Hemodynamic simulation of complete transposition of the great arteries for optimal treatment strategies based on its circulatory physiology.

Our study aimed to elucidate the role of different shunts and provide novel insights into optimal treatment approaches for complete transposition of the great arteries (TGA), which is characterized by unique and complicated circulatory dynamics. We constructed a computational cardiovascular TGA model and manipulated cardiovascular parameters, such as atrial septal defect (ASD) and patent ductus arteriosus (PDA) sizes, to quantify their effects on oxygenation and hemodynamics. In addition, ASD flow patterns were investigated as innovative indications for balloon atrial septostomy (BAS). Our model of TGA with an intact ventricular septum (TGA-IVS) showed that a large ASD can achieve sufficient mixing for survival without PDA, and the presence of PDA is detrimental to oxygen delivery. A treatment strategy for TGA-IVS that enlarges the ASD as much as possible by BAS and PDA closure would be desirable. In TGA with a ventricular septal defect (TGA-VSD), the VSD allows for higher oxygenation and reduces the detrimental effects of PDA on systemic circulation. In TGA-VSD, both strategies of enlarging the ASD by BAS with a closed PDA and adjusting the PDA in response to pulmonary vascular resistance (PVR) reduction without BAS may be effective. The simulated ASD flow patterns showed that the sharp peak left-to-right flow pattern in systole (σ-wave) reflected the hemodynamically significant ASD size, independent of PDA, VSD, and PVR. The ASD flow pattern visualized by Doppler echocardiography provides clinical insights into the significance of an ASD and indications for BAS, which are not readily apparent through morphological assessment.NEW & NOTEWORTHY Complete transposition of the great arteries (TGA) represents complex and unique circulation that is dependent on blood mixing through multiple interacting shunts. Consequently, the role of each shunt and the treatment strategy remain unclear. We developed a mathematical model of TGA circulation, revealing the significant influence of atrial septal defect (ASD) on oxygenation and hemodynamics. The blood flow pattern through the ASD reflects its hemodynamic impact and helps determine treatment strategies.

Monitoring Berlin Heart EXCOR by computer vision: A preliminary implementation and evaluation.

BACKGROUND: EXCOR Pediatric is one of the most commonly used ventricular assist devices (VAD) for small children; it requires visual inspection of the diaphragm movement to assess its operating status. Although this visual inspection can only be performed by trained medical professionals, it can also be attempted by the recent advances in computer vision technology. METHODS: Movement of the diaphragm in the operating EXCOR VAD was recorded as movies and annotated frame-by-frame in three classes according to the state of the diaphragm: "fill," "mid," and "empty." Three models, MobileNetV3, EfficientNetV2, and MobileViT, were trained using the frames, and their performance was evaluated based on the accuracy and area under the receiver operating characteristic curve (AROC). RESULTS: A total of 152 movies were available from two participants. Only the 10 mL pumps were used. Ninety-eight movies were used for annotation and frame extraction, and 7949 frames per class were included in the analysis. The macro-average accuracies of the three models were 0.88, 0.91, and 0.93, and the AROC were 0.99, 0.98, and 0.99 for MobileNetV3, EfficientNetV2, and MobileViT, respectively. CONCLUSION: Image recognition models based on lightweight deep neural networks could detect the diaphragm state of EXCOR VAD with sufficient accuracy, although there were limited variations in the dataset. This suggests the potential of computer vision for the automated monitoring of the EXCOR diaphragm position.

Practice and Safety of Static Balloon Atrial Septostomy Based on a Nationwide Registry Data.

BACKGROUND: Balloon atrial septostomy (BAS) is an essential catheterization procedure for congenital heart lesions. Recently, a balloon catheter for static BAS was approved for the first time in Japan as an alternative to the conventional pull-through BAS. Despite the expected increase in the use of static BAS, reports on its safety are scarce worldwide.Methods and Results: Data on static and pull-through BAS registered in a national registry between 2016 and 2018 were collected. During the study period, 247 sessions of static BAS and 588 sessions of pull-through BAS were performed on a total of 674 patients. Patients who underwent static BAS were older (P<0.001). The incidence of serious adverse events (4.3% vs. 0.9%, P=0.03) and the overall incidence of adverse events (8.1% vs. 3.2%, P=0.03) were higher in static BAS than in pull-through BAS. Among patients who underwent static BAS, the risk factor for adverse events was a body weight <3 kg at the time of the procedure (odds ratio: 4.3 [confidence interval: 1.7-11], P=0.003). CONCLUSIONS: This nationwide study revealed differences in patient background between static and pull-through BAS, as well as a higher incidence of adverse events related to static BAS. Patients weighing <3 kg are at high risk for adverse events after static BAS and may require surgical and circulatory support backup.

Stent Implantation for Congenital Heart Diseases in Japan　- Comprehensive Analysis From the Japanese Society of Congenital Interventional Cardiology Registry.

BACKGROUND: Stent implantation for vascular stenosis associated with congenital heart diseases is commonly performed as an off-label procedure in Japan because there is no officially approved stent for any congenital heart disease.Methods and Results:We analyzed data from the Japanese Society of Congenital Interventional Cardiology Registry collected from January 2016 to December 2018. Patients who underwent stent implantation were enrolled in the present analysis. During the study period, there were 470 procedures, 443 sessions, and 391 cases. Of 443 sessions, 427 (96.4%) succeeded procedurally. There were no differences in the procedural success rates among age groups. In all, 416 sessions (367 patients; 94%) resulted in survival to 30 days after catheter intervention. Of 392 admissions, 357 patients (91%) survived to discharge. Only 4 deaths were directly related to stent implantation. Some in-hospital complications were observed during 55 of 443 sessions. Both hospital deaths and serious complications were significantly more frequent in the group with various preoperative risk factors. CONCLUSIONS: Although not officially approved for congenital heart diseases in Japan, stent implantation in congenital heart diseases has been widely and routinely performed for many years with safety and efficacy. The aim of stenting was variable and broad because of many different applications and morphological variations. These data may facilitate approval of such an important device in Japan.

Poor Myocardial Compaction in a Patient with Recessive MYL2 Myopathy.

Recessive mutations in the Myosin regulatory light chain 2 (MYL2) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive MYL2 myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive MYL2 cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.

Prognostic factors of acute neurological outcomes in infants with traumatic brain injury.

PURPOSE: The purpose of this study is to clarify risk factors for poor neurological outcomes and distinctive characteristics in infants with traumatic brain injury. METHODS: The study retrospectively reviewed data of 166 infants with traumatic intracranial hemorrhage from three tertiary institutions in Japan between 2002 and 2013. Univariate and multivariate analyses were used to identify clinical symptoms, vital signs, physical findings, and computed tomography findings associated with poor neurological outcomes at discharge from the intensive care unit. RESULTS: In univariate analysis, bradypnea, tachycardia, hypotension, dyscoria, retinal hemorrhage, subdural hematoma, cerebral edema, and a Glasgow Coma Scale (GCS) score of ≤ 12 were significantly associated with poor neurological outcomes (P < 0.05). In multivariate analysis, a GCS score of ≤ 12 (OR = 130.7; 95% CI, 7.3-2323.2; P < 0.001), cerebral edema (OR = 109.1; 95% CI, 7.2-1664.1; P < 0.001), retinal hemorrhage (OR = 7.2; 95% CI, 1.2-42.1; P = 0.027), and Pediatric Index of Mortality 2 score (OR = 1.6; 95% CI, 1.1-2.3; P = 0.018) were independently associated with poor neurological outcomes. Incidence of bradypnea in infants with a GCS score of ≤ 12 (25/42) was significantly higher than that in infants with GCS score of > 12 (27/90) (P = 0.001). CONCLUSIONS: Infants with a GCS score of ≤ 12 are likely to have respiratory disorders associated with traumatic brain injury. Physiological disorders may easily lead to secondary brain injury, resulting in poor neurological outcomes. Secondary brain injury should be prevented through early interventions based on vital signs and the GCS score.

Frequency, clinical manifestations, and outcomes of Staphylococcus lugdunensis Bacteremia in children.

BACKGROUND: Staphylococcus lugdunensis (S. lugdunensis) is known as a common cause of clinically significant infections in adults although the clinical importance of S. lugdunensis isolates from pediatric samples is less known. The aim of this study is to assess the incidence, characteristics, and outcomes of S. lugdunensis bacteremia (SLB) in children. METHODS: From January 2009 to March 2014, all blood culture isolates were retrospectively screened for S. lugdunensis. We analyzed the isolates for antimicrobial susceptibility and patients who had developed SLB by reviewing the electronic medical records. Additionally, we identified mecA and blaZ for available isolates by polymerase chain reaction (PCR). RESULTS: Of the 647 positive blood cultures during the period, 277 (42.8%) yielded coagulase negative Staphylococcus (CoNS), and 10 of 277 CoNS were S. lugdunensis (3.6% of all CoNS isolates). Of eight SLB episodes identified, seven (87.5%) were considered to have clinically significant bacteremia. All patients had underlying diseases, and all SLB were either healthcare-associated or hospital acquired. There was no infectious endocarditis (IE) development. All patients were treated with antibiotics and recovered without sequelae. We found that the isolates in our study showed higher antibiotic resistance to penicillin (8/8: 100%) and oxacillin (6/8: 75.0%) than previously reported. Among isolates available, we detected mecA in all four isolates resistant to oxacillin and blaZ in 5 of 6 isolates resistant to penicillin. CONCLUSIONS: S. lugdunensis is a rare but an important cause of bacteremia in children.

Accuracy of the history of injury obtained from the caregiver in infantile head trauma.

OBJECTIVE: We investigated the accuracy of parental reports of infant trauma history. METHODS: We retrospectively reviewed 166 infants from 3 tertiary institutions in Japan that had suffered a traumatic intracranial hemorrhage between 2002 and 2013. The infants were classified into 3 groups based on the parents' report of the mechanism of injury: the low-risk group consisted of injuries sustained from falling off a height below 3 ft. (n=84); the middle-to-high-risk group comprised other mechanisms of injury (n=54); and the unknown-risk group consisted of unknown mechanisms of injury (n=28). The severity, neurological outcomes, clinical features, and evaluation for abuse were compared among these 3 groups. RESULTS: Infants in the low-risk group had a higher severity, a worse neurological outcome, and a higher percentage of household injuries, retinal hemorrhage, subdural hematoma, and subdural hematoma suggestive of abusive head trauma (AHT) than those in the middle-to-high-risk group (P<.05). Infants in the unknown-risk group had the highest severity and the worst neurological outcomes, and a higher rate of features suggestive of AHT (P<.05). CONCLUSIONS: The accuracy of the history obtained from the caregivers of infants may be low in severe infantile head trauma. Therefore, medical professionals should treat the mechanism of injury obtained from caregivers as secondary information and investigate for possible AHT in cases with inconsistencies between the history that was taken and the severity of the injury observed.

Interleukin-8-producing primary cardiac undifferentiated sarcoma in a child with sustained fever.

We report the case of a 12-year-old boy with primary undifferentiated sarcoma of the left atrium. He had sustained fever during the clinical course and multiple lung and brain metastases. Chemotherapy and irradiation were ineffective; he died 41 days after hospitalization. On retrospective analysis, interleukin-8 (IL-8) was elevated; this was supported by immunohistochemistry and gene expression analysis of tumor samples. IL-8 continued to increase with tumor progression accompanied by elevated neutrophil count and C-reactive protein. IL-8 is involved in malignant tumor proliferation, migration, and angiogenesis and may have been related to the clinical condition and prognosis in the present case.

Decreased granulomatous reaction by polyurethane-coated stent in the trachea.

BACKGROUND: Reducing granulomatous reaction for stent implantation is important for the treatment of tracheobronchomalacia because formation of granuloma leads to refractory complication causing further respiratory distress. The purpose of this study was to clarify granulomatous reaction of newly innovated coated stents compared to non-coated metal stents. METHODS: Materials and animal experiments were performed using the newly invented metallic stent (laser-cut stainless steel with a coating of polyurethane). In the materials experiment, the correlation between the holding force and deformity was tested by a compressor. In the animal examination, coated stents were orally implanted into the trachea in five rabbits, while non-coated stents were implanted in another five rabbits. After 3 weeks' observation, the inner diameter was measured by 3-D computed tomography, and the number of granulation tissues was counted by bronchofiberscope. Histological investigation followed in both groups. RESULTS: In the materials experiment, new stents demonstrated a holding force similar to stainless steel stents. In the animal experiment, no difference was found in the inner diameter of the coated and non-coated stent groups (5.70 ± 0.17 vs 5.60 ± 0.27, P = 0.07). However, the number of granulation tissues was higher in non-coated stents than in coated stents (1.60 ± 0.55 vs 0.40 ± 0.55, P < 0.01). Histological investigation showed direct attachment of metal to the tracheal wall around the non-coated stents where epithelial structure was destroyed, while tracheal epithelia were preserved in the group of coated stents. CONCLUSIONS: The new polyurethane-coated metallic stent maintains enough holding force, and reduces histobiological reaction to foreign bodies in this experiment.

Clinical significance and normal reference value of serum creatinine to cystatin C ratio in children.

BACKGROUND & AIMS: Sarcopenia is a serious problem in adults and children. However, limited modalities are available for diagnosing pediatric sarcopenia. The serum creatinine to cystatin C ratio (Cre/CysC ratio) is a promising method for muscle quantification, although its clinical significance in the pediatric population is unknown. This study aimed to evaluate the relationship between the Cre/CysC ratio and physical performance. METHODS: This was a single-center retrospective study. Patients aged <15 years who had visited the University of Tokyo Hospital for measurements of serum creatinine and cystatin C levels, body height, and body weight were included. The patients were assigned according to their age (<2 or ≥2 years), and the relationship between the Cre/CysC ratio and physical performance at the time of measurement was analyzed. RESULTS: We included 266 patients, revealing a significant relationship between Cre/CysC ratio and physical performance in children aged ≥2 years (p < 0.001) but not in children aged <2 years (p = 0.42). The repeater-operator curve analysis of Cre/CysC to predict bedridden status showed good performance (the area under the curve was 0.82 (95% CI, 0.75-0.89)) and the cut-off value 0.44 had good accuracy (sensitivity 0.87, specificity 0.61). CONCLUSIONS: The Cre/CysC ratio was a significant marker of impaired physical performance, and a Cre/CysC ratio <0.44 accurately predicted bedridden status in children aged >2 years.

Prediction of adverse cardiovascular events in children using artificial intelligence-based electrocardiogram.

BACKGROUND: Convolutional neural networks (CNNs) have emerged as a novel method for evaluating heart failure (HF) in adult electrocardiograms (ECGs). However, such CNNs are not applicable to pediatric HF, where abnormal anatomy of congenital heart defects plays an important role. ECG-based CNNs reflecting neurohormonal activation (NHA) may be a useful marker of pediatric HF. This study aimed to develop and validate an ECG-derived marker of pediatric HF that reflects the risk of future cardiovascular events. METHODS: Based on 21,378 ECGs from 8324 children, a CNN was trained using B-type natriuretic peptide (BNP) and the occurrence of major adverse cardiovascular events (MACEs). The output of the model, or the electrical heart failure indicator (EHFI), was compared with the BNP regarding its ability to predict MACEs in 813 ECGs from 295 children. RESULTS: EHFI achieved a better area under the curve than BNP in predicting MACEs within 180 days (0.826 versus 0.691, p = 0.03). On Cox univariable analyses, both EHFI and BNP were significantly associated with MACE (log10 EHFI: hazard ratio [HR] = 16.5, p < 0.005 and log10 BNP: HR = 4.4, p < 0.005). The time-dependent average precisions of EHFI in predicting MACEs were 32.4%-67.9% and 1.6-7.5-fold higher than those of BNP in the early period. Additionally, the MACE rate increased monotonically with EHFI, whereas the rate peaked at approximately 100 pg/mL of BNP and decreased in the higher range. CONCLUSIONS: ECG-derived CNN is a novel marker of HF with different prognostic potential from BNP. CNN-based ECG analysis may provide a new guide for assessing pediatric HF.

Over-investigation and overtreatment in pediatrics: a survey from the European Academy of Paediatrics and Japan Pediatric Society.

Introduction: Avoiding over-investigation and overtreatment in health care is a challenge for clinicians across the world, prompting the international Choosing Wisely campaign. Lists of recommendations regarding medical overactivity are helpful tools to guide clinicians and quality improvement initiatives. We aimed to identify the most frequent and important clinical challenges related to pediatric medical overactivity in Europe and Japan. Based on the results, we aim to establish a (European) list of Choosing Wisely recommendations. Methods: In an online survey, clinicians responsible for child health care in Europe and Japan were invited to rate 18 predefined examples of medical overactivity. This list was compiled by a specific strategic advisory group belonging to the European Academy of Paediatrics (EAP). Participants were asked to rate on a Likert scale (5 as the most frequent/important) according to how frequent these examples were in their working environment, and how important they were considered for change in practice. Results: Of 2,716 physicians who completed the survey, 93% (n = 2,524) came from 17 countries, Japan (n = 549) being the largest contributor. Pediatricians or pediatric residents comprised 89%, and 51% had 10-30 years of clinical experience. Cough and cold medicines, and inhaled drugs in bronchiolitis were ranked as the most frequent (3.18 and 3.07 on the Likert scale, respectively), followed by intravenous antibiotics for a predefined duration (3.01), antibiotics in uncomplicated acute otitis media (2.96) and in well-appearing newborns. Regarding importance, the above-mentioned five topics in addition to two other examples of antibiotic overtreatment were among the top 10. Also, IgE tests for food allergies without relevant medical history and acid blockers for infant GER were ranked high. Conclusion: Overtreatment with antibiotics together with cough/cold medicines and inhaled drugs in bronchiolitis were rated as the most frequent and important examples of overtreatment across countries in Europe and Japan.

Ventricular strain changes in monochorionic twins with and without twin-to-twin transfusion syndrome.

OBJECTIVE: The objective of the study was to investigate whether vector velocity imaging (VVI), a non-Doppler speckle tracking ultrasound technology, is feasible in twin pregnancies and can aid management of twin-twin transfusion syndrome (TTTS). STUDY DESIGN: Twenty-seven women pregnant with monochorionic diamniotic twins affected by TTTS and 28 monochorionic pregnancies that did not develop TTTS were included in a prospective case-control study at a fetal medicine center. Fetal echocardiograms were recorded with dummy electrocardiography to retain original frame rates when exported for offline speckle tracking analysis using Syngo-VVI software (Siemens Corp, Munich, Germany). Right and left ventricular (LV) free wall Lagrangian strain was measured from the original coordinates. Within-twin pair ventricular strain differences including relationship to Quintero staging and response to laser therapy for TTTS were analyzed by Wilcoxon signed-rank test. RESULTS: The VVI strain measurements could be analyzed in 182 of 200 TTTS and 96 of 112 non-TTTS control ventricles. Within-pair strain was concordant in non-TTTS controls. Recipient LV strain was reduced at all Quintero stages compared with donors (P < .01). Recipient right ventricular strain was reduced only in stages 3 and 4 (P < .01). Strain improved at a median of 2 weeks following successful laser therapy. Intertwin differences in strain were independent of weight discordance. CONCLUSION: Recipient LV strain is reduced in stages 1 and 2 TTTS. Within-pair strain discordance may distinguish early TTTS from growth discordance and guide timing of and management following treatment.