Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell-Derived Cardiac Spheroids.

BACKGROUND: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts. METHODS: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2×107 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6×107 CMs). RESULTS: Recipients of hiPSC-CSs containing 2×107 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation: 26.2±2.1%; 19.3±1.8%; P<0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P<0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P<0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6×107 CMs. CONCLUSIONS: We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products.

[Chronic Kidney Disease:Key Points for Intraoperative and Postoperative Management].

Chronic kidney disease( CKD) is a challenge in cardiac surgery in elderly patients, making intraoperative and postoperative management critical. Although sodium glucose co-transporter 2( SGLT2) inhibitors have nephroprotective effects, it's important to discontinue them three days before surgery and resume them when food intake is possible. Nephroprotective perioperative management of CKD stage 3-4 patients requires different approaches at each stage, with blood pressure control and nutritional counseling being key. For patients with CKD stage 5, postoperative management includes circulatory management in the intensive care unit and assessment of the need for and timing of hemodialysis. Continuous renal replacement therapy( CRRT) is common, but recently the use of multiple dialysis modalities (multimodal approach) has increased. This multimodal approach, which aims to avoid CRRT trauma, may contribute to improved outcomes.

Mature human induced pluripotent stem cell-derived cardiomyocytes promote angiogenesis through alpha-B crystallin.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to treat heart diseases; however, the optimal maturity of hiPSC-CMs for effective regenerative medicine remains unclear. We aimed to investigate the benefits of long-term cultured mature hiPSC-CMs in injured rat hearts. METHODS: Cardiomyocytes were differentiated from hiPSCs via monolayer culturing, and the cells were harvested on day 28 or 56 (D28-CMs or D56-CMs, respectively) after differentiation. We transplanted D28-CMs or D56-CMs into the hearts of rat myocardial infarction models and examined cell retention and engraftment via in vivo bioluminescence imaging and histological analysis. We performed transcriptomic sequencing analysis to elucidate the genetic profiles before and after hiPSC-CM transplantation. RESULTS: Upregulated expression of mature sarcomere genes in vitro was observed in D56-CMs compared with D28-CMs. In vivo bioluminescence imaging studies revealed increased bioluminescence intensity of D56-CMs at 8 and 12 weeks post-transplantation. Histological and immunohistochemical analyses showed that D56-CMs promoted engraftment and maturation in the graft area at 12 weeks post-transplantation. Notably, D56-CMs consistently promoted microvessel formation in the graft area from 1 to 12 weeks post-transplantation. Transcriptomic sequencing analysis revealed that compared with the engrafted D28-CMs, the engrafted D56-CMs enriched genes related to blood vessel regulation at 12 weeks post-transplantation. As shown by transcriptomic and western blot analyses, the expression of a small heat shock protein, alpha-B crystallin (CRYAB), was significantly upregulated in D56-CMs compared with D28-CMs. Endothelial cell migration was inhibited by small interfering RNA-mediated knockdown of CRYAB when co-cultured with D56-CMs in vitro. Furthermore, CRYAB overexpression enhanced angiogenesis in the D28-CM grafts at 4 weeks post-transplantation. CONCLUSIONS: Long-term cultured mature hiPSC-CMs promoted engraftment, maturation and angiogenesis post-transplantation in infarcted rat hearts. CRYAB, which was highly expressed in D56-CMs, was identified as an angiogenic factor from mature hiPSC-CMs. This study revealed the benefits of long-term culture, which may enhance the therapeutic potential of hiPSC-CMs.

Mechanism of sac expansion without evident endoleak analyzed with X ray phase-contrast tomography.

Objective: Synchrotron radiation-based X ray phase-contrast tomography (XPCT) was used in this study to evaluate abdominal aorta specimens from patients with sac expansion without evidence of an endoleak (endotension) following endovascular aortic repair (EVAR) for an abdominal aortic aneurysm (AAA). The aim of this study was to analyze the morphologic structure of the aortic wall in patients with this condition and to establish the cause of the endotension. Methods: Human aortic specimens of the abdominal aorta were obtained during open repair, fixed with formalin, and analyzed among three groups. Group A was specimens from open abdominal aortic aneurysm repairs (n = 7). Group E was specimens from sac expansion without an evident endoleak after EVAR (n = 7). Group N was specimens from non-aneurysmal "normal" cadaveric abdominal aortas (n = 5). Using XPCT (effective voxel size, 12.5 µm; density resolution, 1 mg/cm3), we measured the density of the tunica media (TM) in six regions of each sample. Then, any changes to the elastic lamina and the vasa vasorum were analyzed pathologically. The specimens were immunohistochemically examined with anti-CD31 and vascular endothelial growth factor antibodies. Results: The time from EVAR to open aortic repair was 64.2 ± 7.2 months. There were significant differences in the thickness of the TM among three groups: 0.98 ± 0.03 mm in Group N; 0.31 ± 0.01 mm in Group A; and 0.15 ± 0.03 mm in Group E (P < .005). There were significant differences in the TM density among the groups: 1.087 ± 0.004 g/cm3 in Group N; 1.070 ± 0.001 g/cm3 in Group A; and 1.062 ± 0.007 g/cm3 in Group E (P < .005). Differences in the thickness and density of the TM correlated with the thickness of the elastic lamina; in Group N, uniform high-density elastic fibers were observed in the TM. By contrast, a thinning of the elastic lamina in the TM was observed in Group A. A marked thinness and loss of elastic fibers was observed in Group E. CD31 immunostaining revealed that the vasa vasorum was localized in the adventitia and inside the outer third of the TM in Group N, and in the middle of the TM in Group A. In Group E, the vasa vasorum advanced up to the intima with vascular endothelial growth factor-positive cells in the intimal section. Conclusions: XPCT could be used to demonstrate the densitometric property of the aortic aneurysmal wall after EVAR. We confirmed that the deformation process that occurs in the sac expansion after EVAR without evidence of an endoleak could be explained by hypoxia in the aortic wall.

Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration.

Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.

Central extracorporeal membrane oxygenation with left-ventricular vent for fulminant myocarditis: a retrospective study.

PURPOSE: Fulminant myocarditis presents as acute severe heart failure and requires mechanical cardiocirculatory support. Left-ventricular (LV) decompression is necessary for the successful recovery of these patients. This retrospective study aimed to evaluate the functional outcomes of providing central extracorporeal membrane oxygenation (ECMO) with LV decompression for the treatment of refractory fulminant myocarditis. METHODS: Between January 2015 and February 2021, seven consecutive fulminant myocarditis patients (mean age: 41.1 ± 26.1 years) received central ECMO support with transapical LV decompression, with an 18 French cannula integrated into the ECMO circuit in a Y-fashion. The baseline characteristics and postoperative outcomes of the patients were collected. RESULTS: On admission, all patients received prior peripheral ECMO, and 85.7% (6/7) of patients received prior intra-aortic balloon pumping. However, all patients had refractory cardiogenic shock that failed prior to decompression. Six patients recovered successfully after a mean ECMO support of 20.0 ± 11.5 days and five patients had no recurrence of cardiac decompensation. The mean ICU and mean hospital stays were 36.7 ± 23.5 days and 60.6 ± 24.9 days, respectively. Hospital mortality was 28.6% (2/7). Two patients died due to sepsis and stroke during hospitalization. CONCLUSIONS: Central ECMO with an LV vent was effective for fulminant myocarditis refractory to percutaneous cardiopulmonary support therapy and other therapies.

Association between postoperative delirium and heart rate variability in the intensive care unit and readmissions and mortality in elderly patients with cardiovascular surgery.

This study aimed to investigate the relationship between heart rate variability (HRV), a parameter of the autonomic nervous system activity (ANSA), and postoperative delirium and postoperative events. This retrospective cohort study included elderly patients aged 65 years or older who were admitted to the intensive care unit (ICU) after cardiovascular surgery. ANSA was measured using HRV parameters for 1 h at daytime and 1 h at night-time before ICU discharge. The primary endpoint was the effect of HRV parameters and delirium on mortality and readmission rates within 1 year after discharge, and the secondary endpoint was the association between HRV parameters and delirium. Cox proportional hazards models were used to examine the association between HRV parameters and postoperative events by adjusting for delirium and pre and postoperative information. A total of 71 patients, 39 without delirium and 32 with delirium, met the inclusion criteria. The incidence of death and readmission within 1 year was significantly higher in the delirium group and in the group with higher daytime HF (high frequency power) and r-MSSD (square root of the squared mean of the difference of successive NN intervals), parameters of the parasympathetic nervous system activity (PNSA), than that in other groups. Furthermore, the delirium group had significantly higher HF and r-MSSD than the nondelirium group. Even after adjusting for confounding factors in the multivariate analysis, a trend of higher daytime HF and r-MSSD was observed, indicating a significant effect on the occurrence of combined events within 1 year of discharge. ICU delirium has been associated with higher daytime HF and r-MSSD, parameters of PNSA. ICU delirium was a prognostic factor, and increased daytime PNSA may worsen the prognosis of elderly patients after cardiovascular surgery.

[Successful Removal of Intrapericardial Needle using Needle Guidance System].

A 41-year-old man stuck himself with needle through his pericardium during suicide attempt. Chest radiography revealed several needles in the bilateral lung fields as well. Computed tomography (CT) and echocardiography showed massive pericardial effusion and a needle penetrating the pericardium. The patient was initially treated conservatively, including pericardial drainage, and, seven days later, we removed the needle using syngo Needle Guidance in hybrid operating room. The length of skin incision was only 2 cm, and the postoperative course was uneventful. No previous studies, to the best of our knowledge, have shown the use of syngo Needle Guidance to remove a needle in the pericardial cavity. This surgical procedure is minimally invasive for the patient.

Left Coronary Cusp with Fenestration Adherent to the Aortic Wall.

An aortic valve with a coronary cusp adherent to the aortic wall is a rare anomaly. Furthermore, an adherent coronary cusp with fenestration is even rarer. Here, we report a case of aortic valve regurgitation with an adherent and fenestrated left coronary cusp. A 45-year-old man with complaints of dyspnea on exertion was hospitalized. Clinical examination revealed severe aortic valve regurgitation associated with poor cardiac function. He had a history of cardiac murmur present since childhood; however, the details of his cardiac history are unknown. During surgery, a fenestrated left coronary cusp adherent to the aortic wall was observed. Following resection of all aortic cusps, we performed an aortic valve replacement with a mechanical valve. The postoperative recovery was uneventful. In this case, the left coronary artery was perfused by a small fenestration in the adherent coronary cusp. In such cases, the adherent coronary cusp should be released to alleviate the possibility of sudden death and ischemic myocarditis.

Intimal Sarcoma after Endovascular Abdominal Aortic Aneurysm Repair.

A 72-year-old man, who was treated 10 years earlier with endovascular aortic aneurysm repair, presented with a fever. Considering the concern of stent graft infection, the patient was treated with antibiotics, but his condition did not improve. He underwent stent graft resection and reconstruction with a Dacron graft. Pathological analysis of the aortic wall and computed tomography revealed recurrent intimal sarcoma, and the patient underwent resurgery. During follow-up, he underwent two additional resections for local recurrence, but he died 17 months later. Our results suggest that intimal sarcoma should be considered during the follow-up after endovascular aortic aneurysm repair.

Decreased activities of daily living at discharge predict mortality and readmission in elderly patients after cardiac and aortic surgery: A retrospective cohort study.

ABSTRACT: Recently, activities of daily living (ADL) were identified as a prognostic factor among elderly patients with heart disease; however, a specific association between ADL and prognosis after cardiac and aortic surgery is not well established. We aimed to clarify the impact of ADL capacity at discharge on prognosis in elderly patients after cardiac and aortic surgery.This retrospective cohort study included 171 elderly patients who underwent open operation for cardiovascular disease in a single center (median age: 74 years; men: 70%). We used the Barthel Index (BI) as an indicator for ADL. Patients were classified into 2 groups according to the BI at discharge, indicating a high (BI ≥ 85) or low (BI < 85) ADL status. All-cause mortality and unplanned readmission events were observed after discharge.Thirteen all-cause mortality and 44 all-cause unplanned readmission events occurred during the median follow-up of 365 days. Using Kaplan-Meier analysis, a low ADL status was determined to be significantly associated with all-cause mortality and unplanned readmission. In the multivariable Cox proportional hazard models, a low ADL status was an independent predictor of all-cause mortality and unplanned readmission after adjusting for age, sex, length of hospital stay, and other variables (including preoperative status, surgical parameter, and postoperative course).A low ADL status at discharge predicted all-cause mortality and unplanned readmission in elderly patients after cardiac and aortic surgery. A comprehensive approach from the time of admission to postdischarge to improve ADL capacity in elderly patients undergoing cardiac and aortic surgery may improve patient outcomes.

Another route of CO2 gas excretion independent of red blood cells in human lungs.

We demonstrated pulmonary arteriolar blood flow-mediated CO2 gas excretion in rabbit lungs. The shear stress stimulation produced CO2 gas in cultured human endothelial cells of pulmonary arterioles via the activation of F1/Fo ATP synthase. To confirm the findings in human subjects undergoing the operation with heart-lung machines, we aimed to evaluate the effects of a stepwise switch, from a partial to a complete cardiopulmonary bypass, of the circulatory blood volume (BV, 100% = 2.4 × cardiac index), on the end-expiratory CO2 pressure (PetCO2), maximal flow velocity in the pulmonary artery (Max Vp), the inner diameter (ID) of pulmonary artery, pulmonary arterial CO2 pressure (P mix v CO2), pulmonary arterial O2 pressure (P mix v O2), hematocrit (Hct), pH, the concentration of HCO3-, and base excess (BE) in mixed venous blood in 9 patients with a mean age of 72.3 ± 3.4 years. In addition, the effects of the decrease in Hct infused with physiological saline solution (PSS) on PetCO2 were investigated in the human subjects. An approximately linear relationship between the PetCO2 and Max Vp was observed. The pumping out of 100% BV produced little or no change in the Hct, pH, P mix v CO2, and P mix v O2, respectively. The hemodilution produced by intravenous infusion of PSS caused a significant decrease in the Hct, but not in the PetCO2. In conclusion, another route of CO2 gas excretion, independent of red blood cells, may be involved in human lungs.

Strategies to improve outcomes for acute type A aortic dissection with cerebral malperfusion.

OBJECTIVES: We aimed to identify predictors of postoperative permanent neurological deficits (PNDs) and evaluate the early management of cerebral perfusion in patients undergoing surgical repair of acute type A aortic dissection with cerebral malperfusion. METHODS: Between October 2009 and September 2018, a total of 197 patients with acute type A aortic dissection underwent aortic replacement. Of these, 42 (21.3%) patients had an imaging cerebral malperfusion (ICM). ICM was assessed preoperatively, which also revealed whether dissected supra-aortic branch vessels were occluded or narrowed by a thrombosed false lumen. After September 2017, early reperfusion and extra-anatomic revascularization were performed in cases with ICM. RESULTS: Hospital mortality rates for cases with ICM were 4.8% (2/42). Before September 2017, PND were observed in 6 patients (54.5%) with preoperative neurological symptoms (n = 11), and 7 patients (33.3%) without neurological symptoms (n = 21) in patients with ICM. Occlusion or severe stenosis of supra-aortic branch vessels (odds ratio, 7.66; P < 0.001), regardless of preoperative clinical neurological symptoms, was a risk factor for PND. After September 2017, 7 of 10 patients with ICM underwent early reperfusion and extra-anatomic revascularization. PND did not occur in any of these 7 patients. CONCLUSIONS: Occlusion or severe stenosis of supra-aortic branch vessels is a predictor of PND risk in patients undergoing surgery for acute type A aortic dissection. Early reperfusion and extra-anatomic revascularization may reduce the risk of neurological complications in patients with ICM, with or without neurological symptoms.

Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo.

Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect "heart regeneration", replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia.

Skeletal muscle quality affects patient outcomes in acute type A aortic dissection.

OBJECTIVES: Although skeletal muscle quantity is linked to surgical outcomes, quality remains unexamined. In this study, we evaluated whether skeletal muscle quality and quantity could predict surgical outcomes in acute type A aortic dissection (ATAAD). METHODS: Skeletal muscle quality and quantity were evaluated using computed tomography (CT) values and the psoas muscle mass index, respectively. From May 2004 to December 2017, 324 ATAAD patients underwent aortic replacement after CT scans and psoas muscle mass index measurements. Patients were grouped into intramuscular fat (IMF; n = 55) and non-IMF (n = 269) deposition groups. RESULTS: The mean ages of the patients were 72.3 ± 9.7 and 66.8 ± 12.1 years (P = 0.002), and hospital mortality rates were 3.6% (2/55) and 7.4% (20/269; P = 0.393) for IMF and non-IMF deposition groups, respectively. IMF deposition was a risk factor for a deterioration in activities of daily living at discharge by multivariable analysis [odds ratio 0.33, 95% confidence interval (CI) 0.16-0.69; P = 0.003]. The mean follow-up was 43.9 ± 36.8 months. The 5-year survival was significantly worse for the IMF deposition group (IMF 73.8% vs non-IMF 88.2%; P = 0.010). The multivariable Cox proportional hazard analysis showed that IMF deposition significantly predicted poor survival (hazard ratio 3.26, 95% CI 1.47-7.24; P = 0.004), unlike psoas muscle mass index and age. CONCLUSIONS: Skeletal muscle quality, defined by IMF deposition, was an independent predictor of overall survival and postoperative activities of daily living dependence risk in patients undergoing surgery for ATAAD. Thus, IMF deposition may be an additional risk factor for estimating late outcomes of ATAAD surgery.

T Cell-Specific Adaptor Protein Regulates Mitochondrial Function and CD4+ T Regulatory Cell Activity In Vivo following Transplantation.

The T cell-specific adaptor protein (TSAd), encoded by the SH2D2A gene, is an intracellular molecule that binds Lck to elicit signals that result in cytokine production in CD4+ T effector cells (Teff). Nevertheless, using Sh2d2a knockout (KO; also called TSAd-/-) mice, we find that alloimmune CD4+ Teff responses are fully competent in vivo. Furthermore, and contrary to expectations, we find that allograft rejection is accelerated in KO recipients of MHC class II-mismatched B6.C-H-2bm12 heart transplants versus wild-type (WT) recipients. Also, KO recipients of fully MHC-mismatched cardiac allografts are resistant to the graft-prolonging effects of costimulatory blockade. Using adoptive transfer models, we find that KO T regulatory cells (Tregs) are less efficient in suppressing Teff function and they produce IFN-γ following mitogenic activation. In addition, pyrosequencing demonstrated higher levels of methylation of CpG regions within the Treg-specific demethylated region of KO versus WT Tregs, suggesting that TSAd, in part, promotes Treg stability. By Western blot, Lck is absent in the mitochondria of KO Tregs, and reactive oxygen species production by mitochondria is reduced in KO versus WT Tregs. Full transcriptomic analysis demonstrated that the key mechanism of TSAd function in Tregs relates to its effects on cellular activation rather than intrinsic effects on mitochondria/metabolism. Nevertheless, KO Tregs compensate for a lack of activation by increasing the number of mitochondria per cell. Thus, TSAd serves as a critical cell-intrinsic molecule in CD4+Foxp3+ Tregs to regulate the translocation of Lck to mitochondria, cellular activation responses, and the development of immunoregulation following solid organ transplantation.

Establishment of a Healthcare System for Patients With Adult Congenital Heart Disease in Collaboration With Children's Hospital　- The Nagano Model.

BACKGROUND: Despite the best efforts of pediatricians, healthcare for adult patients with congenital heart disease (ACHD) has proven challenging because of the increased numbers. This study presents the process of establishing an ACHD care system as a collaborative effort between Shinshu University Hospital and Nagano Children's Hospital. Methods and Results: Establishing an outpatient clinic for transition, a cooperation agreement for in-patient care between the 2 hospitals, and quality management of diagnostic imaging and educational meetings for adult cardiologists were the 3 major challenges. Of the 99 patients who visited the transition clinic in the children's hospital between May 2014 and December 2016, 3 returned to the pediatrician's clinic. Between June 2013 and December 2017, 273 patients visited the ACHD center in Shinshu University Hospital. Until December 2017, mortality and fatal arrhythmia were noted in 3 and 2 cases, respectively. Catheter ablation for arrhythmia was performed in 12 cases, and 4 cases of pregnancy with moderate/severe ACHD or estimated as high risk were managed with healthy livebirths. Surgical interventions for moderate/severe ACHD were performed in collaboration with the children's hospital or Sakakibara Heart Institute. CONCLUSIONS: Patients were successfully transferred to adult cardiology departments. Surgical and nonsurgical interventions for ACHD were provided. Collaboration between adult and pediatric cardiologists assists in the establishment of healthcare systems for ACHD.

Impact of Frailty on Outcomes in Acute Type A Aortic Dissection.

BACKGROUND: Although frailty is used to predict morbidity and mortality, its effect on the outcomes of acute type A aortic dissection has not been examined. Therefore, the objective of this study was to evaluate the role of frailty in predicting postoperative morbidity and mortality of patients with acute type A aortic dissection. METHODS: A retrospective analysis of a prospectively maintained database was undertaken for all patients (n = 310) undergoing aortic surgery between May 2004 and March 2017. Frailty was evaluated using an index consisting of age more than 70 years, body mass index less than 18.5 kg/m2, serum creatinine greater than 1.2 mg/dL, anemia, history of stroke, hypoalbuminemia, and the psoas muscle area index. One point was given for each criterion met, for a frailty score between 0 and 7. Frailty was defined as a score of 3 or more. RESULTS: Of all patients, 106 (34.2%) were defined as frail. Inhospital mortality rates of frail versus nonfrail patients were not significantly different (10.4% versus 8.3%, respectively; p = 0.54). Incidences of postoperative major morbidities without reexploration for bleeding were also not statistically different. Five-year survival rates were significantly worse for frail patients than for nonfrail patients (57.7% versus 85.1%, respectively; p = 0.0001). A frailty score of 3 or greater was associated with late mortality, and long-term outcomes were clearly stratified by frailty score. CONCLUSIONS: Frailty, as defined using a seven-component frailty index, can serve as an independent predictor of the risk of late mortality for patients undergoing surgery for acute type A aortic dissection. Such frailty markers, all of which are easily assessed preoperatively, may provide valuable information for patient counseling and risk stratification before aortic surgery.

Analysis of surgical treatment of Masaoka stage III-IV thymic epithelial tumors.

OBJECTIVE: The purpose of this study is to elucidate the outcomes after surgical resection of Masaoka stage III-IV thymic epithelial tumors. METHODS: We retrospectively reviewed patients with Masaoka stage III-IV thymic epithelial tumor who underwent surgical resection from January 1995 to January 2017. The clinicopathological features, surgical procedures, and postoperative outcomes were investigated. RESULTS: Thirteen patients with thymoma and 18 patients with thymic carcinoma were assessed. The postoperative Masaoka stages were III/IVa/IVb = 8/4/1 in thymoma and III/IVa/IVb = 11/2/5 in thymic carcinoma. In patients with thymoma, the World Health Organization pathological subtypes were A/B1/B2/B3 = 2/1/4/6. We performed combined resection and reconstruction for brachiocephalic vein or superior vena cava in 3 patients with thymoma and 7 patients with thymic carcinoma. In all patients, the patency rate of the grafts was very low for the left brachiocephalic vein and well maintained for the right brachiocephalic vein. Macroscopically and pathologically complete resection was achieved in 11 and 6 patients with thymoma, respectively, and in 15 and 9 patients with thymic carcinoma, respectively. The 10-year survival rates were 85.7% in thymoma and 70.3% in thymic carcinoma. Postoperative recurrences were observed in 2 and 9 patients with thymoma and thymic carcinoma, respectively. Recurrences were observed within 5 and 10 years after surgery in 2 patients with thymoma and within 2 years in all patients with thymic carcinoma. CONCLUSIONS: Patients with Masaoka stage III-IV thymic epithelial tumor showed relatively favorable long-term survival after surgical treatment. Therefore, aggressive surgical resection for complete resection may be a treatment option for these conditions.