A retrospective study of perioperative clinical seizures and epilepsy in children after operation for CHD.

This study investigated the incidence and risk factors of perioperative clinical seizure and epilepsy in children after operation for CHD. We included 777 consecutive children who underwent operation from January 2013 to December 2016 at Kanagawa Children's Medical Center, Kanagawa, Japan. Perinatal, perioperative, and follow-up medical data were collected. Elastic net regression and mediation analysis were performed to investigate risk factors of perioperative clinical seizure and epilepsy. Anatomic CHD classification was performed based on the preoperative echocardiograms; cardiac surgery was evaluated using Risk Adjustment in Congenital Heart Surgery 1. Twenty-three (3.0%) and 15 (1.9%) patients experienced perioperative clinical seizure and epilepsy, respectively. Partial regression coefficient with epilepsy as the objective variable for anatomical CHD classification, Risk Adjustment in Congenital Heart Surgery 1, and the number of surgeries was 0.367, 0.014, and 0.142, respectively. The proportion of indirect effects on epilepsy via perioperative clinical seizure was 22.0, 21.0, and 33.0%, respectively. The 15 patients with epilepsy included eight cases with cerebral infarction, two cases with cerebral haemorrhage, and three cases with hypoxic-ischaemic encephalopathy; white matter integrity was not found. Anatomical complexity of CHD, high-risk cardiac surgery, and multiple cardiac surgeries were identified as potential risk factors for developing epilepsy, with a low rate of indirect involvement via perioperative clinical seizure and a high rate of direct involvement independently of perioperative clinical seizure. Unlike white matter integrity, stroke and hypoxic-ischaemic encephalopathy were identified as potential factors for developing epilepsy.

Clinical features of very-low-birthweight infants with congenital heart disease.

BACKGROUND: Few studies have investigated the developmental prognosis of very-low-birthweight (VLBW) infants with congenital heart diseases (CHDs). This study aimed to determine the mortality and morbidity, including the developmental prognosis, of VLBW infants with CHD. METHODS: This single-center, retrospective cohort study included VLBW infants admitted to the neonatal intensive care unit from January 2006 to December 2011. Perinatal records were reviewed for CHD diagnosis, treatment details, comorbidities, mortality, and long-term neurodevelopmental outcomes. The characteristics and neurological developmental quotients at around the age of 3 years were compared among the following three groups of VLBW infants with CHDs: biventricular circulation without intervention (without surgery), biventricular circulation with intervention (catheter intervention or one-stage surgery), and single-ventricular circulation (Fontan-type multiple-stage surgery). RESULTS: Among a total of 449 VLBW infants admitted during this period, 45 (10.0%) infants had CHDs, including 25 infants with congenital abnormalities (chromosomal abnormalities and/or multiple anomalies). All 13 infants who died before discharge had congenital abnormalities. The incidence rates of comorbidities were not higher in VLBW infants with CHDs than in those without CHDs. The developmental quotients of the no-surgery, catheter intervention or one-stage surgery, and Fontan-type multiple-stage surgery groups were 87.2 ± 10.9, 91.3 ± 4.7, and 63.7 ± 8.6, respectively. CONCLUSIONS: The neurological development at around the age of 3 years in VLBW infants with biventricular circulation was in the borderline-to-normal range; however, that in infants with single-ventricular circulation was poor. Further studies are needed to comprehend the neurological development of VLBW infants with CHDs better.

Rapid two-stage Starnes approach in high-risk neonates with Ebstein anomaly.

OBJECTIVES: The purpose of this study is to review the short- and long-term outcomes of high-risk neonates with Ebstein anomaly treated with a newly developed rapid 2-stage Starnes procedure, which is aimed at reducing the size of the enlarged right side of the heart. METHODS: Fifty-two foetuses with Ebstein anomaly were analysed in this study and divided into 2 groups. The control group comprised 25 foetuses, referred to us before 2008, and the study group was composed of 27 foetuses, referred to us after 2009. The right atrial area index was defined as high risk when it was >1.5. We applied our management approach to 6 high-risk neonates in the study group. This approach consisted of reducing the size of the right side of the heart through a 2-stage process: (i) right atrial plication without the use of a bypass and (ii) a Starnes procedure. Cox proportional hazards models were used to evaluate the effects of our management approach on the survival rates of the neonates. RESULTS: The mean follow-up period was 7.5 ± 3.3 years. All 6 high-risk neonates in the study group survived. The overall hazard ratio was 0.12 (95% confidence interval of 0.03-0.43) in the study group as compared with the control group (P = 0.0007). A Fontan operation was completed in all but 1 case, with the remaining case awaiting a Fontan operation. CONCLUSIONS: We suggest that a rapid 2-stage Starnes approach can be effective in the treatment of high-risk neonates with Ebstein anomaly.

Mode of death and predictors of mortality in adult Fontan survivors: A Japanese multicenter observational study.

BACKGROUND: Mortality rates may be high in adult Fontan patients; however, the clinical determinants remain unclear. PURPOSE: We conducted a prospective multicenter study of adult Fontan survivors to determine the 5-year mortality rate and clarify the determinants. METHOD AND RESULTS: We followed 600 adult Fontan survivors from 40 Japanese institutions (307 men, 28 ±â€¯7 years old, follow-up: 18 ±â€¯6 years). The New York Heart Association (NYHA) functional class I and II was 51% and 42%, respectively. During the follow-up period of 4.1 ±â€¯1.6 years, 33 patients died, and the 5-year survival rate was 93.5%. The mode of death was heart failure in 11 patients (34%), arrhythmia or sudden death in 8 (24%), cancer in 5 (15%), perioperative problems and hemostatic problems in 4 each (12% for each), and infection in 1 (3%). Left isomerism, prior hospitalization, protein losing enteropathy (PLE), pulmonary arteriovenous fistulae, NYHA functional class, impaired hemodynamics, hyponatremia, hepatorenal dysfunction, and use of diuretics were associated with a high mortality rate (p < 0.05-0.0001). Further, PLE (hazard ratio [HR]: 14.4), left isomerism (HR: 3.5), and NYHA (HR: 2.4) independently predicted a high 5-year high mortality (p < 0.05 for all). The incidence of cancer-related mortality increased markedly with age >40 years. CONCLUSIONS: Majority of the Japanese adult Fontan survivors had good functional status, with an acceptable 5-year survival rate. However, the significant prevalence of non-cardiac mortality highlights Fontan pathophysiology as a multi-organ disease that requires a multidisciplinary management strategy to improve the long-term outcome.

Health-promotion and disease-prevention behaviors of primary-care practitioners.

BACKGROUND: In the 1990s the primary focus of medicine was shifted to disease prevention. Accordingly, it became the responsibility of primary-care physicians to educate and counsel the general population not only on disease prevention specifically but health promotion generally as well. Moreover, it was, and is still today, considered important that physicians provide positive examples of health-promotion behaviors to patients. The purpose of this study was to investigate physicians' health-promotion behaviors and to identify the factors that influence them. METHODS: We conducted a postal and e-mail survey of the 371 members of the Physician Association of Cheonan City between May 16th and June 25th, 2011. The questionnaire consisted of 18 items, including questions relating to sociodemographic factors, screening tests for adult diseases and cancer, and health habits. RESULTS: There were 127 respondents. The gender breakdown was 112 men (88.2%) and 15 women (11.8%), and the mean age was 47.8 years. Fifty-nine (46.4%) were family physicians or interns, and 68 (53.6%) were surgeons. Twenty-six percent (26%) were smokers, and 74.8% were drinkers; 53.5% did exercise; 37% had chronic diseases; 44.9% took periodic cancer screening tests, and 72.4% took periodic screening tests for adult diseases. CONCLUSION: It was found that general characteristics and other health-promotion behaviors of physicians do not affect physicians' practice of undergoing periodic health examination.

Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine treatment in lung cancer cells.

Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G(1) population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.

Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions.

Human gastric cancer SNU 484 cells express mutant p16, which migrates slower than the wild-type p16. We constructed an expression vector containing human p16 cDNA to evaluate the cytotoxic effects of exogenous p16 expression on SNU 484 cell proliferation and to explore the potential use of p16 in cancer gene therapy. The stable transfectant expressing wild-type p16, showed a 2-fold slower growth rate than mock and non-infected cells through down-regulation of CDK4-dependent kinase activity. When cells were transiently transfected with mock or p16 encoded vector, the mock cells showed larger survival colonies than those of wild-type p16. Furthermore, p16-expressing stable transfectant was readily progressed into cell death by combination with treatment of chemotherapeutic drug in a dose-dependent manner. According to western blot analysis, both decreased expression of pRB and increased expression of E2F-1 may contribute to the susceptibility of cell death. Our data indicate that exogenous wild-type p16 induces delayed cell proliferation and promotes chemo-sensitivity in the gastric cancer cell line, implying the promise of p16 in cancer gene therapy.