Purpose : Easy and safe implantability, good post-operative valve function and good long-term durability are required for any bioprosthetic valve implanted in aortic position. The Carpentier Edwards Perimount Magna valve (Magna) was introduced in 2009 and the St. Jude Medical Trifecta valve (Trifecta) was introduced in 2012 to our institution. In this study, we compared implantability, early post-operative valve function and structural valve deterioration (SVD) between these two valves. Patients and Methods : Between January 2009 and December 2019, Magna or Trifecta were electively implanted for 254 patients (Magna 151 patients and Trifecta 103 patients) and these patients were included in this study. Implantability was evaluated by occurrence of intraoperative valve dysfunction. Early post-operative valve function was evaluated by mean pressure gradient (m-PG) and indexed aortic valve area (AVAI) by ultrasonography performed 10 days after surgery. The relationship between indexed bioprosthetic valve orifice area calculated from internal diameter (GOAI) and AVAI was evaluated. If there was a significant relationship between GOAI and AVAI, maximum body surface area (BSA) to obtain AVAI≥0.85 cm2/m2 was estimated from 99% reliable interval of regression line. Results : Age, gender, and BSA did not differ between the two groups. There was no intraoperative valve dysfunction in Magna ; however we experienced one patient with severe aortic regurgitation due to stent distortion by the aortic wall during surgery with the 25 mm Trifecta valve. For this patient, Trifecta was replaced with Magna intra-operatively. In the 19 mm valve, AVAI was significantly larger (1.12±0.27 cm2/m2 vs. 0.88±0.21 cm2/m2, p<0.001) and m-PG was significantly lower (8.7±2.7 mmHg vs. 17.2±6.3 mmHg, p<0.001) in Trifecta. The frequency of AVAI<0.85 cm2/m2 (24% vs. 49%, p=0.036) and the frequency of m-PG≥20 mmHg (0% vs. 26%, p=0.006) were significantly less in Trifecta. There was significant relationship between GOAI and AVAI in both valves. Maximum BSA to obtain AVAI ≥0.85 cm2/m2 was estimated as 1.35 m2 in Magna and 1.50 m2 in Trifecta. In the 21 mm valve, AVAI was significantly larger (1.14±0.23 cm2/m2 vs. 0.92±0.22 cm2/m2, p<0.001) and m-PG was significantly lower (7.8±3.2 mmHg vs. 14.6±4.7 mmHg, p<0.001) in Trifecta. The frequency of AVAI<0.85 cm2/m2 was significantly less in Trifecta (11% vs. 42%, p=0.002) ; however, the frequency of m-PG≥20 mmHg did not differ significantly. There was a significant relationship between GOAI and AVAI in Magna and Trifecta. Maximum BSA to obtain AVAI ≥0.85 cm2/m2 was estimated as 1.49 m2 in Magna and 1.70 m2 in Trifecta. In the 23 and 25 mm valves, AVAI was significantly larger and m-PG was significantly lower in Trifecta. However neither the frequency of AVAI<0.85 cm2/m2 nor m-PG≥20 mmHg differed between the two valves. There was one early (27 months after surgery) SVD due to leaflet tear in Trifecta and two SVDs due to leaflet calcification more than 10 years after surgery in Magna. Conclusion : For Trifecta implantation, valve size selection seemed to be important and larger valves should be avoided with narrow ST junctions. Selection of 19 and 21 mm Magna valves should be limited for the patient with a BSA less than 1.35 and 1.49 m2 respectively. In Trifecta, early SVD might occur and careful follow-up is necessary.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT). METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes. RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS. CONCLUSION CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.

Background : Post-operative fluid management after cardiac valvular surgery is very important. In our institute, carperitide 0.0125 γ was started during surgery and oral furosemide 20-40 mg/day and spironolactone 25 mg/day were started at post-operative day (POD) 1 as the standard therapy. Tolvaptan, vasopressin V2 receptor antagonist, was started when fluid retention such as pleural effusion occurred. With this strategy, the frequency of pleural drainage was more than 40%. Therefore we changed our standard therapy in February 2018. In this new standard therapy, carperitide (0.0125 γ) was started and maintained until oral intake became possible and tolvaptan 7.5 mg was started with furosemide 20 mg and spironolactone 25 mg as oral medicine usually at POD 1. In this study, whether tolvaptan prevents pleural effusion or not after cardiac surgery was examined. Subjects and Methods : Sixty-four patients were operated during February 2017 and December 2018 were included in this study. Thirty-two patients operated in the period until January 2018 served as control group and were compared with 32 patients for whom tolvaptan was started on POD 1 (tolvaptan group). Results : There was no significant difference between two groups for background, operative procedure, operation time, cardiopulmonary bypass time, aortic cross clamp time and fluid balance during procedure. Tolvaptan was given to all patients in the tolvaptan group and in 22% of patients in the control group. Oral furosemide dose (tolvaptan group 21±5 mg/day, control group 31±20 mg/day, p＝0.0112), and the frequency of patients with intravenous furosemide administration (tolvaptan group 9%, control group 44%, p＝0.0038) were significantly less in tolvaptan group. In the tolvaptan group, intravenous furosemide administrated only once in all patients, whereas the frequency of intravenous furosemide administration was 1-32 times, average 6.6 times in control group. Tolvaptan was stopped within 1 week because of too much urination in two patients and the elevation of liver enzyme in two patients without any adverse effects. Post-operative urination volume until POD 5 did not differ. In both groups, body weight increased at POD 1 and 2 and returned to pre-operative weight at POD 3. Pleural effusion was significantly less in the tolvaptan group at POD 3 (tolvaptan group : none 66%, small amount 22%, moderate amount 3%, drain tube inserted 9%, control group : none 16%, small amount 34%, moderate amount 13%, drain tube inserted 38%, p＝0.0003), at POD 7 (tolvaptan group : none 72%, small amount 28%, vs., control group : none 47%, small amount 19%, moderate amount 22%, drain tube inserted 13%, p＝0.0041) and at discharge (tolvaptan group : none 94%, small amount 6%, vs., control group : none 69%, small amount 22%, moderate amount 9%, p＝0.0301). The frequency of pleural drainage was also less in the tolvaptan group (tolvaptan group 9.4%, control group 44%, p＝0.0038). Conclusion : After cardiac valvular surgery, tolvaptan started at POD 1 is very effective to reduce the frequency of pleural effusion and pleural drainage, and careful checking for too much urination and the elevation of liver enzymes is mandatory.

Following the revision of nursing care remuneration in FY 2015, our health service facility for the elderly made improved support available based on the outcomes of rehabilitation case conferences (RCCs) we convened for users of visiting rehabilitation services. In this study, we conducted a survey to investigate the implementation status of the RCC outcomes by respondents,including service users, their family members, and healthcare professionals,at our facility and the changes observed in service users who participated in the RCCs.Survey items inquired about the basic attributes of service users, RCC topics discussed, status of participation in the RCCs by occupation,and independence in activities of daily living (ADL) of elderly disabled people.The topics covered in the RCCs were classified using the International Classification of Functioning,Disability,and Health.In total,85 of 108 people who needed nursing care (34 men, 51 women; mean age 81.4±9.4 years;mean duration of service use 16.3 months) participated in the RCCs.The majority of topics covered in the RCCs concerned ADL and environmental factors,and more than half of the respondents participated in RCCs several times.Because ADL and environmental factors were discussed most,it can be said that the RCC concerning visiting rehabilitation services for users living at home is an effective means of expanding ADL and instrumental ADL. An advantage of holding RCCs is that the users themselves can clarify the current status and future goals. Also, from the service provider perspective, multidisciplinary cooperation becomes easier and helps to further improve support for users.

Objective : The ascending aortic cannulation (Ao-C) is the routine procedure for cardiopulmonary bypass (CPB) in our hospital. However, for patients with diseased ascending aorta, such as severely calcified aorta, dissected or aneurysmal aorta, we used brachiocephalic artery (BCA) cannulation. The effectiveness and simplicity of BCA cannulation was evaluated. Methods : For patients with diseased ascending aorta, BCA was cannulated when the diameter of BCA is larger than 10 mm and is free from calcification, since January 2013. There were 62 patients who underwent aortic valve replacement (AVR) for aortic valve stenosis and BCA cannulation was applied for 11 patients. Standard Ao-C was used for remaining 51 patients. There were 44 patients with dissected or aneurysmal ascending aorta and BCA cannulation was applied for 7 patients, axillary artery perfusion was used for 15 patients and standard Ao-C was used for 22 patients. Consciousness level at the time of awaking from general anesthesia and any complication related with BCA cannulation was evaluated for the effectiveness. Simplicity was evaluated by the time required to establish CPB after skin incision. Results : In AVR patients, there was 1 patient with delayed consciousness level recovery with BCA cannulation and this patient was found to have cerebral infarction by CT. Intraoperative aortic dissection, probably due to BCA cannulation was observed in 1 patient, very old fragile and long period steroid user. In diseased ascending aorta patients, no patient suffered neurological accident nor any complication due to cannulation. In AVR patients, the time required to establish CPB after skin incision was 51+/-9 min in BCA cannulation and 47+/-10 min in Ao-C patients (p=0.34). In diseased ascending aorta patients, the time required to establish CPB after skin incision was 49+/-49 min in BCA cannulation and 51+/-16 min (p=0.82). Conclusion : BCA cannulation is a very simple and safe technique to establish CPB for patients with diseased ascending aorta. However great care should be taken, and BCA cannulation should be avoided for the long term steroid users or patients with connective tissue disease.

The ability of human deciduous tooth dental pulp cells (HDDPCs) to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medicine. Realization of this potential depends on efficient and optimized protocols for the genetic manipulation of HDDPCs. In this study, we demonstrate the use of a PiggyBac (PB)-based gene transfer system as a method for introducing nonviral transposon DNA into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection efficiency of the PB-based system was significantly greater than previously reported for electroporation-based transfection of plasmid DNA. Using the neomycin resistance gene as a selection marker, HDDPCs were stably transfected at a rate nearly 40-fold higher than that achieved using conventional methods. Using this system, it was also possible to introduce two constructs simultaneously into a single cell. The resulting stable transfectants, expressing tdTomato and enhanced green fluorescent protein, exhibited both red and green fluorescence. The established cell line did not lose the acquired phenotype over three months of culture. Based on our results, we concluded that PB is superior to currently available methods for introducing plasmid DNA into HDDPCs. There may be significant challenges in the direct clinical application of this method for human dental tissue engineering due to safety risks and ethical concerns. However, the high level of transfection achieved with PB may have significant advantages in basic scientific research for dental tissue engineering applications, such as functional studies of genes and proteins. Furthermore, it is a useful tool for the isolation of genetically engineered HDDPC-derived stem cells for studies in tooth regenerative medicine.
Cells, Cultured ; DNA Transposable Elements ; Dental Pulp ; cytology ; Humans ; Induced Pluripotent Stem Cells ; cytology ; Nerve Tissue Proteins ; genetics ; Tooth, Deciduous ; cytology ; Transfection

The ability of human deciduous tooth dental pulp cells (HDDPCs) to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medicine. Realization of this potential depends on efficient and optimized protocols for the genetic manipulation of HDDPCs. In this study, we demonstrate the use of a PiggyBac (PB)-based gene transfer system as a method for introducing nonviral transposon DNA into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection efficiency of the PB-based system was significantly greater than previously reported for electroporation-based transfection of plasmid DNA. Using the neomycin resistance gene as a selection marker, HDDPCs were stably transfected at a rate nearly 40-fold higher than that achieved using conventional methods. Using this system, it was also possible to introduce two constructs simultaneously into a single cell. The resulting stable transfectants, expressing tdTomato and enhanced green fluorescent protein, exhibited both red and green fluorescence. The established cell line did not lose the acquired phenotype over three months of culture. Based on our results, we concluded that PB is superior to currently available methods for introducing plasmid DNA into HDDPCs. There may be significant challenges in the direct clinical application of this method for human dental tissue engineering due to safety risks and ethical concerns. However, the high level of transfection achieved with PB may have significant advantages in basic scientific research for dental tissue engineering applications, such as functional studies of genes and proteins. Furthermore, it is a useful tool for the isolation of genetically engineered HDDPC-derived stem cells for studies in tooth regenerative medicine.

We performed transatrial repair of postinfarction posterior ventricular septal defect (VSP) in a 69-year-old man who was transferred to our hospital with a diagnosis of posterior acute myocardial infarction and VSP. Coronary angiogram revealed total occlusion of the right coronary artery at #3 and 75% stenosis of the left circumflex artery at #13. UCG revealed the ventricular septal defect on the posterior ventricular septum without LV wall motion abnormality. Surgical repair was planned around 3-4 weeks later because his hemodynamic state was stable without inotropes nor IABP support upon arrival. Under general anesthesia, standard median sternotomy was performed and cardiopulmonary bypass was established with the ascending aorta and bicaval cannulation. Cardiac arrest was achieved with antegrade cold crystalloid cardioplegic solution and an oblique right atrial incision was made. The VSP was visualized via the tricuspid valve. The location of VSP was confirmed with saline injection from the LA vent line. VSP was closed with two patches, consist of a Teflon felt and a bovine pericardial patch, from the left and right ventricle side with six 4-0 polypropylene mattress sutures. Also coronary artery bypass for LCx was performed with a saphenous vein graft. The postoperative course was uneventful. There was no residual ventricular septal shunt and LV function was normal by UCG. Right atrial approach for surgical repair seemed to be useful for posterior VSP.

Absent pulmonary valve (APV) syndrome is a rare anomaly that is usually associated with tetralogy of Fallot (TOF) and causes severe respiratory distress by compression of the trachea. Mortality following surgical repair in these patients is increased, especially in infants presenting with severe respiratory compromise. Preoperative ventilator dependency and age at operation are risk factors for mortality after surgical repair. Between 1995 and 1999, 5 patients underwent surgical treatment for TOF with APV. The mean age at operation was 9 months (range: 1 to 29 months), and the mean weight at operation was 5.2kg (3.6-9.1kg). Among these patients, 3 patients presented with severe respiratory distress caused by dilatation of aneurysmal pulmonary artery (pulmonary artery index>2,000) and 2 of these patients were dependent on a respirator prior to surgical treatment. Reduction of dilated pulmonary artery, including anterior wall resection and posterior placation, was performed in all patients. In the patients with severe preoperative respiratory compromise, the right ventricular outflow tract was reconstructed with an extracardiac conduit with autologous pericardial valve leaflets to avoid pulmonary valve regurgitation after the operation and a transannular patch with a PTFE valve was used in 2 patients without respiratory compromise. One patient died suddenly 7 months after surgical intervention. Three of the surviving patients underwent a second right ventricular outflow tract reconstruction because of progressive right ventricular outflow tract stenosis. In two of these patients the right ventricular outflow tract was reconstructed with an extracardiac conduit with autologous pericardial valve leaflets at first operation. All surviving patients are well without any physical limitations and have been placed in NYHA class I. Despite the need for reoperation for right ventricular outflow tract stenosis, aggressive surgical treatment for TOF with APV has produced a satisfactory mid-term outcome.