Effect of esaxerenone on ischaemia and reperfusion injury in rat hearts.

OBJECTIVES: In myocardial infarction, the addition of mineralocorticoid receptor blockers to standard therapies, such as angiotensin-converting enzyme inhibitors or beta-blockers, reportedly reduces mortality and cardiac events. We investigated whether the non-steroidal mineralocorticoid receptor blocker esaxerenone has cardioprotective effects and its protective mechanisms. METHODS: Isolated rat hearts were Langendorff-perfused (constant pressure, 80 mmHg) with oxygenated Krebs-Henseleit bicarbonate buffer and reperfused for 60 min; afterwards, recovery of function (left ventricular pressure, measured with an intraventricular balloon) and myocardial injury were measured. In a preliminary study, we determined the optimal concentration of esaxerenone required for myocardial protection. Next, esaxerenone was administered in the pre- and post-ischaemic phases to determine the optimal timing of administration. In addition, we assessed coronary flow response to acetylcholine with and without esaxerenone. We examined whether esaxerenone-induced cardioprotection was prevented by targeting putative components in the preconditioning manner (the mitochondrial ATP-sensitive potassium [KATP] channel). RESULTS: Myocardial protection by esaxerenone was observed when esaxerenone was administered before ischaemia but not after ischaemia. The coronary flow response to acetylcholine was significantly better in the esaxerenone group than in the control group. The cardioprotective effect of esaxerenone was eliminated by the mitochondrial KATP channel blocker, 5-hydroxy decanoate. CONCLUSIONS: This study confirmed the myocardial protective effect of the pre-ischaemic administration of esaxerenone. Esaxerenone may contribute to coronary endothelial protection and exert pharmacological preconditioning via the mitochondrial KATP channel.

Successful surgical experience for acute severe aortic valve regurgitation with acquired Gerbode defect: A case report.

INTRODUCTION AND IMPORTANCE: The incidence of acquired Gerbode defect has been increasing due to advances in cardiac imaging technology, and some closure methods have been introduced. PRESENTATION OF CASE: A 58-year-old man developed cardiogenic shock due to acute severe aortic valve regurgitation with an acquired Gerbode defect caused by infective endocarditis. Emergency surgery was performed. A large patch with a 0.4 mm extended-polytetrafluoroethylene (e-PTFE) sheet covered with autologous pericardium was used to close the Gerbode defect, and a bioprosthetic valve was used for aortic valve replacement. CLINICAL DISCUSSION: Large patch closure with 0.4 mm e-PTFE sheet and autologous pericardium for fragile Gerbode defect caused by infective endocarditis might be effective with regard to sturdiness, good fitting to the tissue, and excellent resistance to bacteria. CONCLUSION: We encountered a rare case of cardiogenic shock due to acute severe aortic valve regurgitation and acquired Gerbode defect caused by infective endocarditis. In our case, large-patch closure for perforation in a fragile membranous septum was effective.

Cardioprotective effect of St. Thomas' Hospital No. 2 solution against age-related changes in aquaporin-7-deficient mice.

OBJECTIVE: This study aimed to investigate whether St. Thomas' Hospital No. 2 solution (STH2) is equally effective in both young and aged aquaporin-7-knockout (AQP7-KO) mice and the mechanisms by which the intra-myocardial adenosine triphosphate (ATP) content is altered during ischemia without aquaporin-7. METHODS: In study 1, isolated hearts of male wild-type (WT) and AQP7-KO mice (< 12 weeks old) were Langendorff perfused with 5-min STH2 prior to a 20-min global ischemia (GI) or 25-min GI without STH2. Similarly, in Study 2, hearts from WT and AQP7-KO mice (≥ 24 weeks old) were subjected to 2-min STH2 infusion prior to GI. In study 3, intra-myocardial ATP content was compared before (sham) and after (control or STH2) ischemia in mature WT and AQP7-KO mice. RESULTS: In study 1, troponin T levels (ng/g wet weight) of WT and AQP7-KO hearts were significantly lower in the STH2 groups (75.6 ± 45.9 and 80.2 ± 52.2, respectively) than in the GI groups (934.0 ± 341.1 and 1089.3 ± 182.5, respectively). In Study 2, troponin T levels in aged WT and AQP7-KO mice were 566.5 ± 550.0 and 547.8 ± 594.3, respectively (p = 0.9561). In Study 3, ATP levels (µmol/g protein) in the sham, control, and STH2 AQP7-KO mice groups were 4.45, 2.57, and 3.37, respectively(p = 0.0005). CONCLUSIONS: The present study revealed the cardio-protective efficacy of STH2 in an experimental model of isolated AQP7-KO young and aged murine hearts. Further, STH2 preserved intra-myocardial ATP during ischemia with Krebs-Henseleit buffer perfusion in the Langendorff setting.

Impact of System-F in Delivering Vascular Plugs for Aortic Side Branch Embolization During Endovascular Aneurysm Repair.

PURPOSE: This study aimed to illustrate the utility of our original system to deliver vascular plugs into aortic side branches during endovascular aneurysm repair (EVAR). TECHNIQUE: Our device, which we named "System-F," consists of a 14 Fr sheath, a 12 Fr long sheath with a side hole, a stiff guidewire as a shaft, and a parallelly-inserted delivery catheter navigated through the side hole into the aneurysm sac. Vertical motion and horizontal rotation of the side hole allow multidimensional movement of the delivery catheter within the aneurysm. This system was applied in 7 cases undergoing EVAR; 4 inferior mesenteric arteries and 14 lumbar arteries were embolized using vascular plugs. Type II endoleak (T2EL) was not observed in the follow-up survey of any case. Conclusion: The applicability of System-F for vascular plug placement in the side branches of abdominal aortic aneurysms has the potential to achieve high delivery capability and be widely applied for the prevention of T2EL. CLINICAL IMPACT: System-F has potential to change the strategies of pre-EVAR embolization.

Comparison of Slow-Infusion Magnetic Resonance Angiography with Sequential K-Space Filling and Computed Tomography Angiography to Detect the Adamkiewicz Artery.

BACKGROUND: Radiographic detection of the Adamkiewicz artery (AKA) before aortic surgery helps to avoid spinal cord ischemia (SCI). We applied magnetic resonance angiography (MRA) using gadolinium enhancement (Gd-MRA) by means of the slow-infusion method with sequential k-space filling and compared AKA detectability with that of computed tomography angiography (CTA). METHODS: A total of 63 patients with thoracic or thoracoabdominal aortic disease (30 with aortic dissection [AD] and 33 with aortic aneurysm) who underwent both CTA and Gd-MRA to detect AKA were evaluated. The detectability of the AKA using Gd-MRA and CTA were compared among all patients and subgroups based on anatomical features. RESULTS: The detection rates of the AKAs using Gd-MRA and CTA were higher in all 63 patients (92.1% vs. 71.4%, P = 0.003). In AD cases, the detection rates using Gd-MRA and CTA were higher in all 30 patients (93.3% vs. 66.7%, P = 0.01) as well as in 7 patients whose AKA originated from false lumens (100% vs. 0%). In aneurysm cases, the detection rates using Gd-MRA and CTA were higher in 22 patients whose AKA originated from the nonaneurysmal parts (100% vs. 81.8%, P = 0.03). In clinical, SCI was observed in 1.8% of cases after open or endovascular repair. CONCLUSIONS: Despite the longer examination time and more complicated imaging techniques compared to those of CTA, the high spatial resolution of slow-infusion MRA may be preferable for detecting AKA before performing various thoracic and thoracoabdominal aortic surgeries.

Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry.

Human parechovirus (PeV-A) is an RNA virus that belongs to the family Picornaviridae and it is currently classified into 19 genotypes. PeV-As usually cause mild illness in children and adults. Among the genotypes, PeV-A3 can cause severe diseases in neonates and young infants, resulting in neurological sequelae and death. In this study, we identify the human myeloid-associated differentiation marker (MYADM) as an essential host factor for the entry of six PeV-As (PeV-A1 to PeV-A6), including PeV-A3. The infection of six PeV-As (PeV-A1 to PeV-A6) to human cells is abolished by knocking out the expression of MYADM. Hamster BHK-21 cells are resistant to PeV-A infection, but the expression of human MYADM in BHK-21 confers PeV-A infection and viral production. Furthermore, VP0 capsid protein of PeV-A3 interacts with one extracellular domain of human MYADM on the cell membrane of BHK-21. The identification of MYADM as an essential entry factor for PeV-As infection is expected to advance our understanding of the pathogenesis of PeV-As.

Effectiveness of the Gerdq Questionnaire for Diagnosing Gastroesophageal Reflux Disease After Esophagectomy for Esophageal Cancer.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common complication after esophagectomy with gastric tube reconstruction. The GerdQ questionnaire was developed for diagnosing GERD in primary care patients. Its effectiveness in patients after esophagectomy remains unknown. In this study, we evaluated the usefulness of the GerdQ questionnaire for diagnosing GERD after esophagectomy for esophageal cancer. MATERIALS AND METHODS: A total of 124 patients with esophageal cancer underwent right transthoracic esophagectomy with gastric tube reconstruction between January 2010 and December 2016. Esophagogastroduodenoscopy and 24-hour esophageal pH-metry were performed at 1 month, 1 year, and 2 years postoperatively. The GerdQ questionnaire was administered at the same postoperative time points. We assessed any correlation between the GerdQ scores and the endoscopy and pH-metry findings. RESULTS: The incidence rates of GERD at 1 month, 1 year and 2 years post-surgery were 31.6%, 46.9%, and 49.2%, respectively. The GerdQ questionnaire showed 77% sensitivity and 56% specificity for diagnosing GERD at 2 years after esophagectomy when the cutoff point was 7. However, the optimal cutoff points were different at each postoperative time, and the scores showed some imbalance between sensitivity and specificity. Regurgitation may be a useful indicator, as the frequency of regurgitation was significantly higher in patients with GERD than in patients without GERD at 1 year (P = 0.046) and 2 years postoperatively (P = 0.048). CONCLUSION: The GerdQ questionnaire is not a useful diagnostic tool for GERD in patients who have undergone esophagectomy for esophageal cancer.

Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice.

Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10-10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.

[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.

USP10 Inhibits Aberrant Cytoplasmic Aggregation of TDP-43 by Promoting Stress Granule Clearance.

TAR DNA-binding protein 43 (TDP-43) is a causative factor of amyotrophic lateral sclerosis (ALS). Cytoplasmic TDP-43 aggregates in neurons are a hallmark pathology of ALS. Under various stress conditions, TDP-43 localizes sequentially to two cytoplasmic protein aggregates, namely, stress granules (SGs) first and then aggresomes. Accumulating evidence suggests that delayed clearance of TDP-43-positive SGs is associated with pathological TDP-43 aggregates in ALS. We found that ubiquitin-specific protease 10 (USP10) promotes the clearance of TDP-43-positive SGs in cells treated with proteasome inhibitor, thereby promoting the formation of TDP-43-positive aggresomes, and the depletion of USP10 increases the amount of insoluble TDP-35, a cleaved product of TDP-43, in the cytoplasm. TDP-35 interacted with USP10 in an RNA-binding-dependent manner; however, impaired RNA binding of TDP-35 reduced the localization in SGs and aggresomes and induced USP10-negative TDP-35 aggregates. Immunohistochemistry showed that most of the cytoplasmic TDP-43/TDP-35 aggregates in the neurons of ALS patients were USP10 negative. Our findings suggest that USP10 inhibits aberrant aggregation of TDP-43/TDP-35 in the cytoplasm of neuronal cells by promoting the clearance of TDP-43/TDP-35-positive SGs and facilitating the formation of TDP-43/TDP-35-positive aggresomes.

USP10 inhibits the dopamine-induced reactive oxygen species-dependent apoptosis of neuronal cells by stimulating the antioxidant Nrf2 activity.

Nrf2 is an antioxidant transcriptional activator in many types of cells, and its dysfunction plays key roles in a variety of human disorders, including Parkinson's disease (PD). PD is characterized by the selective loss of dopaminergic neurons in PD-affected brain regions. Dopamine treatment of neuronal cells stimulates the production of reactive oxygen species (ROS) and increases ROS-dependent neuronal apoptosis. In this study, we found that the ubiquitin-specific protease 10 (USP10) protein reduces dopamine-induced ROS production of neuronal cells and ROS-dependent apoptosis by stimulating the antioxidant activity of Nrf2. USP10 interacted with the Nrf2 activator p62, increased the phosphorylation of p62, increased the interaction of p62 with the Nrf2 inhibitor Keap1, and stimulated Nrf2 antioxidant transcriptional activity. In addition, USP10 augmented dopamine-induced Nrf2 translation. Taken together, these results indicate that USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells and suggest that USP10 activators are promising therapeutic agents for oxidative stress-related diseases, including PD.

Intraoperative Cone Beam CT in Hybrid Operation Room for Pediatric Scoliosis Patients: Comparison of Pedicle Screw Violation Rate at Normal and Low Radiation Doses.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: This study aimed to determine the effect of reducing the radiation dose of intraoperative cone beam computed tomography (CBCT) during posterior spinal fusion (PSF) for pediatric scoliosis on the rate of pedicle screw (PS) violation. SUMMARY OF BACKGROUND DATA: Intraoperative CBCT for pediatric scoliosis improves the accuracy of PS insertion in PSF. However, few reports have addressed the PS perforation rate from reduced radiation doses in hybrid navigation. METHODS: We evaluated 855 PSs inserted into 58 pediatric scoliosis patients (11 male and 47 female, mean age: 16.6 yr) who underwent PSF using CBCT. A radiation dose of 1/3 or 1/5 of the normal dose (ND) was defined as a low dose (LD). After PS insertion, intraoperative CBCT images were reviewed to assess the degree of PS perforation. G2-3 (i.e., perforations of 4 mm or more) was defined as a violation. The PS violation rate was compared between the groups, and factors associated with violations were examined. RESULTS: A total of 567 and 288 screws were inserted in the ND group and LD group, respectively. The PS violation rate was comparable at 1.8% in the ND group and 1.7% in the LD group. Multiple logistic regression analysis showed that distance from the upper instrumented vertebra (UIV) was an independently associated factor of PS violation (+1 vertebra, operation room 0.73, P   =  0.038). In addition, the mean height of patients with PS violations (148.8 ±â€Š3.6 cm) was significantly shorter than that of patients without violations (157.9 ±â€Š1.2 cm) ( P  = 0.034). CONCLUSION: There was no increase in PS violation rate with lower doses of radiation for intraoperative navigation CBCT. Extra care is warranted for vertebrae close to the UIV and patients of shorter stature.Level of Evidence: 3.

The optineurin/TIA1 pathway inhibits aberrant stress granule formation and reduces ubiquitinated TDP-43.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease characterized by the formation of cytoplasmic ubiquitinated TDP-43 protein aggregates in motor neurons. Stress granules (SGs) are stress-induced cytoplasmic protein aggregates containing various neuropathogenic proteins, including TDP-43. Several studies have suggested that SGs are the initial site of the formation of pathogenic ubiquitinated TDP-43 aggregates in ALS neurons. Mutations in the optineurin (OPTN) and TIA1 genes are causative factors of familial ALS with TDP-43 aggregation pathology. We found that both OPTN depletion and ALS-associated OPTN mutations upregulated the TIA1 level in cells recovered from heat shock, and this upregulated TIA1 increased the amount of ubiquitinated TDP-43. Ubiquitinated TDP-43 induced by OPTN depletion was localized in SGs. Our study suggests that ALS-associated loss-of-function mutants of OPTN increase the amount of ubiquitinated TDP-43 in neurons by increasing the expression of TIA1, thereby promoting the aggregation of ubiquitinated TDP-43.

A Case of Human Immunodeficiency Virus-Positive Patient Diagnosed during the Treatment of Right Internal Iliac Pseudoaneurysm.

Isolated internal iliac artery aneurysms are rare, and there are no reports of human immunodeficiency virus (HIV)-related vasculitis in Japan. We report our experience with a 51-year-old man diagnosed with acquired immunodeficiency syndrome, discovered during the postoperative course when the patient exhibited remittent fever and susceptibility to infection after emergency interventional radiology therapy for a right isolated internal iliac artery aneurysm. The patient had positive treponema pallidum particle agglutination test result before admission, and tests for sexually transmitted disease showed positive results for HIV H-1 antibodies. The repeated fevers were attributed to HIV infection-related susceptibility.

Impact of chest subcutaneous fat on the occurrence of central venous port-related infectious complications in cancer patients.

PURPOSE: There is no concrete evidence to support the association between the amount of subcutaneous fat area (SFA) in the central venous port-insertion site (precordium) and port-related complications. We aimed to investigate the relationship between SFA in the midclavicular line and postoperative infectious complications in patients undergoing port-insertion surgery. METHODS: This was a single-institute and historical cohort study of 174 patients who underwent first central venous port implantation surgery for chemotherapy between January 2014 and December 2018. SFA in the midclavicular line was measured using preoperative computed tomography scans. The patients were divided into three groups according to SFA amount tertiles, and we investigated the association of SFA with infectious and all-cause complication events within 1 year. RESULTS: Within a median follow-up of 306 days, the patients with intermediate SFA had significantly higher infection-free survival than those with low and high SFA (low vs. intermediate vs. high: 80.4% vs. 97.7% vs. 83.4%, respectively, p=0.034). In contrast, there was no significant difference in the overall complication-free survival among the groups (low vs. intermediate vs. high: 80.4% vs. 88.9% vs. 81.8%, respectively, p=0.29). Low SFA was independently associated with high risk of infectious complications (hazard ratio, 9.45; 95% confidence interval, 1.07-83.22, p=0.043). CONCLUSION: Low SFA in the midclavicular line was an independent risk factor for infectious complications in the chemotherapy setting. This practical indicator can be useful for optimizing patients' nutritional status and when considering other types of vascular access to support administration of intravenous chemotherapy.

Total endovascular repair for a persistent sciatic artery aneurysm with widespread limb-threatening arterial occlusion.

In the present report, we have described the case of a 79-year-old woman who presented with acute right lower limb ischemia and was diagnosed with bilateral persistent sciatic arteries and a right persistent sciatic artery aneurysm. Concomitant widespread thrombotic occlusion was present, extending from the orifice of the right internal and external iliac arteries to the below-the-knee popliteal artery. These complicated lesions were successfully treated using only percutaneous endovascular procedures, including stent-graft placement, bare metal stent implantation, and thrombolysis. Our report illustrates how a combination of techniques can achieve total endovascular repair of a persistent sciatic artery aneurysm accompanied by occlusion of the internal and external iliac arteries.

Preoperative Magnetic Resonance Cholangiopancreatography for Detecting Difficult Laparoscopic Cholecystectomy in Acute Cholecystitis.

Previous studies have shown that signal intensity variations in the gallbladder wall on magnetic resonance imaging (MRI) are associated with necrosis and fibrosis in the gallbladder of acute cholecystitis (AC). However, the association between MRI findings and operative outcomes remains unclear. We retrospectively identified 321 patients who underwent preoperative magnetic resonance cholangiopancreatography (MRCP) and early laparoscopic cholecystectomy (LC) for AC. Based on the gallbladder wall signal intensity on MRI, these patients were divided into high signal intensity (HSI), intermediate signal intensity (ISI), and low signal intensity (LSI) groups. Comparisons of bailout procedure rates (open conversion and laparoscopic subtotal cholecystectomy) and operating times were performed. The recorded bailout procedure rates were 6.8% (7/103 cases), 26.7% (31/116 cases), and 40.2% (41/102 cases), and the median operating times were 95, 110, and 138 minutes in the HSI, ISI, and LSI groups, respectively (both p < 0.001). During the multivariate analysis, the LSI of the gallbladder wall was an independent predictor of both the bailout procedure (odds ratio [OR] 5.30; 95% CI 2.11-13.30; p < 0.001) and prolonged surgery (≥144 min) (OR 6.10, 95% CI 2.74-13.60, p < 0.001). Preoperative MRCP/MRI assessment could be a novel method for predicting surgical difficulty during LC for AC.