Outcomes of Surgical Interrupted Aortic Arch Repair in 181 Patients With Biventricular Circulation.

BACKGROUND: This study compared the outcomes of primary and staged surgery for interrupted aortic arch (IAA) with biventricular circulation. METHODS: A search of our surgical database identified 181 patients with biventricular anatomy who underwent surgical repair of IAA between 1982 and 2022. The patients were divided according to whether they underwent surgery in 1982 to 2001 or 2002 to 2022 and were categorized according to their anomalies into a simple group and a complex group. Repair was 1-stage in 130 patients (71.8%) and 2-stage in 51 (28.2%). RESULTS: There were 6 early deaths (3.3%) and 9 (5.0%) late deaths. The 20-year actuarial survival rate was 91.7%. The 20-year survival rate was 94.7% in the simple group and 82.9% in the complex group (P = .007); the respective rates were 91.7% and 96.8% in 1982 to 2001 (P = .63) and 68.4% and 90.1% in 2002 to 2022 (P = .012). Multivariate analysis identified a complex anomaly and surgery performed in 1982 to 2001 to be risk factors for mortality. Aortic arch reintervention was required in 26 patients (balloon dilation, n = 15; surgical, n = 11). The 15-year freedom from reintervention rate improved from 67.8% in 1982 to 2001 to 89.8% in 2002 to 2022 (P = .041). Multivariate analysis identified type of surgical approach and emergent surgery to be risk factors for reintervention on the aortic arch. CONCLUSIONS: The results of IAA surgery have improved in recent years, especially for complex cases. Development of surgical techniques and individualized treatment strategies could reduce postoperative mortality and morbidity. However, follow-up for recurrence of aortic arch obstruction is necessary.

Surgical Management of Norwood Procedure for Atypical Aortic Arch.

Background: Postoperative restenosis of the aortic arch after the Norwood procedure is still an important complication that significantly affects surgical outcomes. The rarity of the Norwood procedure for atypical aortic morphology means appropriate arch reconstruction methods and postoperative complications are still unknown. This study aimed to assess the rate of arch reintervention and clinical outcomes after the Norwood procedure for atypical aortic arch. Methods: This retrospective single-center study was conducted between 2001 and 2022. Sixteen patients were identified, eight with a right aortic arch, five with transposition of the great arteries, one with a right aortic arch and transposition of the great arteries, and two with a large tortuous patent ductus arteriosus connected to the opposite side of the descending aorta. We selected and performed four different surgical techniques depending on each aortic arch morphology. Results: Except for one case, autologous tissue-only arch reconstruction was possible. There was one operative death and four late deaths. Overall, no patients required any surgical or catheter-based reintervention for the aortic arch. On the other hand, left pulmonary artery stenosis due to a narrow subaortic space was found in two patients. Conclusions: The Norwood procedure for atypical aortic arch was performed with good results by choosing the appropriate technique for each morphology. On the other hand, pulmonary artery stenosis is likely to occur especially in the transposition of the great arteries group. Therefore, careful surgical method selection or further improvement of the technique that allows retroaortic space should be considered.

Acute Dapagliflozin Administration Ameliorates Cardiac Surgery-Associated Acute Kidney Injury in a Rabbit Model.

BACKGROUND: Several studies have shown that sodium-glucose cotransporter-2 inhibitors have a renoprotective effect on acute kidney injury (AKI), but their effect on cardiac surgery-associated AKI is unknown. METHODS AND RESULTS: AKI was induced in 25 rabbits without diabetes mellitus by cardiopulmonary bypass (CPB) for 2 h and they were divided into 5 groups: sham; dapagliflozin-treated sham; CPB; dapagliflozin-treated CPB; and furosemide-treated CPB (n=5 in each group). Dapagliflozin was administered via the femoral vein before initiating CPB. Kidney tissue and urine and blood samples were collected after the surgical procedure. There were no differences in the hemodynamic variables of each group. Dapagliflozin reduced serum creatinine and blood urea nitrogen concentrations, and increased overall urine output (all P<0.05). Hematoxylin and eosin staining showed that the tubular injury score was improved after dapagliflozin administration (P<0.01). Dapagliflozin administration mitigated reactive oxygen species and kidney injury molecule-1 as assessed by immunohistochemistry (both P<0.0001). Protein expression analysis showed improvement of inflammatory cytokines and apoptosis, and antioxidant enzyme expression was elevated (all P<0.05) through activation of the nuclear factor erythroid 2-related factor 2 pathway (P<0.01) by dapagliflozin. CONCLUSIONS: Acute intravenous administration of dapagliflozin protects against CPB-induced AKI. Dapagliflozin may have direct renoprotective effects in renal tubular cells.

Sutureless Repair of Extracardiac Univentricular Total Anomalous Pulmonary Venous Connection.

BACKGROUND: This study aimed to evaluate the results of sutureless repair of extracardiac total anomalous pulmonary venous connection (TAPVC) with a functional single ventricle at a single institution, including changes in the anastomotic site over time. METHODS: The database contained 98 patients with single-ventricle anatomy who underwent extracardiac TAPVC repair from 1996 to 2022. The median age and body weight at surgery were 59 days and 3.8 kg, respectively. Eighty-seven patients had heterotaxy syndrome, and 42 had preoperatively obstructed TAPVC. Primary sutureless repair was performed in 18 patients, 13 of whom were neonates. The cross-sectional area of the anastomotic site of the atrium and pericardium was divided by the body surface area, and the changes in this value over time were assessed. The median follow-up was 5.2 years (range, 0-19.4 years). RESULTS: Operative mortality and late mortality occurred in 2 (2.0%) and 38 (38.8%) patients, respectively. The actuarial survival rate at 5 years postoperatively was 56.2%. Multivariate analysis identified preoperatively obstructed TAPVC as a risk factor for mortality. Recurrent pulmonary venous stenosis (PVS) developed in 25 patients, thus giving a 5-year rate of freedom from PVS of 64.9%. Multivariate analysis revealed that sutureless repair significantly decreased the incidence of recurrent PVS. The cross-sectional anastomotic area tended to grow in accordance with the patients' growth. CONCLUSIONS: Sutureless repair of extracardiac TAPVC with univentricular anatomy achieved acceptable results. The anastomotic site tended to grow over time and contributed to a decline in the rate of recurrent PVS.

Downregulation of Sparc-like protein 1 during cisplatin-induced inhibition of myogenic differentiation of C2C12 myoblasts.

Patients with cancer often experience muscle atrophy, which worsens their prognosis. Decreased muscle regenerative capacity plays an important role in the complex processes involved in muscle atrophy. Administration of cisplatin, a cancer chemotherapeutic agent, has been implicated as a cause of muscle atrophy. In this study, we examined whether cisplatin affects the differentiation of myoblasts into myotubes. We treated C2C12 myoblasts with a differentiation medium containing cisplatin and its vehicle during for 8 days and observed the changes in the expression of myosin heavy chain (MyHC) and myogenin in the myoblasts. Cisplatin was injected in mice for 4 consecutive days; on Day 5, the mice quadriceps muscles were sampled and examined. The expression of MyHCs increased and that of myogenin decreased after cisplatin treatment. The secretion of acidic cysteine-rich proteins (e.g., Sparc proteins) reportedly promotes C2C12 myoblast differentiation. Therefore, we investigated the Sparc family gene expression during myogenesis in C2C12 myoblasts after cisplatin treatment. Of all the genes investigated, Sparc-like protein 1 (Sparcl1) expression was significantly suppressed by cisplatin on Days 4-8. Simultaneous treatment with recombinant mouse Sparcl1 almost inhibited the cisplatin-induced suppression of total MyHC and myogenin protein levels. Moreover, Sparcl1 expression decreased in the skeletal muscles of mice, leading to cisplatin-induced muscle atrophy. Our results suggest that cisplatin-induced myogenesis suppression causes muscle atrophy and inhibits the expression of Sparcl1, which promotes C2C12 cell differentiation during myogenesis.

COL8A1 facilitates the growth of triple-negative breast cancer via FAK/Src activation.

PURPOSE: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, and treatment options are limited because of the lack of signature molecules and heterogeneous properties of cancer. COL8A1 expression is higher in breast cancer than in normal tissues and is strongly correlated with worse overall survival in patients with breast cancer. However, the biological function of COL8A1 on cancer progression is not fully understood. In this study, we investigated the biological function of COL8A1 on TNBC progression. METHODS: COL8A1-deficient cells were generated using the CRISPR-Cas9 system. The tumor growth and metastasis of TNBC cells were evaluated using three-dimensional culture (3D) methods and xenograft mouse models. The activation of focal adhesion kinase (FAK)/Src by COL8A1 in TNBC cells was evaluated by immunoblotting. RESULTS: COL8A1 expression was primarily distributed into TNBC cell lines. Further, relapse-free survival in TNBC patients with the MSL subtype was strongly associated with the COL8A1 expression. MDA-MB-231 and Hs578T cells, classified as the MSL subtype, strongly express COL8A1, and COL8A1 protein expression was induced by hypoxia in both cell lines. Loss of COL8A1 expression inhibited spheroid /tumor growth and metastasis in vitro and in vivo. Further, exogenous COL8A1 promoted TNBC growth via the FAK/Src activation. Finally, the spheroid growth of MDA-MB-231 and Hs578T cells was inhibited by defactinib, a FAK inhibitor, without cytotoxicity. CONCLUSION: These results indicate that COL8A1-mediated FAK/Src activation produces a more aggressive phenotype in TNBC, and its target inhibition may be an efficacious treatment for TNBC.

Ascending aortic extension to enlarge the retroaortic space in children after the Norwood procedure.

Left pulmonary artery stenosis is a well-recognized complication following the Norwood procedure. We herein report two cases in which ascending aortic extension was performed to enlarge the retroaortic space in children with left pulmonary artery stenosis after the Norwood procedure. We used graft interposition in the ascending aorta to increase the retroaortic apace and concomitantly performed extended left pulmonary artery reconstruction. This procedure obtains a more balanced distribution of the pulmonary blood flow, which is crucial to achieve good Fontan circulation.

Fossil decapods from the Upper Quaternary in Shinjima Island in Kagoshima, Kyushu, Japan, and description of a new species of ghost shrimp (Axiidea, Eucalliacidae).

Five species of decapod crustaceans, including Calliax nishiki sp. nov. (Axiidea, Eucalliacidae) and Carcinoplax longimana (de Haan), are described from the upper part of the Moeshima Silt Bed (latest Pleistocene to Holocene: ca 13,000 to 8,000 cal BP). Ten decapods, including Laticallichirus grandis (Karasawa Goda) and Ebalia tuberculosa (A. Milne-Edwards) are described from the Moeshima Shell Bed (Holocene: ca 8,000 to 2,000 cal BP). Calliax nishiki is abundant and Carcinoplax longimana is common in the decapod assemblage of Moeshima Silt Bed. The new species of Calliax seems to have dispersed around the deep marine setting with a reducing environment. The decapod assemblage of the Moeshima Shell Bed is characterized by a predominance of L. grandis. The present record suggests that L. grandis is abundant under sandy and gravelly bottoms mixed with shells of the lower sublittoral to subtidal zones during the Quaternary.

Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma.

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of airway hyperresponsiveness (AHR), a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM is unknown. The current study examined the hypothesis that relaxation induced by PACAP is reduced in bronchial smooth muscle (BSM) of allergic asthma. The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Twenty-four hours after the last antigen challenge, the main bronchial smooth muscle (BSM) tissues were isolated. Tension study showed a BSM hyperresponsiveness to acetylcholine in the OA-challenged mice. Both quantitative RT-PCR and immunoblot analyses revealed a significant decrease in PAC1 receptor expression in BSMs of the diseased mice. Accordingly, in the antigen-challenged group, the PACAP-induced PAC1 receptor-mediated BSM relaxation was significantly attenuated, whereas the relaxation induced by vasoactive intestinal polypeptide was not changed. These findings suggest that the relaxation induced by PACAP is impaired in BSMs of experimental asthma due to a downregulation of its binding partner PAC1 receptor. Impaired BSM responsiveness to PACAP might contribute to the AHR in asthma.

A case of cardiac strangulation following epicardial pacemaker implantation.

An 8-year-old boy had undergone permanent epicardial pacemaker implantation with a Y-shaped bipolar ventricular lead on day 6 after birth for treatment of congenital complete atrioventricular block. He was found to have pulmonary stenosis and mitral stenosis by follow-up echocardiography. Further studies including computed tomography and cardiac catheterization revealed that the pacemaker lead had completely encircled the cardiac silhouette and was in a state of "cardiac strangulation". We removed the previous pacing leads and generator and implanted a new epicardial dual-chamber pacing system in the right atrium and right ventricle. Additionally, an expanded polytetrafluoroethylene sheet was placed between the new leads and the heart to prevent recurrence of cardiac strangulation.

Early palliative balloon pulmonary valvuloplasty in neonates and young infants with tetralogy of Fallot.

We aim to clarify the efficacy of early palliative balloon pulmonary valvuloplasty (BPV) in neonates and young infants (< 60 days) with tetralogy of Fallot (TOF). We performed palliative BPV in 31 subjects, regardless of the presence of cyanosis, with Z score of the pulmonary valve diameter (PVD) less than - 2.00. Primary and secondary endpoints were to avoid early surgical interventions for subjects within 6 months of age and to undergo the pulmonary valve-sparing procedure at corrective surgery, respectively. We studied factors associated with these outcomes among them. BPV was performed at 19 days (14-33) of age and with a weight of 3.34 kg (3.02-3.65). Systemic oxygen saturation, Z score of the PVD, and pulmonary arterial index (PAI) were 87% (81-91), - 3.56 (- 4.15 to - 2.62), and 128 mm2/m2 (102-157), respectively. There were 16 and 13 subjects who avoided early surgical interventions and transannular repair, respectively. At the primary endpoint, there was no significant difference in age, weight, systemic oxygen saturation, and Z score of the PVD and PAI between the groups. However, there was a significant difference in the infundibular morphology (severe: mild-to-moderate, 8:8 vs 13:2, P = 0.029) between the groups. We performed prophylactic BPV within 30 days after birth in 7 acyanotic TOF patients with severe infundibular obstruction, among whom 5 avoided early surgical intervention. At the secondary endpoint, there were no significant difference in weight, systemic oxygen saturation, but in sex, age at BPV, and Z score of the PVD. Early palliative BPV prevented early surgical intervention in half of the neonates and young infants with TOF, which depended upon the degree of infundibular obstruction. However, early palliative BPV did not contribute to avoid transanular patch right-ventricular outflow repair among them.

Use of computed tomography-guided biopsy to detect Peptostreptococcus micros-induced mycotic abdominal aortic aneurysm after endovascular repair.

Mycotic aortic aneurysm (MAA) is rare but lethal. Detection of the causative bacteria is important for successful treatment. In some cases, however, no micro-organisms are detected by repeated blood cultures. Open surgery is the standard procedure for MAA, but endovascular intervention is also performed. An aneurysm specimen cannot be taken for culture when using an endovascular approach, decreasing the opportunity to detect the causative organism. We performed successful endovascular repair in a rare case of a Peptostreptococcus micros-induced MAA as detected by postoperative computed tomography-guided biopsy. This case may help to establish appropriate medical treatment for MAAs.

[How to Place Percutaneous Cardiopulmonary Support(PCPS)].

Cannulation for percutaneous cardiopulmonary support (PCPS) is usually performed percutaneously. However, cut down exposure of the vessels is needed if percutaneous cannulation is difficult. Once the vessels are exposed, cannulas can be placed either by a direct cut down cannulation or by a Seldinger technique. Vascular access is usually achieved through femoral vessels, but other large vessels can be used in specific patient conditions. For instance, neck vessels are commonly used for veno-venous extracorporeal membrane oxygenation (ECMO). In patients who cannot come off cardiopulmonary bypass, direct cannulation of the aorta and right atrium( central ECMO) is a simple way. Complications related to cannulation are bleeding, vascular injury, arterial embolism, and distal malperfusion. Thoracic surgeons must have up-to-date information and become proficient in these procedures.

Sarcopenia impairs health-related quality of life in cirrhotic patients.

AIM: Sarcopenia is associated with poor health-related quality of life (HRQOL) in the general population. However, in cirrhotic patients, as the development of sarcopenia is closely related to declined liver function, which also impairs HRQOL, whether sarcopenia deteriorates HRQOL independently from declined liver function remains unclear. The aim of this study was to clarify the impact of sarcopenia on HRQOL impairment in cirrhotic patients. PATIENTS AND METHODS: A total of 88 cirrhotic patients [median age, 69 years; range: 31-79 years; 49 male (55.7%), 45 with hepatocellular carcinoma (51.1%)] were analyzed. We measured HRQOL using the 36-item Short-Form Health Survey version 2 questionnaire and identified factors contributing to scores lower than 50 in physical component summary (PCS), mental component summary, and role-social component summary (RCS) scores. RESULTS: Twenty-four (27.2%) patients had sarcopenia. PCS and RCS scores were significantly lower in patients with sarcopenia compared with those without sarcopenia. Patients with Child-Pugh (CP) classification B or C showed significantly lower scores in PCS and RCS than those with CP classification A. On multivariate analysis, the presence of sarcopenia was the only factor associated with low PCS scores [odds ratio (OR): 11.6; P = 0.031]. Female sex (OR: 3.34; P = 0.034), CP classification B or C (OR: 3.19; P = 0.037), and presence of sarcopenia (OR: 4.64; P = 0.016) were identified as independent factors for low RCS scores. CONCLUSION: Sarcopenia independently impairs physical and role-social HRQOL in cirrhotic patients.

Endovascular Repair for Ruptured Axillary Artery Aneurysm Proximal to Hemodialysis Access.

Axillary artery aneurysms are uncommon and potentially high-risk lesions threatening the upper extremities. In hemodialysis patients, arteriovenous fistulae creation rarely triggers aneurysmal degeneration and arterial aneurysms in inflow arteries. These aneurysms are usually treated by surgical repair. However, this may lead to complications because of the anatomical complexity surrounding aneurysms of axillary arteries. We report a patient undergoing hemodialysis who had a ruptured ipsilateral axillary artery aneurysm proximal to vascular access. We successfully treated it by endovascular repair with the GORE Excluder AAA contralateral leg endoprosthesis, approaching from the left brachial artery proximal to the shunt. No complications occurred during 15 months after the endovascular repair.

Pulmonary arterial compliance is a useful predictor of pulmonary vascular disease in congenital heart disease.

Histopathological assessment of the pulmonary arteries is crucial to determine the surgical indications in patients with congenital heart disease (CHD) and intractable pulmonary vascular disease (PVD). We aimed to clarify whether pulmonary hemodynamic parameters can predict PVD in patients with CHD and pulmonary arterial hypertension (PAH) We performed histopathological evaluations of lung specimens and cardiac catheterizations in 27 patients with CHD-PAH. We divided these patients into the patients with and without PVD, and compared pulmonary hemodynamic parameters including pulmonary arterial compliance (Cp) between two groups. Age at lung biopsy was 4 (2-7) months. There were 16 patients with trisomy 21. Cardiac diagnosis included ventricular septal defect in 16, atrial septal defect in 5, atrioventricular septal defect in 4, and others in 2. There were 11 patients with histopathologically proven PVD (Heath-Edwards classification grade ≥ 3 in 5; the index of PVD ≥ 1.1 in 3; extremely thickened media in 6; hypoplasia of the pulmonary arteries in 3). Cp in the patients with PVD was significantly lower than that in patients without PVD (0.99 [0.74-1.42] vs 1.56 [1.45-1.88], p = 0.0047), although there was no significant difference in the ratio of systemic to pulmonary blood flow, pulmonary arterial pressure, and resistance between two groups. A Cp cutoff value of < 1.22 ml/mmHg m2 as a predictor of PVD yielded a sensitivity and a specificity of 93% and 64%, respectively. Pulmonary arterial compliance can be a predictor of PVD among patients with CHD-PAH.

Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells.

It has recently been recognized that inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), upregulate the secretion of matrix metalloproteinase-9 (MMP-9) from cancer cells and thereby promote peritoneal dissemination. In this study, we found that TNF-α also stimulated peritoneal mesothelial cells to secrete MMP-9 as assessed by zymography. MMP-9 gene expression in mesothelial cells induced by TNF-α was confirmed by quantitative RT-PCR analysis. We then utilized the reconstituted artificial mesothelium, which was composed of a monolayer of mesothelial cells cultured on a Matrigel layer in a Boyden chamber system, to examine the effects of TNF-α on carcinoma cell invasion. The transmigration of MKN1 human gastric carcinoma cells through the reconstituted mesothelium was promoted by TNF-α in a dose-dependent manner. The increased MKN1 cell migration was partially inhibited by the anti-α3 integrin antibody, indicating that the invasion process involves an integrin-dependent mechanism. Finally, we observed that the invasion of MMP-9-knockdown MKN1 cells into Matrigel membranes was potentiated by the exogenous addition of purified proMMP-9. These results suggest that TNF-α-induced MMP-9 secretion from mesothelial cells plays an important role in the metastatic dissemination of gastric cancer.

Utility of contrast-enhanced ultrasonography with perflubutane in evaluating indications for diagnostic percutaneous tumor biopsy in a case of hepatic sclerosed hemangioma.

Sclerosed hemangioma is difficult to distinguish from intrahepatic cholangiocarcinoma or liver metastasis due to their imaging resemblance, thus pathological diagnosis is often required; however, percutaneous biopsy entails a risk of dissemination if the tumor is malignant. Perflubutane, a contrast agent of ultrasonography, has a characteristic feature of being phagocytosed by Kupffer cells. Hepatic malignant lesions contain few or no Kupffer cells, therefore, they are shown as a contrast defect. We report a case in which contrast enhanced ultrasonography (CEUS) with perflubutane was useful to evaluate indications for percutaneous tumor biopsy. A 69-year-old woman had a hypoattenuating mass with slight enhancement in peripheral lesion of the tumor in the arterial phase on dynamic computed tomography. From the arterial phase to the delayed phase, the hypoattenuating area was gradually and slightly enhanced, and peripheral enhancement also increased gradually, appearing as ring enhancement. We considered intrahepatic cholangiocarcinoma, liver metastasis, and sclerosed hemangioma as differential diagnoses. Most of the tumor did not display contrast defects in the post-vascular phase on CEUS, therefore, we considered the possibility of malignancy was low and performed percutaneous biopsy. The tumor was diagnosed as sclerosed hemangioma. CEUS may be useful in evaluating indications for diagnostic percutaneous tumor biopsy.

Sutureless pericardial marsupialization for the repair of congenital right pulmonary veins atresia.

We present a very rare case of isolated right pulmonary veins atresia in a 4-year-old girl. As the presence of a pulsatile blind pulmonary venous confluence adjacent to the left atrium was demonstrated by preoperative right pulmonary arterial wedge angiography, we applied sutureless pericardial marsupialization for the repair of right pulmonary veins atresia. She is currently 8 years old without pulmonary veins stenosis.