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.

Serologic status and vaccine response against hepatitis B virus after allogeneic hematopoietic cell transplantation in pediatric patients.

BACKGROUND: Although vaccination against hepatitis B virus (HBV) is recommended for hematopoietic cell transplantation (HCT) recipients, previous studies evaluating serologic status and immunologic response to HBV vaccination in pediatric allogeneic HCT recipients are not enough. OBJECTIVE: This study aimed to evaluate serologic status against HBV and immunologic responses to HBV vaccination in children and adolescents receiving allogeneic HCTs. METHODS: Medical records of the enrolled 61 pediatric patients < 19 years of age who received their first allogeneic HCTs were retrospectively reviewed. RESULTS: Twenty-two (36.1%) of the enrolled patients were positive for hepatitis B surface antibody (HBsAb) after HCT. Chronic graft-versus-host disease was significantly associated with negative HBsAb status after HCT (p = 0.01). With one dose of HBV vaccination after HCT, 40.5% of the vaccinated patients became positive for HBsAb. No clinical factor was associated with the positive conversion of HBsAb after vaccination. CONCLUSIONS: Considering the unsatisfactory seropositive rate and vaccine response against HBV and the lack of significant clinical and laboratory factors predicting serostatus in HCT recipients, universal three doses of HBV vaccination should be necessary after allogeneic HCT.

One-year changes in the pediatric emergency department caused by prolonged coronavirus disease 2019 pandemic.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits. METHODS: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic. RESULTS: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001). CONCLUSIONS: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective.

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.

Factor analysis of the Korean version of the Illness Cognition Questionnaire for adolescents with chronic illness.

AIM: The purpose of this study was to examine the reliability and validity of the Korean version of the Illness Cognition Questionnaire. METHODS: A total of 237 adolescent Participants ages 13-20 years were collected from two hospitals for purposes of the study. The participants were diagnosed with blood cancer, congenital heart disease, paediatric rheumatoid arthritis, multiple sclerosis and diabetes mellitus. RESULTS: The Illness Cognition Questionnaire is composed of three subscales and 18 items. Exploratory factor analysis and confirmatory factor analysis were performed for all 18 items. The data used in the exploratory factor analysis were obtained from 126 adolescents with blood cancer. The data used for confirmatory factor analysis were obtained from 111 adolescents who had chronic diseases. The three-factor model of 18 items showed general fitness close to the standard but not a very good fit. CONCLUSIONS: This study indicated that the Korean version of the Illness Cognition Questionnaire is reasonable to use for Korean adolescents with chronic illness. The authors recommend that the meaning of Item 10 be clarified from 'I have learned to accept the limitations imposed by my illness' to 'I have learned to positively accept the limitations imposed by my illness'.

Enterococcal bacteremia in febrile neutropenic children and adolescents with underlying malignancies, and clinical impact of vancomycin resistance.

PURPOSE: Enterococci are a common cause of bacteremia in immunocompromised patients. Although the increase of vancomycin-resistant enterococci (VRE) makes appropriate antibiotic therapy difficult, clinical characteristics of enterococcal bacteremia and the impact of VRE infection on outcomes have rarely been reported in immunocompromised children. METHODS: We enrolled children and adolescents (< 19 years of age) with underlying malignancies who were diagnosed with enterococcal bacteremia during febrile neutropenia between 2010 and 2017. Medical records of the enrolled children were retrospectively reviewed to evaluate the clinical characteristics of enterococcal bacteremia and impact of VRE infection on outcomes. RESULTS: Thirty-six episodes of enterococcal bacteremia were identified in 30 patients. VRE infection was identified in 11 episodes (30.6%); the 7- and 30-day mortalities were 27.8% and 44.4%, respectively. Acute lymphoblastic leukemia (50.0%) and acute myeloid leukemia (30.6%) were the most common underlying disorders. Three (8.3%) of the patients were in complete remission, and palliative and reinduction chemotherapies were administered in 47.2% and 36.1% of episodes, respectively. Empirical antibiotic therapy was appropriate in 64.0% of patients with vancomycin-susceptible enterococcal infection and in none of the VRE-infected patients (p = 0.001). However, the 30-day mortality was not significantly different between the two patient groups (44.0% vs. 45.5%, p = 1.000). CONCLUSIONS: Most episodes of enterococcal bacteremia occurred in advanced stages of underlying malignancies, and still showed high mortality. The prognosis seemed to be related to the underlying disease condition rather than vancomycin resistance of the isolated enterococci, although the number of enrolled patients was small.

First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012.

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival.

The antipyretic efficacy and safety of propacetamol compared with dexibuprofen in febrile children: a multicenter, randomized, double-blind, comparative, phase 3 clinical trial.

BACKGROUND: We aimed to compare the antipyretic efficacy, safety, and tolerability between oral dexibuprofen and intravenous propacetamol in children with upper respiratory tract infection (URTI) presenting with fever. METHODS: Patients aging from 6 months to 14 years admitted for URTI with axillary body temperature ≥ 38.0 °C were enrolled and randomized into the study or control group. Patients in the study group were intravenously infused with propacetamol and subsequently oral placebo medication was administered. Patients in the control group were intravenously infused with 100 mL of 0.9% sodium chloride solution without propacetamol and then oral dexibuprofen was administered. We checked the body temperature of all patients at 0.5 h (hr), 1 h, 1.5 h, 2 h, 3 h, 4 h, and 6 h after oral placebo or dexibuprofen had been applied. RESULTS: A total of 263 patients (125 in the study group) were finally enrolled. The body temperatures of patients in the study group were significantly lower until 2 h after administration (37.73 ± 0.58 vs 38.36 ± 0.69 °C (p < 0.001), 37.37 ± 0.53 vs 37.88 ± 0.69 °C (p < 0.001), 37.27 ± 0.60 vs 37.62 ± 0.66 °C (p < 0.001), 37.25 ± 0.62 vs 37.40 ± 0.60 °C (p = 0.0452), at 0.5 h, 1 h, 1.5 h, and 2 h, respectively). The two groups showed no significant differences in terms of the range of body temperature decrease, the Area Under the Curve of body temperature change for antipyretic administration-and-time relationship, the maximum value of body temperature decrease during the 6 h test period, the number of patients whose body temperature normalized (< 37.0 °C), the mean time when first normalization of body temperature, and the development of adverse events including gastrointestinal problem, elevated liver enzyme, and thrombocytopenia. CONCLUSIONS: Intravenous propacetamol may be a safe and effective choice for pediatric URTI patients presenting with fever who are not able to take oral medications or need faster fever control. TRIAL REGISTRATION: CRIS KCT0002888 . Date of registration: July 31st, 2013.

Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study.

BACKGROUND: Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients. METHODS: Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and ß-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined. RESULTS: Thirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal ß-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%. CONCLUSIONS: Mortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

Treatment of children with acute lymphoblastic leukemia with risk group based intensification and omission of cranial irradiation: A Korean study of 295 patients.

BACKGROUND: Recent studies indicate 70-80% event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL). In this study, we report the outcome of 295 children and adolescents treated at our institution, with stratification into four risk groups, and omission of cranial irradiation in all patients. PROCEDURE: Patients were diagnosed from January 2005 to December 2011 and classified and treated as low, standard, high, and very high risk groups. A delayed intensification phase was given twice for high and very high risk groups. None of the patients received cranial irradiation for central nervous system (CNS) prophylaxis. RESULTS: The 10-year EFS and overall survival (OS) were 78.5 ± 2.5% and 81.9 ± 2.7%, respectively. EFS according to risk group was as follows: low risk 91.2 ± 3.7%, standard risk 98.1 ± 1.9%, high risk 81.5 ± 4.3%, very high risk 59.4 ± 5.3%. In a multivariate analysis, high hyperdiploidy and infant ALL were significant predictors of EFS. Cumulative incidence of any relapse, isolated CNS relapse, and any CNS relapse were 17.1 ± 2.3%, 1.5 ± 0.7%, and 2.3 ± 0.9%, respectively. Other events included infection-related deaths during remission induction chemotherapy (3), primary refractory disease (2), and treatment-related deaths in first complete remission (8). CONCLUSIONS: In this single-institution study of Korean pediatric ALL patients, risk group based intensification with omission of cranial irradiation resulted in EFS comparable to previous studies, excellent survival of low- and standard-risk patients, and a low rate of CNS relapse.

Founder haplotype analysis of Fanconi anemia in the Korean population finds common ancestral haplotypes for a FANCG variant.

A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population.

Aminoglycoside therapy for childhood urinary tract infection due to extended-spectrum ß-lactamase-producing Escherichia coli or Klebsiella pneumoniae.

BACKGROUND: The rate of urinary tract infections (UTIs) due to extended-spectrum ß-lactamase (ESBL)-producing bacterial strains requiring carbapenem therapy has been increasing in children. This study was conducted to evaluate the effect of non-carbapenem antibiotic therapy on childhood UTIs caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae. METHODS: Medical records of children diagnosed with febrile UTIs due to E. coli or K. pneumoniae between 2010 and 2014 were retrospectively reviewed. The enrolled children were divided into two groups: the ESBL group and the non-ESBL group. Clinical characteristics and therapeutic responses were compared between the two groups. RESULTS: A total of 211 episodes of UTI (204 caused by E. coli; seven caused by K. pneumoniae) were identified in 205 children. Twenty-two (10.4 %) episodes were categorized into the ESBL group. There was no significant difference in the type of antibiotic administered between the two groups. No carbapenems were administered; however, aminoglycosides were administered for 79.1 % of the total episodes. Although empirical antibiotics were appropriate for more episodes in the non-ESBL group compared with the ESBL group (100.0 % vs. 90.9 %, p = 0.011), there were no significant differences in the frequency of defervescence, bacterial eradication from the urine, acute pyelonephritis and vesicoureteral reflux or fever duration between the two groups. CONCLUSIONS: Non-carbapenem antibiotics showed favourable therapeutic effects on childhood UTIs caused by ESBL-producing strains. Aminoglycosides can be an alternative to carbapenems in such cases.

Serum galactomannan index for early prediction of mortality in immunocompromised children with invasive pulmonary aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is the most common invasive fungal disease in immunocompromised patients, and it has a 30 % mortality rate despite appropriate antifungal therapy. This retrospective study was performed to determine risk factors for mortality in immunocompromised children with IPA. METHODS: Medical records of 45 probable/proven IPA cases diagnosed in children with hematologic/oncologic diseases were reviewed. Selected cases were divided into the survival (n = 30) and fatality (n = 15) groups based on survival at 12 weeks after antifungal therapy. Clinical characteristics and serum galactomannan indices (GMIs) were compared between the two groups. RESULTS: Significantly more children in the fatality group were male (p = 0.044), not in complete remission of the underlying malignancies (p = 0.016), and had received re-induction/salvage or palliative chemotherapy (p = 0.035) than those in the survival group. However, none of these factors was significantly associated with mortality in a multivariate analysis. Serum GMIs were higher in the fatality group than in the survival group during the entire period of antifungal therapy, and serum GMI at 1 week after antifungal therapy was most significantly associated with mortality. A serum GMI > 1.50 at 1 week after antifungal therapy exhibited a sensitivity and specificity of 61.5 % and 89.3 %, respectively, in predicting mortality within 12 weeks after antifungal therapy. CONCLUSIONS: Higher serum GMI in the early phase of antifungal therapy was associated with mortality in immunocompromised children with IPA. These children should receive more intensive care for IPA than others.

A small Askin's tumor presenting with early onset of chest pain.

Most primitive neuroectodermal tumor of the chest wall destroy the rib, chest wall muscles, diaphragm, and lung or extend into the spinal compartment, resulting in a large-sized tumor and symptoms. In contrast, we recently encountered a rare case of Askin's tumor presenting with early-onset chest pain despite the small size. After resection of the tumor and adjuvant chemotherapy, the patient remains disease-free over 3 years of follow-up.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children.

Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) or rabbit antithymocyte globulin (n=158) combined with cyclosporine as first-line therapy between 1992 and 2010. The response rates were comparable between the horse and rabbit antithymocyte globulin groups at 3 months [46% (136/294) versus 42% (66/153), P=0.55] and 6 months [60% (178/292) versus 55% (87/143), P=1.0]. Using multivariate analysis, differences in antithymocyte globulin preparations were not associated with response rates. However, 2-year and 10-year overall survival rates in the horse antithymocyte globulin group were significantly better than those in the rabbit antithymocyte globulin group (2-year overall survival: 96% versus 87%, 10-year overall survival: 92% versus 84%, P=0.004). On the basis of multivariate analysis, use of rabbit antithymocyte globulin was a significant adverse factor for overall survival (hazard ratio = 3.56, 95% confidence interval, 1.53 - 8.28, P=0.003). Rabbit antithymocyte globulin caused more profound immunosuppression, which might be responsible for the higher incidence of severe infections. Considering that there are no studies showing the superiority of rabbit antithymocyte globulin over horse antithymocyte globulin, horse antithymocyte globulin should be recommended as a first-line therapy. However, our results justify the use of rabbit antithymocyte globulin as first-line therapy if horse antithymocyte globulin is not available.

Fluctuations in pathogenic CD4+ T-cell subsets in a murine sclerodermatous model of chronic graft-versus-host disease.

To determine the roles of CD4+ T-cell (Th) subsets, including Th17 cells, in the development of chronic graft-versus-host disease (cGVHD), we used a Th-dependent cGVHD model comprising B10.D2 donor and BALB/c recipient mice. The clinical GVHD score increased beginning at day +14, peaked at day +42, and remained elevated until day +70. In the skin, increased dermal thickness was apparent at day +14, and maintained with few changes until day +70. In contrast, the liver had peak pathologic scores at day +28, and the tissue damage began to improve at day +56. To determine possible associations between improvement of liver pathology and changes in Th subsets, we analyzed Th subsets using flow cytometry. Th1 frequencies in the livers were greater than other Th subsets throughout the disease course, but the frequencies decreased over time. Notably, Th17 cells were rarely detected during earlier periods, but emerged at day +56, which correlated with the improved hepatic inflammation. In contrast, other Th subsets (Th2 and regulatory T cells) did not change significantly during the disease course. These results indicate the association of attenuation on cGVHD with a later emergence of Th17 cells and concomitant decrease of Th1 cells.

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.

A case of myocarditis following neonatal meningitis caused by coxsackievirus B1 in spite of intravenous immunoglobulin treatment.

Enteroviral infection is one of the most common neonatal infections, and most patients recover without complications. This report describes a neonate who experienced meningitis followed by myocarditis. A 4-day-old boy was admitted with fever, diagnosed with enteroviral meningitis and treated with intravenous immunoglobulin (IVIG). However, myocarditis was subsequently diagnosed in spite of IVIG treatment, and coxsackievirus B1 (CXB1) was revealed as a cause. A left ventricular aneurysm persisted even though the patient recovered with repeated high-dose IVIG treatment and cardiac supportive care. This report describes a rare case where myocarditis developed several days after a diagnosis of CXB1 meningitis in spite of IVIG treatment. It is important to pay attention to the patient's clinical condition until the end of the second viremia of enterovirus and to consider high-dose IVIG treatment when treating enteroviral infections for neonates.