children with chronic liver diseases and related nutritional assessment methods.

[Research advances in association between childhood obesity and gut microbiota].

In recent years, more and more studies have noted the close association between gut microbiota and the development and progression of obesity. Gut microbiota may act on obesity by increasing energy intake, affecting the secretion of intestinal hormones, inducing chronic systemic inflammation, and producing insulin resistance. This article reviews the association between childhood obesity and gut microbiota, as well as possible mechanisms, in an attempt to provide a reference for the etiology, prevention and treatment of childhood obesity.

[A clinical study of invasive fungal disease in children without underlying diseases].

OBJECTIVE: To investigate the clinical features of invasive fungal disease (IFD) in children without underlying diseases. METHODS: The clinical data of 49 children without underlying diseases who were diagnosed with IFD were retrospectively studied. RESULTS: Fungal pathogens were detected in 37 (76%) out of 49 patients, including Cryptococcus neoformans (17 children, 46%), Candida albicans (10 children, 27%), Aspergillus (3 children, 8%), and Candida parapsilosis (3 children, 8%). Fungal pneumonia (17 children, 46%) was the most commonly seen disease, with Candida albicans as the major pathogen (9 children, 53%). The 49 children had at least one high-risk factor for infection, including the use of antibiotics, a long length of hospital stay, and invasive procedures. Of all the children, 82% did not respond well to antibiotic treatment or experienced recurrent pyrexia. Among the 24 children who underwent G tests, 17 (71%) showed positive results. All the children were given antifungal therapy, and among these children, 37 (75%)were cured, 3 (6%) were still in the treatment, 5 (10%) died, and 4 (8%) were lost to follow-up. CONCLUSIONS: In IFD children without underlying diseases, Cryptococcus neoformans and Candida are the main pathogens, and lung infection is the most common disease. Long-term use of high-dose antibiotics may be an important risk factor for fungal infection. The IFD children without underlying diseases are sensitive to antifungal drugs and have a satisfactory prognosis.

[A visualization study of research papers on childhood tuberculous meningitis in China and abroad over the past decade].

OBJECTIVE: To introduce co-word analysis into the analysis of the current research status of childhood tuberculous meningitis, to compare the similarities and differences in research topics of the field in China and abroad over the past decade, and to discover the advantages and weak links in the study field in China. METHODS: PubMed, CNKI, VIP, and Wanfang Data were searched for the articles which met the inclusion criteria. Ucinet 6.0 and Netdraw were used for co-occurrence analysis, and the co-article relationship between high-frequency key words was visualized. RESULTS: A total of 226 articles abroad and 186 Chinese articles on childhood tuberculous meningitis were obtained. The figures for co-occurrence analysis of high-frequency key words in research articles on childhood tuberculous meningitis in China and abroad were successfully plotted. Compared with the studies in China, the studies abroad were more sophisticated and well-developed, with more studies on drug-resistant tuberculosis, the relationship between tuberculosis and AIDS, and the epidemiology of tuberculosis. The key words listed in the studies abroad were more standard. The studies in China on childhood tuberculous meningitis concentrated on vaccination and nursing. CONCLUSIONS: In general, the studies on childhood tuberculous meningitis in China and abroad have the same directions. The studies abroad have a complicated network and use more standard key words. The studies on childhood tuberculous meningitis are well conducted in China. However, more studies are needed for drug-resistant tuberculosis, the relationship between tuberculosis and AIDS, and the epidemiology of tuberculosis in future.

[Preparing Bifidobacteria for Quantitative Detections].

OBJECTIVES: To compare different preparation methods for quantitative real-time PCR (qPCR) detection of Bifidobacteria. METHODS: Standard strains of Bifidobacteria were prepared with concentration gradients using strain DNA, PCR product amplification and purification, and plasmid DNA methods. The concentrations of Bifidobacteria were determined with ultraviolet spectrophotometer and real-time quantitative PCR. RESULTS: Greater than 0.99 R 2 in values of standard curves were achieved by all three preparation methods. The plasmid DNA method obtained a higher level of concentration and purity of Bifidobacteria than the other two methods ( P<0.01). CONCLUSIONS: The plasmid DNA method produces high quality preparations and is more suitable for real-time quantitative PCR, which can provide a reference for the molecular biological detection of Bifidobacteria.

[A young boy with elevated aminotransferases in physical examination--Two novel missense mutations associated with Wilson's disease were found].

A 3-year-old boy had abnormal liver function, which was found in physical examination, for 5 months before admission. He had no symptoms such as anorexia, poor appetite, and jaundice, had normal growth and development, and showed no hepatosplenomegaly. Laboratory examination revealed significantly reduced ceruloplasmin (35 mg/L), as well as negative hepatotropic virus, cytomegalovirus, and Epstein-Barr virus. There were normal muscle enzymes, blood glucose, and blood ammonia and negative liver-specific autoantibodies. The boy had negative K-F ring and normal 24-hour urine copper (0.56 µmol/L). The ATP7B gene testing for the boy, his sister, and their parents detected two novel missense mutations in the boy and his sister, i.e., compound heterozygous mutations in exon 7 (c.2075T>C, p.L692P) and exon 13 (c.3044T>C, p.L1015P), which were inherited from their father and mother, respectively. Wilson's disease was confirmed by genetic diagnosis in the boy and his sister. The boy and his sister were given a low-copper diet. The boy was administered with penicillamine for decoppering and zinc supplement against copper uptake. His sister received zinc supplement alone because no clinical symptoms were observed. The boy showed normal liver function in the reexamination after 3 months of treatment.

[Epidemiological study on nasal carriage in hospitalized children infected with Staphylococcus aureus].

OBJECTIVE: To study the relationship between nasal carriage and Staphylococcus aureus (S. aureus) infection in hospitalized children. METHODS: Fifty-six hospitalized children infected with S. aureus were recruited in this study. Nasal swabs were collected and cultured, and the nasal carriage rate of S. aureus was examined. PVL virulence gene and mecA resistance gene were both detected in clinical strains and nasal carriage strains by PCR. RESULTS: Twenty-two (39%) of the 56 children had nasal carriage of S. aureus, and most of them (18 cases) were younger than one year. Among these 22 children, 11 (50%) had previous hospitalization over the past year. In the infected strains, the rate of methicillin-resistant S. aureus (MRSA) was 29% (16/56), while it was 32% (7/22) in carriage strains. The mecA positive results in clinical strains were consistent with the results in nasal carriage strains. Among 5 PVL-positive nasal carriage strains, 4 (90%) could be matched with their clinical strains, all of which were MRSA. CONCLUSIONS: Nasal carriage is a potential risk factor for S. aureus infection. Nosocomial transmission may lead to nasal carriage, which can cause S. aureus infection. The isolation rate of MRSA is high in hospitalized children infected with S. aureus, which implies that more attention is needed for this situation. The isolates from noses may be clonally identical to the isolates from clinical secretions, and the homology between them needs to be confirmed by multi-locus sequence typing.

[Expression of CD20 in B-cell precursor acute lymphoblastic leukemia and its correlation with clinical outcomes].

OBJECTIVE: To determine whether expression of CD20 is associated with clinical outcomes of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). METHODS: 271 newly diagnosed childhood BCP-ALL during January 2009 to May 2013 were enrolled in this study. The patients were treated in line with the Chinese Childhood Leukemia Group ALL 2008 protocol (CCLG-ALL 2008). The clinical feature, early therapeutic response and clinical outcomes of the patients with a CD20 positive (CD20+ BCP) expression were compared with those with a CD20 negative (CD20- BCP) expression. RESULTS: CD20- BCP accounted for 45.76% (124 cases) of all participants. There were no significant differences between CD20- BCP and CD20- BCP patients in gender distribution, age, WBC counts when diagnosis was made, proportion of prednisone poor responders, and distribution of risk categories (P > 0.05). Patients of 10 years or older comprised 25.81% and 14.29% of CD20+ BCP and CD20- BCP patients, respectively (P = 0.017). Pro-B and pre-B cases accounted for 43.55% and 59.86% of CD20- BCP patients respectively, compared with 56.45 and 40.14% in CD20- BCP patients (P = 0.007). CD20+ BCP patients had 12.20% Philadelphia positive ALL and 6.50% BCP-ALL with TEL-AML1 fusion gene, compared with 4.86% (P = 0.03) and 18.06% (P = 0.005) in those of CD20 BCP. No significant differences were found between the two groups of patients in 15-day (77.50% vs. 74.13%, P = 0.525) and 33-day (95.04% vs. 95.83%, P = 0.757) complete remission rates. No significant differences (P > 0.05) were found in predicted 4-year event-free survival CEFS (78.00% +/- 4.96%) vs. (79.05% +/- 5.40%)) and predicted 4-year overall survival (OS (83.01% +/- 6.13%) vs. (93.64% +/- 2.46%)) between the two groups of patients either. CONCLUSION: CD20 positivity was not found to be associated with worse prognosis of children with BCP-ALL. More studies are needed to validate the correlation between CD20 and unfavorable outcomes in BCP-ALL.