A Salmonella enterica Serovar Oranienburg Clone Caused a Cluster of Bacteremia Cases in Persons With No Recognizable Underlying Diseases in Japan.

Background: Salmonella enterica subspecies enterica serovar Oranienburg (SO) is a foodborne pathogen but rarely causes systemic infections such as bacteremia. Between July and September 2018, bacteremia cases caused by SO were identified in 12 persons without any underlying medical conditions in the southern Kyushu area of Japan. Methods: Randomly amplified polymorphic DNA (RAPD) analysis was performed to investigate the genetic similarity of the 12 bacteremia-related strains and other Japanese isolates. Furthermore, a series of whole-genome sequence (WGS)-based phylogenetic analyses was performed with a global SO strain set (n = 1648). Results: The resolution power of RAPD was insufficient to investigate the genetic similarity between the bacteremia-related strains and other strains. WGS-based phylogenetic analyses revealed that the bacteremia-related strains formed a tight cluster along with 2 strains isolated from asymptomatic carriers in 2018 in the same area, with a maximum within-cluster single-nucleotide polymorphism (SNP) distance of 11. While several strains isolated in the United States and the United Kingdom were found to be closely related to the bacteremia-related strains, 2 strains isolated in 2016 in the southern Kyushu area were most closely related, with SNP distances of 4-11 and 5-10, and had the same plasmids as the bacteremia-related strains. Conclusions: The 12 bacteremia cases identified were caused by a single SO clone. As none of the bacteremia patients had any underlying diseases, this clone may be prone to cause bacteremia. Although further analyses are required to understand its virulence, particular attention should be given to this clone and its close relatives in the surveillance of nontyphoidal salmonellae.

Efficacy of bezafibrate for preventing myopathic attacks in patients with very long-chain acyl-CoA dehydrogenase deficiency.

BACKGROUND: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a mitochondrial fatty acid oxidation disorder that causes episodic attacks, such as general fatigue, hypotonia, myalgia, and rhabdomyolysis accompanied by lack of energy. As yet, there are no preventative drugs for these VLCADD-associated metabolic attacks. PATIENTS AND METHODS: We conducted an open-label, non-randomized, multi-center study into the effects of bezafibrate on five patients with VLCADD. Bezafibrate was administered for 4 years, and we analyzed the number of myopathic attacks requiring hospitalization and treatment infusions. RESULTS: The number of myopathic attacks requiring infusions of 24 h or longer significantly decreased during the study period. The patients' ability to conduct everyday activities was also improved by the treatment. CONCLUSION: Our findings show the potential long-term efficacy of bezafibrate in preventing myopathic attacks for patients with VLCADD.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan; 2nd report QOL survey.

INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by a defective mitochondrial fatty acid oxidation (FAO) enzyme. We recently reported that bezafibrate improved patient quality of life (QOL) based on the SF-36 questionnaire score in patients with FAODs during a 50-week, open-label, clinical trial. Herein we conducted further survey assessments of the trial patients to define the long-term efficacy and safety of bezafibrate. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in five patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and one patient with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 15.9 years; range, 5.8-26.4 years). The bezafibrate administration was continued for a further 102-174 weeks after the 24-week treatment described in our previous study. QOL was quantitated using the 36-Item Short Form Health Survey (SF-36) questionnaire, which constitutes eight components: physical functioning (PF), role limitation due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. RESULTS: PF was elevated in all patients and continued to rise during the study, with the total QOL scores increased from baseline in five of the six cases. In particular, three patients older than 20 years showed treatment efficacy, and all subcategories of QOL were elevated in two of these cases. CONCLUSION: Our findings supported one of the stated benefits of bezafibrate in improving QOL for patients with FAODs.

ß2 microglobulin and lactate dehydrogenase are indices of different features of Mycoplasma pneumoniae-associated community-acquired lower respiratory tract infection for severity evaluation in children.

Using the hospital records, we retrospectively assessed whether urinary ß2 microglobulin/creatinine ratio (UBCR) and lactate dehydrogenase (LD) values could be used to estimate the severity of Mycoplasma pneumoniae-associated lower respiratory tract infection (MP-LRTI). We studied 48 patients with MP-LRTI (median age, 7.5 years; range, 3-14 years) admitted to Kagoshima City Hospital and examined the relationships of the UBCR or LD values with fever and pulmonary tissue damage (hypoxemia and severity assessments on chest radiographs). Patients were assigned to four groups based on whether they had fever and/or hypoxemia. Patients with high fever showed significantly higher UBCR values than those without (P < 0.05), whereas those with hypoxemia showed higher LD values than those without (P = 0.001). The maximum body temperature on admission was closely associated with the UBCR but not with LD levels. In chest radiography assessments, LD levels were significantly higher in patients with severe than mild or moderate MP-LRTI. A cut-off LD level of 530 IU/L showed a very high sensitivity (100%) and specificity (93%). Although UBCR values were higher in patients with severe MP-LRTI, the differences were not statistically significant. Our study shows that the UBCR is associated with body temperature, whereas LD levels may serve as an index of pulmonary tissue damage in children with MP-LRTI.

Two siblings with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency suffered from rhabdomyolysis after l-carnitine supplementation.

INTRODUCTION: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive mitochondrial fatty acid oxidation disorder and presents as hypoketotic hypoglycemia or rhabdomyolysis during childhood. l-Carnitine supplementation for patients with VLCAD deficiency is controversial. Herein, we describe two siblings with VLCAD deficiency who experienced more frequent episodes of rhabdomyolysis after l-carnitine supplementation. CASE PRESENTATION: Case 1 involved a 6-year-old boy who was diagnosed with VLCAD deficiency after repeated episodes of hypoketotic hypoglycemia at 3 years of age. He developed rhabdomyolysis more frequently after starting l-carnitine supplementation. Case 2 involved an 8-year-old boy, the elder brother of case 1, who was also diagnosed with VLCAD deficiency by sibling screening at the age of 5 years. He first developed rhabdomyolysis during a common cold after treatment with l-carnitine. Both patients had fewer rhabdomyolysis episodes after the cessation of l-carnitine supplementation. CONCLUSION: Our cases suggest that l-carnitine supplementation can increase rhabdomyolysis attacks in patients with VLCAD deficiency.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan.

INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). RESULTS: The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. CONCLUSION: In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations.

Adipokines and the prediction of the accumulation of cardiovascular risk factors or the presence of metabolic syndrome in elementary school children.

BACKGROUND: Information is limited about how adipokines predict the accumulation of cardiovascular (CV) risk factors or the presence of metabolic syndrome (MS) in children. METHODS AND RESULTS: The subjects were 321 children (200 boys and 121 girls; 109 normal and 212 obese) aged 6-12 years. Obesity was defined as a body mass index of >or= the 95(th) percentile for age and sex. MS was defined by using the newly established Task Force criteria. The levels of the adipokines--adiponectin, leptin, ghrelin, high sensitive C-reactive protein (CRP) and resistin--were measured. Regression analyses revealed that high leptin levels were predictive of the accumulation of CV risk factors in normal weight, obese, and entire (normal weight and obese) group of subjects. High CRP in the normal weight group and low adiponectin in the obese and the entire groups were also independently predictive of the accumulation of risk factors. A high leptin level was solely predictive of the presence of MS in obese and entire groups. CONCLUSIONS: Leptin was the most sensitive marker for predicting the accumulation of CV risk factors and the presence of MS in elementary school children. Primary prevention is important because both leptin and adiponectin levels abruptly worsened when children obtained any 1 risk factor.

Association between the number of cardiovascular risk factors and each risk factor level in elementary school children.

BACKGROUND: Little is known regarding the association between numbers of cardiovascular (CV) risk factors and the level of each risk factor in elementary school children based on a longitudinal study. METHODS AND RESULTS: A descriptive study of 319 obese children aged 6-11 years who participated in a screening program for comorbidity of obesity between 2003 and 2005, and who participated in consecutive years thereafter, was performed. Abdominal obesity, hypertension, dyslipidemia (low high-density lipoprotein-cholesterol levels and/or high triglyceride levels), and raised fasting glucose levels were used as the CV risk factors. Metabolic syndrome and each CV risk factor were defined using the criteria newly established by a Task Force financed by the Health and Labour Science Research in Japan. An increase in the total number of CV risk factors implied a worsening of each CV risk factor level over a 1-year interval, and vice versa. Abdominal obesity in males and insulin resistance in females were prevalent in children who were at elementary school level. CONCLUSIONS: We should assess not only obesity but all CV risk factor levels, because a cluster of risk factors implies a worsening of the individual risk factor levels in children as young as those in elementary school.

Early diagnosis of Kawasaki disease in patients with cervical lymphadenopathy.

BACKGROUND: Among typical patients with Kawasaki disease (KD), a few KD patients present with only fever and cervical lymphadenopathy at admission (KDL). These patients have a significant risk for misdiagnosis, delay in treatment for KD, and development of coronary artery abnormalities. Therefore, the development of an easy tool for early diagnosis in these patients is desirable. METHODS AND RESULTS: Patients who presented with only fever and cervical lymphadenopathy at admission were studied. Of these, 14 patients were eventually diagnosed with KD (KDL) and 24 patients were successfully treated using antibiotics (control). KDL patients were significantly older than control patients (P > 0.022). Among the laboratory findings, neutrophil counts (P > 0.003), C-reactive protein (CRP; P < 0.001), and aspartate aminotransferase (AST; P > 0.018) were significantly different between the groups. To discriminate KDL patients from controls, cut-off points of the aforementioned parameters (KDL indices) were determined using the receiver operating characteristic curves in order to maximize sensitivity and accuracy (age, 5.0 years; neutrophil counts, 10,000 /microL; CRP, 7.0 mg/dL; AST, 30 IU/L). One point was assigned if a subject exceeded the cut-off point in a KDL index. If a patient with three or four KDL indices was considered to have KD, the sensitivity was 78% and the specificity 100%. None of the patients with one or zero KDL index developed KD. CONCLUSIONS: KDL indices may be helpful in discriminating KDL from lymphadenitis at admission. It is important to monitor the symptoms of KD in a patient with three or four KDL indices at admission.

Metabolic syndrome in overweight and obese Japanese children.

OBJECTIVE: To determine the prevalence of and sex differences related to the metabolic syndrome among obese and overweight elementary school children. RESEARCH METHODS AND PROCEDURES: Subjects were 471 overweight or obese Japanese children. Children meeting at least three of the following five criteria qualified as having the metabolic syndrome: abdominal obesity, elevated blood pressure, low high-density lipoprotein-cholesterol levels, high triglyceride levels, and high fasting glucose levels. Fasting insulin levels were also examined. RESULTS: Japanese obese children were found to have a significantly lower prevalence (17.7%) of the metabolic syndrome than U.S. obese adolescents (28.7%, p = 0.0014). However, Japanese overweight children had a similar incidence (8.7%) of the metabolic syndrome compared with U.S. overweight adolescents (6.8%). Hyperinsulinemia in girls and abdominal obesity in boys are characteristic features of individual metabolic syndrome factors in Japanese children. DISCUSSION: The prevalence of the metabolic syndrome is not lower in preteen Japanese overweight children than in U.S. overweight adolescents, although it is significantly lower in Japanese obese preteen children than in U.S. obese adolescents. Primary and secondary interventions are needed for overweight preteen children in Japan.

Predictive factors in the success of intervention to treat obesity in elementary school children.

BACKGROUND: Currently, a generalizable conclusion on the effectiveness of treatment programs for childhood obesity cannot be drawn, and how practical and effective the intervention strategies are remains a controversial subject. METHODS AND RESULTS: In the present study 36 obese elementary school children who visited an intervention program at least 4 times were followed for 12 months or more. A stepwise regression analysis was performed using the decrease in the percent relative body weight (%RBW) at 12 months after the first visit as a dependent variable, and the decrease in the %RBW and nutritional data between 2 successive visits as independent variables. The analysis revealed 4 significant predictive factors: (1) a higher ratio of energy intake from protein (20%) recommended at the first visit, (2) a greater decrease in the %RBW between the first and second visits, (3) higher age, and (4) a higher concentration of alanine aminotransferase at the first visit. CONCLUSION: Providing a strong motivation to change eating and activity behavior at the early stage of intervention and recommending diets with higher ratios of energy intake from protein are the most practical and effective strategies for treating obesity.

Prevention of mildly overweight children from development of more overweight condition.

BACKGROUND: A follow-up study has reported that not only highly obese but also mildly obese children are becoming heavier during the elementary school children. Then we determined the effect of programs for the screening and treatment of overweight elementary school children whether the programs prevented mildly overweight children from development of more overweight condition. METHODS: Subjects were 40 overweight children who participated in both screening and treatment programs. As controls, only 240 children who participated in the screening program were used. The mean observation periods of the subjects and controls were 14 and 12 months, respectively. RESULTS: In both groups, older and heavier children significantly decreased their indices of overweight (percent relative body weight; %RBW), indicating that mildly obese children worsened their %RBW. However, the incidence of children who worsened their %RBW was significantly lower in the subjects (5 of 40) than in the controls (133 of 240) (P < 0.0001). Finally, the subjects significantly reduced their mean %RBW (P < 0.0001) and the controls significantly worsened it (P = 0.0093). CONCLUSION: The treatment program was found important because it prevents mildly overweight children who may worsen their overweight indices without the program from developing more overweight condition.

Patients diagnosed with Kawasaki disease before the fifth day of illness have a higher risk of coronary artery aneurysm.

BACKGROUND: A fever lasting for at least 5 days is an essential characteristic of the original diagnostic criteria of Kawasaki disease (KD). However, it is not difficult for an experienced physician to confirm the diagnosis of KD before the fifth day of fever. The aim of this study is to investigate the effect of intravenous gamma globulin therapy (IVGG) in KD initiated before the fifth day of illness. METHODS: A total of 125 patients treated with IVGGwere divided into group A (IVGG was initiated before the fifth day of illness, n= 46) and group B (IVGG was initiated at the fifth day or after, n= 79). Patients' characteristics,laboratory findings, treatments and outcomes were compared between the groups. RESULTS: White blood cell count value, C-reactive protein and Harada's score showed no difference between the groups. A significantly higher average value of alanine aminotransferase(ALT) was observed in group A. Although the treatments were identical in both groups, the average duration of fever from the initial day of IVGG in group A was significantly longer than in group B. The incidence of aneurysm in group A was significantly higher than that in group B. Stepwise regression analysis using aneurysm as a dependent variable revealed that group A and ALT were significant. CONCLUSIONS: Patients diagnosed with KD before the fifth day of illness showed a poor response to IVGG. This observation might be related to high ALT values. Further examination concerning the modification of treatment in such patients is necessary.