Phospholipid analysis of two influenza A virus-infected cell lines differing in their viral replication kinetics.

Fluctuations in phospholipid composition in infected cells during influenza A virus replication were analyzed using two different susceptible host cell lines: H292 cells, exhibiting a rapid cytopathic effect, and A549 cells, exhibiting a retarded cytopathic effect. Microarray analysis demonstrated that A549 cells recognized influenza A virus invasion, expression of pathogen recognition genes was affected, and antiviral genes were activated. On the other hand, H292 cells did not display such an antiviral state, and in these cells, rapid virus amplification and a rapid cytopathic effect were observed. Levels of ceramide, diacylglycerol, and lysolipids were higher in virus-infected cells than in the corresponding mock-infected cells at the later stages of infection. The accumulation of these lipids in IAV-infected cells occurred together with viral replication. The relationship between the characteristic features of ceramide, diacylglycerol, and lysolipid in the plasma membrane, where enveloped viruses are released, and their role in viral envelope formation are discussed. Our results indicate that viral replication disturbs cellular lipid metabolism, with consequences for viral replication kinetics.

Prolonged Sedentary Bouts Are Critically Involved in All-Cause Mortality in Patients on Chronic Hemodialysis: A Prospective Cohort Study.

We investigated the link between prolonged sedentary bouts and all-cause mortality in patients on chronic hemodialysis, using a prospective cohort. A total of 104 outpatients on chronic hemodialysis from 2013 to 2019, aged 71.4±11.4 years, were enrolled. Prolonged sedentary bouts (≥ 30 min and ≥60 min) (min and bouts) and relative prolonged sedentary bouts (≥ 30 min and ≥ 60 min) (%) on the patients' non-hemodialysis days were measured by a tri-accelerometer, and we also analyzed the patients' clinical parameters. The relationship between prolonged sedentary bouts and all-cause mortality was evaluated by a survival analysis and the Cox proportional hazard model. Thirty-five patients died during the follow-up period. A Kaplan-Meier analysis detected significant differences in the survival rate between two groups stratified by the median for all prolonged sedentary-bout parameters. After the adjustment for confounding factors, all of the prolonged sedentary-bout parameters were determinant factors for all-cause mortality. These results indicate that prolonged sedentary bouts on non-hemodialysis days were closely related to all-cause mortality in the patients on hemodialysis.

Relation between Prolonged Sedentary Bouts and Health-Related Quality of Life in Patients on Chronic Hemodialysis.

This study aimed to investigate the link between prolonged sedentary bouts and health-related quality of life (QOL) in patients on chronic hemodialysis (CHD). A total of 84 outpatients on CHD, aged 71.6±11.8 years, were enrolled in this cross-sectional study. Parameters for prolonged sedentary bouts [i.e., ≧ 30 min (% and bout) and ≧ 60 min (% and bout)] were measured using a triaxial accelerometer. Health-related QOL (HRQOL) was evaluated by the Euro-QOL (EQ-5D). Clinical parameters were obtained from medical records. Relatively prolonged sedentary bouts (%) were 44.0±18.2 (≧ 30 min) and 29.8±16.5 (≧ 60 min) for total days. Prolonged sedentary bouts (bouts) were 6.2±2.7 (≧ 30 min) and 2.7±1.6 (≧ 60 min) for total days. EQ-5D scores were 0.728±0.220. All prolonged sedentary bout parameters were negatively correlated with EQ-5D scores, except for prolonged sedentary bouts (≧ 60 min) (min) and relatively prolonged sedentary bouts (%) on hemodialysis days. Multiple regression analysis showed that prolonged sedentary bout parameters were an important factor in EQ-5D scores even after adjusting for confounding factors for total and non-hemodialysis days. Our results suggested that prolonged sedentary bouts were closely associated with HRQOL in patients on CHD, especially on non-hemodialysis days.

Altered plasma levels of lysophospholipids in response to adrenalectomy of rats.

The aim of this study was to investigate effects of reduced stress hormone by adrenalectomy on rat plasma levels of lysophosphatidic acid (LPA) and other lysophospholipids. We measured activities of lysophospholipase D (lysoPLD) in plasma and lipid phosphate phosphatase (LPP) in blood by determining choline and inorganic phosphate, respectively. LPA, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS) and lysophosphatodylglycerol were quantified by LC-MS/MS. In adrenalectomized rats, plasma levels of LPA, LPE, LPS and LPI, but not LPC, were increased. The increased level of LPA were due to decreased LPC level, increases plasma activity of lysoPLD toward LPC and decreased LPP activity toward LPA. Daily injections of deoxycoricosterone into rats selectively reversed increased level of LPS. Our results suggest enzymatic mechanism for increased plasma level of LPA, and indicate that the circulating levels of lysophospholipids including LPA in rats are differently affected by artificial suppression of release of adrenergic hormones.

Emergency aortic valve replacement complicated by unmanaged pheochromocytoma.

A 53-year-old male undergoing emergency aortic valve replacement for infective endocarditis developed a hypertensive crisis early during the operation. Suspecting a pheochromocytoma, intravenous phentolamine was immediately administered, after which the procedure was completed as scheduled. Although quite rare, a pheochromocytoma can be encountered during emergency open heart surgery; thus, early recognition of abnormal blood pressure change and appropriate management are important. Here, we present details of blood pressure control mainly by use of phentolamine, in this case, to demonstrate effective management of a hypertensive crisis during emergency cardiac surgery because of a pheochromocytoma.

[Tips for Use of Chordal Guide System for Easy Adjustment of Appropriate Artificial Chordae Length in Patients Undergoing Minimally Invasive Mitral Valve Repair].

OBJECTIVES: In patients who require minimally invasive mitral valve repair (MICS-mitral), it is difficult to determine the appropriate length of artificial chordae, position, and number of artificial chordae. The Memo 3D Rechord, a complete prosthetic ring associated with a temporary chordal guide system comprised of yellow loops that function as a reference guide for automatically determining the height of neo-chordae. We sought to evaluate our tips for use of this system. METHODS: Five patients (1 male, mean 68 years old) who underwent MICS-mitral using artificial chordae with the Memo 3D Rechord were evaluated. Prior to surgery, we assessed the prolapse position using 3-dimensional( 3D) echocardiography to decide the number and positions of the artificial chordae. Polytetrafluoroethylene (PTFE) sutures were passed through the papillary muscles and the free margin of the prolapsed leaflet, then appropriate positioning of the PTFE chordae was performed using a saline test. The PTFE chordae were passed through the loops and the free margin of the prolapsed leaflet was brought to the posterior annulus. Then, the PTFE sutures were tied and the temporary loop system removed. RESULTS: All patients had posterior leaflet prolapse. The number of the artificial chordae was 2 in 3 patients, and 1 in 2. The base of the artificial chordae was attached to the anterior papillary muscle in 3patients and posterior in 4. Additional indentation closure was required in 1 patient. All mitral valve repairs were performed successfully. Postoperative echocardiography mitral regurgitation( MR) grade was trivial in 5. CONCLUSIONS: Using our technique, it was possible to decide the appropriate length and position of the artificial chordae and MICS-mitral for leaflet prolapse with the Memo 3D Rechord is a simple and reproducible method.

Which Patients Are Candidates for Minimally Invasive Mitral Valve Surgery?　- Establishment of Risk Calculators Using National Clinical Database.

BACKGROUND: Although minimally invasive mitral valve surgery via a right minithoracotomy (MICS-mitral) is widely performed, no tool to evaluate its risk has been reported. We sought to establish MICS-mitral risk calculators using a national clinical database for selection of appropriate patients.Methods and Results:Between 2008 and 2015, 3,240 patients (mean age 59±14 years, males 1,950) underwent a MICS-mitral procedure in Japan and were registered in a national clinical database. We examined mortality and composite outcome (operative mortality, stroke, reoperation for bleeding) using multivariate analysis, then developed a risk calculator for each using stepwise analysis. Operative mortality was 1.1% and the composite outcome rate was 5%. In multivariate analysis, risk factors for operative mortality were shown to be age, respiratory dysfunction, thoracic aortic disease, myocardial infarction, body mass index >30, NYHA class IV, moderate or severe aortic regurgitation, mitral valve replacement, multiple valve surgery, and annual cases <10. ROC curve analysis of our prediction formulas for mortality and composite outcome revealed an area under the curve for operative mortality of 0.877 (95% confidence interval: 0.82-0.94, P<0.01) and for composite outcome of 0.665 (95% confidence interval: 0.62-0.71, P<0.01). CONCLUSIONS: We developed risk calculator formulas using risk factors associated with both operative mortality and composite outcome. The present risk calculator formula is useful for patient selection and may influence future applications for this procedure.

Relationship between Sedentary Behavior and All-cause Mortality in Japanese Chronic Hemodialysis Patients: A Prospective Cohort Study.

We investigated the relationship between sedentary behavior and all-cause mortality in patients undergoing hemodialysis. A total of 71 patients (39 men, 32 women, aged 72.1±11.7 years) were enrolled in this longitudinal study. Their sedentary behavior was measured using a tri-accelerometer that provides relative values per daily wearing time. We classified the sedentary behavior time into 2 groups (under the median: short-sedentary behavior (SB) group; over the median: long-SB group) and compared the groups' clinical parameters. We compared the groups' survival rates by using Kaplan-Meier curves and the log-rank test, and we performed multivariate analyses by a Cox-proportional hazard model to evaluate the relationship between the sedentary behavior and the survival rate. Twenty patients (28.2%) died during the observation period. The survival rate of the short-SB group was significantly higher than that of the long-SB group. Sedentary behavior was thus an important factor for all-cause mortality even after adjusting for confounding factors by a Cox-proportional hazard model. Sedentary behavior is closely linked to all-cause mortality, especially total days and non-hemodialysis days, and reducing sedentary behavior may be beneficial to reduce the all-cause mortality of patients on chronic hemodialysis.

Phosphorylation of epidermal growth factor receptor at serine 1047 in cultured lung alveolar epithelial cells by bradykinin B2 receptor stimulation.

Accumulating evidence indicates that epidermal growth factor receptor (EGFR) is desensitized by phosphorylation of serine 1047 (Ser1047). We and other groups have reported that stimulation of a receptor of tumor-necrosis factor α (TNFα) and Toll-like receptor 5 (TLR5) induced the phosphorylation of Ser1047 through activation of p38 mitogen-activated protein kinase (p38 MAPK) in cultured lung alveolar epithelial A549 cells. However, phosphorylation of EGFR at Ser1047 by stimulation of any G-protein coupled receptors (GPCRs) has not been reported in any cultured cells. In the present study, we first confirmed that A549 cells expressed bradykinin (BK) B2 receptor, and then, we examined whether BK treatment of A549 cells activated MAPKs and induced the phosphorylation of EGFR at Ser1047. Immunoblotting analysis and reporter gene assays indicated that BK activated the pathways of extracellular signal-regulated kinase (ERK) and p38 MAPK. Inhibitor studies suggested that Gq/11 was mainly involved in the activation of ERK and p38 MAPK. We found that stimulation of the BK B2 receptor, but not the BK B1 receptor, induced phosphorylation of EGFR at Ser1047. Pharmacological experiments indicated that both ERK and p38 MAPK were involved in the phosphorylation of EGFR. These results strongly suggested that BK regulates EGFR functions in lung alveolar epithelial cells. In addition, we found that BK treatment increased the mRNA level of dual specificity MAPK phosphatase 5 (DUSP5) in an ERK-dependent manner, which suggested that a negative feedback mechanism of ERK existed in the cells.

Effect of the Initial Strategy for Active Endocarditis Complicated With Acute Heart Failure.

BACKGROUND: Early surgery for infective endocarditis (IE) with acute heart failure (AHF) is recommended, despite clinical results being unclear. We investigated the effect of initial treatment in such patients. Methods and Results: Outcomes for 470 patients with active IE who underwent valvular surgery during 2009-2016 were reviewed. Of them, 177 had symptomatic AHF when diagnosed with IE (excluding those with cardiogenic shock or intubated for AHF). They were divided into 2 groups based on initial treatment: Group S (underwent valvular surgery immediately; n=74) and Group M (received initial medical treatment for infection and HF; n=103). The median (interquartile range) waiting period from diagnosis to surgery in Groups S and M was 1 (1-3) and 15 (8-33) days, respectively (P<0.001). The 5-year survival rate was higher in Group S than Group M (80% vs. 64%; P=0.108). Group M was divided into Group P (initial medical treatment was effective and elective surgery was performed; n=62) and Group E (emergency surgery was necessary during medical treatment; n=41); overall 5-year survival was significantly worse in Group E than Group P (42% vs. 79%; P<0.012). In Group M, multivariate analysis indicated that Staphylococcus aureus infection (odds ratio 3.82; 95% confidence interval 1.19-13.3; P=0.024) was a significant risk factor for conversion to emergency surgery. CONCLUSIONS: Considering poor outcomes of emergency surgery for medically refractory HF, early surgery may be a reasonable option for IE patients, especially those with S. aureus infection.

Relationship between Sedentary Behavior and Health-Related Quality of Life in Patients on Chronic Hemodialysis.

We explored the relationship between sedentary behavior and the health-related quality of life (HRQOL) in patients on chronic hemodialysis. A total of 60 outpatients, aged 71.1±12.0 years, were enrolled in this cross-sectional study. Sedentary behavior was measured using a tri-accelerometer and HRQOL was evaluated by the Euro-QOL questionnaire (EQ-5D). The relationship between the patients' sedentary behavior and HRQOL was evaluated by simple and multiple correlation analyses. The relative sedentary behavior (%) for total days was 73.7±12.9% and the EQ-5D scores were 0.688±0.233. Relative sedentary behavior (%) was negatively correlated with EQ-5D scores for total days, hemodialysis days and non-hemodialysis days. The relative light-intensity physical activity (LPA) (%) and relative moderately vigorous-intensity physical activity (MVPA) (%) were correlated with EQ-5D scores. Multiple regression showed that the relative sedentary behavior (%) had a clinical impact on EQ-5D scores after adjusting for confounding factors for total, hemodialysis and non-hemodialysis days. Sedentary behavior is closely linked to HRQOL, and reducing sedentary behavior may be beneficial to improve the HRQOL of patients on chronic hemodialysis.

[Postoperative Atrial Fibrillation in Patients who Underwent Thoracic Aortic Surgery].

PURPOSE: Postoperative atrial fibrillation (POAF) is a very common and important complication occurring after open heart surgery. Risk factors and prevention measure including ß blocker use have been reported mainly in regard to patients who underwent coronary artery bypass grafting, while little is known about POAF following thoracic aortic surgery. In the present study, we examined risk factors related to POAF and effective prevention of POAF in patients who underwent thoracic aortic surgery. PATIENTS AND METHODS: We evaluated 95 consecutive patients who underwent thoracic aortic surgery since 2010. We analyzed the relationship between perioperative factors and occurrence of POAF in the study cohort, as well as in 62 patients who had perioperative intravenous ß blocker (landiolol) administration. RESULTS: Following surgery, 21 (22%) of the patients had new onset POAF. The occurrence of POAF was related to that of stroke. Univariate analysis showed that age was a risk factor for POAF. In patients with landiolol, risk factors for POAF were age, arch aneurysm, and timing of landiolol administration. Six patients developed POAF during landiolol administration. However, of 56 patients who had not have POAF during landiolol administration, 8 developed POAF after stopping landiolol. CONCLUSION: Our findings show that the risk factor of POAF after thoracic aortic surgery is age, while perioperative administration of landiolol may reduce POAF incidence.

The efficacy of tolvaptan in the perioperative management of chronic kidney disease patients undergoing open-heart surgery.

PURPOSE: The perioperative management of chronic kidney disease (CKD) patients undergoing open-heart surgery is challenging. In this study, we evaluated the effects of tolvaptan in CKD patients after open-heart surgery. METHODS: Between 2010 to 2015, 731 patients underwent open-heart surgery in our hospital. We consecutively selected 71 patients with stage IIIa-IV CKD and divided them into two groups. Those who received tolvaptan postoperatively were defined as the "Tolvaptan group" (n = 25) and those who did not were defined as the "Non-tolvaptan group" (n = 46). We compared the urine volume of postoperative days (POD) 1 and 2, the number of days to return to preoperative body weight (BW), and the change in the postoperative estimated glomerular filtration rate (eGFR). RESULTS: In the tolvaptan group, the urine volume was significantly larger (P = .04) and the duration to preoperative BW tended to be shorter. Overall, the postoperative change in the eGFR tended to be better in the tolvaptan group (P = .008). In particular, we found a significantly better trend in CKD stage IV (P = .04) patients and in the patients, whose cardiopulmonary bypass (CPB) time was longer than 120 min (P = .03). CONCLUSIONS: Tolvaptan can safely be used for CKD patients undergoing open-heart surgery and can provide a feasible urine volume without leading to a deterioration of their renal function.

Relationship between Changes in Physical Activity and Changes in Health-related Quality of Life in Patients on Chronic Hemodialysis with 1-Year Follow-up.

In a longitudinal study, we examined the link between changes in physical activity and changes in health-related quality of life (HRQOL) in patients on chronic hemodialysis. Seventy-one patients (43 males, 28 females; aged 70.9±10.6 years) on chronic hemodialysis in September 2013 were enrolled. The data of the 43 patients whose complete measurements were taken again in September 2014 were used for the longitudinal analysis. Clinical parameters including age, height, dry weight, duration of hemodialysis, blood pressure (BP), blood triglyceride and HDL cholesterol levels, physical activity, and HRQOL were evaluated. Physical activity was measured by a tri-accelerometer, and HRQOL was evaluated by the EuroQol questionnaire (EQ-5D). In the first cross-sectional analysis, EQ-5D scores were significantly correlated with daily step counts (steps per day) on all days and non-hemodialysis days. In the second longitudinal analysis, in the women, changes in EQ-5D scores were positively correlated with changes in daily step counts on all days. In all patients, changes in EQ-5D were weakly and negatively correlated with changes in physical activity (1-3 METs: min per day) on hemodialysis days. Promoting daily physical activity may improve the HRQOL in patients on chronic hemodialysis, especially in women.

Annular dynamics after mitral valve repair with different prosthetic rings: A real-time three-dimensional transesophageal echocardiography study.

PURPOSE: We assessed the effects of different types of prosthetic rings on mitral annular dynamics using real-time three-dimensional echocardiography (RT3DE). METHODS: RT3DE was performed in 44 patients, including patients undergoing mitral annuloplasty using the Cosgrove-Edwards flexible band (Group A, n = 10), the semi-rigid Sorin Memo 3D ring (Group B, n = 17), the semi-rigid Edwards Physio II ring (Group C, n = 7) and ten control subjects. Various annular diameters were measured throughout the cardiac cycle. RESULTS: We observed flexible anterior annulus motion in all of the groups except Group C. A flexible posterior annulus was only observed in Group B and the Control group. The mitral annular area changed during the cardiac cycle by 8.4 ± 3.2, 6.3 ± 2.0, 3.2 ± 1.3, and 11.6 ± 5.0 % in Group A, Group B, Group C, and the Control group, respectively. The dynamic diastolic to systolic change in mitral annular diameters was lost in Group C, while it was maintained in Group A, and to a good degree in Group B. In comparison to the Control group, the mitral annulus shape was more ellipsoid in Group B and Group C, and more circular in Group A. CONCLUSION: Although mitral regurgitation was well controlled by all of the types of rings that were utilized in the present study, we demonstrated that the annulus motion and annulus shape differed according to the type of prosthetic ring that was used, which might provide important information for the selection of an appropriate prosthetic ring.

Psychological distress between chronic hemodialysis patients with and without low back pain.

OBJECTIVE: The aim of this study was to compare psychological distress between patients on chronic hemodialysis with and without chronic low back pain (CLBP). SUBJECTS AND METHODS: A total of 72 patients on chronic hemodialysis, aged 72.9 ± 10.8 years, were enrolled in this cross-sectional study. Psychological distress using the K6, questionnaire for CLBP, and physical activity using the tri-accelerometer were evaluated. RESULTS: Twenty-nine patients (40.3 %) were having CLBP. The K6 scores were 4.0 ± 4.6 and physical activity (n = 55) was 1.0 ± 1.0 METs h/day. K6 scores in patients on chronic hemodialysis with CLBP were significantly higher than those in patients on chronic hemodialysis without CLBP even after adjusting for sex, age, duration of hemodialysis and physical activity. CONCLUSION: These results suggest that higher psychological distress was a fundamental feature in patients on chronic hemodialysis with CLBP.

Novel method of evaluating liver stiffness using transient elastography to evaluate perioperative status in severe heart failure.

BACKGROUND: The aim of the present study was to assess the efficacy of a non-invasive method, transient elastography (FibroScan), in measuring liver stiffness (LS), and whether LS can be used as a marker of cardiac - and hence perioperative - status. METHODS AND RESULTS: Perioperative LS was prospectively measured using a FibroScan in 30 patients (21 male; 42.2 ± 13.3 years old) who underwent left ventricular assist device (LVAD) implantation. LS was checked pre- and postoperatively, then analyzed in regard to perioperative status. Preoperative LS was 13.3 ± 13.0 kPa (normal, <5.5 kPa), and was abnormal in 77% of patients. Four required bilateral VAD. LS in patients with bilateral VAD tended to be higher than in LVAD patients (25.1 ± 22.7 vs. 11.5 ± 10.5 kPa, P=0.051). No patient with LS ≤ 7.0 kPa required a right VAD. The incidence of major adverse events was lower in patients with LS ≤ 12.5 kPa (25% vs. 80%, P<0.05). There were also no mortalities among patients with LS ≤ 12.5 kPa. CONCLUSIONS: LS was correlated with preoperative severity in patients with severe heart failure and reflected liver congestion, and may be useful to predict the requirement of right VAD, as well as postoperative complications in patients with LVAD implantation. This novel modality may be a useful non-invasive assessment method for management of severe heart failure.

Tricuspid annular dynamics before and after tricuspid annuloplasty- three-dimensional transesophageal echocardiography.

BACKGROUND: Little is known about the impact of tricuspid annuloplasty (TAP) on annular dynamics. We assessed tricuspid annular dynamics using 3-D transesophageal echocardiography (3D-TEE) before and after TAP with different types of prosthetic ring. METHODS AND RESULTS: 3D-TEE of the tricuspid valve was acquired in 30 patients (TAP with rigid ring [RR], n=8; TAP with flexible ring [FR], n=10; control, n=12). Tricuspid annular dimensions (circumference, area, annular height, anteroposterior [AP], septolateral [SL] diameter) were measured throughout the cardiac cycle. All postoperative tricuspid annular dimension parameters were significantly reduced by TAP, while the AP/SL ratio was significantly increased (before, 0.96±0.16; after, 1.03±0.06; P<0.05). The difference in annular area between diastole and systole was significantly smaller in the TAP groups (11.6%) than in the control (27.9%, P<0.05). Annular height in the FR patients was significantly lower than in the RR group, while the postoperative AP/SL ratio was lower in the RR than the FR and control groups. Change in annular area was not seen in RR patients, while it was seen in the FR and control groups. CONCLUSIONS: Annulus motion and shape differ according to the type of prosthetic ring used, although tricuspid regurgitation was well controlled by all types of ring utilized. The present results provide important information for selection of an appropriate prosthetic ring for TAP.

In vivo assessment of novel stentless valve in the mitral position.

BACKGROUND: We conducted in vivo examinations of a newly designed stentless mitral valve (SMV), formed by suturing 2 leaflets with the "legs" serving as chorda tendinea, made from bovine pericardium, to a flexible ring. METHODS AND RESULTS: Seven pigs underwent implantation of the SMV constructed with a 23-mm (n=5) or 25-mm (n=2) Duran ring. Baseline echocardiography examinations were used to evaluate the annular anteroposterior diameter, and distance between the mitral annulus (MA) and papillary muscles (PMs) to determine SMV-leg length. After removing the native valve, the SMV-legs were fixed to the anterior and posterior PMs, followed by fixation of the ring to the native MA. Immediately after surgery, all animals presented none or trivial mitral regurgitation, with mean and peak trans-SMV pressure gradient values of 1.9±0.8 and 6.0±3.1 mmHg, respectively. The mean length of the SMV-leg was 19.4±3.9 mm, which correlated with the distance between anterior and posterior MA-PM (r=0.96 and 0.94, respectively, P<0.01 for both). The discrepancy between the anteroposterior diameter of the ring (outside diameter) and that of the native valve was 1.0±2.9 mm, which correlated with the trans-SMV pressure gradient (r=0.81, P=0.025). CONCLUSIONS: In our preliminary study, the SMV demonstrated excellent diastolic inflow dynamics and closing function in vivo. Preoperative precise assessment of MV configuration may serve as a basis for selection of appropriate ring size and SMV-leg length.