Yosuke Fukushima

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.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 cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine if 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 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-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 cardiac function improvement at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC-infusion upon request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life (QOL) after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in controls (+6.4% [SD 5.5] vs. +1.3% [3.7]; P=0.003). In study B, a late CDC-infusion in 17 controls increased the ventricular function at 3 months compared with baseline (38.8% [SD 7.7] vs. 34.8% [7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD 6.6] vs. 35.0% [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 QOL, 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 QOL in patients, and reduce parenting stress for their families. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

Intracoronary Cardiac Progenitor Cells in Single Ventricle PhysiologyNovelty and Significance: 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.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 cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine if 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 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-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 cardiac function improvement at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC-infusion upon request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life (QOL) after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in controls (+6.4% [SD 5.5] vs. +1.3% [3.7]; P=0.003). In study B, a late CDC-infusion in 17 controls increased the ventricular function at 3 months compared with baseline (38.8% [SD 7.7] vs. 34.8% [7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD 6.6] vs. 35.0% [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 QOL, 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 QOL in patients, and reduce parenting stress for their families. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

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.

Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS 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.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 cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine if 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 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-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 cardiac function improvement at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC-infusion upon request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life (QOL) after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in controls (+6.4% [SD 5.5] vs. +1.3% [3.7]; P=0.003). In study B, a late CDC-infusion in 17 controls increased the ventricular function at 3 months compared with baseline (38.8% [SD 7.7] vs. 34.8% [7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD 6.6] vs. 35.0% [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 QOL, 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 QOL in patients, and reduce parenting stress for their families. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

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.

Evaluation of oral wetness using an improved moisture-checking device for the diagnosis of dry mouth

Abstract Purpose In 2013, we reported the results of a third-generation oral moisture-checking device in a multicentre clinical study involving patients with dry mouth and healthy volunteers. Subsequently, several improvements have been made to the third-generation device, and a fourth-generation device is now commercially available. This study aimed to confirm the usefulness of this improved fourth-generation device in the diagnosis of dry mouth and to assess the physiological wetness of lingual mucosa by using this device. Materials and Method This multicentre study comprised subjects with dry mouth (dry mouth group) and those without dry mouth (healthy group). Results In this study, the degree of moisture was considerably different between the two groups. Receiver operating characteristic analysis revealed an area under the curve value of 0.831. Sensitivity and specificity values were close to 80% in cases where the degree of moisture ≥29.6 was defined as normal, ≤27.9 was defined as dry mouth, and 28.0–29.5 was defined as borderline dry mouth. Conclusions These results suggest that the improved fourth-generation moisture-checking device can be used for the diagnosis of oral dryness.

Balloon Atrial Septostomy in Hypoplastic Left Heart Syndrome with Restrictive Atrial Septum

Rashkind balloon atrial septostomy (BAS) can be challenging in infants with hypoplastic left heart syndrome (HLHS) and small atrial septal defect (ASD).

A two-year follow-up of surgical and non-surgical treatments in patients with masticatory muscle tendon-aponeurosis hyperplasia

This study re-examined the usefulness of surgery for the management of masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) through a comparison of the outcomes between patients who underwent surgery and those who did not. The duration of follow-up was 2 years. Twenty-eight patients who attended the study hospital and were given a diagnosis of MMTAH were included. Nineteen patients underwent surgery (surgical group) and nine patients were instructed to open their mouths wide once a day and did not undergo surgery (non-surgical group). Maximum mouth opening, impairment of daily activities, satisfaction, and the status of mouth opening training were evaluated after surgery. The mean increase in mouth opening after 2 years was 20.2mm in the surgical group and 2.4mm in the non-surgical group. Adequate mouth opening training led to satisfactory results 2 years postoperative, and sustained mouth opening training for 6 months after surgery was a key factor for obtaining good outcomes. The general condition and personality of individual patients should be evaluated carefully before surgery to estimate whether or not they can endure the pain associated with postoperative mouth opening training. The results of this study suggest that the surgical procedure is useful for the management of MMTAH.

Intracoronary Cardiac Progenitor Cells in Single Ventricle PhysiologyNovelty and Significance

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.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 cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine if 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 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-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 cardiac function improvement at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC-infusion upon request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life (QOL) after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in controls (+6.4% [SD 5.5] vs. +1.3% [3.7]; P=0.003). In study B, a late CDC-infusion in 17 controls increased the ventricular function at 3 months compared with baseline (38.8% [SD 7.7] vs. 34.8% [7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD 6.6] vs. 35.0% [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 QOL, 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 QOL in patients, and reduce parenting stress for their families. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.

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).