Assessment of anthracycline-induced cardiotoxicity in childhood cancer survivors during long-term follow-up using strain analysis and intraventricular pressure gradient measurements.

BACKGROUND: Cardiac dysfunction due to cardiotoxicity from anthracycline chemotherapy is a leading cause of morbidity and mortality in childhood cancer survivors (CCS), and the cumulative incidence of cardiac events has continued to increase. This study identifies an adequate indicator of cardiac dysfunction during long-term follow-up. PROCEDURE: In total, 116 patients (median age: 15.5 [range: 4.7-40.2] years) with childhood cancer who were treated with anthracycline were divided into three age groups for analysis (C1: 4-12 years of age, C2: 13-18 years of age, C3: 19-40 years of age), and 116 control patients of similar ages were divided into three corresponding groups (N1, N2, and N3). Layer-specific strains were assessed for longitudinal strain (LS) and circumferential strain (CS). The total and segmental intraventricular pressure gradients (IVPG) were also calculated based on Doppler imaging of the mitral inflow using Euler's equation. RESULTS: Conventional echocardiographic parameters were not significantly different between the patients and controls. All layers of the LS and inner and middle layers of the basal and papillary CS in all ages and all IVPGs in C2 and C3 decreased compared to those of corresponding age groups. Interestingly, basal CS and basal IVPG in CCS showed moderate correlation and both tended to rapidly decrease with aging. Furthermore, basal IVPG and anthracycline dose showed significant correlations. CONCLUSIONS: Basal CS and total and basal IVPGs may be particularly useful indicators of cardiotoxicity in long-term follow-up.

Approach to the Seamless Management of Inflammatory Bowel Disease, Considering Special Situations, Shared Decision-Making, and Disease Burden.

BACKGROUND: While the number of inflammatory bowel disease (IBD) patients has been steadily increasing, a lot of effective treatments have become available, including biological drugs. However, there still exists no effective treatment universally for all types of IBD patients. We have continuously discussed "Total Care" for IBD patients in the 3 consecutive annual meetings of the Japanese Gastroenterological Association from the 14th meeting to the 16th meeting in 2018-2020. SUMMARY: In the 14th meeting, we summarized cross-sectional issues under the title "From Total Care to Microbiota" as for their subthemes. In the 15th meeting, under the title of "Consensus and Pitfalls in Special Situations," we discussed the thiopurine treatment for the patients in their childhood or pregnancy and lactation period as well as the cytapheresis treatment for elderly patients. In the 16th meeting, under the title "Future Issues in Special Situations: Including Disease Burden," we discussed about the issues in childhood-onset IBD, including transitional care and the new option of combination of treatments in their adulthood and their disease burdens. Key Messages: "Total Care" for IBD patients should be considered from a broad perspective with shared decision-making. It is imperative to involve medical staff members for careful handling of a wide range of disease burdens.

Assessment of early diastolic intraventricular pressure gradient in the left ventricle among patients with repaired tetralogy of Fallot.

Assessment of left ventricular (LV) dysfunction is vital in patients with repaired tetralogy of Fallot (rTOF). The early diastolic intraventricular pressure gradient (IVPG) in the LV plays an important role in diastolic function. IVPG is calculated as the intraventricular pressure difference divided by the LV length, which allows to account for differences in LV size and therefore calculate IVPG in children. We aimed to investigate the mechanisms of LV diastolic dysfunction by measuring mid-to-apical IVPG as an indicator of the active suction force sucking blood from the left atrium into the LV. We included 38 rTOF patients and 101 healthy controls. The study population was stratified based on age group into children (4-9 years), adolescents (10-15 years), and adults (16-40 years). IVPGs were calculated based on mitral inflow measurements obtained using color M-mode Doppler echocardiography. Although total IVPGs did not differ between rTOF patients and controls, mid-to-apical IVPGs in adolescents and adults were smaller among rTOF patients than among controls (0.15 ± 0.05 vs. 0.21 ± 0.06 mmHg/cm, p < 0.05; 0.09 ± 0.07 vs. 0.17 ± 0.05 mmHg/cm, p < 0.001; respectively). Additionally, only mid-to-apical IVPG correlated linearly with peak circumferential strain (ρ = 0.217, p = 0.011), longitudinal strain (ρ = -0.231, p = 0.006), torsion (ρ = -0.200, p = 0.018), and untwisting rate in early diastole (ρ = -0.233, p = 0.006). In rTOF, the mechanisms underlying diastolic dysfunction involve reduced active suction force, which correlates with reduced LV deformation in all directions.

Assessment of the Family History of Patients With Ulcerative Colitis at a Single Center in Japan.

OBJECTIVES: The prevalence of ulcerative colitis (UC) differs by country, which is likely due to differences in genetic factors among ethnicities. Moreover, the prevalence of pediatric UC with a family history (FH) is 4.1% in Japanese patients; its clinical course begins at an early age and is more severe. Recently, a genome-wide association study identified 3 new susceptibility loci for adult Japanese patients with UC. METHODS: To assess the effects of FH in patients with UC, 60 children were enrolled. Age at diagnosis, clinical features of the initial symptoms, and family structure were assessed in patients with and without an FH. The 3 new loci were examined in patients who provided informed consent. RESULTS: Of the patients with UC, 10 (16.7%) had an FH involving first-degree relatives, including 7 mothers, 1 father, and 2 sisters. There was a trend toward a younger age at onset in the positive FH group. There were, however, no significant differences in the clinical characteristics of the patients regardless of FH. From the genomic analyses, there were significant differences in the polymorphisms of the solute carrier family 26, member 3 (SLC26A3) between those with and without an FH. CONCLUSIONS: Although the etiology of UC remains unknown, there were no observed relation between clinical symptoms and FH. SLC26A3 may, however, contribute to the pathogenesis of UC in Japanese individuals with an FH.

Assessment of the developmental change in the left atrial volume using real time three-dimensional echocardiography.

AIMS: Real time 3D echocardiography (RT3DE) has been applied for the assessment of left atrial (LA) function in patients with adult heart disease; however, LA function is not well known in children. We aimed at determining the normal range of LA volume (LAV) using RT3DE and the feasibility and reproducibility of this method in healthy subjects and at elucidating the developmental changes in the LAV with aging. METHODS AND RESULTS: In this study, 359 healthy people (mean age, 23.9 ± 21.3; range, 0.1-76.4 years) were enrolled. We performed transthoracic RT3DE and measured the maximum and minimum LAV. Simultaneously, we measured the LAV using the 2D biplane Simpson's method. Inter-observer and intra-observer variability and the agreement of LAV measurements between RT3DE and 2DE were assessed in a subset of subjects. The RT3DE feasibility for LAV measurement was 93%. Both maximum and minimum LAVs exponentially increased with age and linearly increased with increasing of body surface area (BSA). The LA distensibility, which demonstrates LA reservoir function, decreased with age and BSA. The LAVs measured by RT3DE were significantly smaller than those measured by the 2D biplane Simpson's method. The 3D volumetric method had favorable intra-observer and inter-observer agreement. CONCLUSION: The reference values of LAV from early infancy to adulthood were obtained using RT3DE, which could be useful for future studies in children with congenital heart disease. RT3DE is a reproducible method and a feasible tool for evaluating the LAV in children. LA reservoir function is likely to decrease with age and increasing of body size.

Non-invasive assessment of liver fibrosis in patients after the Fontan operation.

BACKGROUND: This study analyzed the change in liver fibrosis markers after the Fontan operation and investigated their clinical usefulness as an index of congestive liver fibrosis. METHODS: The study enrolled 24 patients who underwent the Fontan operation between January 1994 and December 2008. We subdivided the postoperative period into four intervals and then compared the hepatological markers during each. Eighteen patients underwent postoperative cardiac catheterization and the correlation between hepatological markers and the inferior vena cava (IVC) pressure was analyzed. RESULTS: The mean age of the patients was 138.6 months and the mean interval between the Fontan operation and the examination was 97.8 months. Type IV collagen was extremely high in every interval (I, 286 ± 93; II, 265 ± 93; III, 305 ± 143; IV, 206 ± 70), while none of the laboratory variables changed significantly in each interval. A significant positive correlation was observed between type IV collagen and the IVC pressure, but no significant correlation with any other hepatological marker was detected. CONCLUSIONS: No specific parameter that reflects the progress in liver fibrosis was identified in this study. The possibility exists that type IV collagen reflects the degree of hepatic congestion.

A need for play specialists in Japanese children's wards.

The importance of distraction techniques and play therapy for sick children has long been recognised by nurses in the UK and other western countries. Although these techniques are not so well established in Japan there is growing interest in them. The authors conducted a survey and found that children's nurses in Japan appreciated the value of distraction techniques and play therapy. They argue that attitudes to using them on children's wards in Japan are changing, but there is still a lack of training and few play specialists.

Assessment of Growth Disturbance in Japanese Children with IBD.

In Japan, there is as yet no report on growth retardation in children with IBD. We therefore investigated the cause of growth retardation in Japanese children with IBD. We investigated the height, body weight, serum levels of albumin, IGF-I, CRP, and cytokines, and the amount of corticosteroid administered in children with Crohn's disease (CD, n = 15) and ulcerative colitis (UC, n = 18). Our results suggest that growth retardation is already present before the initial visit in children with CD, and chronic inflammation may be responsible this growth disturbance. Moreover, the amount of PSL used may contribute to growth retardation by decreasing the serum levels of IGF-I in children with IBD.

Resting energy expenditure and plasma leptin levels in adolescent girls with anorexia nervosa.

OBJECTIVE: Our aim was to examine the relationship between resting energy expenditure (REE) and circulating leptin levels during long-term refeeding in adolescent girls with anorexia nervosa (AN). METHOD: We measured REE, the plasma leptin level, the free T(3) level, body surface area (BSA), and dietary energy intake in AN adolescents before and 8 weeks after refeeding therapy. RESULTS: All parameters in AN subjects before the refeeding therapy were significantly lower than those in AN subjects after the therapy and in the controls. There were no significant differences in REE and BSA between posttherapy AN subjects and controls, but plasma leptin levels in the posttherapy AN subjects were still significantly lower than those in the controls. Significant correlations between REE and BSA were detected in the AN subjects both before and after the refeeding therapy, but REE did not correlate significantly with plasma leptin level in either of the AN groups. DISCUSSION: Our results suggest that the REE in AN subjects after long-term refeeding therapy is not associated with the changes in plasma leptin levels but with BSA.

Retinal neurodevelopmental assessment with electroretinogram in patients with biliary atresia.

BACKGROUND: To evaluate the effect of n-3 polyunsaturated fatty acid (PUFA) deficiency on the development of retinal function in children with biliary atresia (BA), we examined serum fatty acid levels and performed electororetinogram (ERG) in patients with BA. METHODS: The study group was composed of one male and four female BA patients (8-14 years) with serum bilirubin levels ranging from 0.40 to 1.48 mg/dL. All of the subjects were born as full-term infants. The fatty acid composition of total lipids in serum was analyzed by gas chromatography before the Kasai operation, approximately 10 months after the Kasai operation, and at the time of the ERG study. The ERG was recorded using corneal contact lens electrodes. RESULTS: Two of the five patients showed decreased levels of arachidonic acid and docosahexaenoic acid (DHA) before and after the operation, but no abnormal findings on ERG were detected in these patients. The other three patients had decreased levels of alpha-linolenic acid or DHA after the operation, but again, no abnormalities were found on ERG. CONCLUSION: These results suggest that insufficiencies of DHA and other n-3 PUFA in full-term infants might not have an influence on later ERG results.