Background: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). Methods: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. Results: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = −0.430, P = 0.036), H. influenzae (rs = −0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). Conclusion In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

BACKGROUND: Mycobacterium bovis Bacille Calmette-Guérin (BCG) osteitis, a rare complication of BCG vaccination, has not been well investigated in Korea. This study aimed to evaluate the clinical characteristics of BCG osteitis during the recent 10 years in Korea. METHODS: Children diagnosed with BCG osteitis at the Seoul National University Children's Hospital from January 2007 to March 2018 were included. M. bovis BCG was confirmed by multiplex polymerase chain reaction (PCR) in the affected bone. BCG immunization status and clinical information were reviewed retrospectively. RESULTS: Twenty-one patients were diagnosed with BCG osteitis and their median symptom onset from BCG vaccination was 13.8 months (range, 6.0–32.5). Sixteen children (76.2%) received Tokyo-172 vaccine by percutaneous multiple puncture method, while four (19.0%) and one (4.8%) received intradermal Tokyo-172 and Danish strain, respectively. Common presenting symptoms were swelling (76.2%), limited movement of the affected site (63.2%), and pain (61.9%) while fever was only accompanied in 19.0%. Femur (33.3%) and the tarsal bones (23.8%) were the most frequently involved sites; and demarcated osteolytic lesions (63.1%) and cortical breakages (42.1%) were observed on plain radiographs. Surgical drainage was performed in 90.5%, and 33.3% of them required repeated surgical interventions due to persistent symptoms. Antituberculosis medications were administered for a median duration of 12 months (range, 12–31). Most patients recovered without evident sequelae. CONCLUSION: Highly suspecting BCG osteitis based on clinical manifestations is important for prompt management. A comprehensive national surveillance system is needed to understand the exact incidence of serious adverse reactions following BCG vaccination and establish safe vaccination policy in Korea.
Child ; Drainage ; Femur ; Fever ; Humans ; Immunization* ; Incidence ; Korea* ; Methods ; Multiplex Polymerase Chain Reaction ; Mycobacterium bovis* ; Mycobacterium* ; Osteitis* ; Punctures ; Retrospective Studies ; Seoul ; Tarsal Bones ; Vaccination

The authors regret that one co-author (Kyung-Hyo Kim) was missing in the article.

PURPOSE: To evaluate the clinical efficacy and safety of uterine artery embolization (UAE) using N-butyl-2-cyanoacrylate (NBCA) in patients with postpartum hemorrhage (PPH). MATERIALS AND METHODS: From February 2010 to May 2018, 14 patients (age: 28–39 years; mean: 33 years) underwent UAE using NBCA among 82 patients with PPH. Medical records were retrospectively reviewed to evaluate the patients characteristics, cause of PPH, embolization procedure, and outcomes. RESULTS: Angiograms revealed extravasation (n = 10) or pseudoaneurysm (n = 4) in all patients. The causes of PPH were hysterotomy or hysterectomy related arterial injury (n = 11), cervical laceration (n = 2), and abnormal placentation (n = 1). UAE was performed with NBCA in all patients. Additional UAE with gelatin sponge particles was performed in two patients. Additional non-uterine artery embolization was performed in three patients. Coagulopathy was found in five (35.7%) patients. The technical and clinical success rates were 92.9% and 85.7%, respectively. One patient died from multi-organ failure eight days after UAE. One patient with abnormal placentation had pelvic organ ischemia due to multiple pelvic artery embolization. CONCLUSION UAE using NBCA is safe and effective for the patients with PPH showing extravasation or pseudoaneurysm.

Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramembrane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha (TNF-α) converting enzyme, which is the molecule responsible for the release of TNF-α. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of TNF-α release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative TNF-α related disease, was induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity of the CIA was measured by traditional clinical scores and histopathological analysis of hind limb joints. A rota-rod test and grip strength test were employed to evaluate the severity of CIA based on losses of physical functions. The results indicated that Rhbdf2 mutant mice showed clear alleviation of the clinical severity of CIA as demonstrated by the significantly lower severity indexes. Moreover, a grip strength test was shown to be useful for the evaluation of physical functional losses by CIA. Overall, the results showed that the Rhbdf2 gene has a significant effect on the induction of CIA, which is related to TNF-α.
Animals ; Arthritis, Experimental* ; Chickens ; Collagen Type II ; Extremities ; Hand Strength ; Humans ; Joints ; Mice ; Mice, Knockout* ; Serine Proteases ; Tumor Necrosis Factor-alpha

PURPOSE: We aimed to identify the epidemiology and the clinical characteristics of human parainfluenza virus type 4 (HPIV-4) infection compared to HPIVs 1–3 infections in Korean children. METHODS: We reviewed medical records of children with HPIV infection who visited Seoul National University Children's Hospital from 2015 to 2017. Detection of respiratory viruses was performed using real time-polymerase chain reaction (rt-PCR), which could differentiate HPIVs 1–4. Diagnosis was classified as a febrile illness, upper respiratory tract infection (URI), croup, bronchiolitis, or pneumonia. The epidemiology, demographic features, and clinical characteristics among HPIV types were compared. The clinical data were analyzed only for the previously healthy children. RESULTS: Of the 472 children diagnosed with HPIV infection, 108 (22.9%) were previously healthy: 24 (22.2%), 19 (17.6%), 39 (36.1%), and 26 (24.1%) in HPIV types 1, 2, 3, and 4, respectively. The median age of children with HPIV-4 infection was 11 (0–195) months: the proportion of children aged < 2 years and 2 to < 5 years were 65.4% and 19.2%, respectively. Clinical diagnoses of HPIV-4 infection were bronchiolitis (38.5%), pneumonia (30.8%), and URI (30.8%). Croup was the most prevalent in HPIV-2 (21.1%) and none in HPIV-4 infection (P=0.026). Hospital admission rates among HPIV types were not significantly different (P> 0.05). CONCLUSIONS: We observed seasonal peak of HPIV-4 infection in 2015 and 2017. HPIV-4 was a common respiratory pathogen causing lower respiratory tract infection in hospitalized children.
Bronchiolitis ; Child ; Child, Hospitalized ; Croup ; Diagnosis ; Epidemiology ; Humans ; Medical Records ; Parainfluenza Virus 4, Human ; Paramyxoviridae Infections ; Pneumonia ; Respiratory Tract Infections ; Seasons ; Seoul

BACKGROUND: Invasive bacterial infections in apparently immunocompetent children were retrospectively analyzed to figure causative bacterial organisms in Korea. METHODS: A total of 947 cases from 25 university hospitals were identified from 2006 to 2010 as a continuance of a previous 10-year period study from 1996 to 2005. RESULTS: Escherichia coli (41.3%), Streptococcus agalactiae (27.7%), and Staphylococcus aureus (27.1%) were the most common pathogens in infants < 3 months of age. S. agalactiae was the most prevalent cause of meningitis and pneumonia and E. coli was the major cause of bacteremia without localizing signs in this group. In children 3 to 59 months of age, Streptococcus pneumoniae (54.2%), S. aureus (20.5%), and Salmonella spp. (14.4%) were the most common pathogens. S. pneumoniae was the leading cause of pneumonia (86.0%), meningitis (65.0%), and bacteremia without localizing signs (49.0%) in this group. In children ≥ 5 years of age, S. aureus (62.8%) was the predominant pathogen, followed by Salmonella species (12.4%) and S. pneumoniae (11.5%). Salmonella species (43.0%) was the most common cause of bacteremia without localizing signs in this group. The relative proportion of S. aureus increased significantly over the 15-year period (1996–2010) in children ≥ 3 months of age (P < 0.001), while that of Haemophilus influenzae decreased significantly in both < 3 months of age group (P = 0.036) and ≥ 3 months of age groups (P < 0.001). CONCLUSION: S. agalactiae, E. coli, S. pneumoniae, and S. aureus are common etiologic agents of invasive bacterial infections in Korean children.
Bacteremia ; Bacterial Infections ; Child ; Epidemiology ; Escherichia coli ; Haemophilus influenzae ; Hospitals, University ; Humans ; Infant ; Korea ; Meningitis ; Pneumonia ; Retrospective Studies ; Salmonella ; Staphylococcus aureus ; Streptococcus agalactiae ; Streptococcus pneumoniae

Blackwater fever is a serious clinical syndrome manifested by acute intravascular hemolysis, fever, and the passage of black or red urine, which is classically associated with falciparum malaria and irregular administration of quinine. In Korea, Plasmodium vivax is the only endemic malaria circulating; a number of imported cases of falciparum malaria have been reported in patients following return from international travel to a malaria endemic area. Therefore, it is important for health care professionals including pediatricians to be aware of the falciparum malaria and its clinical courses. Herein, we report a case of a 14-year-old girl with severe falciparum malaria that was complicated by blackwater fever.
Adolescent ; Blackwater Fever* ; Child* ; Delivery of Health Care ; Female ; Fever ; Hemolysis ; Humans ; Korea ; Malaria* ; Malaria, Falciparum ; Plasmodium vivax ; Quinine

PURPOSE: The aim of this study was to identify the pathogens of blood stream infection (BSI) in children with hemato-oncologic disorders, to analyze susceptibility patterns of microorganisms to guide empirical antimicrobial therapy, and to compare temporal trends of the pathogen and antimicrobial susceptibility with those of previous studies. METHODS: We retrospectively analyzed the medical records of children with hemato-oncologic disorders whose blood culture grew pathogens at the Seoul National University Children's Hospital between 2011 and 2015. RESULTS: A total of 167 patients developed 221 episodes of bacteremia. Among 229 pathogens, gram-negative bacteria (GNB) accounted for 69.0% (64.0% in 2002 to 2005, 63.4% in 2006 to 2010); gram-positive bacteria (GPB) accounted for 28.8% (31.3% in 2002 to 2005, 34.6% in 2006 to 2010); and fungus accounted for 2.2%. Among GNB, Klebsiella species (53.2%, 84/158) and Escherichia coli (19.6%, 31/158) were common. Staphylococcus aureus (48.5%, 32/66) and viridans streptococci (21.2%, 14/66) were frequently isolated among GPB. The susceptibilities of oxacillin and vancomycin in GPB were 54.8% and 96.9% (51.5% and 95.5% in 2002 to 2005; 34.1% and 90.5% in 2006 to 2010), respectively, whereas in GNB, the susceptibilities of cefotaxime, piperacillin/tazobactam, and imipenem were 73.2%, 77.2%, and 92.6% (75.9%, 82.8%, and 93.4% in 2002 to 2005; 62.8%, 82.9%, 93.8% and in 2006 to 2010), respectively. There were no significant differences in the proportion of etiologic agents or the antimicrobial susceptibilities between the current study and that of the previous two studies from 2002 to 2010. Overall fatality rate was 13.1%. CONCLUSIONS: GNB predominated in BSI among children with hemato-oncologic disorders. The etiology of bacteremia and antimicrobial susceptibility were comparable to those of the previous studies. Thus, piperacillin/tazobactam can be used as the initial empirical antimicrobial agent in febrile neutropenia.
Bacteremia* ; Cefotaxime ; Child* ; Escherichia coli ; Febrile Neutropenia ; Fungi ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Humans ; Imipenem ; Klebsiella ; Korea ; Medical Records ; Oxacillin ; Retrospective Studies ; Rivers ; Seoul ; Staphylococcus aureus ; Vancomycin ; Viridans Streptococci

In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and trafficking of tumor necrosis factor-alpha (TNF-α) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarified that the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease. Thus, this review focuses on our understanding of iRhoms and the involved mechanisms in the cellular processes.
Alzheimer Disease ; Breast Neoplasms ; Cell Membrane ; Down-Regulation ; Drosophila ; Endoplasmic Reticulum ; Esophageal Neoplasms ; Humans ; Keratoderma, Palmoplantar, Diffuse ; Ligands ; Peptide Hydrolases ; Receptor, Epidermal Growth Factor ; Serine Proteases ; Tumor Necrosis Factor-alpha