Effects of oral antidiabetic drugs and glucagon-like peptide-1 receptor agonists on left ventricular diastolic function in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.

The present study aimed to compare the effects of oral antidiabetic drugs (OADs) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on left ventricular diastolic function in patients with type 2 diabetes mellitus using a network meta-analysis of randomized controlled trials (RCTs). Literature searches were conducted on Medline, the Cochrane Controlled Trials Registry, and ClinicalTrials.gov . RCTs that assessed the effects on left ventricular diastolic function of OADs and GLP-1RAs in patients with type 2 diabetes were included. The outcome was the value (E/e') obtained by dividing peak early diastolic transmitral flow velocity (E) by the mitral annular early diastolic velocity (e'). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated from a random-effects network meta-analysis. Eight RCTs (592 patients) identified in a literature search met the eligibility criteria for this study and were included in the network meta-analysis. Compared with placebo, liraglutide was the only drug that caused a significant improvement in left ventricular diastolic function (SMD, - 0.65; 95% CI, - 1.23 to - 0.08). In addition, when the effects on left ventricular diastolic function were evaluated across drugs, liraglutide alone caused a significant improvement in left ventricular diastolic function compared with OADs (sitagliptin, linagliptin, pioglitazone, rosiglitazone, voglibose, and glimepiride). From the perspective of preventing the onset of heart failure, the administration of liraglutide for type 2 diabetes is promising.

Verification of the predictive validity for mortality of the SARC-F questionnaire based on a meta-analysis.

BACKGROUND: Although the association between SARC-F questionnaire positivity and mortality has previously been studied, the results are inconsistent. Testing the predictive validity of the SARC-F questionnaire for clinically relevant outcomes of vital prognoses is important. AIM: The objective of this study was to test the predictive validity of SARC-F by conducting a meta-analysis on the association between SARC-F, a screening tool for sarcopenia, and mortality. METHODS: This meta-analysis used the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar databases for literature searches. Studies that examined the relationship between SARC-F questionnaire positivity and mortality and reported hazard ratios or odds ratios and 95% confidence intervals were included. A random-effects model was used for statistical analyses, and pooled hazard ratios, pooled odds ratios, and 95% confidence intervals were calculated. RESULTS: Through the literature search, we found five studies (7501 individuals) that met the eligibility criteria for this study. The pooled hazard ratio for SARC-F questionnaire positivity and mortality was 1.87 (95% confidence interval 1.41-2.46; P < 0.001), indicating a significant association. The pooled odds ratio for SARC-F questionnaire positivity and mortality was 1.97 (95% confidence intervals 1.10-3.53; P = 0.02), showing a significant association. CONCLUSIONS: There was a significant association between SARC-F positivity and future mortality, indicating the predictive validity of the SARC-F questionnaire. TRIAL REGISTRATION: Not applicable.

Factors associated with social isolation and being homebound among older patients with diabetes: a cross-sectional study.

OBJECTIVE: We aimed at investigating factors associated with social isolation and being homebound in older patients with diabetes. DESIGN: Cross-sectional study. SETTINGS: Those undergoing outpatient treatments at Ise Red Cross Hospital, Mie Prefecture. PARTICIPANTS: Patients with diabetes aged ≥65 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Social isolation was defined as indulging in less than one interaction per week with individuals other than cohabiting family members. We defined homebound as going outside home less than once a day. To identify factors associated with social isolation and being homebound, we performed logistic regression analysis. The dependent variable was social isolation or homebound and independent variables were basic attributes, glycaemic parameters, complications and treatment details. RESULTS: We analysed 558 cases (320 men and 238 women). Among these, 174 (31.2%) were socially isolated; meanwhile, 87 (15.6%) were homebound. The glycoalbumin/haemoglobin A1c ratio (OR 4.52; 95% CI 1.07 to 19.1; p=0.040) and the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) scores (OR 0.72; 95% CI 0.57 to 0.90; p=0.006) had significant associations with social isolation. TMIG-IC scores (OR 0.78; 95% CI 0.66 to 0.92; p=0.003) and insulin use (OR 4.29; 95% CI 1.14 to 16.1; p=0.031) were associated with being homebound. CONCLUSION: In older patients with diabetes, glycaemic fluctuations and insulin use are associated with social isolation and being homebound, respectively. In addition, a decline in higher level functional capacity is a common factor associated with social isolation and being homebound. Thus, it is important to pay attention to social isolation and being homebound when a decline in higher level functional capacity, increased glycaemic fluctuations and insulin use in older patients with diabetes are observed.

Preparation of the Japanese Version of the Diabetes Caregiver Activity and Support Scale and Verification of Its Reliability and Validity.

PURPOSE: The purpose of the study was to adapt and psychometrically evaluate a Japanese language version of the Diabetes Caregiver Activity and Support Scale (D-CASS-J) to be culturally relevant for people with diabetes living in Japan. METHODS: A Japanese translation of the original version of the D-CASS was prepared, corrected, and back-translated. Family caregivers of patients with diabetes mellitus ages ≥65 years who visited the outpatient diabetes clinic of Ise Red Cross Hospital were included. Cronbach's α coefficients were calculated as an assessment of internal consistency. Exploratory factor analyses were performed to verify construct validity. Hierarchical multiple regression analyses were performed using depression as the dependent variable and D-CASS-J and other variables as explanatory variables. Pearson's correlation coefficients between D-CASS-J scores and the support burden scale scores were calculated to verify criterion-related validity. RESULTS: This analysis included 268 subjects. Cronbach's α coefficient was .86. Factor analyses showed the same single-factor structure as the original version of the D-CASS. Hierarchical multiple regression analyses based on the conceptual model demonstrated construct validity. D-CASS-J scores were significantly correlated with support burden scale scores. CONCLUSIONS: For family caregivers of elderly patients with diabetes in Japan, D-CASS-J can be used as a tool to evaluate difficulties experienced while providing support to patients.

Frequency of Social Isolation and Homeboundness and Their Relationships with High-Level Functional Capacity in Elderly Diabetic Patients.

PURPOSE: To determine the frequency of social isolation (hereinafter, isolation) and homeboundness in elderly diabetic patients and to investigate their relationships with high-level functional capacity. PATIENTS AND METHODS: Subjects were diabetic outpatients aged 65 years and older who were visiting the Japanese Red Cross Ise Hospital. Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) was used to evaluate high-level functional capacity. Isolation was defined as having less than one interaction per week with someone other than co-habiting family members. Homeboundness was defined as leaving the house less than once a day. Multiple regression analysis was performed with the TMIG-IC score as the dependent variable and isolation and homeboundness as independent variables. RESULTS: Four hundred fifty-one patients were included in the analysis. The frequency of isolation and homeboundness affected 37% and 13.3% of men and 28.9% and 20.6% of women, respectively. The adjusted partial regression coefficient of the TMIG-IC scores of isolated, homebound, and isolated+homebound men was -0.94 [95% confidence interval (CI), -1.68 to -0.21; P = 0.012], -0.27 (95% CI, -1.93 to 1.39; P = 0.746), and -4.03 (95% CI, -5.37 to -2.68; P < 0.001) in relation to that of the non-isolated and non-homebound group as reference. In women, the respective coefficients to the reference were -1.33 (95% CI, -2.93 to 0.25; P = 0.099), -0.65 (95% CI, -2.56 to 1.26; P = 0.501), and -3.01 (95% CI, -4.92 to -1.1; P = 0.002), respectively. CONCLUSION: The frequency of isolation was high in both female and male elderly diabetic patients. In men, there was a significant relationship between isolation and decline in high-level functional capacity. In both men and women, there was a significant relationship between isolation+homeboundness and decline in high-level functional capacity.

Preparation, Reliability, and Validity of a Japanese Version of the "Satisfaction of Treatment among Caregivers of Dependent Type 2 Diabetic Patients" Questionnaire.

The aim of this study was to prepare a Japanese version of the "Satisfaction of Treatment among Caregivers of Dependent Type 2 Diabetic Patients" (STCD2-J) questionnaire, which is used to assess the satisfaction of family caregivers with respect to the treatment for elderly patients with type 2 diabetes mellitus who require support. In addition, the reliability and validity of the STCD2-J questionnaire were analyzed. A Japanese version of the original STCD2 questionnaire was prepared, revised, and back-translated; the back-translated version was sent to the authors of the original version for confirmation. Family caregivers of patients with type 2 diabetes mellitus aged ≥65 years who regularly underwent medical examinations at the diabetes mellitus outpatient clinic of Ise Red Cross Hospital were included. Cronbach's α coefficient was calculated to assess internal consistency. Exploratory factor analyses were performed to assess construct validity, and Pearson's correlation coefficients between STCD2-J score and HbA1c as well as the degree of satisfaction with patients' blood glucose levels, depression, and negative self-assessment of nursing care were calculated to assess criterion-related validity. This study included 208 individuals (55 males and 153 females). Cronbach's α coefficient was 0.88. Factor analyses showed a single-factor structure both with and without rotation. The STCD2-J scores were significantly inversely correlated with HbA1c (r = -0.27, P < 0.001). Significant correlations were observed between the STCD2-J scores and degree of satisfaction with patients' blood glucose levels (r = 0.43, P < 0.001), depression (r = -0.20, P = 0.003), and negative self-assessment of nursing care (r = -0.19, P = 0.004). The reliability and validity of the STCD2-J questionnaire were confirmed. The STCD2-J questionnaire can be used in Japan as a tool to assess the satisfaction of family caregivers with the treatment of elderly patients with type 2 diabetes mellitus requiring support.

Effects of Flash Glucose Monitoring on Dietary Variety, Physical Activity, and Self-Care Behaviors in Patients with Diabetes.

The aim of this study was to evaluate the effects of flash glucose monitoring on dietary variety, physical activity, and self-care behavior in patients with diabetes. This study included outpatients with diabetes using insulin who presented at the Department of Diabetes and Metabolism of the Ise Red Cross Hospital. Before initiating flash glucose monitoring and 12 weeks after its initiation, blood glucose-related parameters were assessed and self-administered questionnaires were completed (Dietary Variety Score (DVS), the International Physical Activity Questionnaire (IPAQ), the Summary of Diabetes Self-Care Activities Measure (SDSCA), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ)) and compared between the two time points. We analyzed 42 patients with type 1 diabetes mellitus and 48 patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus, but not type 1 diabetes mellitus, there was an increase in moderate/high category scores for IPAQ (P < 0.001) and for treatment satisfaction reported via DTSQ. Furthermore, in patients with type 2 diabetes mellitus, the glycemic excursion index improved significantly and HbA1c decreased significantly (from 7.7 (1.2) to 7.4 (0.8), P = 0.025). Results showed that standard deviation and mean amplitude of glycemic excursions significantly decreased in patients with type 1 diabetes mellitus (from 71.2 (20.4) to 66.2 (17.5), P = 0.033 and from 124.6 (31.9) to 108.1 (28.4), P < 0.001, respectively). Flash glucose monitoring is a useful tool to improve physical activity in patients with type 2 diabetes.

Correction to: Development of a Japanese version of the SARC-F for diabetic patients: an examination of reliability and validity.

The article Development of a Japanese version of the SARC-F for diabetic patients: an examination of reliability and validity, written by Satoshi Ida, Kazuya Murata, Daiki Nakadachi, Yuki Ishihara, Kanako Imataka, Akihiro Uchida, Kou Monguchi, Ryutaro Kaneko, Ryoko Fujiwara and Hiroka Takahashi was originally published electronically on the publisher's internet portal (currently SpringerLink) on 10 November 2016 without open access.

[Relationship of sarcopenic obesity with left ventricular diastolic dysfunction in elderly patients with diabetes].

AIM: This study aimed to examine the relationship of obesity, sarcopenia, and sarcopenic obesity (SO) with left ventricular diastolic dysfunction (LVDD) in elderly patients with diabetes. METHODS: Subjects included in this study were patients with diabetes ≥65 years of age and who were receiving treatment on an outpatient basis at the Ise Red Cross Hospital. To determine the presence of LVDD, we divided the early diastolic left ventricular filling velocity (E) by the early mitral annular motion velocity (E') (E/E'), which was measured using tissue Doppler imaging. To evaluate sarcopenia, SARC-F-J, a self-administered questionnaire consisting of five items, was used. Obesity was defined as a body mass index >25. Using a multiple logistic regression analysis with LVDD as the dependent variable and sarcopenia, obesity, and SO as explanatory variables, we calculated the odds ratios of LVDD for each variable. RESULTS: The subjects were 291 (157 male and 134 female) patients. Among male patients, the odds ratios after moderating for LVDD in the sarcopenia, obese, and SO groups were 0.82 (95% confidence interval [CI) ], 0.20 to 3.27, P=0.784), 1.92 (95% CI, 0.69 to 5.32, P=0.207), and 6.41 (95% CI, 1.43 to 28.53, P=0.015), respectively, whereas among female patients, these ratios were 1.31 (95% CI, 0.31 to 5.51, 0.708), 1.41 (95% CI, 0.45 to 4.37, P=0.551), and 3.18 (95% CI, 0.93 to 10.9, P=0.064), respectively. CONCLUSIONS: In male elderly patients with diabetes, SO was significantly correlated with LVDD. We believe that it is important to consider LVDD when examining male elderly patients with SO.

Association between dynapenia and decline in higher-level functional capacity in older men with diabetes.

AIM: The present study aimed to investigate an association between dynapenia or sarcopenia and higher-level functional capacity in older diabetes patients. METHODS: Diabetes outpatients aged ≥65 years were prospectively enrolled. Dynapenia and sarcopenia were defined by criteria of the Asian Working Group for Sarcopenia, and higher-level functional capacity was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). Multiple regression analysis included TMIG-IC scores as the dependent variable and dynapenia or sarcopenia as the explanatory variables. RESULTS: The present study included 204 patients. The regression coefficient of the relationship between dynapenia and covariance-adjusted TMIG-IC in men was -1.26 (95% confidence interval -2.35 to -0.17, P = 0.024), and that of sarcopenia and TMIG-CI adjusted for covariates was 0.65 (95% confidence interval -1.26 to 2.58, P = 0.500). We observed no significant correlation between TMIG-IC scores and dynapenia or sarcopenia in women. CONCLUSIONS: A statistically significant association was found between dynapenia and decline of higher-level functional capacity in older men with diabetes. Geriatr Gerontol Int 2018; 18: 1393-1397.

Relationship between sarcopenia and depression in older patients with diabetes: An investigation using the Japanese version of SARC-F.

AIM: The purpose of the present study was to investigate the relationship between sarcopenia and depression in older patients with diabetes using the Japanese version of SARC-F. METHODS: Participants included patients with diabetes aged ≥65 years who were undergoing outpatient treatment at the Ise Red Cross Hospital, Ise, Japan. Depression was measured using the Japanese version of the Patient Health Questionnaire 9, which is a nine-item questionnaire. Sarcopenia was assessed using the Japanese version of SARC-F, a self-administered questionnaire comprising five question items. Multiple logistic regression analysis with depression as the dependent variable and sarcopenia as the explanatory variable was used to calculate the odds ratio for depression in patients with sarcopenia. RESULTS: A total of 275 patients (167 men, 108 women) were the study participants. The adjusted odds ratio for depression in male patients with sarcopenia was 5.76 (95% CI 1.83-18.12, P = 0.003). The adjusted odds ratio for depression in female patients with sarcopenia was 2.62 (95% CI 0.68-10.05, P = 0.159). CONCLUSIONS: A statistically significant relationship was shown between sarcopenia and depression in older male patients with diabetes. We believe that drawing the attention of physicians to sarcopenia prevalence by using the Japanese version of SARC-F will contribute to the detection of depression in older male patients with diabetes. Geriatr Gerontol Int 2018; 18: 1318-1322.

[A comparison of the associations of dynapenia and sarcopenia with fear of falling in elderly diabetic patients].

AIM: To comparatively investigate whether dynapenia and sarcopenia, as defined by the Asian Working Group for Sarcopenia (AWGS), are associated with fear of falling in elderly patients with diabetes. METHODS: The subjects were outpatients with diabetes who were at least 65 years of age when they visited our hospital. Sarcopenia was evaluated based on the AWGS definition. The cutoff values for the appendicular skeletal mass index (multi-frequency bioelectrical impedance method), grip strength, and walking speed were, respectively, 7.0 kg/m2 for men and 5.7 kg/m2 for women, 26 kg for men and 18 kg for women, and ≤0.8 m/s for both men and women. Those with grip strength of less than or equal to the cutoff value were considered to have dynapenia. Fear of falling was assessed by a self-administered questionnaire survey with the Fall Efficacy Scale (FES) Japanese version. A multiple regression analysis was conducted using the FES score as a dependent variable and dynapenia or sarcopenia and moderators as explanatory variables. RESULTS: A total of 202 patients (male, n=127; female, n=75) were analyzed in this study. The FES scores of the patients with and without sarcopenia did not differ to a statistically significant extent in either male or female patients. The multiple regression analysis revealed a statistically significant association between dynapenia and the FES score in men (P=0.028). CONCLUSIONS: In elderly outpatients with diabetes, no association was found between sarcopenia and the fear of falling in either men or women. In contrast, a statistically significant association was found between dynapenia and fear of falling in men. This suggests the importance paying attention to the fear of falling when examining elderly male diabetes patients with dynapenia.

Association Between Sarcopenia and Mild Cognitive Impairment Using the Japanese Version of the SARC-F in Elderly Patients With Diabetes.

OBJECTIVES: The purpose of this study was to investigate the association between sarcopenia and mild cognitive impairment (MCI) in elderly patients with diabetes using the Japanese version of the simple 5-item questionnaire (SARC-F-J). DESIGN: Cross-sectional study. SETTING: Community hospital in Japan. PARTICIPANTS: Subjects were people with diabetes aged 65 years and older being treated on an outpatient basis at the Ise Red Cross Hospital. MEASUREMENTS: We used the Japanese version of the self-administered cognitive test Test Your Memory (TYM-J) to measure MCI and the self-administered questionnaire SARC-F-J, consisting of 5 items, to evaluate sarcopenia. We conducted a multiple logistic regression analysis with MCI as the dependent variable and sarcopenia as the explanatory variable to calculate the odds ratio of sarcopenia in association with MCI. RESULTS: A total of 250 cases (150 men and 100 women) were included in our study. The prevalence of sarcopenia in this sample was 19.5% and that of MCI was 40.3%. The adjusted odds ratio of sarcopenia in association with MCI was 2.96 (95% confidence interval, 1.09-7.70, P = .032). CONCLUSION: A statistically significant association was found between sarcopenia and MCI in an assessment of elderly patients with diabetes using the SARC-F-J.

Development of a Japanese version of the SARC-F for diabetic patients: an examination of reliability and validity.

BACKGROUND: SARC-F is a 5-item, self-administered questionnaire developed to screen sarcopenia. To date, no Japanese version of the SARC-F has been developed. AIMS: To create a Japanese version of the SARC-F (SARC-F-J), a questionnaire for diabetic patients, and to investigate its reliability and validity. METHODS: This was a cross-sectional study. A Japanese translation of the SARC-F was created and revised, and the authors of the original version of the SARC-F verified the back-translation. The questionnaire was tested in diabetic outpatients aged ≥65 years who had received treatment at our hospital. After 14 weeks, the kappa coefficient was used to evaluate the retest reliability. Using the diagnostic criteria for sarcopenia based on the European Working Group on Sarcopenia in Older People as the reference standard, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the SARC-F-J. RESULTS: The study comprised 207 patients (men, 60.8%; women, 39.2%). The kappa coefficient was 0.66. For men and women, the sensitivities were 14.6 and 33.3%, specificities were 85.8 and 72.4%, positive predictive values were 33.3 and 17.3%, and negative predictive values were 65.7 and 86.2%, respectively. DISCUSSION: The probability of identifying the condition is considered high when patients are diagnosed with sarcopenia using SARC-F-J. CONCLUSIONS: The retest reliability of SARC-F-J was regarded to be good. When EWGSOP was assumed as a reference, the specificity of SARC-F-J was high. Because the sensitivity was low, patients with sarcopenia could not be screened, and hence, attention is needed.

Effect of trelagliptin on vascular endothelial functions and serum adiponectin level in patients with type 2 diabetes: a preliminary single-arm prospective pilot study.

BACKGROUND: Trelagliptin, an oral DPP-4 inhibitor, which is administered once per week and characterized by a long half-life in blood. The effects of trelagliptin on vascular endothelial functions have not been clarified to date. The objective of the present study was to examine the effects of trelagliptin on vascular endothelial functions in patients with type 2 diabetes mellitus (DM) using flow-mediated dilatation (FMD), adiponectin, and asymmetric dimethylarginine (ADMA) as evaluation indicators. METHODS: This study was a preliminary single-arm prospective pilot study. The subjects of this study were type 2 DM patients aged 20-74 years, who visited our outpatient department. The patients were treated with trelagliptin, and their FMD, adiponectin, and ADMA levels were measured at baseline and at 12 weeks after initial treatment to determine the changes during the study period. RESULTS: A total of 27 patients, excluding three dropouts, were included in the population for analysis. Trelagliptin treatment showed no significant changes in FMD (2.42 ± 2.7% at baseline vs. 2.66 ± 3.8% post-treatment, P = 0.785) and ADMA (0.41 ± 0.0 µg/mL at baseline vs. 0.40 ± 0.0 µg/mL post-treatment, P = 0.402). Trelagliptin treatment resulted in a significant increase of serum adiponectin level (7.72 ± 6.9 µg/mL at baseline vs. 8.82 ± 8.3 µg/mL post-treatment, P < 0.002). CONCLUSIONS: In this pilot study, trelagliptin treatment showed no significant changes in FMD. On the other hand, it was believed that trelagliptin treatment may increase serum adiponectin level. Trial Registration http://www.umin.ac.jp (Trial ID UMIN000018311).

[Remarkable effect of a modified ketogenic diet in a boy with focal seizures followed by epileptic spasms in a cluster].

A modified ketogenic diet was demonstrated to be remarkably effective in a child with intractable symptomatic focal epilepsy with combined seizures of focal seizures and epileptic spasms (ES) in a cluster (ESC). ES started at 8 months of age and disappeared with ACTH therapy. At the age of 13 months, the child began to have intractable focal seizures that, later, were followed by ESC 10 times a day. Brain MRI showed only a non-specific diffuse cerebral atrophy. Interictal EEG showed high amplitude diffuse disorganized slow waves with prominent sharp waves predominant over the bilateral occipital region. We started a modified ketogenic diet (mKD) treatment without fasting or a water/calorie limitation. Since the 20th day of mKD, the patient has been seizure free (6 months) without adverse effects. EEG showed remarkable improvement and he has some improvement in the developmental milestones. A modified ketogenic diet is easier to start and continue compared to the classic ketogenic diet, and should be tried in intractable epilepsies that are not treatable surgically early in life from the developmental prognosis point of view.

[Effectiveness of topiramate in eleven patients with Dravet syndrome].

Dravet syndrome is a rare, but highly refractory epilepsy syndrome. As conventional drugs are not effective, introduction of new effective drugs in clinical use will benefit patients with this disease. We assessed the effectiveness of topiramate (TPM) as adjunctive therapy in 11 patients with Dravet syndrome. TPM was started at doses ranging from 10 to 50 mg/day (0.57 to 2.0 mg/kg/day), and the dosage was increased gradually up to the maximum dose (9 mg/kg/day) depending on efficacy and tolerability. The frequencies of convulsive seizures (generalized tonic-clonic seizures, unilateral seizures, partial onset generalized tonic-clonic seizures) during two months before starting TPM, two months after starting TPM, and the fifth and sixth months after starting TPM were determined. The mean dose (mean +/- SD) of TPM at the second month was 2.7 +/- 1.5 mg/kg/day (1.0-5.7 mg/kg/day, n= 11), and that at the sixth month was 4.5 +/- 2.2 mg/kg/day (1.0-7.3 mg/kg/day, n=10). Evaluation at the second month revealed that one of 11 patients (9%) became seizure-free, six patients (54%) showed greater than 50% seizure reduction, three patients (27%) showed less than 50% seizure reduction, and one patient (9%) had aggravation of convulsive seizures resulting in discontinuation of TPM at the first month. Evaluation at the sixth month revealed that one of 10 patients (10%) was seizure-free, seven patients (70%) had greater than 50% seizure reduction, two patients (20%) had less than 50% seizure reduction, and no patient (0%) had aggravation. Adverse effects were observed in five patients; dizziness in three patients, sleepiness in three patients, and oligohidrosis in one patient. In the present study, TPM was useful as an adjunctive therapy to reduce the frequency of convulsive seizures in patients with Dravet syndrome. A large-scale efficacy study of TPM for Dravet syndrome is warranted.

Genomic copy number variations at 17p13.3 and epileptogenesis.

Deletion of the terminal end of 17p is responsible for Miller-Dieker syndrome (MDS), which is characterized by lissencephaly, distinctive facial features, growth deficiency, and intractable seizures. Using microarray-based comparative genomic hybridization, 3 patients with epilepsy were revealed to have genomic copy number aberrations at 17p13.3: a partial LIS1 deletion in a patient with isolated lissencephaly and epilepsy, a triplication of LIS1 in a patient with symptomatic West syndrome, and a terminal deletion of 17p including YWHAE and CRK but not LIS1 in a patient with intractable epilepsy associated with distinctive facial features and growth retardation. In this study, it was suggested that the identified gain or loss of genomic copy numbers within 17p13.3 result in epileptogenesis and that triplication of LIS1 can cause symptomatic West syndrome.

Detection of submicroscopic disease in the bone marrow and unaffected testis of a child with T-cell acute lymphoblastic leukemia who experienced "isolated" testicular relapse.

Testicular relapse has an impact on the prognosis of boys with acute lymphoblastic leukemia (ALL). Because isolated testicular relapse often precedes hematological relapse, systemic therapy is required in addition to local therapy. However, a rationale for the use of a combination of systemic chemotherapy and local therapy is unclear. A 12-year-old boy with T-ALL suffered from isolated testicular relapse at 27 months after diagnosis. He was successfully treated with systemic chemotherapy with orchiectomy and prophylactic irradiation to the contralateral testis. We retrospectively estimated the minimal residual disease in the bone marrow (BM) and the testis by detection of clone-specific T-cell receptor rearrangement of leukemic cells. We detected leukemic cells in the affected testis at relapse, as well as in the BM at initial diagnosis. In addition, we confirmed submicroscopic disease in the unaffected testis and the BM at relapse. We conclude that molecular analysis could reveal the submicroscopic disease in the patient with apparently isolated testicular relapse. This finding may provide a rationale for intensified systemic treatment of patients with isolated testicular relapse.

Iodine-131-metaiodobenzylguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.