Long-term results following off-pump coronary-artery bypass grafting in left ventricular dysfunction.

Severe left ventricular (LV) dysfunction is an independent risk factor for early and long-term mortality after coronary-artery bypass grafting (CABG). Off-pump CABG (OPCAB) significantly reduces the early incidence of major complications in high-risk patients. Moreover, bilateral internal thoracic artery (BITA) grafting after CABG is associated with improved long-term outcomes. We aimed to evaluate the impact of multivessel OPCAB with BITA grafting for complete revascularization on postoperative and long-term outcomes in patients with low LV ejection fraction (EF). We included 121 patients with EF ≤ 30.0% who underwent isolated multivessel OPCAB (average LVEF, 24.8%) between April 2007 and December 2019. Sixty-six patients received BITA grafts, while 55 had single internal thoracic artery (SITA) grafts. We conducted multivariate analyses to examine the correlation between perioperative data and late mortality rate. The early mortality rate was 1.65%. After excluding in-hospital mortality cases, we performed long-term follow-up of 119 patients. Early postoperative echocardiography showed significant LVEF improvement in 89 (75.2%) patients. However, LVEF remained ≤ 30.0% in 30 (24.8%) patients. We recorded 15 and 30 cases of cardiac death and cardiac events, respectively, during the long-term follow-up period. Postoperative LVEF ≤ 30.0% (P < 0.01) and no use of BITA grafting (P = 0.03) were significant predictors of cardiac death and events; moreover, hemodialysis was a significant predictor of all-cause mortality rather than cardiac death. Multivessel OPCAB in patients with severe LV dysfunction was associated with acceptable in-hospital mortality and early postoperative improvement in LV function. Additionally, OPCAB with BITA grafting may provide long-term benefits with respect to cardiac death and events. However, the long-term benefits were significantly limited in patients without early postoperative improvement in LV function and patients with chronic hemodialysis.Clinical registration number: 5590 (14/5/2020 Tokyo Women's Medical University).

Propensity score-matched comparison of total arterial off- and on-pump coronary artery bypass with complete revascularization.

Little is known regarding the long-term (> 10 years) outcomes and risk factors of total arterial coronary artery bypass grafting (CABG). This study evaluated the long-term outcomes and risk factors for all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) following total arterial on-pump CABG (ONCAB) or off-pump CABG (OPCAB) with complete revascularization. This retrospective cohort analysis enrolled patients with stable angina who underwent total arterial CABG with complete revascularization in our institute between July 2000 and June 2019. The endpoints were all-cause mortality and MACCE incidence, including a comparison between OPCAB and ONCAB. Long-term (10-year) outcomes were analyzed using propensity score-matched pairs, and risk factors were evaluated using univariate and multivariate analyses. Overall, 401 patients who underwent primary total arterial CABG were classified into the OPCAB (n = 269) and ONCAB (n = 132) groups. Using propensity score matching (PSM), 88 patients who underwent OPCAB were matched with 88 patients who underwent ONCAB. The mean follow-up period was 7.9 ± 6.3 years. No significant difference in all-cause mortality (hazard ratio, 1.04; 95% confidence interval, 0.53-2.04; p = 0.9138) and MACCE incidence (hazard ratio, 1.06; 95% confidence interval, 0.68-1.65; p = 0.7901) was observed between the two groups. Renal failure requiring dialysis was a significant risk factor for mortality (p < 0.0001) and MACCEs (p = 0.0003). Long-term outcomes of total arterial OPCAB and ONCAB with complete revascularization showed similar findings using PSM. Renal failure requiring dialysis was a significant risk factor for mortality and morbidity.Journal standard instruction requires an unstructured abstract; hence the headings provided in abstract were deleted. Kindly check and confirm.Thank you for your kindness.Clinical registration number 5598, Tokyo Women's Medical University Hospital.

Arteriolar hyalinization at 0-hour biopsy predicts long-term graft function in deceased kidney transplantation.

OBJECTIVES: Regarding the relationship between donor kidney quality and renal graft function after deceased kidney transplantation (KTx) following donation after cardiac death (DCD), the evaluation timing varies depending on the study. Evaluation of histology and changes in long-term renal graft function is limited. METHODS: A retrospective single-center study included 71 recipients who underwent 0-hour biopsy for KTx from DCD. The recipients were divided into two groups to evaluate factors related to renal graft function (study1). The two groups were categorized as stable graft function and poor graft function with the change of estimated glomerular filtration rate (eGFR) after KTx. The recipients were then divided into four groups to assess whether the factors identified in study1 were related to the change in long-term renal graft function (study2). They were categorized as follows: Improved, Stable, Deteriorated, and Primary non-function with the change of eGFR after KTx. RESULTS: In study1, donor age ≥ 50 years (29.5% vs. 65.2%; p = 0.09), banff arteriolar hyalinosis (ah) score (0.66 ± 0.78 vs. 1.2 ± 1.0; p = 0.018), and presence of glomerulosclerosis (43.2% vs. 76.2%; p = 0.017) were significant risk factors for poor long-term graft function. When the recipients were divided into four groups, the severity of ah correlated well with changes in long-term renal function. CONCLUSIONS: We can predict the shift in long-term renal graft function after KTx from DCD according to the severity of ah by 0-hour biopsy.

Pharmacological study on the enhancing effects of U46619 on guinea pig urinary bladder smooth muscle contraction induced by acetylcholine and α,ß-methylene ATP and the possible involvement of protein kinase C.

We examined whether U46619 (a prostanoid TP receptor agonist) could enhance the contractions of guinea pig urinary bladder smooth muscle (UBSM) in response to acetylcholine (ACh) and an ATP analog (α,ß-methylene ATP (αß-MeATP)) through stimulation of the UBSM TP receptor and whether protein kinase C (PKC) is involved. U46619 (10-7 M) markedly enhanced UBSM contractions induced by electrical field stimulation and ACh/αß-MeATP (3 × 10-6 M each), the potentiation of which was completely suppressed by SQ 29,548 (a TP receptor antagonist, 6 × 10-7 M). PKC inhibitors did not attenuate the ACh-induced contractions enhanced by U46619 although they partly suppressed the U46619-enhanced, αß-MeATP-induced contractions. While phorbol 12-myristate 13-acetate (PMA, a PKC activator, 10-6 M) did not enhance ACh-induced contractions, it enhanced αß-MeATP-induced contractions, an effect that was completely suppressed by PKC inhibitors. αß-MeATP-induced contractions, both with and without U46619 enhancement, were strongly inhibited by diltiazem. U46619/PMA enhanced 50 mM KCl-induced contractions, the potentiation of which was partly/completely attenuated by PKC inhibitors. These findings suggest that U46619 potentiates parasympathetic nerve-associated UBSM contractions by stimulating UBSM TP receptors. PKC-increased Ca2+ influx through voltage-dependent Ca2+ channels may partially play a role in purinergic receptor-mediated UBSM contractions enhanced by TP receptor stimulation.

[Semi-acute Surgery for Ventricular Septal Perforation After Unsuccessful Intra-aortic Balloon Pumping Support:Report of a Case].

Ventricular septal perforation( VSP) after acute myocardial infarction( MI) is a serious condition that requires surgical treatment. However, good outcome is not always obtained. The mortality rate of VSP is particularly high in cases whom emergency surgery is performed early in the course of the disease, and the timing of surgery is known to affect prognosis. In this case report, the patient assisted with intra-aortic balloon pump. VSP closure surgery (a modified David-Komeda technique) underwent 8 days after MI onset. Except for mild residual shunt, the patient experienced no adverse event during postoperative course and was discharged 30 days after the surgery. This case illustrated timing of surgery as well as adequate mechanical cardiopulmonary assistance and surgical technique is important.

[Branched Thoracic Endovascular Aortic Repair for Aortic Arch Aneurysm Following Severe Combined Valvular Disease:Report of a Case].

A 79-years-old frail man with severe combined valvular disease was referred to our hospital. Furthermore, chest computed tomography( CT) showed a saccular aneurysm in the aortic arch. We chose two staged repairs for risk reduction. As a first stage double valve replacement and tricuspid annuloplasty were performed. Three months later, we performed successful branched thoracic endovascular aortic repair( TEVAR) used physician modified Najuta which had hydrogel-reinforced fenestrations to provide a more secure connection with the bridging graft than fenestrations alone. Staged surgery with branched TEVAR used physician modified Najuta is a useful strategy in patients who have complex cardiac disease combined with aortic arch aneurysm.

The mouse homolog of the mutant WASp responsible for human X-linked neutropenia renders granulopoiesis ineffective.

Severe congenital neutropenia (SCN) is characterized by severe neutropenia and recurrent critical infections. X-linked neutropenia (XLN) is caused by a gain-of-function mutation in the Wiskott-Aldrich syndrome gene (WAS), the product of which (WASp) is expressed only in blood cells, especially during neutrophil maturation. To investigate the mechanism of neutropenia, we established a novel knock-in mouse line expressing WASp-I292T. WASp-I292T neutrophils exhibited activated (dysregulated) actin polymerization. Although WASp-I292T mice did not recapitulate neutropenia, neutrophil levels were increased in the bone marrow, and extramedullary hematopoiesis was observed. Bone marrow neutrophils from WASp-I292T mice exhibited attenuated transmigration. These abnormalities were associated with downregulation of NFκB and TP53 and faulty activation of their downstream pathways.

A 3D printed hydrostatic skeleton for an earthworm-inspired soft burrowing robot.

Moving through soil is challenging for robots, particularly for soft robots. Herein, we propose a support structure, based on the hydrostatic skeleton of earthworms, to overcome this problem. To create extremely flexible, thin-walled, worm-sized deformed segments, a specialized 3D printer for low-hardness rubber was utilized. To obtain large radial deformation, we investigated the properties of the soft materials for 3D printing and the geometry of the segments. Notably, segments are deformed with multiply-wound shape memory alloy wires. We constructed an earthworm robot by connecting shape memory alloy-driven segments in series and experimentally demonstrated that this robot could propel in the soil. The proposed robot is unique in that it has a small diameter of 10 mm and exhibits a peristaltic motion in soil.

Examining the Use of an Artificial Intelligence Model to Diagnose Influenza: Development and Validation Study.

BACKGROUND: The global burden of influenza is substantial. It is a major disease that causes annual epidemics and occasionally, pandemics. Given that influenza primarily infects the upper respiratory system, it may be possible to diagnose influenza infection by applying deep learning to pharyngeal images. OBJECTIVE: We aimed to develop a deep learning model to diagnose influenza infection using pharyngeal images and clinical information. METHODS: We recruited patients who visited clinics and hospitals because of influenza-like symptoms. In the training stage, we developed a diagnostic prediction artificial intelligence (AI) model based on deep learning to predict polymerase chain reaction (PCR)-confirmed influenza from pharyngeal images and clinical information. In the validation stage, we assessed the diagnostic performance of the AI model. In additional analysis, we compared the diagnostic performance of the AI model with that of 3 physicians and interpreted the AI model using importance heat maps. RESULTS: We enrolled a total of 7831 patients at 64 hospitals between November 1, 2019, and January 21, 2020, in the training stage and 659 patients (including 196 patients with PCR-confirmed influenza) at 11 hospitals between January 25, 2020, and March 13, 2020, in the validation stage. The area under the receiver operating characteristic curve for the AI model was 0.90 (95% CI 0.87-0.93), and its sensitivity and specificity were 76% (70%-82%) and 88% (85%-91%), respectively, outperforming 3 physicians. In the importance heat maps, the AI model often focused on follicles on the posterior pharyngeal wall. CONCLUSIONS: We developed the first AI model that can accurately diagnose influenza from pharyngeal images, which has the potential to help physicians to make a timely diagnosis.

Trans-cuff leakage in bio-Bentall operation.

We have reported a case of trans-cuff leakage that occurred in a composite graft of bio-Bentall operation. The leakage resolved several months after surgery, similar to the trans-cuff leakage seen in simple aortic valve replacement. We have proposed hypotheses on the mechanism of trans-cuff leakage during a bio-Bentall operation and suggested ways to prevent it from occurring.

Koopman and Perron-Frobenius operators on reproducing kernel Banach spaces.

Koopman and Perron-Frobenius operators for dynamical systems are becoming popular in a number of fields in science recently. Properties of the Koopman operator essentially depend on the choice of function spaces where it acts. Particularly, the case of reproducing kernel Hilbert spaces (RKHSs) is drawing increasing attention in data science. In this paper, we give a general framework for Koopman and Perron-Frobenius operators on reproducing kernel Banach spaces (RKBSs). More precisely, we extend basic known properties of these operators from RKHSs to RKBSs and state new results, including symmetry and sparsity concepts, on these operators on RKBS for discrete and continuous time systems.

[Aortic Regurgitation and Stanford Type A Aortic Dissection with Antiphospholipid Antibody Syndrome:Report of a Case].

Antiphospholipid antibody syndrome (APS) is associated with high morbidity and mortality resulting from hemorrhagic or thromboembolic events and compromised host immunity due to steroid use. We reported a successful surgery for aortic valve regurgitation (AR) and dissecting aortic aneurysm (DAA) in the ascending aorta in a patient with APS. A 75-year-old woman with AR and primary APS was transferred to our institute because of fever and dyspnea. She was given a diagnosis of pneumonia and congestive heart failure (CHF). Enhanced computed tomography (CT) incidentally revealed chronic DAA. After medical treatment for CHF and pneumonia, elective surgery to replace the aortic valve and ascending aorta was performed. We paid special caution to intraoperative hemostasis and perioperative anticoagulation management. No adverse event was observed in this patient's postoperative clinical course, and she was discharged home.

[Giant Right Coronary Artery Pseudoaneurysm:Report of a Case].

Giant coronary artery aneurysm is very rare and there is no clear consensus regarding its treatment. Herein, we report a case of this unusual entity. The patient was a 75-year-old man in whom follow-up coronary angiography showed leakage of contrast agent from one of the #4 posterior descending( #4PD) branch of the right coronary artery. Enhanced computed tomography (eCT) revealed a giant pseudoaneurysm with a maximum diameter of 55 mm. Percutaneous balloon angioplasty had been performed in the same vessel for angina pectoris 20 years earlier. We excluded the pseudoaneurysm from arterial perfusion by closing both the wall defect and the culprit branch under cardiopulmonary bypass. There was no need for revascularization because there was another #4PD branch nearby. No adverse events were observed after surgery. Postoperative eCT scans confirmed that the aneurysm was completely thrombosed with no leakage.

Onion (Allium cepa L.)-Derived Nanoparticles Inhibited LPS-Induced Nitrate Production, However, Their Intracellular Incorporation by Endocytosis Was Not Involved in This Effect on RAW264 Cells.

The aim of this study was to evaluate the involvement of nanoparticles prepared from Allium cepa L. as anti-inflammatory agents. In the present study, we identified nanoparticles from Allium cepa L. using the ultracentrifugation exosome purification method. The nanoparticles were referred to as 17,000× g and 200,000× g precipitates, and they contained quercetins, proteins, lipids, and small-sized RNA. The nanoparticles inhibited nitric oxide production from lipopolysaccharide (LPS)-stimulated RAW264 cells without cytotoxic properties. Cellular incorporation was confirmed by laser microscopic observation after PKH26 staining. The inhibition of caveolae-dependent endocytosis and macropinocytosis significantly prevented the incorporation of the nanoparticles but had no effect on the inhibition of nitric oxide in RAW264 cells. Collectively, the identified nanoparticles were capable of inhibiting the LPS response via extracellular mechanisms. Taken together, the way of consuming Allium cepa L. without collapsing the nanoparticles is expected to provide an efficient anti-inflammatory effect.

Decreased Excretion of Urinary Exosomal Aquaporin-2 in a Puromycin Aminonucleoside-Induced Nephrotic Syndrome Model.

Urinary exosomes, small extracellular vesicles present in urine, are secreted from all types of renal epithelial cells. Aquaporin-2 (AQP2), a vasopressin-regulated water channel protein, is known to be selectively excreted into the urine through exosomes (UE-AQP2), and its renal expression is decreased in nephrotic syndrome. However, it is still unclear whether excretion of UE-AQP2 is altered in nephrotic syndrome. In this study, we examined the excretion of UE-AQP2 in an experimental rat model of nephrotic syndrome induced by the administration of puromycin aminonucleoside (PAN). Rats were assigned to two groups: a control group administered saline and a PAN group given a single intraperitoneal injection of PAN (125 mg/kg) at day 0. The experiment was continued for 8 days, and samples of urine, blood, and tissue were collected on days 2, 5, and 8. The blood and urine parameters revealed that PAN induced nephrotic syndrome on days 5 and 8, and decreases in the excretion of UE-AQP2 were detected on days 2 through 8 in the PAN group. Immunohistochemistry showed that the renal expression of AQP2 was decreased on days 5 and 8. The release of exosomal marker proteins into the urine through UEs was decreased on day 5 and increased on day 8. These data suggest that UE-AQP2 is decreased in PAN-induced nephrotic syndrome and that this reflects its renal expression in the marked proteinuria phase after PAN treatment.

Urinary extracellular vesicular release of aquaporins in patients with renal transplantation.

BACKGROUND: Diuresis has been observed within a week following renal transplantation, suggesting that the procedure causes acute disturbance of renal water homeostasis. Aquaporin (AQP) 1 and AQP2, important proteins for renal water reabsorption, have been identified in urinary extracellular vesicles (uEV-AQP1 and -AQP2), and experimental studies have shown that the presence of uEV-AQP1 and -AQP2 may be an indicator of their levels of expression in the kidney. However, the release patterns of uEV-AQP1 and -AQP2 during the acute phase following renal transplantation are largely unknown. METHODS: In this study, we examined the release of uEV-AQP1 and -AQP2 in recipients until 6 days (day 6) after renal transplantation. At Miyazaki prefectural Miyazaki Hospital, Japan, uEVs were obtained from 7 recipients, all of whom had received renal allografts from living donors. uEVs were isolated by differential centrifugation. RESULTS: Immunoblotting analysis showed that the release of uEV-AQP2 was significantly decreased on day 1 in comparison with a control sample (from 3 healthy volunteers), accompanied by high urine output and low urine osmolality. Thereafter, the level increased gradually to the control level by day 6. The release pattern of uEV-AQP1 was similar to that of uEV-AQP2, but the levels did not reach statistical significance in comparison with the control level at any of the time points examined. Evaluation of the relationship between urinary osmolality and uEV-AQPs revealed a significant correlation for uEV-AQP2, but not for uEV-AQP1. CONCLUSION: These results indicate that acute diuresis after renal transplantation might be due to a decrease in the renal expression of AQP2, whose level can be estimated from the amount released in uEVs.

Analysis of the prevalence of systemic de novo thrombotic microangiopathy after ABO-incompatible kidney transplantation and the associated risk factors.

OBJECTIVES: To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation and risk factors associated with this condition. METHODS: A total of 201 patients who received living-donor kidney transplantation (114 patients with ABO-identical kidney transplantation and 87 patients with ABO-incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti-A and anti-B antibodies were purified from human plasma, and these antibodies' bindings to human kidney were investigated in vitro. RESULTS: ABO-incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8-8.9, P < 0.001) after transplantation. Multivariate logistic regression analysis showed that non-use of mycophenolate mofetil, pretreatment immunoglobulin G antibody titer ≥64-fold and pretransplant immunoglobulin M antibody titer ≥16-fold were significant risk factors for systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation. Microvascular inflammation of 1-h post-transplant biopsy could be observed more frequently in thrombotic microangiopathy patients than in non-thrombotic microangiopathy patients. Anti-A and anti-B antibodies purified from human plasma showed a strong in vitro reaction against human kidney when the antibody titer was ≥16-fold. CONCLUSIONS: Antibody titer should be decreased to ≤16-fold until the day of ABO-incompatible kidney transplantation by desensitization therapy including mycophenolate mofetil. The 1-h biopsy results might help to diagnose systemic de novo thrombotic microangiopathy.

Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats.

Acute kidney injury (AKI) is an important risk factor for the development of chronic kidney disease (CKD), and an alteration in renal water handling has been observed during the transition of AKI to CKD. Urinary exosomal release of aquaporin-1 (AQP1) and AQP2, important proteins for renal water handling, has recently been reported to predict their levels of renal expression. Therefore, we examined the patterns of urinary exosomal release of AQP1 and AQP2, and the exosomal marker proteins tumor susceptibility 101 protein (TSG101) and ALG-2 interacting protein X (Alix), in the acute and chronic phases following induction of AKI by renal bilateral ischemia/reperfusion (I/R) in rats. Blood tests and histological examinations indicated that AKI occurred before at 7 days after renal I/R ( day 7) and that renal fibrosis developed progressively thereafter. Immunoblotting demonstrated significant decreases in the urinary exosomal release of AQP1 and AQP2 during severe AKI. Urinary exosomal release of Alix and TSG101 was significantly increased on day 7. These data were also confirmed in rats with unilateral renal I/R causing more serious AKI. Urinary exosomal release of either the Ser-256- or Ser-269-phosphorylated form of AQP2, both of which are involved in apical trafficking of AQP2, was positively correlated with that of total AQP2. These results suggest that urinary exosomal release of AQP1 and AQP2 is reduced in I/R-induced AKI, whereas that of Alix and TSG101 is increased in the initial phase of renal fibrosis. Furthermore, apical trafficking of AQP2 appears to be related to urinary exosomal release of AQP2.

[Floating Thrombus in Descending Aorta;Report of a Case].

We report a very rare case of floating thrombus in the thoracic descending aorta (TDA). A 54-yearold man complaining of severe lower abdominal pain was admitted to our facility. Enhanced computed tomography demonstrated a filling defect in the TDA, embolism of the superior mesenteric artery (SMA), and bilateral renal infarction. Transesophageal echocardiography revealed that the mass in the TDA was pedunculated, floating, and multiple with maximal diameter of 30 mm. To avoid bowel necrosis, we proceeded with emergent thrombectomy of the SMA. The TDA, including the mass, was removed en bloc for diagnostic confirmation and replaced with prosthesis under cardiopulmonary bypass for prevention of recurrent embolism. The postoperative course was uneventful. On histological examination, the mass proved to be a blood clot on the atherosclerotic wall. No recurrent thrombosis was observed during the 1-year follow-up period.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis during pregnancy.

An 11-week pregnant, 32-year-old Japanese woman who had recovered from infectious mononucleosis visited our center due to fever, anorexia, and bilateral hypochondrial pain. Blood tests revealed leukopenia, thrombocytopenia and elevated ferritin. She was diagnosed with hemophagocytic lymphohistiocytosis (HLH). A high viral load of the Epstein-Barr virus (EBV) was recognized, indicating EBV-HLH. She was treated with a single dose of dexamethasone to protect the fetus. However, the disease was uncontrollable, necessitating etoposide and cyclosporine administration. Remission was obtained with these medications, and she has remained in remission for the 10 months since completion of chemotherapy. Although the occurrence of EBV-HLH during pregnancy is rare, it is possible that a change in cellular immunity associated with the pregnancy may contribute to EBV-HLH development.