Principles of antibiotic therapy in pediatric emergency department

Infectious diseases are among the most common conditions seen in pediatric emergency departments. Of these, in bacterial infections, appropriate antibiotic therapy should be started quickly. Specific antibiotic therapy is optimally driven by microbiologic diagnosis, predicated on isolation of the pathogenic organism, and supported by antimicrobial susceptibility testing. However, given the inherent difficulties that can arise in collecting specimens from pediatric patients, and given the high risk of mortality and disability associated with serious bacterial infections in very young infants, much of pediatric infectious disease practice is based on a clinical diagnosis with empirical use of antibacterial agents. Therefore, it is important to know the age-appropriate differential diagnosis with respect to likely pathogens. This information affects the choice of antimicrobial agent and also the dose, dosing interval, and route of administration. The patterns of antimicrobial resistance in the community and for the potential causative pathogen being empirically treated must also be considered. Antimicrobial resistance has reached crisis proportions, driven by the emergence of new resistance mechanisms and by overuse of antibiotics. It is important for practitioners to use antibiotics only as necessary, with the narrowest feasible antimicrobial spectrum, to help thwart emergence of resistance

Community-acquired pneumonia in children: updated perspectives on its etiology, diagnosis, and treatment

Pneumonia is a common pediatric infectious disease that is familiar to pediatricians and a major cause of hospitalization worldwide. Recent well-designed epidemiologic studies in developed countries indicated that respiratory viruses are detected in 30%–70%, atypical bacteria in 7%–17%, and pyogenic bacteria in 2%–8% of children hospitalized with community-acquired pneumonia (CAP). The etiological distribution of CAP varies widely by child age and the epidemiological season of the respiratory pathogen. Moreover, diagnostic tests, particularly for the detection of Streptococcus pneumoniae and Mycoplasma pneumoniae, the 2 major bacterial pathogens involved in pediatric CAP, have several limitations. Therefore, management and empirical antimicrobial therapy for children with CAP should be applied in a stepwise manner based on recent epidemiological, etiological, and microbiological evidence

Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

Monoclinic and Correlated Metal Phase in VO_2 as Evidence of the Mott Transition: Coherent Phonon Analysis

In femtosecond pump-probe measurements, the appearance of coherent phonon oscillations at 4.5 THz and 6.0 THz indicating the rutile metal phase of VO_2 does not occur simultaneously with the first-order metal-insulator transition (MIT) near 68^oC. The monoclinic and correlated metal(MCM) phase between the MIT and the structural phase transition (SPT) is generated by a photo-assisted hole excitation which is evidence of the Mott transition. The SPT between the MCM phase and the rutile metal phase occurs due to subsequent Joule heating. The MCM phase can be regarded as an intermediate non-equilibrium state.Comment: 4 pages, 2 figure

Usefulness of interferon-γ release assay for the diagnosis of latent tuberculosis infection in young children

PurposeLatent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-γ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI.MethodsWe performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011–June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol.ResultsAmong 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-γ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-γ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects.ConclusionThe lack of decrease in interferon-γ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients

Hyperchloremia is associated with poor renal outcome after coronary artery bypass grafting

Background Hyperchloremia is associated with the risks of several morbidities and mortality. However, its relationship with acute kidney injury (AKI) and end-stage renal disease (ESRD) in patients undergoing coronary artery bypass grafting (CABG) remains unresolved. Methods A total of 2977 patients undergoing CABG between 2003 and 2015 were retrospectively reviewed from two tertiary hospitals. Patients were categorized by serum chloride levels into normochloremia (95–105 mmol/L), mild hyperchloremia (106–110 mmol/L), and severe hyperchloremia (> 110 mmol/L). The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD were calculated after adjustment for multiple covariates. The death-adjusted risk of ESRD was additionally evaluated. Results Postoperative AKI occurred in 798 patients (26.5%). The hyperchloremia group had a higher risk of AKI than the normochloremia group, wherein the risk was incremental depending on the severity of hyperchloremia, as follows: ORs were 1.26 (1.06–1.51) and 1.95 (1.52–2.51) in the mild and severe hyperchloremia groups, respectively. During a median period of 7 years (maximum 15 years), 70 patients (2.3%) had ESRD. The severe hyperchloremia group was at an elevated risk of ESRD compared with the normochloremia group, with an HR of 2.43 (1.28–4.63). Even after adjusting for the competing risk of death, hyperchloremia was associated with the risk of ESRD. Conclusions Preoperative hyperchloremia is associated with poor renal outcomes such as AKI and ESRD after CABG. Accordingly, serum chloride should be monitored in patients undergoing CABG.This research was supported by grant No. 2019R1A2C1085411 from the National Research Foundation

Association of timed up and go test outcomes with future incidence of cardiovascular disease and mortality in adults aged 66 years: Korean national representative longitudinal study over 5.7 years

The timed up and go test (TUG) is one of the most widely used tests of mobility. We aimed to examine whether the TUG is associated with cardiovascular (CV) events, CV mortality, and all-cause mortality. Subjects in the senior cohort database of the Korean National Health Insurance Service (2002–2013) who completed the TUG as part of the National Screening Program for Transitional Ages (NSPTA) during 2007–2008 were identified. An abnormal TUG result was defined as a time ≥ 10 s. Cox proportional hazard models were used to assess the associations between TUG results and CV events, CV mortality, and all-cause mortality. The mean follow-up period was 5.7 years. Incidence rates of CV events in the normal and abnormal TUG groups were 7.93 and 8.98 per 1000 person-years, while CV mortality rates were 0.96 and 1.51 per 1000 person-years, respectively. In a fully adjusted model, we found that abnormal TUG results were not associated with the incidences of CV events and CV mortality. However, abnormal TUG results (≥10 s) resulted in a 2.9-fold increase in CV mortality in women (adjusted hazard ratio 2.90, 95% confidence interval 1.15–7.30). Further, participants lacking certain CV risk factors, such as current cigarette smoking, obesity, or diabetes, had a higher CV mortality rate when TUG results were abnormal. Abnormal TUG results in subjects aged 66 years were associated with future CV mortality in women and in subjects without obesity, diabetes, or cigarette smoking. In patient with mobility impairment, physicians should consider CV disease risk, especially in women.This study was supported by the Hammi Group [0620140890 (2013–2607)], Seoul, Korea. The funder had no role in the design or conduct of the stud

Altered renal sodium transporter expression in an animal model of type 2 diabetes mellitus

Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance

A Case of Minimal Change Disease Treated Successfully with Mycophenolate Mofetil in a Patient with Systemic Lupus Erythematosus

The World Health Organization classifies lupus nephritis as class I to V or VI. However, a few cases of minimal change glomerulopathy have been reported in association with systemic lupus erythematosus (SLE). Mycophenolate mofetil has been shown to be effective for treatment of minimal change disease and lupus nephritis. A 24-year-old woman diagnosed with SLE five years prior to presentation complained of a mild generalized edema. The urinalysis showed microscopic hematuria and proteinuria. The assessed amount of total proteinuria was 1,618 mg/24 hours. A renal biopsy demonstrated diffuse fusion of the foot processes of podocytes on electron microscopy. Mycophenolate mofetil was started in addition to the maintenance medications of prednisolone 10 mg/day and hydroxychloroquine 400 mg/day. After six months of treatment, the microscopic hematuria and proteinuria resolved, and the total urine protein decreased to 100 mg/24 hours

Proteinuria in a Boy with Infectious Mononucleosis, C1q Nephropathy, and Dent's Disease

C1q nephropathy is a proliferative glomerulopathy with extensive mesangial deposition of C1q. A three-year old boy presented with a nephrotic-range proteinuria during an acute phase of Epstein-Barr virus (EBV) infection, and he had a family history of Dent's disease. The renal biopsy findings were compatible with C1q nephropathy. However, EBV in situ hybridization was negative. The CLCN5 gene analysis revealed an R637X hemizygous mutation, which was the same as that detected in his maternal cousin, the proband of the family. The causal relationship between EBV infection and C1q nephropathy remains to be determined. Moreover, the effects of underlying Dent's disease in the process of C1q nephropathy has to be considered