Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors.

Malignant melanoma (MM) is one of the most common tumors in both dogs and humans. As canine MM (CMM) and human MM (HMM) have similar clinical characteristics, CMM appears to be a good clinical model for HMM. We previously demonstrated that the introduction of a synthetic double-strand-microRNA-634 (miR-634) mimic triggered apoptotic cell death by directly targeting the genes associated with cytoprotective processes in various human cancer cell lines, including those of HMM. This study aimed to investigate the antitumor effects of the local administration of miR-634 on spontaneous CMMs to provide a basis for future applications of miR-634 formulations in HMM treatment. We found that miR-634 administration induced apoptosis in CMM cell lines in vitro via downregulation of Asct2, Nrf2, and survivin expression, similar to the mechanisms in HMM cell lines. Furthermore, intratumoral miR-634 administration induced antitumor effects in four of seven spontaneous CMM cases, with no adverse effects. Local administration of miR-634 to lung metastasis under ultrasound guidance induced tumor shrinkage. These results confirm the antitumor effect of the local administration of miR-634 in spontaneous CMM, a model for spontaneous HMM, thereby providing a novel treatment strategy for HMM.

The impact of the National Health Program on diabetes incidence among working-age men with prediabetes: A regression discontinuity analysis of a nation-wide database in Japan.

AIM: This study aimed to investigate the impact of the National Health Program in Japan ("Specific Health Check-ups and Specific Health Guidance") on diabetes prevention among working-age men with prediabetes. METHODS: This study used a regression discontinuity design, based on the program's criterion that the program starts at age 40 or older and that the intervention is provided only to prediabetic individuals with abdominal obesity, to assess the impact of the program on the diabetes incidence in a total of 49,848 men with prediabetes, aged 37-42 years. RESULTS: The National Health Program in which interventions were provided for individuals aged 40 years or over with both prediabetes and abdominal obesity was associated with a decrease in diabetes incidence rate equivalent to 10.1 reduction/1000 person-years. The relative risk was 0.75. However, among those without abdominal obesity and not subjected to the intervention, there was no significant change in the diabetes incidence at age 40. CONCLUSIONS: The National Health Program in Japan was associated with a decrease in the incidence of diabetes among working-age men with prediabetes and abdominal obesity and may have a meaningful impact among working-age men.

Incidence and risk factor of vocal cord paralysis following slide tracheoplasty for congenital tracheal stenosis: a retrospective observational study.

BACKGROUND: Slide tracheoplasty for congenital tracheal stenosis (CTS) has been shown to improve post-operative outcomes, but the incidence and risk factors of vocal cord paralysis (VCP) following slide tracheoplasty remain unclear. This study aimed to review our experience of slide tracheoplasty for CTS with a focus on post-operative VCP. METHODS: Twenty-eight patients, who underwent tracheal reconstruction with or without cardiovascular repair at Kobe Children's Hospital between June, 2016 and March, 2020 were enrolled in this retrospective observational study. They were divided into two groups based on the presence of a pulmonary artery sling (PA sling). Perioperative variables were compared between the two groups. RESULTS: Twenty-one of the 28 patients underwent concomitant repair for associated cardiovascular anomalies, including 15 patients with PA sling. The overall incidence of VCP following slide tracheoplasty was 28.6%. The incidences of VCP were 46.7% in patients with CTS and PA sling, which were 14.3% in CTS patients without cardiovascular anomalies. The only risk factor associated with VCP following slide tracheoplasty was a concomitant repair for PA sling. Post-operatively, the duration of nasogastric tube feeding in patients with VCP was significantly longer than that in patients without VCP. CONCLUSIONS: The incidence of VCP following slide tracheoplasty for CTS was high, especially in concomitant repair cases for PA sling. Routine screening and evaluation of VCP soon after post-operative extubation is required for its appropriate management.

Factors influencing exclusive breastfeeding rates until 6 months postpartum: the Japan Environment and Children's Study.

This research aimed to examine the efficacy of the early initiation of breastfeeding within 1 h of birth, early skin-to-skin contact, and rooming-in for the continuation of exclusive breastfeeding until 6 months postpartum. The research used data from the Japan Environment and Children's Study (JECS), a nationwide government-funded birth cohort study. A total of 80,491 mothers in Japan between January 2011 and March 2014 who succeeded or failed to exclusively breastfeed to 6 months were surveyed in JECS. Multiple logistic regression model was used to analyse the data. The percentage of mothers who succeeded in exclusively breastfeeding to 6 months is 37.4%. Adjusted odds ratios were analysed for all 35 variables. Early initiation of breastfeeding (adjusted odds ratio [AOR]: 1.455 [1.401-1.512]), early skin-to-skin contact (AOR: 1.233 [1.165-1.304]), and rooming-in (AOR: 1.567 [1.454-1.690]) affected continuation of exclusive breastfeeding. Regional social capital (AOR: 1.133 [1.061-1.210]) was also discovered to support the continuation of breastfeeding. In contrast, the most influential inhibiting factors were starting childcare (AOR: 0.126 [0.113-0.141]), smoking during pregnancy (AOR: 0.557 [0.496-0.627]), and obese body type during early pregnancy (AOR: 0.667 [0.627-0.710]).

Clinical application of a new ternary polymer, SEC-1 coat™, for pediatric cardiopulmonary bypass circuits: a prospective randomized pilot study.

OBJECTIVE: The use of biocompatible materials to reduce the systemic activation of inflammation and coagulation pathways is expanding rapidly. However, there have been few clinical studies of biocompatible circuits for pediatric cardiopulmonary bypass. This pilot study aimed to preliminarily evaluate the biocompatibility of SEC-1 coat™ (SEC) for cardiopulmonary bypass circuits in pediatric cardiac surgery. METHODS: Twenty infants undergoing cardiac surgery for isolated ventricular septal defects at Kobe Children's Hospital were assigned randomly to an SEC-coated (SEC group, n = 10) or heparin-coated (control group, n = 10) circuit. Perioperative data and the following markers were prospectively analyzed: platelet counts and interleukin-6, interleukin-8, C3a, ß-thromboglobulin, and thrombin-antithrombin complex levels. RESULTS: Neither patient characteristics nor postoperative clinical outcomes differed significantly between the SEC and control groups. Platelet counts markedly decreased during cardiopulmonary bypass in both groups, but were significantly better preserved in the SEC group. Fewer patients needed postoperative platelet transfusions in the SEC group. After cardiopulmonary bypass termination, serum levels of ß-thromboglobulin and thrombin-antithrombin complex were significantly lower in the SEC than in the control group. Although the differences were not statistically significant, serum levels of interleukin-6, interleukin-8, and C3a had a tendency toward being lower in the SEC group, with good preservation of leukocyte counts, fibrinogen, and antithrombin III. CONCLUSION: SEC-1 coat™ for cardiopulmonary bypass circuits have good biocompatibility with regard to platelet preservation and in terms of attenuating inflammatory reaction or coagulation activation during pediatric cardiac surgery. It can be beneficial in pediatric as well as adult cardiac surgery.

Clinical outcomes after tracheoplasty in patients with congenital tracheal stenosis in 1997-2014.

BACKGROUND: Mortality and morbidity of congenital tracheal stenosis (CTS) remain high. The aim of this study was to determine the factors predicting 12-month survival and 2-month successful extubation after tracheoplasty in patients with CTS. METHODS: Retrospective chart reviews were conducted in patients with CTS undergoing tracheoplasty at a single institution between 1997 and 2014. Patients' characteristics at disease onset and tracheoplasty were summarized. Twelve-month survival rate and 2-month extubation rate without tracheotomy after tracheoplasty were analyzed. RESULTS: We reviewed 81 patients' records. Multivariate analysis for 12-month survival revealed that older age (>2 months, hazard ratio [HR]: 0.08, 95% confidence interval [CI]: 0.02-0.36) or heavier body weight (>4.4 kg, HR: 0.13, 95% CI: 0.02-0.73) at tracheoplasty was a predictive factor for survival. Body weight at tracheoplasty (>8.2 kg, HR: 3.83, 95% CI: 1.88-7.79), preoperative balloon dilatation (HR: 0.30, 95% CI: 0.12-0.78), and carina involvement (HR: 0.36, 95% CI: 0.19-0.69) were predictive factors for successful extubation. CONCLUSIONS: Although CTS management is individualized, age or body weight at tracheoplasty needs to be considered and assessed for survival, as well as preoperative balloon dilatation, and carina involvement for successful extubation. LEVELS OF EVIDENCE: Level III.

Bronchoscopic assessments and clinical outcomes in pediatric patients with tracheomalacia and bronchomalacia.

BACKGROUND: Tracheomalacia and bronchomalacia (TM/BM) are one of the serious causes of airway obstruction in infants and children. This study reviewed our bronchoscopic assessments and clinical outcomes in pediatric patients with TM/BM, and investigated risk factors of surgical intervention for TM/BM. METHODS: Fifty-seven consecutive patients who were diagnosed as TM/BM by bronchoscopy between 2009 and 2013 were reviewed retrospectively. They were divided into two groups according to the presence (group E, n = 26) or absence (group N, n = 31) of acute life-threatening events and extubation failure (ALTE/EF). The severity of TM/BM was evaluated by Oblateness Index which was obtained from bronchoscopic images. RESULTS: Oblateness Index was significantly higher in Group E than in Group N. Patients in Group E underwent surgical intervention for TM/BM more frequently, and had significantly longer intubation period and hospital stay. Clinical symptoms of ALTE/EF, Oblateness Index ≥ 0.70, and multiple malacic lesions were significant risk factors indicating surgical events in patients with TM/BM. CONCLUSIONS: Patients with TM/BM who had ALTE/EF had more severe malacic lesions indicating surgical intervention, and worse clinical outcomes. Oblateness Index is a simple and semi-quantitative index for bronchoscopic assessment of TM/BM, and can be one of the prognostic tools to predict clinical severity of pediatric TM/BM.

Clinical equivalency of cardiopulmonary bypass and extracorporeal membrane oxygenation support for pediatric tracheal reconstruction.

OBJECTIVE: Pediatric surgery for congenital tracheal stenosis continues to be a therapeutic challenge, and it often requires cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) for intra-operative extracorporeal cardiorespiratory support. The purpose of this study was to compare the peri-operative outcomes of CPB with ECMO in pediatric tracheal reconstruction. METHODS: Forty-three consecutive patients who underwent tracheal reconstruction without intra-cardiac repair for congenital tracheal stenosis at Kobe Children's Hospital between January 2000 and August 2012 were enrolled in this retrospective study. They were divided into two groups according to intra-operative extracorporeal cardiopulmonary support [CPB (n = 17) or ECMO (n = 26)]. Peri-operative variables were compared between the two groups. RESULTS: The CPB and ECMO groups had similar patient and operative characteristics. However, the CPB group required larger priming volume and higher doses of total heparin injection. Although the ECMO group exhibited less peri-operative bleeding and lower red blood cell requirement, there were no statistically significant differences between the two groups. Compared to the ECMO group, patients in the CPB group had significantly less positive fluid balance during surgery and in the first 24 h after surgery, and exhibited a trend towards higher ratios of PO2 to the fraction of inspired oxygen and lower PCO2 at the time of ICU admission and on post-operative day 1. CONCLUSIONS: Pediatric tracheal reconstruction should be performed with intra-operative CPB or ECMO, after considering the advantages of utilizing each extracorporeal cardiorespiratory support type according to the patient's specific condition and situation.

Clinical assessment of diastolic retrograde flow in the descending aorta for high-flow systemic-to-pulmonary artery shunting.

OBJECTIVE: To investigate whether echocardiographic characteristics in the descending aorta of patients with cyanotic congenital heart disease who have received a systemic-to-pulmonary artery (SP) shunt can indicate shunt flow volume and predict postoperative adverse events related to high-flow shunting. METHODS: Among the 73 consecutive patients who received an SP shunt between 2010 and 2014, data for 53 patients who underwent postoperative Doppler echocardiographic assessment of diastolic retrograde flow in the descending aorta (dAo-RF) were reviewed retrospectively. RESULTS: The mean dAo-RF ratio was 0.50 ± 0.15 at intensive care unit admission and reached its peak level (0.56 ± 0.12) at 24 hours after surgery. All of the patients with a maximal dAo-RF ratio of ≥0.80 had experienced acute heart failure or cardiogenic shock due to postoperative high-flow shunting and required emergent surgical interventions to reduce pulmonary blood flow. Pulse oximetry-measured oxygen saturation and serum lactate level were significantly correlated with dAo-RF ratio, but they had some clinical dispersion to match the postoperative adverse events. CONCLUSIONS: The dAo-RF ratio is a simple, repeatable, and noninvasive index for postoperative assessment of SP shunt flow volume. A high dAo-RF ratio is a significant predictor of postoperative adverse events of high-flow shunting.

Left Subclavian Artery Perfusion During the Norwood Operation for Interrupted Aortic Arch With Aortic Atresia.

The combination of aortic atresia and interrupted aortic arch is a rare condition. We describe a case of Norwood operation for this defect, in which a collateral artery from the descending aorta supplied coronary perfusion. The devised cardiopulmonary bypass technique is discussed, in which the left subclavian artery perfusion was utilized in addition to the cannulation to the descending aorta to secure the cerebral perfusion.

Repair of unbalanced atrioventricular septal defect with small right ventricle.

A 2-month-old boy with trisomy 21, a small right ventricle, and an unbalanced atrioventricular septal defect underwent successful biventricular repair without atrial fenestration. We decided to perform leftward partitioning of the atrioventricular valve to widen the right ventricle inflow tract. This procedure increases the size of the right-sided valve and allows full function of the right ventricle without an atrial communication. This technique should be employed in patients with a small right ventricle and an unbalanced atrioventricular septal defect, as an alternative to atrial septal fenestration or univentricular palliation.

Surgical Repair of Total Anomalous Pulmonary Venous Connection in a Neonate With Mosaic Trisomy 8.

Trisomy 8 mosaicism is a relatively rare chromosomal abnormality and has extremely variable phenotype with a wide range of clinical manifestations. Although no well-defined criteria for cardiac surgical indications are available for patients with mosaic trisomy 8, we present a case of hypoplastic left heart syndrome with total anomalous pulmonary venous connection (TAPVC) in a neonate with mosaic trisomy 8. Although primary sutureless repair of TAPVC with concomitant bilateral pulmonary artery banding was performed successfully in this case, the indications for cardiac surgery in patients with mosaic trisomy 8 should be carefully individualized. The entire dialog with parents and family, including the process of informed consent, is of great importance.

Aortic arch geometry after the Norwood procedure: The value of arch angle augmentation.

OBJECTIVE: Aortic arch reconstruction in the Norwood procedure is occasionally associated with postoperative airway and branch pulmonary artery stenosis, as well as recoarctation. This study investigated geometric changes in the aortic arch after the Norwood procedure and evaluated the efficacy of arch angle augmentation with glutaraldehyde-treated autologous pericardium in aortic arch reconstruction. METHODS: Of 52 consecutive patients who underwent the Norwood procedure between 1998 and 2013, a total of 36 patients who underwent postoperative multidetector-row computed tomographic angiography were reviewed retrospectively, and divided into 2 groups according to whether arch angle augmentation with glutaraldehyde-treated autologous pericardium was performed (AAA group, 26 patients) or not (NA group, 10 patients). RESULTS: The neoaortic arch in the Norwood procedure was characterized by having a significantly smaller angle, being lower in height, and being narrower than that in age-matched control patients with a normal aortic arch. Moreover, all of these arch geometric measurements were significantly larger in the AAA group than in the NA group. Freedom from reintervention and reoperation for bronchomalacia or branch pulmonary artery stenosis, caused by extrinsic compression of the neoaorta, was significantly better at 1 year in the AAA group than in the NA group. Recoarctation of the neoaorta was documented in only 1 (3.8%) patient in the AAA group versus 3 patients (30%) in the NA group. CONCLUSIONS: Arch angle augmentation with glutaraldehyde-treated autologous pericardium in the Norwood procedure creates more aortopulmonary space with a smoother arch angle and diminished incidence of postoperative recoarctation, bronchial compression, or branch pulmonary artery compression.

Dexmedetomidine in combination with midazolam after pediatric cardiac surgery.

OBJECTIVE: Although midazolam is one of the most commonly used sedatives for infants in the intensive care unit, it has well-known disadvantages including a dose-dependent potential to induce tolerance, withdrawal, and hemodynamic depression. The aim of this study was to evaluate the clinical effects of dexmedetomidine combined with midazolam in postoperative intensive care following pediatric cardiac surgery. METHODS: Forty consecutive infants who underwent cardiac surgery for isolated ventricular septal defects from January 2011 to July 2013 were enrolled in this retrospective study. They were divided into two groups according to postoperative sedation regimen: dexmedetomidine sedation with midazolam (n = 20), or midazolam sedation without dexmedetomidine (control group, n = 20). Perioperative variables were compared between the two groups. RESULTS: There were no significant differences in patient characteristics between the two groups. During the first 24 h after intensive care unit admission, heart rate and serum lactate levels were significantly lower in the dexmedetomidine group compared to the control group (p = 0.0292 and p = 0.0027, respectively). The maximal midazolam dose was also significantly lower in the dexmedetomidine group (0.12 ± 0.09 vs. 0.20 ± 0.08 mg kg(-1) h(-1), p = 0.0059). There were no adverse effects of dexmedetomidine such as bradycardia, hypotension, agitation, or seizures. Three (15%) patients in the control group and none in the dexmedetomidine group experienced sudden cardiopulmonary decompensation. CONCLUSIONS: Dexmedetomidine can provide favorable sedative properties with a reduced requirement for concomitant midazolam and stable hemodynamics with tachycardia prevention, for postoperative intensive care following pediatric cardiac surgery.

Staged biventricular repair for absent aortic valve in a neonate.

Congenitally absent aortic valve is an extremely rare and fatal cardiac malformation. We report the case of a neonate with absent aortic valve, an interrupted aortic arch, and a normal-sized left ventricle. At age 9 hours, emergency aortic valve closure and a Norwood procedure were performed to maintain coronary circulation. The patient's postoperative course was complicated because of tracheomalacia and a severely dilated aorta that were treated with reduction aortoplasty at age 4 months. Finally, a staged Yasui procedure was performed at 26 months. To our knowledge, this is the first report of a successful biventricular repair for absent aortic valve.

A left anterior extrapleural approach to adjust right ventricle-pulmonary artery shunt flow using hemostatic clips after the Norwood operation.

Adjusting right ventricle-pulmonary artery shunt flow with placement of hemostatic clips in the Norwood operation is a useful technique for precise control of pulmonary blood flow in the acute postoperative period. This report describes our technique for optimizing right ventricle-pulmonary artery shunt flow with metal clips through a left anterior extrapleural approach, which can be performed safely and minimally invasively without sternal reopening. This procedure may decrease morbidity and contribute to long-term clinical improvement in patients undergoing the Norwood operation.

The left anterior extrapleural approach for innominate artery transection in a patient with tracheostomy and a neurological disorder.

Although innominate artery transection for innominate artery compression of the trachea is recently used for prevention of life-threatening complications (e.g. massive bleeding and obstructive apnoea) in patients with neurological disorders, pre-existing tracheostomy poses a risk of mediastinal infection with sternotomy. We successfully performed innominate artery transection on such a patient via the left anterior extrapleural approach without sternotomy after confirming the anatomical configuration on three-dimensional multidetector row computed tomography angiography.

Beating-heart surgery for hypoplastic left heart syndrome with coronary artery fistulas.

The presence of ventriculocoronary connections in patients with hypoplastic left heart syndrome and mitral stenosis-aortic atresia is a suggested risk factor for myocardial ischemia after surgical palliation. We describe a neonate with this anatomic variant of hypoplastic left heart syndrome who underwent a successful beating-heart Norwood operation, with continuous coronary perfusion. The ventricular condition could be visually confirmed during the procedure, and a postoperative echocardiogram showed preserved ventricular function. This technique is considered an effective option for minimizing myocardial damage in this patient subtype.