Vitamin K prophylaxis in neonates: comparing two different oral regimens.

OBJECTIVE: This prospective study compared PIVKA-II and PT-INR levels in infants who received two vitamin K (VK) prophylactic regimens. METHODS: A single institution administered 119 healthy newborns 2 mg of VK syrup. Infants were assigned to a 3-time regimen (n = 56) with VK at birth, five days (5D), and 1-month-old (1 M), or a 13-time regimen (n = 63) with VK at birth, 5D, and then weekly for 11 weeks. RESULTS: The 13-time regimen significantly lowered PIVKA-II and reduced PT-INR at 1 M in both breastfed (PIVKA-II: 18-16 mAU/mL, p = 0.02; PT-INR: 1.37-1.13, p < 0.01) and formula-fed infants (PIVKA-II: 18-15 mAU/mL, p = 0.01; PT-INR: 1.54-1.24, p < 0.01), compared to baseline measurements taken at 5D. The 3-time regimen did not significantly alter PIVKA-II levels and only improved PT-INR (2.00-1.50, p < 0.01) in formula-fed infants. CONCLUSION: The 13-time VK regimen significantly enhanced coagulation profiles more effectively than the 3-time regimen.

A young child with pediatric multisystem inflammatory syndrome successfully treated with high-dose immunoglobulin therapy.

Pediatric multisystem inflammatory syndrome (MIS-C) is a disease that presents mainly in older children after coronavirus disease 2019 (COVID-19) and is associated with Kawasaki-like symptoms and multiple-organ failure. The number of cases of MIS-C has increased since April 2020, with reports mainly from Europe and the United States. The reason is unclear, but few cases of MIS-C have been reported in Asian countries, including Japan. No treatment has been established for MIS-C. In this study, we report the case of a young boy treated with IVIg for MIS-C by measuring the cytokine profile over time. A 4-year-old boy presented with Kawasaki disease-like symptoms 28 days after a positive result from polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), meeting the World Health Organization criteria for MIS-C diagnosis. Blood tests showed lower levels of C-reactive protein and ferritin, and no decrease in lymphocyte count (<1000/µL) or more increase in fibrinogen than those reported in Japan for MIS-C in school-aged children and older. Neopterin, interleukin (IL)-6, IL-18, soluble tumor necrosis factor receptor (sTNF-R)I and sTNF-RII were all high at disease onset, but neopterin, IL-6, and sTNF-RII rapidly decreased with fever resolution after the second dose of IVIg, while IL-18 and sTNF-RI decreased bimodally. As far as we can determine, this case represents the youngest identified in Japan. The key point of difference between MIS-C and Kawasaki disease is older age in MIS-C, but attention is also needed in infants.

Thyroid function in patients with selenium deficiency exhibits high free T4 to T3 ratio.

Selenium, one of the essential trace minerals, is present in vivo in form of selenoproteins. Iodothyronine deiodinase, a selenoprotein, is involved in the activation and inactivation of thyroid hormone. Therefore, patients with selenium deficiency may present changes in thyroid hormone levels due to inhibition of T4 to T3 conversion; however, this assumption is still under debate. In the present study, we retrospectively investigated the thyroid function in 22 patients with selenium deficiency. Thyroid stimulating hormone (TSH) and free T4 (FT4) levels were increased in 3 (14%) and 5 (23%) patients, respectively, and free T3 (FT3) levels were decreased in 6 (27%) patients. The FT4/FT3 ratio was significantly higher in patients with selenium deficiency than that in the control group. There appeared to be a positive correlation between the decreased rate of selenium levels and FT4/FT3 ratio, thereby indicating that patients with severe selenium deficiency also exhibited abnormal thyroid hormone levels. Furthermore, when selenium was supplemented in seven patients with abnormal thyroid hormone levels, the TSH, FT4, and FT4/FT3 ratio were significantly decreased and FT3 levels were increased. Collectively, patients with selenium deficiency could present the characteristics of not only low FT3 but also high FT4 and FT4/FT3 ratio.

Risk factors of malnutrition in children with severe motor and intellectual disabilities.

BACKGROUND: Children with severe motor and intellectual disabilities (SMID) are at a high risk of malnutrition and often require tube feeding to maintain their nutritional status. However, determining their energy requirements is difficult since inadequate dietary intake, severe neurological impairment, respiratory assistance, and cognitive impairment are all factors that affect malnutrition in SMID. AIM: This study investigated the factors affecting malnutrition and identified problems affecting the nutritional status of children with SMID. METHODS: Forty-two children with SMID with oral motor dysfunction who were receiving home medical care at one of four hospitals were enrolled. Their nutritional status was assessed using a 3-day dietary record, anthropometric measurements, and laboratory tests. The clinical findings associated with malnutrition were compared, and a body mass index (BMI) z-score less than -2SD was defined as malnutrition. The relationship between BMI z-score and other potential predictors was also investigated. RESULTS: Thirty-three (79%) children received tube feeding, and 20 (48%) experienced malnutrition. The median age of the malnourished children was older than that of non-malnourished children. Respiratory assistance was significantly correlated with higher BMI z-score, independent of other potential confounders such as nutrition method, muscle tonus, and energy intake. Cholesterol levels were significantly higher in children receiving a standard infant formula beyond 3 years of age than in those who switched to enteral formula before 3 years of age. CONCLUSIONS: Malnutrition in children with SMID was mainly associated with age or respiratory condition. Energy requirements should be regularly re-evaluated with considering these factors.

Prevalence of undernutrition in Japanese pediatric patients on admission: Comparison of tertiary, acute-care, and rehabilitation hospitals.

BACKGROUND AND OBJECTIVES: There exist many studies in Western countries dealing with pediatric nutritional assessment on admission, but those in Asian countries are comparatively limited. This study aimed at clarifying the prevalence of undernutrition in 3 Japanese pediatric hospitals, especially focusing on their different characteristics. METHODS AND STUDY DESIGN: Study participants included 313 patients aged 1-17 years admitted to a tertiary hospital (175 patients), an acute-care hospital (99 patients), or a rehabilitation hospital (39 patients). On admission, body height, weight, and serum albumin were measured. BMI was calculated by dividing the weight (kg) by the square of height (m). Patients exhibited undernutrition on account of BMI z-score <-2, weight-for-height (W/H) <90%, height-for-age (H/A) <95%, or albumin <3.5 g/dL. RESULTS: The overall prevalence of undernutrition was 53.0%. Among 4 nutritional measures, the prevalence was highest in H/A (33.9%), followed by W/H (26.8%), BMI z-score (17.6%) and albumin (12.8%). A rehabilitation hospital exhibited significantly higher prevalence than that in a tertiary- or acute-care hospital. By the classification of International Statistical Classification of Diseases and Related Health Problems-10, neurological diseases and congenital anomalies showed higher prevalence among the disease categories which had the number of enrolled patients more than twenty. CONCLUSIONS: This study indicates that hospital characteristics and inpatient disease categories are important in the admission evaluation of the likelihood of undernutrition. These observations require consideration by hospital physicians in paediatric nutritional diagnosis and management.

Increased oxidative stress in patients with severe disability: Association with nutrition.

BACKGROUND: Previous studies have described a role of oxidative stress in the pathogenesis of various pediatric disorders, but investigation into oxidative stress status in patients with severe disability remains limited. The aim of the present study was therefore to clarify the oxidative stress status in patients with severe disability, focusing specifically on intake of three major nutrients and micronutrients with antioxidant activities. METHODS: Thirty-one patients with severe disability (mean age, 14.1 ± 7.8 years) were enrolled. Three in vivo biomarkers, plasma biological antioxidant potential (BAP), plasma reactive oxygen metabolite-derived compounds (d-ROM), and urinary 8-hydroxydeoxyguanosine (8-OHdG), were determined for evaluating oxidative status. The dietary intake of three major nutrients and various micronutrients was estimated from dietary records over a 3 day period. RESULTS: In patients with severe disability, BAP was significantly lower and d-ROM and 8-OHdG significantly higher than in historical controls. Among these markers, a significant positive correlation was found in BAP versus d-ROM and d-ROM versus 8-OHdG. On multiple regression analysis, a significant inverse association between 8-OHdG and carotenoid intake was seen. CONCLUSION: The oxidative/antioxidative balance shifts towards oxidative status dominance in patients with severe disability. More research is needed on nutritional intake of antioxidative nutrients to determine whether they can be used to reduce oxidative stress.

Diffusion-weighted MRI for early diagnosis of neonatal herpes simplex encephalitis.

AIM: To determine the early changes and evolutions of brain diffusion-weighted imaging (DWI), and analyze prognostic factors of the early changes among patients with neonatal herpes simplex encephalitis (NHSE). METHOD: We selected patients who developed encephalitis by 28 d after birth; had herpes simplex infection; and who underwent magnetic resonance imaging, including DWI, ⩽7 d of symptom onset. Thirty-two DWI scans between 0 and 28 d after onset in 13 patients and the clinical data were recruited. The distribution, evolution of the lesions, and neurological outcome were analyzed. RESULTS: DWI frequently showed multiple cortical lesions in both hemispheres in the early period and both hemispheres on DWI (8/9 scans at ⩽48 h, 7/7 patients). As time from onset increased, the cortical lesions tended to coincide with subcortical white matter lesions beneath the initial cortical lesions (p<0.01). Lesions from the cortex extended to the subcortical white matter in 7 patients. Deep cerebral lesions, involving basal ganglia, internal capsules, thalamus, were also found in 9 patients ⩽7 d of onset. The distributions of deep cerebral lesions (none/unilateral/bilateral) ⩽7 d of onset showed significant correlations with neurological prognoses (gross motor functions: p<0.01; developmental or intellectual quotient scores: p<0.01). INTERPRETATION: Cortical lesions were main findings of DWI in NHSE in the early period. Bilateral deep cerebral lesions ⩽7 d were highly indicative of poor motor and cognitive outcomes.

Carnitine in severely disabled patients: relation to anthropometric, biochemical variables, and nutritional intake.

BACKGROUND: Carnitine plays a pivotal role in a variety of cellular functions. Carnitine deficiency often occurs in severely disabled patients, especially under valproic acid administration. However, the possible causative factors underlying carnitine deficiency have not been fully identified. The present study aimed at clarifying the association of various anthropometric and biochemical variables, including dietary intake of carnitine, with carnitine levels in severely disabled patients. METHODS: Twenty-six severely disabled patients (mean age: 14.1 years; s.d. 7.8) were enrolled. Plasma carnitine levels were evaluated by an enzyme cycling assay. Estimation of the dietary intake of carnitine was made based on dietary records over a 3-day period. RESULTS: Plasma total and free carnitine levels in patients were significantly lower than those in controls obtained from the previous report. However, the ratios of free carnitine to total carnitine did not change significantly. Free carnitine levels were well correlated with a nutritional intake of carnitine. Administration of not only valproic acid but also other anti-epileptic drugs was found to cause a significant decrease of free carnitine levels after adjusting the nutritional intake of carnitine. Among various anthropometric or biochemical variables, albumin and uric acid showed a significant correlation with free carnitine levels. CONCLUSIONS: Physicians should be aware of the fact that severely disabled patients are at risk for carnitine deficiency even in the absence of valproic acid administration, and pay more attention to the nutritional intake of carnitine.

Children with Down's syndrome display high rates of hyperuricaemia.

AIM: Several studies show that hyperuricaemia, abnormally high levels of uric acid in the blood, frequently occurs in adult Down's syndrome patients, but paediatric research is scarce. We aimed to clarify its prevalence in paediatric Down's syndrome patients and its association with lifestyle-related laboratory variables and nutritional intake, to consider possible effects in later life. METHODS: We compared 52 Down's syndrome patients, from one to 15 years of age, with age-matched controls. Hyperuricaemia was defined using reference values established for children, as uric acid z-scores of more than 2.0. Nutritional intake was estimated using 3-day dietary records. RESULTS: Hyperuricaemia occurred in 17 Down's patients (32.7%) and was significantly higher in Down's patients than the controls. The prevalence was also significantly higher in males. There were no significant differences between hyperuricaemia-positive and hyperuricaemia-negative patients in terms of age, body mass index standard deviation scores, fasting blood glucose, insulin, homeostasis model assessment-insulin resistance and triglyceride, and purine body intake was similar. There were differences in high-density lipoprotein cholesterol. CONCLUSION: We found high rates of hyperuricaemia from early childhood in Down's syndrome patients. This suggests careful management of Down's syndrome patients, as hyperuricaemia is an independent risk factor for lifestyle-related diseases in adulthood.

Efficacy of micafungin in treating four premature infants with candidiasis.

BACKGROUND: Although clinical experience in neonates with candidiasis exists for amphotericin B and fluconazole, these standard treatments are often hindered by drug-associated toxicity or development of resistant strains. The aim of the present study was therefore to investigate the efficacy and tolerability of a new antifungal agent, micafungin (MCFG), for treating Candida infections in premature infants. METHODS: This was a retrospective cohort study. Premature infants diagnosed with Candida infections from October 2003 to July 2004 were brought to the neonatal intensive care unit at the Center of Perinatal Medicine, Nara Medical University Hospital. Four newborns were given 0.5-1.0 mg/kg per day micafungin. RESULTS: Four premature infants (mean +/- SD gestational age, 24.1 +/- 0.9 weeks; mean +/- SD birthweight, 579.3 +/- 80.5 g) experienced complications from Candida infection; two cases of the fungal infection were caused by Candida glabrata and two cases were caused by Candida albicans. MCFG was administered at 0.5 or 1.0 mg/kg per day (mean dosage days, 9.8 +/- 3.1 days) and it decreased beta-D-glucan levels while improving clinical symptoms in all cases. Additionally, there were no apparent side-effects. CONCLUSION: MCFG is both effective and tolerable for use in premature infants suffering from Candida infections.

[Case of severe streptococcus pyogenes pneumonia with streptococcus toxic shock syndrome].

A 30-year-old woman who had until recently been healthy, was transferred to our hospital by ambulance with complaints of dyspnea and pain in both lower limbs. She had 1-week history of sore throat, fever and cough. She had been to a neighboring clinic three days previously, and had been prescribed some medication for bronchitis, but her symptoms had not improved. By the time of admission, she was already in shock and had severe respiratory failure. Laboratory data showed renal dysfunction, disseminated intravascular coagulation, CPK elevation and severe metabolic acidosis. Chest x-ray and CT films revealed consolidation of the entire right lung field. The patient was quickly intubated and we began mechanical ventilation. We immediately initiated broad-spectrum antibiotics, immunogloblin, dopamine hydrochloride and gabexate mesilate, but she died 7 hours later. From cultures of blood and sputum taken from the patient, Streptococcus pyogenes was isolated. On the basis of these clinical and bacteriological findings, we confirmed a diagnosis of pneumonia and toxic shock syndrome caused by Streptococcus pyogenes (STSS). Serologically her M protein was serotyped as M1, and with regard to Streptococcal pyrogenic exotoxin genes were identified as speA and speB. These serological findings were consistent with the most frequent type that causes STSS. In spite of the uncommon cause of community-acquired pneumonia, Streptococcus pyogenes can potentially affect healthy individuals. The pneumonia can be complicated with STSS and so the clinical course may be severe and fulminant. The evidence acquired from this case suggests that in the event of severe pneumonia with shock, we should be aware that this may represent the presence of Streptococcus pyogenes and/or toxic shock syndrome.

Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia.

Propionic acidemia (PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase. This enzyme is composed of two non-identical subunits, alpha and beta, which are encoded by the PCCA and PCCB genes, respectively. An enzyme deficiency can result from mutations in either PCCA or PCCB. To elucidate the mutation spectrum in Japanese patients, we have performed a mutation analysis of 30 patients with PA, which included nine previously reported patients. The study revealed that 15 patients were alpha-subunit deficient and 15 patients were beta-subunit deficient. Seven novel mutations were found (IVS18-6C >G, 1746G >A, C398R, G197E and IVS18+1G >A in the PCCA; A153P and IVS9+1G >T in the PCCB). Among these Japanese patients with alpha-subunit deficiencies, 923-924insT, IVS18-6C >G, and R399Q mutations were frequent and the total allelic frequency of these three mutations combined was 56% (17/30). This is in sharp contrast to the mutation spectrum found in Caucasian patients, where no prevalent mutations have been identified. Among the beta-subunit deficiencies, there were three frequent mutations; R410W, T428I, and A153P, whose allelic frequencies were 30, 26.7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia.

The in vitro analysis of the coagulation mechanism of activated factor VII using thrombelastogram.

We investigated the effects of addition of recombinant activated coagulation factor VII (rFVIIa) to coagulation factor-deficient plasma and whole blood, using thrombelastograms (TEGs). The addition of rFVIIa to factor II- or X-deficient plasma did not correct hemostatic parameters, whereas it produced partial responses in factor V-, VIII- or IX-deficient plasma and good responses in factor VII-, XI- or XII-deficient plasma. Furthermore, the addition of rFVIIa and platelets (30-100 x 10(3)/ micro l) to platelet-poor plasma produced marked corrections, producing TEGs similar to those of platelet-rich plasma. These results indicate that factors II and X are essential for the hemostatic effects of rFVIIa, and that factors V and VIII promote these effects. We believe that TEGs are, at present, one of the most useful tools for evaluating in vitro hemostatic effects of rFVIIa.