Pulmonary Flow Management by Combination Therapy of Hemostatic Clipping and Balloon Angioplasty for Right Ventricular-Pulmonary Artery Shunt in Hypoplastic Left Heart Syndrome.

Controlling pulmonary blood flow in patients who have undergone Norwood palliation, especially early postoperatively, is challenging due to a change in the balance of systemic and pulmonary vascular resistance. We applied a combination therapy of clipping and balloon angioplasty for right ventricle-pulmonary artery (RV-PA) shunt to control pulmonary blood flow, but the influence of the combination therapy on the PA condition is uncertain. Retrospectively analysis was conducted of all infants with hypoplastic left heart syndrome who had undergone Norwood palliation with RV-PA shunt at Okayama University Hospital from January 2008 to September 2022. A total of 50 consecutive patients underwent Norwood palliation with RV-PA shunt in this study period. Of them, 29 patients underwent RV-PA shunt flow clipping, and the remaining 21 had unclipped RV-PA shunt. Twenty-three patients underwent balloon angioplasty for RV-PA shunt with clips. After balloon angioplasty, oxygen saturation significantly increased from 69 (59-76)% to 80 (72-86)% (p < 0.001), and the narrowest portion of the clipped conduit significantly improved from 2.8 (1.8-3.4) to 3.8 (2.9-4.6) mm (p < 0.001). In cardiac catheterizations prior to Bidirectional cavo-pulmonary shunt (BCPS), there were no significant differences in pulmonary-to-systemic flow ratio (Qp/Qs), ventricular end-diastolic pressure, Nakata index, arterial saturation, mean pulmonary artery pressure and pulmonary vascular resistance index. On the other hand, in Cardiac catheterizations prior to Fontan, Nakata index was larger in the clipped group (p = 0.02). There was no statistically significant difference in the 5-year survival between the two groups (clipped group 96%, unclipped group 74%, log-rank test: p = 0.13). At least, our combination therapy of clipping and balloon angioplasty for RV-PA shunt did not negatively impact PA growth. Although there is a trend toward better but not statistically significant difference in outcomes in the clipped group compared to the non-clipped group, this treatment strategy may play an important role in improving outcomes in hypoplastic left heart syndrome.

Stepwise Treatment for Heterotaxy Syndrome and Functional Single Ventricle Complicated by Infra-Cardiac Total Anomalous Pulmonary Venous Connection with Ductus Venosus Stent Placement and Subsequent Occlusion.

Even today, when the surgical outcome of congenital heart disease in the neonatal period has improved, the prognosis for heterotaxy syndrome and functional single ventricle complicated with total anomalous pulmonary venous connection (TAPVC), especially the infra-cardiac type, is catastrophic. We describe a strategy that combines percutaneous ductus venosus (DV) stent placement and occlusion after TAPVC repair to ensure survival from initial surgery to bidirectional cavopulmonary shunt (BCPS) procedure and facilitate subsequent treatment. Three consecutive patients with heterotaxy syndrome and functional single ventricle complicated by infra-cardiac TAPVC treated with our own strategy were retrospectively studied. In two infants, DV stent placement was performed on the day of birth. In one case at 11 days of age. The risk of pulmonary vein obstruction was reduced, and on-pump surgery, including TAPVC repair, was performed on a standby basis. Since the rapid increase in hepatic enzymes occurred on postoperative day 0 to 1 in all cases, percutaneous stent occlusion was performed until postoperative day 3. The procedure improved liver function. One patient died due to severe atrioventricular valve regurgitation, one case underwent BCPS, and one patient was waiting to undergo. DV stent placement can avoid TAPVC repair in the early neonatal period. After TAPVC repair, the portosystemic shunt remained, resulting in hepatic dysfunction, but this could be improved by stent and vertical vein occlusion. A series of stepwise treatments can be useful to help such critically ill infants survive the high-risk neonatal period and achieve good BCPS circulation.

Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial.

RATIONALE: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. OBJECTIVE: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. METHODS AND RESULTS: We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P=0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P<0.0001) and volumes (P<0.001), somatic growth (P<0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status (P<0.0001) and cardiac fibrosis (P=0.014) relative to baseline. CONCLUSIONS: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

Balloon atrial septostomy in hypoplastic left heart syndrome with restrictive atrial septum.

BACKGROUND: Rashkind balloon atrial septostomy (BAS) can be challenging in infants with hypoplastic left heart syndrome (HLHS) and small atrial septal defect (ASD). METHODS: We retrospectively reviewed all infants with HLHS who underwent surgery and BAS between January 2006 and December 2015. The infants were divided into three groups: no BAS; catheter BAS; and open AS. Infants who underwent catheter BAS were divided into two groups based on atrial septal anatomy: standard and complex. RESULTS: Of the 70 patients, 57 (81%) underwent Glenn surgery. Subsequently, a significant difference in survival was observed: 86% (44/51), 91% (10/11), and 25% (2/8) in the no BAS, catheter BAS, and open AS groups, respectively (P = 0.0002). No significant difference was seen between the no BAS and the catheter BAS groups (P = 1.0). In the 56 patients who underwent catheterization after surgery, no intergroup differences in mean pulmonary artery pressure, pulmonary vascular resistance, or pulmonary artery index were found. We classified catheter BAS into standard (n = 5) and complex (n = 5) based on ASD location, and septum thickness. All patients in the standard group underwent complete Rashkind BAS, but in the complex group, only one patient underwent complete Rashkind BAS, with the remaining requiring initial static BAS (P = 0.048). Following septostomy, ASD size, ASD flow, and percutaneous oxygen saturation (SpO2 ) were not significantly different between the two groups. CONCLUSIONS: Catheter BAS is effective in infants with HLHS and a restrictive atrial septum. Infants with standard or complex atrial septum can achieve equivalent outcomes despite more patients often requiring static BAS.

Muscle regulatory factors regulate T1R3 taste receptor expression.

T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic ß-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3(-) and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown. Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells. Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity.

Epilepsy in Children With Congenital Heart Disease: Risk Factors and Characteristic Presentations.

BACKGROUND: Children with a congenital heart disease (CHD) are at a higher risk of developing epilepsy than the general population, but detailed characteristics of CHD-associated epilepsy have not been clarified. The purposes of this study were to determine the risk factors for developing epilepsy associated with CHD and to elucidate the characteristics of such epilepsy. METHODS: We performed a retrospective cohort study based on medical records of pediatric patients with CHD who were born between January 2006 and December 2016, underwent cardiac surgery at Okayama University Hospital, and were followed up until at least age three years. Multivariate logistic regression analysis was used to determine factors particularly associated with epilepsy occurrence. In patients who developed epilepsy, clinical data on seizure characteristics were further investigated. RESULTS: We collected data from 1024 patients, and 41 (4.0%) developed epilepsy. The presence of underlying disease (odds ratio [OR]: 2.413; 95% confidence interval [CI]: 1.150 to 4.883) and the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score category 2 (OR: 4.373; 95% CI: 1.090 to 29.150) and category 5 (OR: 10.385; 95% CI: 1.717 to 89.016) were significantly related to epilepsy occurrence. Of the 41 patients with epilepsy, 15 (including nine with hypoplastic left heart syndrome) had focal impaired awareness seizures specified as autonomic seizures with vomiting, which tends to escape detection. CONCLUSIONS: We clarified the risk factors for developing epilepsy in children with CHD. We also found that autonomic seizure with vomiting is an important symptom in these children.

A Case of Myxoma Arising in the Buccal Mucosa.

Myxomas arising in the oral and maxillofacial areas are extremely rare. This study reports a case of myxoma arising in the soft tissue beneath the buccal mucosa of an 86-year-old man.

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy.

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)-mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy.

A pilot clinical evaluation of oral mucosal dryness in dehydrated patients using a moisture-checking device.

This study included 30 patients (17 males and 13 females; mean age, 73.7 ± 13.1 years) who were diagnosed with dehydration based on vital signs, skin symptoms, and blood test findings by emergency medicine physicians. First, the attending physician of our department measured oral mucosal dryness. Subsequently, the emergency medicine physician blindly divided the severity of dehydration into three stages according to clinical findings and blood test results. In this study, the oral moisture-checking device (Mucus®; Life Co., Ltd., Saitama, Japan) was used to measure the oral mucosal dryness. We examined the oral moisture level for each dehydration severity level and the correlations of each severity level of dehydration with the measured values. Spearman's correlation coefficient (Medcalc version 11.3 for Windows) was used for statistical analysis. P < 0.05 indicated significant differences. Twenty-six patients were diagnosed with dry mouth, and a moderate negative correlation was found between the severity of dehydration and oral moisture degree (r = -0.686). The correlation coefficient for the relationship between oral moisture degree and severity of dehydration was -0.686, indicating a negative correlation (P < .05). These results suggest that the oral mucosal dryness may be a useful index of dehydration severity.

A Case of a Patient Who Is Diagnosed with Mild Acquired Hemophilia A after Tooth Extraction Died of Acute Subdural Hematoma due to Head Injury.

BACKGROUND: Acquired hemophilia A (AHA) is a rare disorder which results from the presence of autoantibodies against blood coagulation factor VIII. The initial diagnosis is based on the detection of an isolated prolongation of the activated partial thromboplastin time (aPTT) with negative personal and family history of bleeding disorder. Definitive diagnosis is the identification of reduced FVIII levels with evidence of FVIII neutralizing activity. CASE REPORT: We report a case of a 93-year-old female who was diagnosed as AHA after tooth extraction at her home clinic. Prolongation of aPTT and a reduction in factor VIII activity levels were observed with the presence of factor VIII inhibitor. AHA condition is mild. However, acute subdural hematoma of this patient occurred due to an unexpected accident in our hospital. Hematoma was gradually increased and the patient died 13 days after admission. DISCUSSION: Although AHA is mild, intracranial bleeding is a life-threatening condition. We also should pay attention to the presence of AHA patients when we extract teeth.

Arrhythmia risk and ß-blocker therapy in pregnant women with long QT syndrome.

BACKGROUND: Pregnancy is one of the biggest concerns for women with long QT syndrome (LQTS). OBJECTIVES: This study investigated pregnancy-related arrhythmic risk and the efficacy and safety of ß-blocker therapy for lethal ventricular arrhythmias in pregnant women with LQTS (LQT-P) and their babies. METHODS: 136 pregnancies in 76 LQT-P (29±5 years old; 22 LQT1, 36 LQT2, one LQT3, and 17 genotype-unknown) were enrolled. We retrospectively analysed their clinical and electrophysiological characteristics and pregnancy outcomes in the presence (BB group: n=42) or absence of ß-blocker therapy (non-BB group: n=94). RESULTS: All of the BB group had been diagnosed with LQTS with previous events, whereas 65% of the non-BB group had not been diagnosed at pregnancy. Pregnancy increased heart rate in the non-BB group; however, no significant difference was observed in QT and Tpeak-Tend intervals between the two groups. In the BB group, only two events occurred at postpartum, whereas 12 events occurred in the non-BB group during pregnancy (n=6) or postpartum period (n=6). The frequency of spontaneous abortion did not differ between the two groups. Fetal growth rate and proportion of infants with congenital malformation were similar between the two groups, but premature delivery and low birthweight infants were more common in those taking BB (OR 4.79, 95% CI 1.51 to 15.21 and OR 3.25, 95% CI 1.17 to 9.09, respectively). CONCLUSIONS: Early diagnosis and ß-blocker therapy for high-risk patients with LQTS are important for prevention of cardiac events during pregnancy and the postpartum period, and ß-blocker therapy may be tolerated for babies in LQT-P cases.

A huge osteolipoma involving the coronoid process: a case report.

A 28-year-old man visited our hospital with the chief complaint of trismus. Computed tomography revealed a well-defined, soft tissue tumor, 66 × 45 × 21 mm, with a distinct boundary in the inner region of the zygomatic arch. The mass contained various sizes of bone-like hard tissue, some of which adhered to the right coronoid process. A contrast-enhanced magnetic resonance image showed that the mass was composed mainly of adipose tissue. Tumorectomy was performed, and the histopathological diagnosis was osteolipoma. At 2-year follow-up, mouth opening had increased from 31 mm to 50 mm. (J Oral Sci 58, 141-144, 2016).

Essential Palatal Tremor Managed by Cognitive Behavioral Therapy.

Background. Essential palatal tremor is a disorder of unknown etiology involving involuntary movement of the uvula and soft palate. Treatment attempts including drugs or surgery have been conducted to cease the rhythmical movement. Case Report. A 55-year-old female visited our department complaining of a sudden, noticeable, intermittent, and rhythmical clicking noise in her throat for five years. Oral examination revealed rhythmical contractions of the soft palate with clicking at the frequency of 120 per min. Magnetic resonance imaging (MRI) examination of the brain performed after consulting with the department of neuropathic internal medicine showed no abnormalities. Thus, essential palatal tremor was diagnosed. The symptoms improved with cognitive behavioral therapy without drugs or surgical treatments. The patient is now able to stop the rhythmical movement voluntarily. Discussion. Cognitive behavioral therapy might be suitable as first-line therapy for essential palatal tremor because the therapy is noninvasive.

Usability of surgical treatment in cases of bisphosphonate-related osteonecrosis of the jaw stage 2 with sequestrum.

OBJECTIVE: This retrospective study was conducted to reveal usability of surgical treatment in the cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) stage 2 with sequestrum. PATIENTS AND METHODS: Study subjects included 18 patients having BRONJ stage 2 with sequestrum and 12 non-BRONJ patients with nearly equal clinical states of BRONJ stage 2. Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results were compared between BRONJ group and non-BRONJ groups. In addition, correlation between treatment methods (conservative therapy, sequestrum curettage, and sequestrectomy) and treatment results and correlation between the administration route of bisphosphonates (BPs) (oral or intravenous) and treatment results were examined statistically. The Student's t-test and Fisher's exact test were performed for statistical analysis. RESULTS: Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results showed no significant differences between the two groups. In the BRONJ group, treatment result of sequestrectomy was significantly better than conservative therapy/sequestrum curettage (P < 0.001), however, no significant difference was observed in the non-BRONJ group. No significant difference was found in correlation between the administration route of BPs and treatment results in the BRONJ group. CONCLUSION: Treatment outcome of sequestrectomy was better than conservative therapy/sequestrum curettage in BRONJ stage 2 cases with sequestrum.

Expression of TLE3 by bone marrow stromal cells is regulated by canonical Wnt signaling.

Transducing-like enhancer of split 3 (TLE3), one of the Groucho/TLE family members, targets Runx2 transcription and suppresses osteoblast differentiation in bone marrow stromal cells (BMSCs). Here, we identify Wnt responsive elements of the TLE3 promoter region through comparative genomic and functional analyses and show that expression of TLE3 is increased by Wnt signaling, which is important for osteoblast differentiation. We also demonstrated that TLE3 is able to suppress canonical Wnt signaling in BMSCs. Taken together, our data suggest that induction of TLE3 by Wnt signaling is part of a negative feedback loop active during osteoblast differentiation.