Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

BACKGROUND: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity. CONCLUSIONS: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

Skin thickness in neonates: Implications for intradermal vaccination.

INTRODUCTION: Intradermal (ID) injection is an alternate route that enhances vaccine immunogenicity and decreases vaccine dose. Regular immunization usually starts at age 2 months, and the limited immune capacity of neonates and young infants makes them vulnerable to infection. Successful ID vaccine delivery in this population requires knowledge of skin thickness. Although skin thickness has been evaluated in infants aged 2 months or older, no comparable data are available for neonates, including preterm neonates. METHODS: This prospective observational study used ultrasonography to assess skin thickness in 70 neonates (35 full-term and 35 preterm neonates) at deltoid, suprascapular, and thigh sites. The measurements were compared in relation to anatomical site, between full-term and preterm infants, and with skin thickness values for children aged 2 months or older, which were collected in our previous study using the same measurement technique. RESULTS: In full-term neonates, skin was significantly thicker at the suprascapular site than at the deltoid and thigh sites (P < 0.05); in preterm neonates, skin was significantly thicker at the suprascapular site than at the thigh site (P < 0.05). Skin thickness values at all three sites were significantly lower in preterm neonates than in full-term neonates (P < 0.05). As compared with skin thickness values for infants aged 2 months, values for full-term neonates were significantly lower for the deltoid and suprascapular sites (P < 0.001). CONCLUSIONS: Skin thickness values for neonates were affected by prematurity and were significantly lower than those for infants aged 2 months. These findings are important in the design of ID injection devices for neonates and young infants.

Role of Maternal Antibodies in Infants with Severe Diseases Related to Human Parechovirus Type 3.

Human parechovirus type 3 (HPeV3) is an emerging pathogen that causes sepsis and meningoencephalitis in young infants. To test the hypothesis that maternal antibodies can protect this population, we measured neutralizing antibody titers (NATs) to HPeV3 and other genotypes (HPeV1 and HPeV6) in 175 cord blood samples in Japan. The seropositivity rate (≥1:32) for HPeV3 was 61%, similar to that for the other genotypes, but decreased significantly as maternal age increased (p<0.001). Furthermore, during the 2014 HPeV3 epidemic, prospective measurement of NATs to HPeV3 in 45 patients with severe diseases caused by HPeV3 infection showed low NATs (≤1:16) at onset and persistently high NATs (≥1:512) until age 6 months. All intravenous immunoglobulin samples tested elicited high NATs to HPeV3. Our findings indicate that maternal antibodies to HPeV3 may help protect young infants from severe diseases related to HPeV3 and that antibody supplementation may benefit these patients.

Skin thickness in young infants and adolescents: Applications for intradermal vaccination.

As compared with standard intramuscular and subcutaneous vaccines, intradermal (ID) vaccines elicit a more potent immune response in both adults and children, with equivalent dosage or antigen dose sparing. Recently, various devices for ID injection have been developed; the length of needles ranges in 0.6-1.5 mm. However, skin thickness must be measured to determine optimal needle length for ID vaccines. Use of ID vaccines in infants and children is appealing because children require more vaccines than do adults; however, information on skin thickness in infants and children is limited. We used ultrasound echography to measure skin thickness in Japanese infants aged 2 months (n=78) and adolescents aged 13-15 years (n=82). Mean (range) deltoid and suprascapular skin thickness was 1.67 mm (1.16-2.39 mm) and 1.83 mm (1.24-2.60 mm), respectively, in infants and 1.81 mm (1.25-3.00 mm) and 2.43 mm (1.51-3.95 mm), respectively, in adolescents. Among infants who underwent re-measurement of skin thickness at age 6 months (n=11), mean deltoid skin thickness (1.84 mm) was significantly greater than at age 2 months (1.60 mm) (P<0.001). In contrast, no significant difference was observed in suprascapular skin thickness (1.79 mm vs. 1.67 mm, respectively; P=0.17). Gender was not associated with skin thickness in either age group. Skin thickness was positively correlated with body weight in adolescents (r=0.43, P<0.001 in deltoid region; r=0.30, P=0.01 in suprascapular region). In conclusion, this is the first study to evaluate skin thickness in different age groups of children, including at age 2 months. Skin thickness gradually increased from age 2 months to age 13-15 years, but no consistent trend was noted in analysis stratified by measurement site, gender, or age. These findings suggest that an appropriate length of ID device needle for infants and children is likely to be less than 1.2mm and a special device with shorter length of needle is warranted for infants and children.

Hyponatremia due to an excess of arginine vasopressin is common in children with febrile disease.

Hypotonic fluids are commonly used for treating hospitalized children. However, an excess of arginine vasopressin (AVP) with impaired free water excretion is thought to contribute to the development of hyponatremia in febrile children. The aim of this two-part study was to define the clinical relationship between hyponatremia and excess AVP. In a retrospective study carried out between 2001 and 2005, we found that approximately 17% of the hospitalized patients had hyponatremia [serum sodium (Na) < 135 mEq/l] upon admission and that the ratio of patients with hyponatremia was significantly higher among febrile patients than among afebrile patients. In a subsequent prospective study, we examined 73 hospitalized patients who presented with acute febrile diseases accompanied by hyponatremia (serum Na <134 mEq/l). Almost all of these patients demonstrated excess AVP, defined as high plasma AVP levels (>1 pg/ml). There were no significant relationships between the levels of AVP and other laboratory variables, including serum sodium, serum osmolality, atrial natriuretic peptide, and brain natriuretic peptide. About 30% (22/73) of the patients fulfilled the criteria of the syndrome of inappropriate secretion of antidiuretic hormone. These findings suggest that fever and other nonosmotic stimuli lead directly to excess AVP and hyponatremia. We therefore recommend that isotonic fluids should be used for patients with prolonged fever and hyponatremia.

Assessment of tear concentrations on therapeutic drug monitoring. III. Determination of theophylline in tears by gas chromatography/mass spectrometry with electron ionization mode.

A simple and sensitive method for the quantitation of theophylline (TP) in tears and plasma developed using gas chromatography/electron-impact ionization/mass spectrometry. Tears were collected by non-invasive Schirmer method. Plasma was pipetted on a Schirmer tear test strip (cutting to 5 mm x 5 mm). Then, TP was converted directly into its pentafluorobenzoyl amide derivative without the need to perform any extraction from the biological fluid absorbed on Schiemer test paper and was quantified by gas chromatography-selected ion recordings with electron ionization mode. The concentrations in tears [C]t correlated very well with those of the free form in the plasma [Cf]p and those of the total form in the plasma [Cb+f]p. The ratios between TP concentrations in tears and plasma (free and total form) were as follows: [C]t/[Cb+f]p=0.53+/-0.20; [C]t/[Cf]p=1.21+/-0.19; [Cf]p/[Cb+f]p=0.44+/-0.14. The ratios of [C]t/[Cb+f]p, [C]t/[Cf]p and [Cf]p/[Cb+f]p were in good agreement with the previously published data.