Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2.

Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.

Serum periostin levels correlate with airway hyper-responsiveness to methacholine and mannitol in children with asthma.

BACKGROUND: Periostin is a matricellular protein, and its synthesis in airway epithelial cells and lung fibroblasts is induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of TH 2-induced airway inflammation, and (importantly) as a measure of the response to TH 2-targeted therapy, has recently been emphasized. We explored the relationship between periostin and airway hyperresponsiveness (AHR) in asthmatic children. METHODS: The study included 83 children aged 6-15 years in an asthmatic group (n = 54) and healthy controls (n = 29). We measured the periostin levels in serum and performed methacholine and mannitol provocation challenges. The responses to mannitol were expressed as the provocative dose causing a 15% fall in the FEV1 (the PD15 dose). RESULTS: Of the 54 subjects with asthma, all had positive methacholine bronchial provocation test (BPT) results and 38 had positive mannitol BPT results. Children with asthma had significantly higher periostin levels than controls [76.0 (65.0-91.8) vs 71.0 (57.5-80.0) ng/mL; P = 0.017]. Periostin levels were significantly correlated with both the methacholine PC20 and mannitol PD15 values. CONCLUSION: Serum levels of periostin, a new biomarker induced by IL-13, were higher in asthmatic children, and were associated with AHR to methacholine and mannitol.

Serum leucine-rich α2-glycoprotein is a useful biomarker for monitoring disease activity in patients with adult-onset Still's disease.

OBJECTIVE: To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are elevated in patients with adult-onset Still's disease (AOSD) and determine their correlation with disease activity parameters. METHOD: We enrolled 39 patients with AOSD, 47 patients with rheumatoid arthritis (RA), and 39 controls. Forty-five serum samples from the patients with AOSD were assayed for LRG using an enzyme-linked immunosorbent assay (ELISA). Comprehensive AOSD activity was determined by a modified Pouchot score. RESULTS: Serum LRG levels were significantly elevated in patients with AOSD (128.8±40.8 ng/mL) compared to those in patients with RA and in controls (33.9±15.2 ng/mL, p<0.001 and 22.4±6.1 ng/mL, p<0.001, respectively). Patients with active AOSD had significantly higher LRG levels than those with inactive disease (141.4±31.3 ng/mL vs. 79.8±37.1 ng/mL, p=0.002). Serum LRG levels were positively correlated with C-reactive protein (CRP; γ=0.387, p=0.015), lactate dehydrogenase (LDH; γ=0.370, p=0.026), ferritin (γ=0.687, p<0.001) levels, and the modified Pouchot score (γ=0.756, p<0.001). Serum LRG levels decreased significantly after treatment in all six patients with active AOSD who had follow-up evaluations (p=0.007). The best cut-off value for LRG to distinguish AOSD from RA was 67.9 ng/mL, with a sensitivity of 92.3% and a specificity of 97.9%. CONCLUSIONS: Serum LRG levels were increased in patients with AOSD and correlated well with disease activity measures. LRG may be a useful biomarker for distinguishing AOSD from RA and for monitoring the disease activity of AOSD.

Risk factors for 30-day mortality in adult patients with pneumococcal bacteraemia, and the impact of antimicrobial resistance on clinical outcomes.

The clinical impact of antimicrobial resistance on the outcome of pneumococcal bacteraemia has remained unclear. This study aimed to evaluate risk factors for mortality and determine the impact of antimicrobial resistance on clinical outcomes. A total of 150 adult patients with pneumococcal bacteraemia were identified over a period of 11 years at Seoul National University Hospital. Of the 150 patients, 122 (81.3%) had penicillin-susceptible (Pen-S) strains and 28 (18.7%) penicillin-non-susceptible (Pen-NS) strains; 43 (28.7%) had erythromycin-susceptible (EM-S) strains and 107 (71.3%) erythromycin-non-susceptible (EM-NS) strains. On multivariate analysis, elevated APACHE II score [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.14-1.34, P<0.001) and presence of solid organ tumour (OR 2.99, 95% CI 1.15-7.80, P=0.025) were independent risk factors for mortality. Neither erythromycin resistance nor penicillin resistance had a significant effect on clinical outcomes. However, for the 76 patients with pneumococcal pneumonia, the time required for defervescence was significantly longer in the EM-NS group than in the EM-S group (5.45 ± 4.39 vs. 2.93 ± 2.56, P=0.03 by log rank test). In conclusion, antimicrobial resistance does not have an effect on mortality in adult patients with pneumococcal bacteraemia.

Effects of psychological behaviour management programme on dental fear and anxiety in children: A randomised controlled clinical trial.

AIM: A psychological behaviour management programme with information and communications technology was developed that includes symbolic modelling, tell-show-do, positive reinforcement and distraction, and provides real-time treatment information. We hypothesised that the programme would help patients feel less stressed and show less uncooperative behaviours and subjective pain. MATERIALS AND METHODS: Forty-eight paediatric patients were recruited from May 2016 to January 2017, and randomly divided into a control group and an experimental group. In the control, patients watched cartoon animations during the first and second treatments. The experimental group watched cartoon animations during the first treatment, and they used the programme during the second treatment. To measure stress, uncooperative behaviour and subjective pain, we recorded the heart rate, Procedure Behaviour Checklist (PBCL) and Wong and Baker's Faces Pain Rating Scale (FPRS). RESULTS: The experimental group resulted in a significantly lower mean heart rate, uncooperative behaviour and subjective pain in the second treatment than did the control group (p<0.001). The differences in heart rate and uncooperative behaviour between the treatments were also significantly greater in the experimental group than in the control group (p<0.001). CONCLUSION: The programme was effective in relieving fear and anxiety as well as learning cooperative behaviour.

Procoagulant and prothrombotic effects of the herbal medicine, Dipsacus asper and its active ingredient, dipsacus saponin C, on human platelets.

BACKGROUND: In spite of the growing popularity of herbal medicines and natural food supplements, their effects on cardiovascular homeostasis remain largely unknown, especially regarding pro-thrombotic risks. OBJECTIVE: In the present study, 21 herbal tea extracts were screened for the procoagulant activities on platelets, an important promoter of thrombosis to examine if herbal medicines or natural products may have prothrombotic risks. We discovered that Dipsacus asper (DA), known to have analgesic and anti-inflammatory effects, potently induced procoagulant activities in platelets. We tried to identify the active ingredient and elucidate the underlying mechanism. RESULTS: Among 10 major ingredients of DA, dipsacus saponin C (DSC) was identified as a key active ingredient in DA-induced procoagulant activities. DSC-induced procoagulant activities were achieved by the exposure of phosphatidylserine (PS) and PS-bearing microparticle generation that were caused by the alteration in the activities of phospholipid translocases: scramblase and flippase. These events were initiated by increased intracellular calcium and ATP depletion. Notably, DSC induced a series of apoptotic events including the disruption of mitochondrial membrane potential, translocation of Bax and Bak, cytochrome c release and caspase-3 activation. The key roles of apoptotic pathway and caspase activation were demonstrated by the reversal of DSC-induced PS exposure and procoagulant activities with the pretreatment of caspase inhibitors. Interestingly, EGTA reversed DSC-induced procoagulant activities and apoptotic events suggesting that an intracellular calcium increase may play a central role. These results were also confirmed in vivo where platelets of the rats exposed to DSC or DA exhibited PS exposure. Most importantly, DSC or DA administration led to increased thrombus formation. CONCLUSION: These results demonstrate that herbal medicines or natural products such as DA or DSC might have prothrombotic risks through procoagulant activation of platelets.

Case report. Sclerosing liver haemangioma with pericapillary smooth muscle proliferation: atypical CT and MR findings with pathological correlation.

We report a case of sclerosing liver haemangioma with pericapillary smooth muscle proliferation in a 63-year-old man who presented with abdominal pain. Because the tumour showed atypical features on CT and MRI, a correct diagnosis could not be made until surgery. In this report, the atypical radiological findings are illustrated and correlated with pathological findings.