Long-Term Outcomes After Aortic Valve Replacement for Aortic Valve Regurgitation　- Importance of Left Ventricular End-Systolic Diameter.

BACKGROUND: We determined the left ventricular end-systolic diameter (LVDs) cut-off value for risk of major adverse cardiac and cerebrovascular events (MACCE) in Japanese asymptomatic or mildly symptomatic patients undergoing aortic valve replacement (AVR) for aortic valve regurgitation (AR), and investigated the effect of left ventricular dilation on long-term postoperative outcomes.Methods and Results: The 168 patients who underwent surgical AVR for AR at Shiga University of Medical Science between January 2002 and December 2022 were included in this study. Receiver operating characteristic curve analysis showed that the cut-off value of preoperative LVDs for the incidence of MACCE was 42.8 mm (area under the curve 0.616). Postoperative outcomes were compared between patients with preoperative LVDs >42.8 mm (n=77) and those with preoperative LVDs ≤42.8 mm (n=91) using propensity score matching. The 10-year estimated rates of freedom from MACCE in those with LVDs >42.8 and ≤42.8 mm were 59.9% and 85.7%, respectively; the curves differed significantly (P=0.004). In multivariable Cox proportional hazard regression analyses, preoperative LVDs >42.8 mm was an independent predictor of MACCE (hazard ratio 2.485; 95% confidence interval 1.239-4.984; P=0.010). CONCLUSIONS: Preoperative LVDs >42.8 mm is associated with an increased risk of MACCE in Japanese patients undergoing AVR for AR.

The two therapeutic strategies of surgical intervention and medical management in a patient with enhanced-fibrinolytic type of disseminated intravascular coagulation after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure.

BACKGROUND: Management of the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by aortic disorders is the two strategies of surgical intervention and medical treatment based on the patient's age and comorbidities. CASE PRESENTATION: An 81-year-old woman with a history of two previous aortic surgeries and chronic heart and renal failure was admitted for uncontrollable subcutaneous hemorrhage. The hemorrhage was caused by the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by periprosthetic graft hematoma after aortic replacement for Stanford type A aortic dissection. Open thoracic hemostasis temporarily controlled the subcutaneous hemorrhage, but she was readmitted for the recurrence seven months after discharge. On the second admission, the combination of anticoagulant and antifibrinolytic agents was successful. CONCLUSION: Management of the enhanced-fibrinolytic type of DIC caused by aortic disorders is important of a successful combination of surgical and medical therapy tailored the patient's condition.

Depletion of tumor-associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin.

In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.

Molecular and Regenerative Characterization of Repair and Non-repair Schwann Cells.

Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs. The RSCs upregulate a group of genes that are related to inflammation, repair, and regeneration, whereas non-RSCs upregulate genes related to myelin maintenance, Notch, and aging. These findings indicate that the RSCs have markedly different cellular, regenerative, and molecular characteristics compared to the non-RSCs, even though the RSCs were just derived from non-RSCs upon injury, thus providing the basis for understanding the mechanisms related to SC mediated repair after peripheral nerve injury.

Off-Pump Bilateral Skeletonized Internal Thoracic Artery Grafting in Octogenarians.

BACKGROUND: We compared postoperative outcomes in octogenarians who underwent off-pump isolated coronary artery bypass grafting for multivessel disease using either skeletonized bilateral or single internal thoracic artery (ITA).Methods and Results: Among 1,532 patients who underwent isolated coronary artery bypass grafting between 2002 and 2021, 173 octogenarians were analyzed retrospectively. After inverse probability of treatment weighting, we found no statistically significant difference regarding patients' preoperative characteristics. No patient experienced deep sternal wound infection. More patients in the single than bilateral ITA group died within 30 days after surgery (5.0% vs. 0%, respectively; P=0.003). The mean follow-up duration was 4.2 years. At 5 years, the freedom from overall death following bilateral versus single ITA grafting was 78.2% and 53.7%, respectively (log-rank test, P=0.003), and freedom from major adverse cardiac and cerebrovascular events (MACCE) was 67.9% and 44.8% respectively (log-rank test, P=0.002). In multivariable Cox models, bilateral ITA grafting was significantly associated with a lower risk of overall death (hazard ratio [HR] 0.555; 95% confidence interval [CI] 0.342-0.903; P=0.018) and MACCE (HR 0.586; 95% CI 0.376-0.913; P=0.018). CONCLUSIONS: Compared with single ITA grafting, off-pump skeletonized bilateral ITA grafting is associated with lower rates of overall death and MACCE in octogenarians undergoing CABG and does not increase the risk of deep sternal wound infection.

Location of the False Lumen Within the Medial Layer in Acute Intramural Hematoma.

BACKGROUND: We compared the location of the false lumen within the medial layer between acute intramural hematoma (AIH) and acute aortic dissection (AAD) using microscopic images of aortic specimens and examined the associations with patient characteristics, CT findings, and late outcomes.Methods and Results: Among 293 patients undergoing surgery for Stanford type A acute aortic syndrome between 2008 and 2018, 45 patients had neither an identifiable intimal tear, flow to the false lumen on preoperative CT or intimal tear by intraoperative observation (AIH group), and 98 patients with patent false lumen were enrolled (AAD group). The AIH group had a significantly thinner outer media thickness (OMT) than the AAD group. The AIH group showed more pericardial effusion, but distal progression of dissection and branch vessel involvement were limited. The change in aortic diameter after surgery was insignificant in the AIH group, whereas in the AAD group it continued to increase. Cumulative incidence of aortic adverse events was significantly higher among AAD patients, but no significant difference was observed in survival between groups. CONCLUSIONS: The AIH group had a significantly thinner OMT than the AAD group, which was significantly associated with a large amount of pericardial effusion, greater false lumen diameter, and limited progression of aortic dissection.

Epidemiology of Acute Aortic Dissection in a General Population of 1.4 Million People in Japan　- Shiga Stroke and Heart Attack Registry.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening cardiovascular disease, with a reported incidence rate ranging from 2.5 to 7.2 per 100,000 person-years in several population-based registries in Western countries, but epidemiological data are lacking in Japan.Methods and Results: The Shiga Stroke and Heart Attack Registry is an ongoing multicenter population-based registry of cerebro-cardiovascular diseases. We enrolled patients who developed AAD, defined by any imaging examination method from 2014 to 2015 in Shiga Prefecture. Death certificates were used to identify cases that were not registered at acute care hospitals. The incidence rates of AAD were calculated by age categories and adjusted using standard populations for comparison. We evaluated differences in patient characteristics between Stanford type A-AAD and type B-AAD subtypes. A total of 402 incident cases with AAD were analyzed. The age-adjusted incidence rates using the 2015 Japanese population and the 2013 European Standard Population were 15.8 and 12.2 per 100,000 person-years, respectively. Compared with cases of type B-AAD, those with type A-AAD were older (75.0 vs. 69.9 years, P=0.001) and more likely to be women (62.3% vs. 28.6%, P<0.001). CONCLUSIONS: Population-based incidence rates of AAD in Japan appear to be higher than in previous reports from Western countries. Incident cases with type A-AAD were older and female predominance.

IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.

Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.

Arthrodesis of the interphalangeal joints of the hand by two-dimensional intraosseous wiring.

BACKGROUND: Numerous techniques for arthrodesis have been described to fix interphalangeal (IP) joints, and the fixation method should be considered on a case-by-case basis. This study aimed to investigate the availability of IP joint arthrodesis of the hand, using a two-dimensional intraosseous wiring (two-DIOW) method. METHODS: A total of 43 joints (19 thumb IP joints, 9 proximal finger interphalangeal (PIP) joints and 15 distal interphalangeal (DIP) joints in 29 patients with a mean age of 66 years (range, 24-85 y) were retrospectively analyzed. All operations were performed with two-DIOW method. We evaluated the bone union rate, correction loss, presence of any surgical complications, and oral steroid use in cases of joint fixation using the two-DIOW method. RESULTS: Of these 43 digits, 42 achieved bone union (97.7%). Non-union was seen in a thumb IP joint of mutilans rheumatoid arthritis. Mean correction loss of deviation was 1.0°, and flexion or extension angulation was 1.6° in the direction of extension. Surgical complications included mild nail deformity in 2 digits and wire irritation necessitating wire removal in 2 digits. Oral steroids were used for 18 of the 43 digits, including 2 digits complicated by nail deformities. There was no infection and skin necrosis in all digits with or without steroid use. CONCLUSIONS: The two-DIOW method appears to offer an effective method of IP joint fixation, but caution should be exercised in digits of severe joint destruction and in the treatment of wire knot.

[Ascending Aortic Replacement and Aortic Valve Replacement in a Patient with Cold Agglutinins].

Cold agglutinins are commonly found in healthy individuals. Cold agglutinins bind to red blood cells at low temperatures, such as during cardiovascular surgery. Agglutination leads to hemolysis and embolism. A 73-year-old man with cold agglutinins disease underwent ascending aortic replacement and aortic valve replacement. As there was no agglutination reaction at 34 degrees centigrade in preoperative testing, we performed the operation under cardiopulmonary bypass and cardioplegia at a temperature above 34 degrees centigrade. He was discharged without any complications.

[Total Arch Replacement with Open Stent Grafting for Chronic Dissecting Aortic Aneurysm with Aberrant Right Subclavian Artery:Report of a Case].

A 59-year-old man was referred to our hospital for surgery for a dissecting aortic aneurysm with an aberrant right subclavian artery( ARSA). He had a history of surgery for atrial septal defect at the age of 3 and developed Stanford type B aortic dissection at the age of 53. The maximum diameter of the aortic aneurysm was 68 mm, and the entry was located close to the ARSA origin. We established cardiopulmonary bypass using the femoral artery and vein and performed a median re-sternotomy. We performed total arch replacement with the open stent-grafting technique. The ARSA was ligated from the right thoracic cavity. Three arch branches were reconstructed in situ, and the right axillary artery was bypassed with a 9 mm Dacron graft. Six months after that operation, reduction of the false lumen was observed. This strategy is considered to be effective for chronic aortic dissection with ARSA.

[Blood pressure and pulse rate changes immediately after bathing and immediately after leaving the bath in elderly people living in the community].

INTRODUCTION: Although the number of deaths in bathtubs in homes and residential facilities for the elderly has been decreasing slightly since 2017, it is still 4,900 (2019), which is almost twice the number of traffic accident deaths. PURPOSE: The purpose of this study was to investigate blood pressure and pulse fluctuations in community-dwelling elderly people during bathing, and to examine the alert range to determine when heat shock occurs. METHODS: Ten elderly men (72.6±3.4/67-78) living in the community were subjected to a 6-minute full-body bath in a bath with a temperature of 41°C, and their blood pressure (SBP, DBP) and pulse (PR) were measured. RESULTS: The SBP of the group whose PR increased by 15/min or more from before bathing to 30 seconds after bathing increased by about 30 mmHg. In the group where PR increased by 15/min or more, the pulse pressure (PP) increased by about 30 mmHg, and in the double product (DP), the abnormal increase of 5,000 DP or more was observed from before bathing to 30 seconds after bathing. DISCUSSION: In the group where PR increased by 15/min or more from before bathing to 30 seconds after bathing, there is a possibility of cerebral hemorrhage immediately after bathing, dizziness, and falls. Analysis of pulse pressure (PP) and double product (DP) also suggests that the burden on the heart is applied 30 seconds after bathing, and sufficient attention is required.

Endovascular treatment of an infectious aneurysm using the selective provocative test and transcranial motor evoked potential monitoring under general anesthesia: a case report.

The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.

Ex-vivo aortic root and coronary artery cast measurement to validate the accuracy of virtual imaging.

BACKGROUND AND AIM OF THE STUDY: To investigate the accuracy of two methods of measuring features in cardiac anatomy, using an objective standard cast model. METHODS: We made a silicone cast using a swine heart. Computerized tomography data of the solidified cast were processed through virtual reality (VR) software and through two-dimensional multiplanar-reconstruction (2D-MPR), and all measurements were compared against physical measurements of the cast. RESULTS: The cast perfectly demonstrated the fine detail of the aortic valve and the proximal parts of coronary arteries. Anatomical features were measured by 3D-VR, 2D-MPR, and directly on the cast. Measurement differences between 2D-MPR and the cast were on average at least 3.6 times larger than those between 3D-VR and the cast. CONCLUSIONS: Based on the observed accuracy, 3D-VR measurements seem considerably more accurate than the current standard 2D-MPR, and 3D-VR may be considered as the next gold standard for 3D measurement of cardiac anatomy in vivo.

Hyperlactatemia as a Risk Stratification for Postinfarction Ventricular Septal Rupture.

BACKGROUND: Surgical repair for postinfarction ventricular septal rupture (VSR) is a challenging operation, especially in the acute phase with unstable hemodynamics. We retrospectively examined the value of measuring lactate, which can be a quantitative indicator of end-organ ischemia caused by multiple factors including ineffective cardiac output, for risk stratification in patients undergoing surgical repair. METHODS: From April 2008 to December 2018, 33 consecutive patients were admitted to our hospital with a diagnosis of VSR and underwent VSR repair surgery within 24 hours of admission. We categorized patients into 3 groups based on the distribution of preoperative blood lactate level: <5 mmol/L (n = 16), 5 to 10 mmol/L (n = 11), and >10 mmol/L (n = 6). RESULTS: There was no intraoperative death, but the prognosis for patients with lactate >10 mmol/L was extremely poor, with a median postoperative survival time of only 23 days [25th percentile 6, 75th percentile 30]. Five of 6 patients (83%) died within 30 days after surgery. The risk-adjusted hazard ratio (95% confidence interval) for mortality per 1 SD (0.41-unit) increase in log-transformed preoperative lactate level (equivalent to a 4.10-fold increase) was 2.85 (1.57 to 5.19). Patients with lactate 5 to 10 mmol/L had 3.95-fold and those with lactate >10 mmol/L had 6.03-fold higher risk of mortality than those with lactate <5 mmol/L. CONCLUSION: Elevation of preoperative serum lactate is significantly associated with mortality in patients who underwent VSR repair. The findings of this study highlight the value of measuring lactate level for risk stratification.

[Stanford Type A Aortic Dissection with Tricuspid Regurgitation in a Patient with Situs Inversus Totalis].

Situs inversus totalis is a congenital anomaly characterized by a mirror image transposition of the normal visceral organs, which makes it difficult to perform aortic surgery accurately. Stanford type A aortic dissection in patients with this condition is very rare and difficult to assess and manage. We report a case of Stanford type A aortic dissection with situs inversus totalis. The patient presented with severe tricuspid regurgitation with annulus enlargement due to chronic atrial fibrillation, requiring ascending aortic replacement and tricuspid annuloplasty. These procedures were performed after the operator swapped the left and right positions during the operation. Postoperative course was uneventful. By carefully checking the preoperative computed tomography images and changing the operator's position during the operation, it is possible to safely perform Stanford type A aortic dissection surgery in patients with situs inversus totalis.

[A Rapidly Growing Cardiac Calcified Amorphous Tumor in a Peritoneal Dialysis Patient:Report of a Case].

A calcified amorphous tumor( CAT) is a non-neoplastic cardiac tumor, which has been reported to be associated with hemodialysis dependent end-stage renal disease. We report a case of CAT attached to mitral annular calcification (MAC) in the posterior leaflet annulus of the mitral valve in a 56-year-old man who had been receiving peritoneal dialysis for three years. The CAT grew to 10 mm long in a half year. Peritoneal dialysis dependent end-stage renal disease is associated with MAC. Additionally, MAC-related CAT has been reported growing rapidly. We should perform periodic echocardiography not only for hemodialysis patients but also for peritoneal dialysis patients. When CAT is diagnosed, operation should be performed early to prevent embolism such as cerebral infarction.

[A Novel Virtual-reality Imaging System in Cardiovascular Surgery:a Potentially Promising Technology for Surgeons].

Adequate preoperative planning may facilitate successful procedures in cardiovascular surgery. We have developed a system named the Vesalius 3D suite, combining three-dimensional (3D) image-processing software with an optic-tracking spatial navigation, allowing quick, accessible 3D image interpretation for virtual reality (VR) exploration and measurement from one or more of a range of imaging modalities. We present a novel method of virtual imaging analysis for preoperative planning and simulation in cardiovascular surgery using this 3D-VR system. Based on unimodal or multimodal medical imaging data, digital imaging and communication in medicine (DICOM) data sets can be reconstructed for 3D visualization. Virtually reconstructed images can be viewed on flat-screen or stereoscopic display, revealing each patient's specific anatomy and the internal structures in exquisite detail. Highly accessible 3D interpretation promptly permits precise measurements of repair-relevant anatomical parameters including geometrically complex shapes. This technology may promote understanding of form and function in the cardiovascular system, and facilitate operative procedures in more challenging cases, and it seems especially valuable for any surgeon to gain experience in practicing for rarely-performed procedures or uncommon patient-specific preoperative surgical rehearsal.

Bilateral Internal Thoracic Artery Grafting in Hemodialysis Patients.

BACKGROUND: We compared postoperative outcomes in hemodialysis (HD) patients who underwent isolated coronary artery bypass grafting (CABG) for multivessel disease using either bilateral or single skeletonized internal thoracic artery.Methods and Results:Among 1,486 patients who underwent isolated CABG between 2002 and 2020, 145 HD patients were retrospectively analyzed. After inverse probability of treatment weighting, there were no significant differences in the preoperative characteristics. No significant differences in 30-day mortality (P=0.551) or postoperative deep sternal wound infection (P=0.778) were observed. However, the bilateral internal thoracic artery grafting group had a lower postoperative stroke rate (0% vs. 4.0%, P=0.019). No significant differences in freedom from all-cause death (P=0.760) and cardiac death (P=0.863) were found. In the multivariate Cox proportional hazards models, bilateral internal thoracic artery grafting was not associated with all-cause death (P=0.246) or cardiac death (P=0.435). CONCLUSIONS: Bilateral internal thoracic artery grafting in HD patients did not improve mid-term outcomes, but it was also not associated with worse postoperative outcomes. Use of the bilateral internal thoracic artery may be an important option in patients with limited conduits to prevent postoperative complications.

Lipoprotein Particle Profiles Compared With Standard Lipids in the Association With Subclinical Aortic Valve Calcification in Apparently Healthy Japanese Men.

BACKGROUND: Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (µmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL).Methods and Results:A community-based random sample of Japanese men aged 40-79 years examined in 2006-2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23-3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23-3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC. CONCLUSIONS: The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.