Hong-Ryang Kil

Early corticosteroid treatment for severe pneumonia caused by 2009 H1N1 influenza virus

A pandemic of the 2009 H1N1 influenza A virus infection occurred worldwide in 2009. Some previously healthy patients experienced rapidly progressive pneumonia leading to acute respiratory distress syndrome (ARDS) and even death. The effect of corticosteroids on these severely affected patients is controversial because of a lack of controlled clinical trials [1]. During the pandemic in South Korea, we observed that early, short-term corticosteroid treatment along with oseltamivir seemed to have a dramatic effect on patients with severe pneumonia, and we proposed a new theory for the pathogenesis of acute lung injury in influenza virus infections [2]. In that study, we wanted to evaluate this beneficial effect of corticosteroid treatment through comparative data based on the use or non-use of corticosteroids at two separate hospitals. The subjects of the study were the pneumonia patients who had severe respiratory distress with hypoxemia at presentation or during admission and who thus required oxygen therapy. The conditions of 17 patients (median of 6 years of age, range of 4 to 9) in our hospital (The Catholic University of Korea, Daejeon St Marys Hospital, Daejeon, South Korea) (use of corticosteroids) and 15 patients (median of 6 years of age, range of 5 to 18) in a neighboring hospital (Chungnam National University Hospital, Daejeon, South Korea) (non-use of corticosteroids) were diagnosed by reverse transcriptase-polymerase chain reaction. The clinical and laboratory characteristics of patients in the two hospitals are shown in Table ​Table1.1. Our results suggested that the severe pneumonia patients who were treated with corticosteroids showed shortened durations of fever and oxygen therapy, rapid resolution of pneumonic infiltrations, and possibly no progression to ARDS. Table 1 Clinical and laboratory characteristics of severe pneumonia patients infected with the 2009 H1N1 virus, with and without corticosteroid treatment It is reported that corticosteroid treatment for adult ARDS patients with 2009 H1N1 virus infection was effective in the improvement of lung injury score [3]. Two recent case series suggest a possible life-saving role of corticosteroids in severely ill adult patients with 2009 H1N1 virus infection unresponsive to other treatments [4,5]. Corticosteroids may not increase the viral load of the patients [4]. To the best of our knowledge, our study may be the first trial addressing an early and preemptive modality before ARDS development in influenza virus infections. Our policy of corticosteroid treatment with a rapid, high-dose (methylprednisolone, 10 mg/kg per day), and short-term (tapered off within a week) schedule did not show any complications in our patients and may avoid the complications that arise from long-term corticosteroid use. Although rapid corticosteroid treatment for patients with severe pneumonia halted clinical and radiographic exacerbation and possibly prevented progression to ARDS in our series, further controlled clinical trials are needed to evaluate the role of corticosteroids for severely affected patients with influenza virus infections.

A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease

Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10−5), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10−11). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10−6) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33–1.51, P=8.93 × 10−6 to 5.24 × 10−8). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10−6). These results provide new insights into the pathogenesis and pathophysiology of KD.

Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment

Purpose This study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients. Methods Clinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204). Results The mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other. Conclusion The severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

BCL2L11 Is Associated With Kawasaki Disease in Intravenous Immunoglobulin Responder Patients

Kawasaki disease (KD) is a self-limited systemic vasculitis of an unknown pathogenesis mainly affecting children <5 years old. KD is a clinically heterogeneous disease; its diagnosis is based on common clinical symptoms, and there is no specific diagnostic test for it. Complete KD is diagnosed when subjects have at least 5 of the following 6 principal clinical signs: fever persisting for ≥5 days, bilateral conjunctival congestion, changes to the lips and oral cavity, polymorphous exanthema, changes to peripheral extremities, and acute nonpurulent cervical lymphadenopathy. The standard treatment for KD is high-dose intravenous immunoglobulin (IVIG), manufactured from normal human immunoglobulin purified from the full plasma of a thousand healthy donors; it reduces the duration of fever and the incidence of coronary artery abnormalities. The anti-inflammatory effects of IVIG are manifested in a wide range of pathological conditions, including immune thrombocytopenia, systemic lupus erythrematosus, Guillain–Barre syndrome, and others. Despite IVIG therapy, however, ≈15% of patients with KD have persistent or recurrent fever with a high risk for coronary artery lesions. In our KD patients data, we also observed significant differences in clinical variables between …

Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease

Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in FCGR2A [odds ratio (OR) = 1.40, P = 9.31 × 10−5], rs12516652 in SEMA6A (OR = 1.87, P = 3.12 × 10−4), and rs5771303 near IL17REL (OR = 1.57, P = 2.53 × 10−5). The male-specific association of FCGR2A, but not SEMA6A and IL17REL, was also replicated in a Japanese population (OR = 1.74, P = 1.04 × 10−4 in males vs. OR = 1.22, P = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in FCGR2A was confirmed in males (OR = 1.48, P = 1.43 × 10−7), but not in the females (OR = 1.17, P = 0.055). The present study demonstrates that p.His167Arg, a KD-associated FCGR2A variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with FCGR2A in KD provide a new insight into KD susceptibility.

Successful use of low molecular weight heparin in intracardiac thrombus of an extremely low birth weight infant.

The sick premature infants have high risk for thrombosis. Although therapeutic options include close observation, anticoagulation, thrombolytic therapy, and thrombectomy, guidelines for the management of neonatal arterial and venous thrombosis vary greatly among different centers. The authors report their experience using low molecular weight heparin (enoxaparin), with safe and successful resolution of right atrial thrombus, in an extremely low birth weight infant.

P wave dispersion on 12-lead electrocardiography in adolescents with neurocardiogenic syncope.

Purpose Neurocardiogenic syncope (NCS) is the most frequent cause of fainting during adolescence. Inappropriate cardiovascular autonomic control may be responsible for this clinical event. The head-up tilt test has been considered a diagnostic standard, but it is cumbersome and has a high false-positive rate. We performed a study to evaluate whether P-wave dispersion (PWD) could be a useful electrocardiographic parameter of cardiac autonomic dysfunction in children with NCS. Methods Fifty-four patients with NCS (28 boys and 26 girls; mean age, 12.3±1.4 years) and 55 age- and sex-matched healthy controls were enrolled. PWD was obtained as the difference between maximum and minimum durations of the P wave on standard 12-lead electrocardiography in all patients and controls Results The value of PWD was significantly higher in the syncope group than in the control group (69.7±19.6 msec vs. 45.5±17.1 msec, respectively; P<0.001). The minimum duration of P wave was shorter in the syncope group than in the control group (43.8±16.8 msec vs. 53.5±10.7 msec, respectively; P<0.001). Left atrial volume was not different between the groups on transthoracic echocardiography Conclusion PWD on echocardiography could be used as a clinical parameter in patients with NCS.