Age-Specific Dose Regimens of Dexmedetomidine for Pediatric Patients in Intensive Care Following Elective Surgery: A Phase 3, Multicenter, Open-Label Clinical Trial in Japan.

OBJECTIVES: To demonstrate the efficacy, safety, and pharmacokinetics of dexmedetomidine as a potential sedative for pediatric surgery patients in the ICU. DESIGN: Phase 3, multicenter, open-label study. SETTING: This study included 61 patients at 13 tertiary hospitals in Japan. PATIENTS: Pediatric patients (≥ 45 wk corrected gestational age to < 17 yr) undergoing intensive care treatment with mechanical ventilation requiring greater than 6 hours estimated duration of sedation following elective cardiac surgery. INTERVENTIONS: Dexmedetomidine was IV administered without a loading dose at age-specific dose regimens 0.2-1.4 (< 6 yr) and 0.2-1.0 µg/kg/hr (≥ 6 yr). The primary endpoint was the percentage of patients who did not require a rescue sedative (midazolam) infusion during mechanical ventilation or for the first 24 hours of a greater than 24 hours ventilation following the commencement of dexmedetomidine administration. MEASUREMENTS AND MAIN RESULTS: Overall, 47 of the 61 patients (77.0%) did not require rescue midazolam. Adverse events were reported in 53 patients (86.9%). Frequently observed adverse events were hypotension (47.5%), bradycardia (31.1%), and respiratory depression (26.2%). Most of these adverse events were mild, a few moderate, and none severe. Although serious adverse events occurred in four patients, including one cardiac tamponade resulting in the withdrawal of dexmedetomidine, none of the adverse events resulted in mortality or were directly related to dexmedetomidine. The plasma dexmedetomidine concentration generally reached the target concentration of 0.3-1.25 ng/mL at 1-2 hours prior to completion of administration or immediately prior to the commencement of tapering. CONCLUSIONS: The age-specific dose regimens of dexmedetomidine without an initial loading dose achieved an adequate sedation level during mechanical ventilation and caused no clinically significant adverse events in the intensive care pediatric patients. These effects were achieved within the therapeutic range of dexmedetomidine plasma concentration and were accompanied by minimal effects on hemodynamics and respiration.

Safety and Efficacy of Landiolol Hydrochloride in Children with Tachyarrhythmia of Various Etiologies.

The safety and efficacy of landiolol have not been fully elucidated in pediatric patients. This study aimed to clarify the safety and efficacy of landiolol in a pediatric cohort. We retrospectively assessed the clinical features of 21 pediatric patients who were administered landiolol at our hospital. We also investigated the rates of sinus rhythm conversion and heart rate response. The median patient age was 7 months (interquartile range 1-13 months). The etiology of tachyarrhythmia was junctional ectopic tachycardia in 10 patients (47.6%), atrial tachycardia in 10 patients (47.6%), and ventricular tachycardia in 1 patient (4.8%). Of the 21 children, 18 (85.7%) had congenital heart defects, including 14 (77.8%) in whom a landiolol infusion was performed perioperatively. The landiolol infusion was effective in 18 pediatric patients (85.7%), as measured by the conversion to sinus rhythm or a reduced heart rate. Atrial tachycardia in the perioperative period was terminated in all patients. Of 7 patients with tachyarrhythmias unrelated to the perioperative period, landiolol was effective in 5. No adverse effects were reported in any patient. Landiolol infusion is effective and safe in pediatric patients with tachyarrhythmia of various etiologies, especially those with atrial tachyarrhythmia during the perioperative period.

Acquired and progressive coronary arterial fistulae in patients with single-ventricle physiology and treated with pulmonary vasodilators.

BACKGROUND: Cardiac dysfunction, arrhythmia, and hepatic fibrosis are well-known complications after right heart bypass surgery in patients with single-ventricle physiology. However, little is known about coronary arterial fistulae, and only a few reports have been published. This study aimed to elucidate the clinical characteristics of these rare coronary arterial fistulae that developed as complications in cases of single-ventricle physiology after right heart bypass surgery. METHODS: We retrospectively investigated the clinical features and courses of patients who developed acquired and progressive coronary arterial fistulae after right heart bypass surgery in our hospital. RESULTS: We identified three cases of coronary arterial fistulae out of 21 patients who underwent right heart bypass surgery. All three cases underwent cardiac catheterisation for post-operative evaluation and were administered pulmonary vasodilators of phosphodiesterase type V inhibitors, antiplatelet, anticoagulation, and diuretics. Moreover, they had common clinical features such as right-dominant single ventricle and long-term exposure to chronic hypoxia. Serial angiograms revealed acquired and progressive coronary arterial fistulae. In addition, coronary arterial fistulae contributed to their symptoms of heart failure. CONCLUSION: Patients with chronic hypoxia and dominant right ventricle, who are treated with phosphodiesterase type V inhibitors, should be followed up after right heart bypass surgery to monitor the possible development of coronary arterial fistulae. Moreover, the indication for pulmonary vasodilators in single-ventricle physiology after right heart bypass surgery should be optimised to avoid adverse effects.

Therapeutic experience with hepatoblastoma associated with trisomy 18.

Trisomy 18 is often fatal, but patients with this disease can now have longer survival due to proactive treatment intervention. However, hepatoblastomas may develop in these patients. In this study, we report four cases of hepatoblastoma associated with trisomy 18. All of the patients had congenital heart disease and three had undergone intracardiac surgical repair. Tumor growth was relatively slow in all cases, and there were no problems with chemotherapy tolerability and surgical resection. Three of the patients are currently disease-free and the fourth is alive with remaining of the tumor. These cases suggest that combined chemotherapy and surgical resection may be an option to treat hepatoblastoma associated with trisomy 18 when cardiac pulmonary function is relatively stable.

Development of a new surgical sheet containing both silk fibroin and thermoplastic polyurethane for cardiovascular surgery.

PURPOSE: The surgical sheets that are currently used for congenital cardiovascular surgery have several drawbacks, including material deterioration, calcification, and pseudo-intimal proliferation resulting in hemodynamic disturbance. The aim of this study was to evaluate a newly developed sheet made from a combination of silk fibroin (SF) and a synthetic polymer, thermoplastic polyurethane (TPU), for surgical use. METHODS: The hybrid SF/TPU sheet was a non-woven fabric with nanofibers that was made using the electrospinning method. The mechanical properties of the SF/TPU sheet were characterized. To determine its biocompatibility, part of the wall of the canine descending aorta was replaced with a SF/TPU sheet as a patch. The patches were removed after 3 months and a histological examination was performed. RESULTS: The flexibility, water permeability, and suture retention strength of the SF/TPU sheet were excellent and equivalent to those of existing sheets. The SF/TPU sheet had excellent handling properties and fit well into the vascular wall without needle hole bleeding. The histological examination revealed that the intimal tissue was restored well over the intraluminal surface of the explanted SF/TPU sheet, the absence of calcium deposition, and minimal inflammatory reaction, without signs of degradation. CONCLUSION: The SF/TPU sheet had excellent mechanical properties and tissue biocompatibility. These favorable features and possible biodegradability of the SF portion warrant a long-term follow-up study.

[Concomitant Operations for Thoracic Aortic Aneurysm and Myasthenia Gravis;Report of a Case].

A 77-year-old man, who had been under medical treatment for myasthenia gravis without thymoma, was diagnosed with aortic arch aneurysm. He underwent total aortic arch replacement and total resection of the thymus through median sternotomy. His symptoms relating to myasthenia gravis dramatically disappeared after the surgery. The serum anti-acetyl chorine receptor antibody decreased from 2.7 to 0.7 nmol/l (N<0.2) with the reduction of oral predonisolone from 12.5 to 5 mg/day at 4 years after the surgery. The concomitant operations significantly improved his quality of life.

[Three Surgical Cases of Quadricuspid Aortic Valve].

Quadricuspid aortic valve is a rare congenital disease. We experienced 3 surgical cases of quadricuspid aortic valve. Patient 1 was a 72-year-old man who was noted to have a quadricuspid aortic valve associated with aortic regurgitation and an ascending aortic aneurysm(51 mm in diameter). He underwent replacement of the aortic valve and the ascending aorta. Patient 2 was a 71-year-old man with severe aortic stenosis, regurgitation, and coronary triple vessel disease. He underwent aortic valve replacement and coronary artery bypass grafting. Preoperative echocardiography revealed no abnormalities in the number of valve leaflets, but quadricuspid aortic valve was identified during surgery. Patient 3 was a 79-year-old man with severe aortic regurgitation, who underwent aortic valve replacement. In all patients, the 4 valve cusps were approximately of the same size. Multi-detector computed tomography is useful for evaluation of valve morphology. Indication of prophylactic ascending aorta replacement in patients with aortic dilatation requires further study.

Surgical treatment of a mycotic pseudoaneurysm of the transverse arch using a rifampicin-impregnated dacron patch in an infant.

We describe a case of successful treatment of mycotic pseudoaneurysm of the transverse aortic arch in a male infant. The aneurysm was resected and the defect was repaired using a patch made from a rifampicin-impregnated Dacron graft.

[Left ventriculoplasty in a patient with suspected takotsubo cardiomyopathy followed by a left ventricular aneurysm].

A 42-year-old woman was admitted with chest pain. Coronary angiography did not reveal any significant stenosis, but left ventriculography showed akinesis and ballooning of the apex with a hyperkinetic basal segment indicating Takotsubo cardiomyopathy. Cerebral embolism occurred after one and a half years because of a left ventricular thrombus. The apical akinesis had worsened to a left ventricular aneurysm (maximum diameter 43 mm). The left ventricle was reconstructed to avoid repeated thrombus formation and cerebral infarction despite anticoagulant therapy. A pathological assessment revealed a fibrotic myocardium, but the cause of the cardiac aneurysm remained unknown. Although the outcome of Takotsubo cardiomyopathy is relatively good, careful observation and appropriate treatment are needed considering the possibility of aggravation.

Compression brace for secondary pectus carinatum in infants and toddlers undergoing cardiac surgery with midline sternotomy.

PURPOSES: This study aimed to retrospectively assess the response to a newly developed compression brace for improving the deformity of the secondary pectus carinatum in infants and toddlers undergoing cardiac surgery with midline sternotomy. Factors affecting the response to the brace were identified. METHODS: Fifty-one children were enrolled. Severity was expressed as the protrusion angle of the sternum obtained from chest X-ray. The patients were divided into two groups by positive or negative binary residuals of the relationship between the angle at the beginning and its percentage change after wearing the brace. Logistic regression analysis was used to identify the influencing factors. RESULTS: Thirty patients (58.8%) showed zero and positive residuals to the relationship (good responders, Group G), whereas 21 patients showed negative residuals (poor responders, Group P). Male sex, severe cardiac anomaly, complex surgical procedure, multiple sternotomy, total duration, and self-discontinuation were associated with poor response to the brace by univariate analysis. The first three factors remained with high odds ratio for poor response by multivariate analysis. No adverse events occurred with the brace. CONCLUSION: Our newly developed compression brace contributed, at least in part, to improve the deformity of the secondary pectus carinatum. Further studies are required to clarify the therapeutic efficacy of anterior chest compression for secondary pectus carinatum.

[A case of fulminant myocarditis successfully treated by percutaneous cardiopulmonary support after 50 minuite-cardiopulmonary resuscitation].

We report a case of an 8-year-old girl with fulminant myocarditis successfully treated with percutaneous cardiopulmonary support (PCPS). She was first taken to our hospital for treatment of suspected infective enterocolitis since her main symptoms were fever, vomiting and diarrhea. On day 2 after admission, her ECG showed wide QRS and echocardiography demonstrated severe hypokinesis. She was transferred to the ICU with suspected acute myocarditis. On admission to the ICU, circulatory collapse was not detected. ECG showed severe bradycardia and ventricular fibrillation after intubation. Cardiopulmonary resuscitation was performed immediately for 50 minutes prior to initiation of PCPS. She was treated intensively with catecholamines, plasma exchange, continuous hemodiafiltration, high-dose gamma-globulin, and high dose methylprednisolone. Hypothermia therapy was also performed. She was weaned from PCPS on day 6 after initiation of PCPS. The patient was finally discharged from the hospital without any neurological complications on day 68 after weaning from PCPS. The proportion of patients in whom cardiopulmonary resuscitation was performed or having ventricular tachycardia or fibrillation were higher in non-survivors than in survivors.

Identification of Cell-Attachment Factors Derived from Green Algal Cells Disrupted by Sonication in Fabrication of Cell Plastics.

Cell plastics which are composed of unicellular green algal cells have been proposed in previous studies. While unicellular green algae can be freely arranged using fabrication processes, a matrix is required to attach the cells together. To date, although the cell contents collected from Chlamydomonas reinhardtii show the possibility of attaching cells, but it is unclear which components can be considered attachment factors. Therefore, in this study, C. reinhardtii cells were disrupted with sonication, and the components were separated and purified with hexane. The cell plastics with only 0.5 wt% of intermediate showed similar mechanical properties to those with 17 wt% and 25 wt% of cell components that were untreated with hexane, meaning that the purified intermediates could function as matrices. The purified intermediate was composed of approximately 60 wt% of protein as the main component, and proteomic analysis was performed to survey the main proteins that remained after hexane treatment. The protein compositions of the cell content and purified intermediate were compared via proteomic analysis, revealing that the existing ratios of 532 proteins were increased in the purified intermediate rather than in the cell content. In particular, the outer structure of each of the 49 proteins-the intensity of which was increased by over 10 times-had characteristically random coil conformations, containing ratios of proline and alanine. The information could suggest a matrix of cell plastics, inspiring the possibility to endow the cell plastics with more properties and functions.

Evaluation of Cell Responses of Saccharomyces cerevisiae under Cultivation Using Wheat Bran as a Nutrient Resource by Analyses of Growth Activities and Comprehensive Gene Transcription Levels.

Wheat bran has high nutritional values and is also cheaper than yeast nitrogen base as an important component of a medium. Although its use in microbial cultivations is expected, research and development has hardly progressed so far. In this study, with experimental Saccharomyces cerevisiae BY4741, the cell responses to wheat bran as a nutrient were evaluated by analyses of cell growth, ethanol production, and comprehensive gene transcription levels. Comparing wheat bran and yeast nitrogen base, BY4741 showed specific growth rates of 0.277 ± 0.002 and 0.407 ± 0.035 as a significant difference. Additionally, wheat bran could be used as a restricted media component like yeast nitrogen base. However, in 24 h of cultivation with wheat bran and yeast nitrogen base, although conversion ratios of ethanol productions showed no significant difference at 63.0 ± 7.2% and 62.5 ± 8.2%, the ratio of cell production displayed a significant difference at 7.31 ± 0.04% and 4.90 ± 0.16%, indicating a different cell response. In fact, the comprehensive evaluation of transcription levels strongly suggested major changes in glucose metabolism. This study indicated that BY4741 could switch transcription levels efficiently to use wheat bran.

Surgical repair of left ventricular noncompaction in a patient with a novel mutation of the myosin heavy chain 7 gene.

Left ventricular noncompaction (LVNC) represents arrest of the normal myocardial compaction process and results in the persistence of multiple prominent ventricular trabeculations and deep intertrabecular recesses. LVNC can be classified into 2 forms: isolated LVNC in the absence of other cardiac anomalies and non-isolated LVNC associated with congenital heart disease. The clinical presentation and the natural history of LVNC are highly variable, ranging from no symptoms to congestive heart failure, arrhythmias, and systemic thromboemboli. LVNC is genetically heterogeneous and can be inherited as an autosomal dominant or X-linked recessive disorder. It is also linked to mutations in several genes, encoding the sarcomeric proteins, such as myosin heavy chain 7 (MYH7). MYH7 encodes the ß-myosin heavy chain, expressed in the cardiac muscle. The operative indication for patients with non-isolated LVNC is unclear. Here, we report the first successful case of surgical repair of a ventricular septal defect (VSD) in an infant with non-isolated LVNC associated with a novel MYH7 mutation. This mutation leads to the substitution of 7 amino acid residues (671-677) in the actin-binding region of the protein. After the VSD operation, the patient's congestive heart failure and pulmonary hypertension improved. His condition has remained stable for 18 months with pharmacotherapy comprising diuretics, an angiotensin converting enzyme inhibitor, and a ß-blocker. Although the postsurgical observational period was short, the findings indicate that LVNC mutation analyses may facilitate surgical decisions and help predict clinical courses.

Improvement of cardiac geometry and function after cardiac resynchronization therapy for relapsed deterioration of pediatric dilated cardiomyopathy due to a noncompacted left ventricle and cardiac dyssynchrony.

We report a pediatric case of successful cardiac resynchronization therapy (CRT) for acute relapsed deterioration of dilated cardiomyopathy with cardiac dyssynchrony due to a noncompacted left ventricle (LV). A 20-month-old female developed severe congestive heart failure, which was classified as New York Heart Association class IV. She failed to thrive despite intravenous inotropic support. Her LV function and dimension improved markedly after CRT. The beneficial effect of CRT in this patient has remained for more than 3 years.

[Malignant disease identified after the emergency cardiac operation].

We experienced 2 patients who died early after emergency cardiac operation because of malignant diseases. In one case, we operated on a 67-year-old woman for infective endocarditis and performed aortic valve replacement, but she died of terminal pancreatic cancer on the 26 postoperative day. In the other case, a 53-year-old woman underwent emergency operation for cardiac tumor of the left atrium. However, the tumor was diagnosed as cardiac sarcoma during the operation, and it could not be completely resected. The sarcoma recurred after 2 months and she passed away. An emergency cardiac operation without enough preoperative examinations sometimes causes a poor prognosis.

[Arterial switch operation for transposition of the great arteries with situs inversus and mirror image dextrocardia].

We report a successful arterial switch operation for complete transposition of great arteries with atrial and visceral situs inversus totalis and mirror image dextrocardia in a 12-day-old infant girl. The aorta was located left side-by-side to the pulmonary trunk with a single coronary artery (mirror image of 1RLCx). After French maneuver, the posterior circumference of the neo-aorta was reconstructed. Then the coronary button was transplanted into the neo-aorta with a trap door technique carefully avoiding any twist and over-stretch. The neo-pulmonary trunk was reconstructed with an autologous pericardial patch and sutured to the longitudinal incision made into the left central pulmonary artery. The baby was discharged from hospital and has been doing well without any morbidity relating myocardial ischemia.

A combination of polyglycolic acid fabric and fibrin glue prevents air leakage from a lung defect.

OBJECTIVES: Air leakage after lung resection is a common morbidity that may lengthen hospital stay. Applying sealant to a lesion is an effective prophylaxis in clinical practice. This study aimed to examine the effect of a combination of a bioabsorbable polyglycolic acid (PGA) fabric and fibrin glue (FG) on air sealing by measuring the in vitro mechanical strength and degradation of the fabric, and in vivo histological changes after implantation. METHODS: A defect was created in the canine left upper lung lobe, and then filled with a fibrinogen solution and covered with a PGA sheet spray-coated with fibrinogen and thrombin. After 1 and 4 weeks, air leakage from the lesion was examined in vivo under airway pressure. Tissue samples were harvested for histological assessment. RESULTS: The mechanical strength of the PGA fabric remained at 80-90% of the baseline level for 1 week in phosphate-buffered saline, and then rapidly decreased to zero thereafter. Air leakage from the lung defect was prevented by the combination of PGA fabric and FG at 1 and 4 weeks. Histological examinations showed that PGA bundles persisted with a non-specific inflammatory response for 2 weeks and then gradually broke into sparse yarns surrounded by collagen fibres and capillaries by 8 weeks. The lung defect was filled with FG at 1 week and by granulation tissue thereafter. CONCLUSIONS: These results provide evidence for the efficacy of a combination of PGA fabric and FG for the prevention of air leakage in the critical period after lung surgery.

Long-term viability and extensibility of an in situ regenerated canine aortic wall using hybrid warp-knitted fabric.

OBJECTIVES: Many surgical materials promoting tissue regeneration have been explored for use in paediatric cardiac surgery. The aim of this study is to evaluate the long-term viability and extensibility of the canine aortic wall regenerated using a novel synthetic hybrid fabric. METHODS: The sheet is a warp-knitted fabric of biodegradable (poly-l-lactic acid) and non-biodegradable (polyethylene terephthalate) yarns coated with cross-linked gelatine. This material was implanted as a patch to fill an oval-shaped defect created in the canine descending aorta. The tissue samples were explanted after 12, 24 or 36 months (N = 3, 2, 2, respectively) for histological examination and biomechanical testing. RESULTS: There was no shrinkage, rupture or aneurysmal change after 24 months. The regenerated wall showed prototypical vascular healing without material degeneration, chronic inflammation, calcification or abnormal intimal overgrowth. Bridging tissue across the patch was well-formed and had expanded over time. The biodegradable yarns had completely degraded at 24 months after implantation, as scheduled, but the regenerated aortic wall demonstrated satisfactory levels of mechanical strength and extensibility in tensile strength tests. CONCLUSIONS: The sheet achieved good long-term viability and extensibility in the regenerated aortic wall. These findings suggest that it is a promising surgical material for repairing congenital heart defects. Further developments of the sheet are required, including clinical studies.