Yohei Akazawa

Increased pretransplant QT dispersion as a risk factor for the development of cardiac complications during and after preparative conditioning for pediatric allogeneic hematopoietic stem cell transplantation

Motoki N, Shimizu T, Akazawa Y, Saito S, Tanaka M, Yanagisawa R, Motoki H, Nakazawa Y, Sakashita K, Iwasaki Y, Shiohara M, Koike K. Increased pretransplant QT dispersion as a risk factor for the development of cardiac complications during and after preparative conditioning for pediatric allogeneic hematopoietic stem cell transplantation.
Pediatr Transplantation 2010: 14:986–992.

Cardiovascular Remodeling and Dysfunction Across a Range of Growth Restriction Severity in Small for Gestational Age Infants – Implications for Fetal Programming –

BACKGROUND The purpose of this study was to clarify cardiovascular structure and function in small for gestational age (SGA) infants across a range of intrauterine growth restriction (IUGR) severity. METHODSANDRESULTS This prospective study included 38 SGA infants and 30 appropriate for gestational age (AGA) infants. SGA infants were subclassified into severe and mild SGA according to the degree of IUGR. Cardiovascular structure and function were evaluated using echocardiography at 1 week of age. Compared with the AGA infants, both the severe and mild SGA infants showed increased left ventricular diastolic dimensions (severe SGA 10.2±2.4, mild SGA 8.2±1.3, and AGA 7.3±0.7 mm/kg, P<0.05 for all) and decreased global longitudinal strain (severe -21.1±1.6, mild -22.5±1.8, and AGA -23.8±1.8%, P<0.05 for all). Severe SGA infants showed a decreased mitral annular early diastolic velocity (severe 5.6±1.4 vs. AGA 7.0±1.3 cm/s, P<0.01) and increased isovolumic relaxation time (severe 51.3±9.2 vs. AGA 42.7±8.2 ms, P<0.01). Weight-adjusted aortic intima-media thickness and arterial wall stiffness were significantly greater in both SGA infant groups. These cardiovascular parameters tended to deteriorate with increasing IUGR severity. CONCLUSIONS SGA infants, including those with mild SGA, showed cardiovascular remodeling and dysfunction, which increased with IUGR severity. (Circ J 2016; 80: 2212-2220).

Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome in a boy with Loeys-Dietz syndrome.

Loeys‐Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder, caused by heterozygous mutations in TGFBR1 or TGFBR2 and characterized by vascular complications (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections) and skeletal manifestations. We here report the first patient with LDS presenting with reversible cerebral vasoconstriction syndrome (RCVS), a clinico‐radiological condition characterized by recurrent thunderclap headaches, with or without neurological symptoms, and reversible vasoconstriction of cerebral arteries. The patient was a 9‐year‐old boy with a heterozygous TGFBR2 mutation, manifesting camptodactyly, talipes equinovarus, and lamboid craniosynostosis. He complained of severe recurrent headaches 2 months after total aortic replacement for aortic root dilatation and a massive Stanford type B aortic dissection. A thoracic CT scan revealed a left subclavian artery dissection. Brain MRI and MRA detected bilateral internal carotid artery constriction along with a cortical subarachnoid hemorrhage without intracranial aneurysms. Subsequently, he developed visual disturbance and a generalized seizure associated with multiple legions of cortical and subcortical increased signals including the left posterior lobe, consistent with posterior reversible encephalopathy syndrome (PRES), a condition characterized by headaches, visual disorders, seizures, altered mentation, consciousness disturbances, focal neurological signs, and vasogenic edema predominantly in the white matter of the posterior lobe. Vasoconstriction of the internal carotid artery was undetectable 2 months later, and he was diagnosed as having RCVS. Endothelial dysfunction, associated with impaired TGF‐β signaling, might have been attributable to the development of RCVS and PRES.

The clinical characteristics of vitamin D deficiency in childhood: a systematic literature review of Japanese patients.

To describe the characteristics of children with vitamin D deficiency, we reviewed the reports of vitamin D deficiency among Japanese children that were published between 1989 and 2008. We identified 25 patients with vitamin D deficiency in 9 published studies and evaluated their clinical characteristics together with those of 3 patients we recently treated. The patients were distributed in two distinct age groups at diagnosis: < 1 year old and > or = 1 year old. The main symptom of the < 1 year old age group was hypocalcemic convulsions and that of the > or = 1 year old age group was bowed legs. Serum calcium, intact PTH, and 1,25(OH)2D levels were significantly lower in the < 1 year age group than in the > or = 1 year age group. It would be useful to find and make early interventions in cases of children at a high-risk of vitamin D deficiency.

Prognostic Significance of QT Interval Dispersion in the Response to Intravenous Immunoglobulin Therapy in Kawasaki Disease

BACKGROUND Kawasaki disease (KD) is classified as a systemic vasculitis syndrome and QT interval dispersion (QTD) has been associated with cardiac involvement and disease activity in patients with cardiovasculitis. We examined whether baseline QTD could predict a response to intravenous immunoglobulin (IVIG) in KD.Methods and Results:QTD was recorded in 86 patients with KD before IVIG, who were separated into IVIG responders (R group; n=62) and nonresponders (N group; n=24). The association between baseline QTD and response to IVIG was investigated, and the predictive response value was compared with conventional risk scores from Gunma and Kurume universities. Baseline-corrected QTDs with Bazetts (QTbcD) and Fridericias (QTfcD) formulae were significantly increased in the N group (R group vs. N group: 31.6 [28.3, 44.0] ms vs. 66.6 [50.5, 76.3] ms and 27.4 [25.2, 39.1] ms vs. 55.2 [42.4, 66.3] ms, respectively, both P<0.001). Multiple logistic regression analysis revealed QTfcD as an independent predictor of a response to IVIG after adjustment for conventional scores (odds ratio: 1.133, 95% confidence interval: 1.061-1.210, P<0.001). Moreover, QTfcD provided incremental predictive value for IVIG nonresponders over Gunma score (increment in global χ2=25.46, P<0.001). CONCLUSIONS QTD was significantly associated with a response to IVIG in KD patients and may represent a useful identifier of IVIG nonresponders with high risk of coronary aneurysm.

Right-to-left shunting in the ductus arteriosus is induced readily by intense crying and rapid postural change in neonates with meconium-stained amniotic fluid.

Objective: To investigate postnatal changes in the direction of blood flow through the ductus arteriosus in neonates with meconium-stained amniotic fluid, we measured preductal and postductal oxygen saturation in normal neonates, neonates with meconium-stained amniotic fluid, and a neonate with persistent pulmonary hypertension of the newborn. Design: Prospective, observational case series report. Setting: A single, tertiary neonatal intensive care unit. Patients: Twelve normal neonates, seven neonates with meconium-stained amniotic fluid, and a neonate with persistent pulmonary hypertension of the newborn. Interventions: SpO2 is simultaneously monitored in the right upper and lower limbs after birth. Measurements and Main Results: Compared with normal neonates, three neonates with meconium-stained amniotic fluid required longer than +2 SD of the mean time for the postductal SpO2 to reach 90% and/or 95%. In a neonate with meconium-stained amniotic fluid, intense crying triggered frequent decreases to <70% in the postductal SpO2 from 25 mins after birth, while the preductal SpO2 remained at 95% or above. When the other newborn with meconium-stained amniotic fluid was held in the fathers arms after 98 mins, the postductal SpO2 decreased rapidly to <80%, while the preductal SpO2 remained at 95%. Thus, 5% or greater difference between the preductal and postductal SpO2 was observed from 25 mins after birth until 120 mins in all neonates with meconium-stained amniotic fluid, whereas the difference disappeared after 25 mins in 12 normal neonates. In a neonate with persistent pulmonary hypertension of the newborn who required vigorous resuscitation, 5% or greater difference between the preductal and postductal SpO2 levels was observed until 6 hrs after birth. Conclusions: Right-to-left shunting in the ductus arteriosus may be induced readily by intense crying and rapid postural change in infants with meconium-stained amniotic fluid. It is important to monitor SpO2 at both pre- and postductal regions until 120 mins after birth in neonates with meconium-stained amniotic fluid and to subject these infants to minimal manipulations.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

Importance Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. Main Outcomes and Measures The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Results Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1–15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7–4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4–3.6) were significantly associated with CE. Conclusions and Relevance Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Intratracheal catheter suction removes the same volume of meconium with less impact on desaturation compared with meconium aspirator in meconium aspiration syndrome.

OBJECTIVE To evaluate the impact of suction technique on the rate of meconium removal, oxygenation, and hemodynamics in an animal experimental model of meconium aspiration syndrome (MAS). METHODS MAS was induced in ventilated rabbits using 3.5 ml/kg of 20% human meconium. Tracheal suction with either catheter suction (CS) or meconium aspirator (MA) was performed after meconium instillation. Percentage of meconium collection rate, PaO(2) trends for 2h after tracheal suction, and acute-phase SpO(2) trends were compared between CS and the other three groups, the tube was withdrawn while meconium was aspirated with an MA, then the trachea was reintubated 5, 10 or 15s after suctioning of meconium. RESULTS Percentage of meconium collection rate and PaO(2) showed no significant differences between groups. The MA group taking 15s for reintubation after meconium suctioning, showed a significantly lower acute-phase SpO(2) than the CS group (P<0.05). The time for SpO(2) to return to >or=90% was also longer in the MA group taking 15s for reintubation than in the CS group (P<0.05). CONCLUSION Intratracheal CS removed the same volume of meconium with less impact on desaturation compared with meconium aspiration in an animal model of MAS. Intratracheal CS may be benefit to remove meconium in non-vigorous infants with meconium-stained amniotic fluid at birth.

Presepsin as a predictor of positive blood culture in suspected neonatal sepsis

Although the incidence of neonatal sepsis is decreasing, neonatal sepsis remains a severe life‐threatening disease. No current biochemical marker can provide perfect diagnostic accuracy for neonatal sepsis. The aim of this study was therefore to evaluate the accuracy of presepsin (P‐SEP) as a novel biomarker of bacterial infection for neonatal sepsis diagnosis.

Impact of Decreased Serum Insulin-Like Growth Factor-1 Levels on Central Aortic Compliance in Small-for-Gestational-Age Infants

Background: Intrauterine growth restriction is associated with arterial hypertension in adulthood; however, the underlying mechanism is unclear. Objectives: We hypothesized that serum insulin-like growth factor-1 (IGF-1) levels affect central aortic elastic properties and structure in small-for-gestational-age (SGA) infants. Methods: Eighteen SGA infants and 22 appropriate-for-gestational-age (AGA) infants were enrolled in this study. The serum IGF-1 level within 1 h of birth and abdominal aortic echo parameters at 1 week of age were retrospectively compared. Results: In the SGA infants, IGF-1 levels (27.6 ± 17.7 vs. 42.6 ± 15 ng/ml, p = 0.006), aortic strain (10.2 ± 3.1 vs. 12.8 ± 3.1%, p = 0.01), and aortic distensibility (0.73 ± 0.19 vs. 0.92 ± 0.34 cm2/dyn × 10-4, p = 0.05) were significantly lower compared with AGA infants. By contrast, blood pressure, aortic intima-media thickness (aIMT) in relation to body weight (383 ± 163 vs. 256 ± 43 μm/kg, p < 0.001), aortic stiffness index in relation to body weight (2.0 ± 1.7 vs. 1.1 ± 0.4, p = 0.005), and arterial pressure-strain elastic modulus (293 ± 72 vs. 242 ± 78 mm Hg, p = 0.04) were higher compared with AGA infants. In the SGA infants, IGF-1 levels were significantly correlated with aortic strain (r = 0.49, p = 0.04), aIMT in relation to body weight (r = -0.61, p = 0.007), and aortic stiffness index in relation to body weight (r = -0.63, p = 0.005). Conclusions: Decreased serum IGF-1 levels in SGA infants may affect the vascular compliance and structure of the central aorta.