Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found ‘AML with myelodysplasia‐related changes’ (AML‐MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia‐related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with ‘AML, not otherwise specified’ (AML‐NOS), patients with ‘AML‐MRC’ presented at a younger age, with a lower white blood cell count, higher incidence of 20–30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms‐like tyrosine kinase 3 internal tandem duplication (FLT3‐ITD), NPM1 and CEBPA mutations. Complete remission rate and 3‐year probability of event‐free survival were significantly worse in ‘AML‐MRC’ patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3‐year overall survival and relapse‐free survival were comparable with ‘AML‐NOS’ patients. By multivariate analysis, FLT3‐ITD was solely associated with worse overall survival. These results support the distinctive features of the category ‘AML‐MRC’ even in children.     

Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia who developed blast crisis: MDS Committee of Japanese Society of Paediatric Haematology/Oncology

Juvenile myelomonocytic leukaemia (JMML) is a rare haematopoietic stem cell disease of early childhood, which can progress to blast crisis in some children. A total of 153 children diagnosed with JMML were reported to the Myelodysplastic Syndrome Committee in Japan between 1989 and 2007; 15 of them (9·8%) had 20% or more blasts in the bone marrow (blast crisis) during the disease course. Blast crisis occurred during observation without therapy (n = 3) or with oral 6‐mercaptopurine treatment (n = 9) and in relapse after haematopoietic stem cell transplantation (HSCT; n = 3). Six patients had a complex karyotype (5 including monosomy 7) and an additional three patients had isolated monosomy 7 at blast crisis. Seven patients received HSCT after blast crisis and four of them achieved remission. Eleven out of the 15 patients died; the cause of death was disease progression in 10 patients and transplant‐related complication in one patient. In summary, patients with blast crisis have poor prognosis and can be cured only by HSCT. The emergence of monosomy 7 and complex karyotype may be characteristic of blast crisis in a substantial subset of children.     

Nonsurgical orthodontic treatment of a hypodivergent adult patient with bilateral posterior scissors bite and excessive overjet

This report illustrates successful nonsurgical orthodontic treatment of a hypodivergent adult patient with bilateral posterior scissors bite (Brodie bite) and excessive overjet. A 26-year-old woman primarily reported maxillary incisor protrusion. She was diagnosed with Class ll division 1 malocclusion with skeletal Class I, short face, low mandibular plane angle and bilateral posterior scissors bite. A lingual arch with anterior bite block and posterior miniscrews with preadjusted edgewise appliances were used to improve the bilateral scissors bite. After achieving molar occlusion, the maxillary first premolars were extracted, and six miniscrews were used to improve the anterior-posterior and vertical discrepancies. After active treatment for 56 months, the convex facial profile with excessively protruded lips was improved and good interdigitation with ideal incisor relationship was achieved. Additionally, the irregular movements of the incisal path and the bilateral condyles during lateral excursion were improved. At 13 months of retention, a satisfactory facial profile, occlusion, and jaw movements were maintained. The treatment results suggest that miniscrews and fixed bite blocks were effective and efficient to facilitate correction of the bilateral scissors bite, excessive overjet, and vertical relationship correction in this nonsurgical orthodontic treatment.     

Ultra-high-speed videography of resin–dentin interface failure dynamics under tensile load

ObjectivesUltra-high-speed (UHS) videography was used to visualize the fracture phenomena at the resin–dentin interface during micro-tensile bond strength (μTBS) test. We also investigated whether UHS videography is applicable for failure-mode analysis.MethodsTen human mid-coronal dentin surfaces were bonded using Clearfil SE Bond either in self-etching (SE) or etch-and-rinse (ER) mode. After 24-h water storage, the samples were cut into beams for μTBS test and tested at a cross-head speed of 1 mm/min. The fracture phenomena at the bonded interface were captured using a complementary metal–oxide–semiconductor digital UHS camera at 299,166 frames per second. The failure modes were classified using UHS videography, followed by scanning electron microscopy (SEM) analysis. The failure-mode distributions determined by UHS videography and SEM analysis were statistically analyzed using Fisher’s exact test with Bonferroni correction.ResultsThe crack-propagation speed exceeded 1,500 km/h. No significant difference was found between the SEM and UHS videography failure-mode distributions in the SE mode. A significant difference appeared between them in the ER mode. Significant differences in the incidence of cohesive failures within the adhesive and at the adhesive–composite interface between the SE and ER modes were identified by both SEM and UHS videography.SignificanceUHS videography enabled visualization of the fracture dynamics at the resin– dentin interfaces under tensile load. However, the resolution at such high frame rate was insufficient to classify the failure mode as precisely as that of SEM. Nevertheless, UHS videography can provide more detailed information about the fracture origin and propagation.     

Comparison of tofogliflozin versus glimepiride as the third oral agent added to metformin plus a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes: A randomized, 24-week,open-label,controlled trial (STOP-OB)

Metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i) is the most common therapy for Japanese patients with type 2 diabetes. This 24-week, multicentre, open-label, parallel-group trial randomized patients on dual therapy to add-on tofogliflozin (20 mg/day, n = 33) or glimepiride (0.5 mg/day, n = 31). The primary outcome was change in body fat percentage. The secondary outcomes included changes in HbA1c, fat mass, fat-free mass, liver function variables and uric acid. Tofogliflozin and glimepiride reduced HbA1c to a similar extent. Body fat percentage did not change from baseline in either group. Fat mass was reduced by tofogliflozin but was increased by glimepiride (by −2.0 ± 1.7 kg and +1.6 ± 1.6 kg, P = .002). Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by −1.3 ± 1.3 kg and +0.9 ± 2.0 kg, P < .001). Alanine aminotransferase and uric acid levels were reduced by tofogliflozin (P = .006 and P < .001, respectively). These data provide novel information useful for selecting the third oral agent for patients whose diabetes is inadequately controlled with metformin plus DPP-4i dual therapy.     

Aldosterone-to-renin ratio and nocturnal blood pressure decline assessed by self-measurement of blood pressure at home: the Ohasama Study

Based on ambulatory blood pressure (BP) monitoring, the aldosterone-to-renin ratio (ARR) has been reported to be associated with a diminished nocturnal decline in BP, generally referred to as a “non-dipping” pattern. The objective of this cross-sectional study was to investigate the association between ARR and the non-dipping pattern based on home BP measurements. This study included 177 participants ≥55 years from the general population of Ohasama (mean age: 67.2 years; 74.6% women); no patient was receiving antihypertensive treatment. The median plasma renin activity (PRA), plasma aldosterone concentration (PAC) and ARR were 0.8?ng/mL/h, 8.1?ng/dL and 9.7?ng/dL per ng/mL/h, respectively. Each 1 SD increase in log-transformed (ln) ARR was significantly associated with the prevalence of the non-dipping pattern after adjustments for possible confounding factors including home morning systolic BP (odds ratio, 1.45; p?=?0.049). However, no significant associations of PRA or PAC with the non-dipping pattern were observed (p?≥?0.2). When participants were divided into four groups according to median levels of home morning and night-time systolic BPs, the group with a higher home morning systolic BP (≥128.4?mmHg) with a higher home night-time systolic BP (≥114.4?mmHg) had the greatest ARR levels (ANCOVA p?=?0.01). These results support the hypothesis that relative aldosterone excess may be related to a non-dipping pattern in a general population and suggest that a non-dipping pattern can be accurately observed by home BP measurements.     

Skin Autofluorescence Predicts Cardiovascular Mortality in Patients on Chronic Hemodialysis

Tissue accumulation of advanced glycation end products (AGE) is thought to contribute to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non‐invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has been reported to be an independent predictor of mortality associated with CVD in Caucasian patients on chronic hemodialysis. The aim of this study was to assess the predictive value of skin autofluorescence on all‐cause and cardiovascular mortality in non‐Caucasian (Japanese) patients on chronic hemodialysis. Baseline skin autofluorescence was measured with an autofluorescence reader in 128 non‐Caucasian (Japanese) patients on chronic hemodialysis. All‐cause and cardiovascular mortality was monitored prospectively during a period of 6 years. During the follow‐up period, 42 of the 128 patients died; 19 of those patients died of CVD. Skin autofluorescence did not have a significant effect on all‐cause mortality. However, age, carotid artery intima‐media thickness (IMT), serum albumin, high‐sensitivity C‐reactive protein (hsCRP), skin autofluorescence and pre‐existing CVD were significantly correlated with cardiovascular mortality. Multivariate Cox regression analysis showed skin autofluorescence (adjusted hazard ratio [HR] 3.97; 95% confidence interval [CI]1.67–9.43), serum albumin (adjusted HR 0.05; 95% CI 0.01–0.32), and hsCRP (adjusted HR 1.55; 95% CI 1.18–2.05) to be independent predictors of cardiovascular mortality. The present study suggests that skin autofluorescence is an independent predictor of cardiovascular mortality in non‐Caucasian (Japanese) patients on chronic hemodialysis.