Mortality among persons with a history of Kawasaki disease in Japan: Can paediatricians safely discontinue follow-up of children with a history of the disease but without cardiac sequelae?

Aim: To clarify the question of whether patients with Kawasaki disease suffer a higher mortality rate after the incidence of the disease in comparison with age-matched healthy individuals. Methods: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new, definite diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001 or their death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results: Of 6576 patients enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio (SMR: the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.15 (95% CI: 0.77-1.66). In spite of the high SMRs during the acute phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the SMR after the acute phase was 0.75 for those without cardiac sequelae, six males (but none of the females) with cardiac sequelae died during this period; and the SMR for the male group with cardiac sequelae was 1.95 (95% CI: 0.71-4.25). The mortality from congenital anomalies of the circulatory system was elevated, but no increase in cancer deaths was observed.

Conclusion: Although it was not statistically significant, the mortality rate among males with cardiac sequelae due to Kawasaki disease appeared to be higher than in the general population. On the other hand, the mortality rates for females with the sequelae and both males and females without sequelae were not elevated.     

Rhabdomyolysis Caused by Gefitinib Overdose

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are common therapeutic agents for EGFR mutation-positive advanced non-small-cell lung cancer. There has been no report of rhabdomyolysis caused by an overdose of EGFR-TKIs. We herein review the existing literature on the subject and report a rare case of rhabdomyolysis due to an overdose of gefitinib, an EGFR-TKI.     

Branched-Chain Fatty Acids Alter the Expression of Genes Responsible for Lipid Synthesis and Inflammation in Human Adipose Cells

Recently, we have demonstrated a decreased level of iso-branched-chain fatty acids (iso-BCFAs) in patients with excessive weight. However, it is still unclear whether BCFAs may influence lipid metabolism and inflammation in lipogenic tissues. To verify this, human visceral adipocytes were cultured with three different concentrations of selected iso-BCFA (14-methylpentadecanoic acid) and anteiso-BCFA (12-methyltetradecanoic acid), and then the expression of genes associated with lipid metabolism (FASN—fatty acid synthase; SREBP1—sterol regulatory element-binding protein 1; SCD1—stearoyl-CoA desaturase; ELOVL4—fatty acid elongase 4; ELOVL6—fatty acid elongase 6; FADS2—fatty acid desaturase 2; FADS1–fatty acid desaturase 1) and inflammation (COX-2—cyclooxygenase 2; ALOX-15—lipoxygenase 15; IL-6—interleukin 6) were determined. This study demonstrates for the first time that incubation with iso-BCFA decreases the expression of adipocyte genes that are associated with lipid metabolism (except FASN) and inflammation. These findings suggest that changes in the iso-BCFA profile in obese patients may contribute to adipose inflammation and dyslipidemia. Further studies should evaluate whether iso-BCFA supplementation in obese patients would be beneficial.     

Effects of Five Amino Acids (Serine,Alanine, Glutamate,Aspartate, and Tyrosine) on Mental Health in Healthy Office Workers: A Randomized,Double-Blind,Placebo-Controlled Exploratory Trial

Background: The importance of maintaining good mental health with overall well-being has recently drawn attention from various spheres of academics and the working population. Amino acid intake has been reported to reduce depression symptoms and other mental health problems. However, the effectiveness of amino acid intake (i.e., single or combined) remains unknown. In this study, we assessed a combination of five amino acids (serine, alanine, glutamate, aspartate, and tyrosine; SAGAT) reported to regulate mental health. Methods: A randomized, double-blind, placebo-controlled exploratory trial was conducted. Participants, aged between 20 and 65 years with fatigue sensation, were randomized to receive either SAGAT or the placebo and ingested them for four weeks. A transient mental work was loaded at day 0 and after four weeks of intervention. As the primary outcomes, the fatigue sensation was assessed. The mood status, cognitive function, work efficiency, and blood marker were also measured as secondary outcomes. Results: The number of participants analyzed for the efficacy evaluation were 20 in SAGAT and 22 in the placebo. There were no significant differences in the primary outcomes. However, as the secondary outcomes, the SAGAT group showed a significant improvement in motivation and cognitive function in the recovery period after mental work loaded in a four-week intervention compared to the placebo. Conclusion: The current findings suggest that SAGAT contributes to maintaining proper motivation and cognitive function. Clinical Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (ID: UMIN 000041221).     

CT diagnosis of primary Budd-Chiari syndrome--membranous obstruction of the inferior vena cava

Five cases with primary Budd-Chiari syndrome due to membranous obstruction of the hepatic segment of the inferior vena cava were examined by CT. In all cases, CT demonstrated caudate lobe enlargement, reticular low density within the liver parenchyma, splenomegaly, and collaterals via the ascending lumbar veins and azygous system. Pathological study revealed liver cirrhosis or fibrosis in all cases. In two cases, calcification was shown in the region of the hepatic segment of the inferior vena cava. Our results suggested that the CT appearance of primary Budd-Chiari syndrome was rather characteristic and useful in diagnosis, although membranous obliteration could not be shown directly on CT.     

Mid-mediastinal parathyroid lesions: Preoperative localization and surgical approach in two cases

Although hyperfunctioning mediastinal parathyroid lesions that require median sternotomy or thoracotomy for removal are occasionally present, the majority are located in the anterior mediastinum closely associated with the thymus. Only eight cases of ectopic hyperfunctioning parathyroid tumors in the middle mediastinum have been reported. We experienced two cases of either persistent or recurrent hyperparathyroidism in which abnormal parathyroid tissue was located in the aorticopulmonary window. One of the patients had a parathyroid adenoma and the other had metastatic lesions of parathyroid carcinoma. In both cases, thallium scanning proved useful in identifying the lesions while computed tomography scan was effective for mediastinal three-dimensional localization. In one case, single photon emission computed tomography imaging with thallium proved beneficial for both identification and localization of the middle mediastinal lesion. The surgical approach used in both cases was different. In one case, left thoracotomy was performed, after which the ligamentum arteriosum was divided, and an adenoma anterior to the left main bronchus and posterior to the left pulmonary artery removed. In the other case, two metastatic tumors of parathyroid carcinoma anterior to the right main bronchus and posterior to the right pulmonary artery were resected through a median sternotomy and opening of the pericardium.     

Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan

BackgroundAnticardiolipin antibodies (aCL) and anti‐β₂‐glycoprotein I antibodies (aβ₂GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ₂GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays.MethodsWe evaluated two manual and three automated assays for aCL and aβ₂GPI of IgG‐ and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well‐defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve.ResultsA variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between‐year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aβ₂GPI‐IgG and aCL‐IgG were generally high (AUC: 0.84−0.93); whereas those for IgM‐class assays were low (AUC: 0.57−0.67), implicating its utility is limited to rare IgG negative APS cases.ConclusionTo ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.     

Effect of Surface Tooling Techniques of Medical Titanium Implants on Bacterial Biofilm Formation In Vitro

The aim of this study was to assess the biofilm formation of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli on titanium implants with CAD-CAM tooling techniques. Twenty specimens of titanium were studied: Titanium grade 2 tooled with a Planmeca CAD-CAM milling device (TiGrade 2), Ti₆Al₄V grade 5 as it comes from CAD-DMLS device (computer aided design-direct metal laser sintering device) (TiGrade 5), Ti₆Al₄V grade 23 as it comes from a CAD-CAM milling device (TiGrade 23), and CAD-DMLS TiGrade 5 polished with an abrasive disc (TiGrade 5 polished). Bacterial adhesion on the implants was completed with and without saliva treatment to mimic both extraoral and intraoral surgical methods of implant placement. Five specimens/implant types were used in the bacterial adhesion experiments. Autoclaved implant specimens were placed in petri plates and immersed in saliva solution for 30 min at room temperature and then washed 3× with 1× PBS. Bacterial suspensions of each strain were made and added to the specimens after saliva treatment. Biofilm was allowed to form for 24 h at 37 °C and the adhered bacteria was calculated. Tooling techniques had an insignificant effect on the bacterial adhesion by all the bacterial strains studied. However, there was a significant difference in biofilm formation between the saliva-treated and non-saliva-treated implants. Saliva contamination enhanced S. mutans, S. aureus, and E. faecalis adhesion in all material types studied. S. aureus was found to be the most adherent strain in the saliva-treated group, whereas E. coli was the most adherent strain in the non-saliva-treated group. In conclusion, CAD-CAM tooling techniques have little effect on bacterial adhesion. Saliva coating enhances the biofilm formation; therefore, saliva contamination of the implant must be minimized during implant placement. Further extensive studies are needed to evaluate the effects of surface treatments of the titanium implant on soft tissue response and to prevent the factors causing implant infection and failure.