Dendritic cells with METTL3 gene knockdown exhibit immature properties and prolong allograft survival.

Maturation of dendritic cells (DCs) initiates adaptive immune responses and thereby provokes allograft rejection. Here, this study aimed to explore the effect of Methyltransferase-like protein 3 (METTL3) silencing on DC function and the role of METTL3-silencing donor DCs in the immune response after mouse heart transplantation. Bone marrow-derived DCs from donor BALB/c mice were infected with lentiviruses expressing METTL3-specific short hairpin RNA (LV-METTL3 shRNA) to silence METTL3. Then METTL3-silencing DCs were treated with lipopolysaccharide (LPS) for another 48 h to induce DC maturation. Recipient C57BL/6 mice were injected with phosphate-buffered saline (PBS), immature DCs, and METTL3 shRNA-DCs prior to the cardiac transplantation involving the transfer of hearts from donor BALB/c mice to recipient C57BL/6 mice. In vitro we demonstrated that METTL3-silencing DCs had lower expression of MHCII, costimulatory molecules (CD80, CD86), and DC-related cytokines (IFN-γ, IL-12) as well as lower ability to activate T-cell proliferation, which were consistent with the characteristics of tolerogenic DCs. In vivo we found that METTL3-silencing donor DCs induced immune tolerance after mouse heart transplantation and prolonged the allograft survival, which might be associated with Th1/Th2 immune deviation. In summary, METTL3-silencing DCs exhibit immature properties and prolong allograft survival.

Exosomes from dendritic cells with Mettl3 gene knockdown prevent immune rejection in a mouse cardiac allograft model.

We have previously demonstrated that Mettl3-silencing dendritic cells (DCs) exhibited immature properties and prolonged allograft survival in a murine heart transplantation model. Exosomes derived from donor DCs (Dex) are involved in the immune rejection of organ transplantation, and blocking Dex transfer may suppress immune rejection. Herein, this study aimed to investigate whether Mettl3 knockdown inhibits the secretion and activity of donor Dex, thereby inhibiting donor Dex-mediated immune rejection. The imDex, mDex, shCtrl-mDex, and shMettl3-mDex were obtained from the culture supernatant of DCs (immature DCs, mature DCs, shCtrl-infected mature DCs, shMettl3-infected mature DCs) derived from donor BALB/c mouse bone marrow and then co-cultured with splenic T cell lymphocyte suspension from recipient C57BL/6 mice in vitro or injected into recipient C57BL/6 mice before the cardiac transplantation. Donor shMettl3-mDex expressed lower concentration of exosomes and lower expression of Mettl3, Dex markers (ICAM-1, MHC-I, MHC-II), as well as lower ability to activate T cell immune response than shCtrl-mDex. Administration of donor shMettl3-mDex attenuated immune rejection after mouse heart transplantation and prolonged the allograft survival. In summary, Mettl3 knockdown inhibits the immune rejection of Dex in a mouse cardiac allograft model.

Comparison of the effects of hemodialysis and hemodiafiltration on left ventricular hypertrophy in end-stage renal disease patients: A systematic review and meta-analysis.

Whether hemodiafiltration (HDF) is better than conventional hemodialysis (HD) in improving left ventricular hypertrophy (LVH), defined as reduction of the left ventricular mass index (LVMi) and increasing the ejection fraction (EF), is unclear. A systematic literature search was performed. Primary outcome was the mean difference between pre- and post-procedural LVMi. Secondary outcome was the mean difference in EF. Seven studies with a total of 845 patients were included. The pooled mean difference between pre-and post-procedural LVMi was -8.0 g/m2 (95% confidence interval [CI] -13.1, -2.8). On subgroup analysis, the mean differences between pre- and post-procedural LVMi for HD and HDF were -6.7 g/m2 (95% CI -14.5, 1.1) and -9.3 g/m2 (95% CI -16.3, -2.3), respectively (P for subgroups = .62). Pooled mean difference between pre- and post-procedural EF was 2.4% (95% CI -1.8, 6.5). On subgroup analysis, the mean differences between pre- and post-procedural EF for HD and HDF were 3.6% (95% CI -2.7, 9.8) and 2.0% (95% CI 2.9, 6.8), respectively (P for subgroups = .68). On meta-regression, age (Beta -0.35 ± 0.05, P < .001) and longer dialysis duration (Beta -0.12 ± 0.02, P < .001) were associated with lower mean difference between pre-and post-procedural EF. No significant effects on changes in LVMi and EF were observed with HDF compared with conventional HD.

Painless retrograde type A aortic dissection followed conservative treatment of type B aortic dissection: a case report.

BACKGROUND: Retrograde type A aortic dissection (RTAD) is a fatal aortic disease secondary to descending aortic dissection, and might be misdiagnosed due to its atypical symptoms lead to catastrophic outcomes. CASE PRESENTATION: We herein reported a case of a 40-year old Chinese non-comorbid man who received conservative treatment for acute type B aortic dissection and progressed to RTAD in a painless manner in a week. After open surgical aortic repair with stented elephant truck technique, the patient survived without obvious complication and cured with a satisfactory outcome in a half-year follow-up. CONCLUSION: This case indicates that RTAD may present without typical symptoms, early diagnosis and open surgical procedure are imperative for treating RTAD.

Elective proximal aortic surgery in patients with renal insufficiency.

BACKGROUND: To evaluate preoperative risk factors and postoperative outcomes in patients with preoperative renal insufficiency undergoing open surgical repair of the aortic root, ascending aorta, or aortic arch. METHODS: Our institutional database was reviewed for all patients undergoing elective aortic root, ascending aorta, and aortic arch open repairs. Patients were separated into two groups based on renal function. Patients with preoperative renal insufficiency were compared to those with normal renal function. Regression analyses were used to identify independent predictors of short and long term postoperative outcomes. RESULTS: The cohort consisted of 2140 patients, of which 55 had preoperative renal insufficiency (PRI). Patients with PRI were older and had worse cardiovascular risk profiles. On presentation, PRI patients were more likely to have lower ejection fraction. There was no difference in operative mortality between the two groups. The most frequent major postoperative complications among renal insufficiency patients were reoperation for bleeding (9.1%, P = .02). Logistic regression analysis indicated that PRI and left ventricular ejection fraction were independent predictors of major adverse events. Long-term survival was significantly reduced in preoperative renal insufficiency patients in the unmatched cohort. CONCLUSIONS: Aortic patients with preoperative renal insufficiency have a higher risk profile of mortality. Renal insufficiency remains an independent predictor of adverse outcomes following aortic surgery and understanding this patient population can guide physicians to improve outcomes.

Intraoperative graft flow profiles in coronary artery bypass surgery: A meta-analysis.

BACKGROUND: Conduits used in coronary artery bypass artery grafting (CABG) have different properties and flow profiles. We compared intraoperative mean graft flow (MGF) between arterial and venous conduits, off-pump CABG (OPCABG) and on-pump CABG (ONCABG) procedures, skeletonized and pedicled internal mammary artery (IMA) grafts, and pulsatility index (PI) between OPCABG and ONCABG, in pairwise meta-analyses. METHODS: Following a systematic literature search, all studies comparing MGF in arterial and venous grafts, were included. The primary endpoint was comparison of pooled MGF between arterial and venous grafts. Secondary endpoints were comparisons of pooled MGF in OPCABG vs ONCABG, anastomosed skeletonized vs pedicled IMA grafts, free skeletonized vs pedicled IMA grafts and PI in OPCABG versus ONCABG. RESULTS: A total of 25 studies with 4443 patients were included. Compared with venous grafts, arterial grafts had lower MGF (standardized mean difference [SMD], -0.28; 95% confidence interval [CI, -0.34; -0.22]; P < .001). OPCABG was associated with significantly lower MGF compared to ONCABG (SMD, -0.29; 95%CI, -0.50; -0.08]; P = .01). No differences were found in MGF between skeletonized vs pedicled IMA after anastomosis (SMD, 0.32; 95%CI [-0.08; 0.71]; P = .11) or in free flow (SMD, 0.76; 95%CI [-0.14; 1.65]; P = .10). No difference was found in PI between OPCABG and ONCABG. At meta-regression, age was associated with higher MGF, while OPCABG was associated with lower MGF. CONCLUSIONS: Intraoperative flow of venous conduits is higher than that of arterial grafts. Compared to OPCABG surgery, graft flow is higher in ONCABG. In skeletonized and pedicled IMA conduits, no difference in flow profiles was found.

Pulmonary artery aneurysms: Preoperative, intraoperative, and postoperative findings.

BACKGROUND: Pulmonary artery aneurysms (PAAs) are a rare but potentially lethal cardiovascular pathology. PAAs tend to develop in young patients with no gender discrepancy; they are most often associated with congenital heart disorders but also with systemic infections, vasculitis, pulmonary arterial hypertension, chronic pulmonary embolism, and malignancies. Dissection and rupture carry significant morbidity and mortality, thus patients require careful management, especially those with associated pulmonary hypertension. Given the rarity of this condition, physicians have yet to establish standard treatment guidelines. Most studies published to date are case reports with one or two patients; here, we describe our experience with six cases of large PAAs treated surgically at our institution. METHODS: We identified and retrospectively analyzed clinical data for patients who underwent surgery for PAAs between 2009 and 2017. RESULTS: The average age at surgery was 59.73 years, five patients were females, and 83.3% had baseline hypertension. Systolic murmurs were the most common clinical finding. The average aneurysmal size was 65.0 mm. We repaired the PAA with a woven Dacron graft (22-26 mm) in four patients. We performed concomitant pulmonary valve procedures on five patients: four replacements and one repair. Mean pump and cross-clamp times were 108.5 and 65 minutes. Operative and 30-day mortality was 0%. Average length of stay was 10.5 days. CONCLUSIONS: Postoperative mortality was 0%; all patients showed improvement of symptoms after surgery. These findings confirm that PAA repair has an acceptable risk profile in select patients.

Assessing Serum Levels of ADAMTS1 and ADAMTS4 as New Biomarkers for Patients with Type A Acute Aortic Dissection.

BACKGROUND Type A AAD, a serious cardiovascular emergency requiring urgent surgery, is the most common and serious AAD. The aim of this study was to investigate the diagnostic value of ADAMTS1 and ADAMTS4 in patients with type A acute aortic dissection (AAD). MATERIAL AND METHODS Immunohistochemistry and qRT-PCR were used to evaluate the protein and mRNA expression levels of ADAMTS1 and ADAMTS4 in 14 type A acute aortic dissection (AAD) tissues and 10 control aortic tissues. Serum ADAMTS1 and ADAMTS4 expression levels in 74 patients with type A AAD, 36 patients with hypertension (HPT), and 34 healthy donors were examined by ELISA. The diagnostic value of serum ADAMTS1 and ADAMTS4 were determined by receiver operator characteristic curve (ROC). Furthermore, the dynamic change of serum ADAMTS1, ADAMTS4, D-dimer, and CRP were detected before and after surgery at different time-points in 14 patients with type A AAD. RESULTS ADAMTS1 and ADAMTS4 protein and mRNA expression levels were found to be significantly higher in 14 type A AAD tissues (p<0.0001) compared with 10 control tissues. Serum ADAMTS1 and ADAMTS4 levels were significant higher in patients with type A AAD than those in the HPT and HD group (p<0.0001 for both). The AUC value, sensitivity, and specificity of ADAMTS1 were 0.9710 (95% CI: 0.9429 to 0.9991), 87.84%, and 97.06%, respectively, and those of ADAMTS4 were 0.9893 (95% CI: 0.9765 to 1.002), 94.59%, and 97.06%, respectively. In addition, serum ADAMTS4 level was gradually decreased with the time extension after surgery, similar to D-dimer change. CONCLUSIONS These data suggest that measurement of serum ADAMTS1 and ADAMTS4 levels could be potential diagnostic biomarkers for type A AAD, and ADAMTS4 might be a risk factor associated with type A AAD.

Cardiac Mass, Aortic Intramural Hematoma, and IgG4-related Disease: A Case Report.

As a designated entity within medicine, immunoglobulin G4 (IgG4)-related disease is relatively new. It is immune-mediated origin, characterized by a tendency for formation of tumefactive lesions, the infiltration of IgG4-positive plasma cells, and frequent but not invariable elevations of IgG4 levels in the serum. IgG4-related cardiac mass accompanying aortic intramural hematoma is an extremely rare clinical presentation. Herein we present the case of a patient who was admitted to our department complaining of severe chest pain. Computed tomographic angiography examination revealed a cardiac mass accompanying an aortic intramural hematoma. He underwent a surgical resection of the cardiac mass and a replacement of the ascending aorta with Hemashield Platinum graft and made an uneventful recovery. A diagnosis of an IgG4-related disease was made based on laboratory results and pathological examination. Corticosteroids were administered postoperatively. This case shows that the heart itself can also be a potential site for IgG4-related disease.

Carbon monoxide potently prevents ischemia-induced high-mobility group box 1 translocation and release and protects against lethal renal ischemia-reperfusion injury.

High-mobility group box 1 (HMGB1) is a chromatin-binding nuclear molecule that has potent proinflammatory effects once released by damaged cells. In some disease models, carbon monoxide (CO) exhibits anti-inflammatory and protective properties. Here, we investigated whether the protective effect of CO on renal ischemia-reperfusion injury is associated with the inhibition of HMGB1 translocation and release. A renal ischemia-reperfusion injury model was established with a 100% mortality rate in untreated mice. Pretreatment with the CO-releasing molecule-2 (CORM-2) resulted in 100% survival, maximal preservation of renal function, a marked reduction in pathological damage, and blunted upregulation of TLR4, RAGE, TNF-α, IL-1ß, IL-6, and MCP1 mRNA. Interestingly, CORM-2 pretreatment almost completely inhibited ischemia-induced HMGB1 nucleocytoplasmic shuttling and release. This inhibition was associated with a decrease in nuclear histone acetyltransferase activity. Indeed, CORM-2 pretreatment inhibited the acetylation and release of HMGB1 during hypoxic culture of primary mouse renal tubular epithelia cells in vitro. Using the same renal ischemia-reperfusion injury model, neutralization of HMGB1 was protective, and administration of exogenous HMGB1 largely reversed the protective effect of CORM-2 on kidney ischemia-reperfusion injury. Thus, CORM-2-delivered CO protects against lethal renal ischemia-reperfusion injury. This protection is correlated with the prevention of HMGB1 nuclear-cytoplasmic translocation and release.

Four-corners traction combined with continuous everting suture technique as a modification in bicaval anastomosis for orthotopic heart transplantation.

BACKGROUND: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. MATERIALS AND METHODS: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. RESULTS: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. CONCLUSIONS: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.

Spinal cord injury after open and endovascular repair of descending thoracic and thoracoabdominal aortic aneurysms: A meta-analysis.

OBJECTIVE: An inclusive contemporary analysis of spinal cord injury (SCI) rates in patients undergoing aneurysm repair and the factors associated with complications has not been performed. METHODS: Following a systematic literature search, studies from 2008 to 2018 on repair of descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA) were pooled in a meta-analysis performed using the generic inverse variance method. The primary outcome was permanent SCI. Secondary outcomes were temporary SCI, operative mortality, long-term mortality, postoperative stroke, and cerebrospinal fluid (CSF) drain-related complications. RESULTS: One-hundred sixty-nine studies (22,634 patients) were included. The pooled rate of permanent SCI was 4.5% (95% confidence interval [CI], 3.8-5.4); 3.5% (95% CI, 1.8-6.7) for DTA and 7.6% (96% CI, 6.2-9.3) for TAAA repair (P for subgroups = .02), 5.7% (95% CI, 4.3-7.5) for open repair and 3.9% (95% CI, 3.1-4.8) for endovascular repair (P for subgroups = .03). Rates for Crawford extents I, II, III, IV, and V aneurysms were 4.0% (95% CI, 3.0-5.0), 15.0% (95% CI, 10.0-22.0), 7.0% (95% CI, 6.0-9.0), 2.0% (95% CI, 2.0-4.0), and 7.0% (95% CI, 2.0-23.0) respectively (P for subgroups <.001). The pooled rates for operative mortality, late mortality at a mean follow-up of 5.0 years, stroke, and temporary SCI were 7.4% (95% CI, 6.1-9.4), 1.0% (95% CI, 0.0-1.0), 4.2% (95% CI, 3.6-4.8), and 3.7% (95% CI, 3.0-4.6), respectively. The pooled rates for severe, moderate, and minor CSF-drain related complications were 5.1% (95% CI, 2.23-11.1), 4.1% (95% CI, 0.6-22.0), and 3.6% (95% CI, 1.2-8.0) respectively. CONCLUSIONS: Despite improvement, both open and endovascular aneurysm repair remain associated with a substantial risk of permanent SCI. The risk is greater for TAAA repair, especially extent II, III, and V.

Overexpression of miR-223 Promotes Tolerogenic Properties of Dendritic Cells Involved in Heart Transplantation Tolerance by Targeting Irak1.

Dendritic cells (DCs) are key mediators of transplant rejection. Numerous factors have been identified that regulate transplant immunopathology by modulating the function of DCs. Among these, microRNAs (miRNAs), small non-coding RNA molecules, have received much attention. The miRNA miR-223 is very highly expressed and tightly regulated in hematopoietic cells. It plays an important role in modulating the immune response by regulating neutrophils and macrophages, and its dysregulation contributes to multiple types of immune diseases. However, the role of miR-223 in immune rejection is unclear. Here, we observed expression of miR-223 in patients and mice who had undergone heart transplantation and found that it increased in the serum of both, and also in DCs from the spleens of recipient mice, although it was unchanged in splenic T cells. We also found that miR-223 expression decreased in lipopolysaccharide-stimulated DCs. Increasing the level of miR-223 in DCs promoted polarization of DCs toward a tolerogenic phenotype, which indicates that miR-223 can attenuate activation and maturation of DCs. MiR-223 effectively induced regulatory T cells (Tregs) by inhibiting the function of antigen-presenting DCs. In addition, we identified Irak1 as a miR-223 target gene and an essential regulator of DC maturation. In mouse allogeneic heterotopic heart transplantation models, grafts survived longer and suffered less immune cell infiltration in mice with miR-223-overexpressing immature (im)DCs. In the miR-223-overexpressing imDC recipients, T cells from spleen differentiated into Tregs, and the level of IL-10 in heart grafts was markedly higher than that in the control group. In conclusion, miR-223 regulates the function of DCs via Irak1, differentiation of T cells into Tregs, and secretion of IL-10, thereby suppressing allogeneic heart graft rejection.

Angiographic Patency of Coronary Artery Bypass Conduits: A Network Meta-Analysis of Randomized Trials.

Background Several randomized trials have compared the patency of coronary artery bypass conduits. All of the published studies, however, have performed pairwise comparisons and a comprehensive evaluation of the patency rates of all conduits has yet to be published. We set out to investigate the angiographic patency rates of all conduits used in coronary bypass surgery by performing a network meta-analysis of the current available randomized evidence. Methods and Results A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the conventionally harvested saphenous vein, the no-touch saphenous vein, the radial artery (RA), the right internal thoracic artery, or the gastroepiploic artery. The primary outcome was graft occlusion. A total of 4160 studies were retrieved of which 14 were included with 3651 grafts analyzed. The weighted mean angiographic follow-up was 5.1 years. Compared with the conventionally harvested saphenous vein, both the RA (incidence rate ratio [IRR] 0.54; 95% CI, 0.35-0.82) and the no-touch saphenous vein (IRR 0.55; 95% CI, 0.39-0.78) were associated with lower graft occlusion. The RA ranked as the best conduit (rank score for RA 0.87 versus 0.85 for no-touch saphenous vein, 0.23 for right internal thoracic artery, 0.29 for gastroepiploic artery, and 0.25 for the conventionally harvested saphenous vein). Conclusions Compared with the conventionally harvested saphenous vein, only the RA and no-touch saphenous vein grafts are associated with significantly lower graft occlusion rates. The RA ranks as the best conduit. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020164492.

Effect of novel bicaval anastomosis technique for transplantation with and without prior cardiac surgery history.

BACKGROUND: To evaluate the graft outcomes after orthotopic heart transplantation (HTx) with a novel bicaval anastomosis technique between recipients with and without a history of prior cardiac surgery. METHODS: Of 70 patients who underwent HTx with a novel four-corners traction bicaval anastomosis technique from August 2017 to November 2019, 60 recipients underwent the HTx procedure as their first cardiac surgery (group A), while 10 recipients underwent HTx after prior cardiac surgery (group B). Patients in the two groups were compared in terms of their preoperative baseline variables such as etiological categories, history of blood transfusion and panel reactive antibody (PRA), intraoperative operation time and blood infusion volume, postoperative treatment time, and complications such as acute rejection and 30-day mortality as well as survival rates. RESULTS: Preoperative variables were comparable in group A and group B except for the history of blood transfusion (0% vs. 90.0%, P<0.001, respectively); the level of PRA was 7.5%±5.8% and 9.5%±10.9% for group A and B, respectively (P=0.583), but the time of the operation was nearly 1 hour longer for group B than group A (all P<0.05). No cases of left atrial thrombosis and donor heart distortion were observed in either group. Reoperation (1.7% vs. 10.0%, P=0.267), infection (0% vs. 10.0%, P=0.142), other postoperative complications as well as the 30-day mortality (1.7% vs. 10.0%, P=0.267), and postoperative survival rates (91.5% vs. 90.0%, P=0.805) were comparable between the two groups (all P>0.05). CONCLUSIONS: Four-corner traction bicaval anastomosis combined with a continuous everting suture technique may result in approximately comparable prognoses for heart recipients with a history of cardiac surgery when compared with those without a history of cardiac surgery and this technique may reduce the incidence of left atrial thrombosis and distortion. Further follow-up of the long-term outcomes will be required to validate these results.

Resistance of neonatal porcine Sertoli cells to human xenoantibody and complement-mediated lysis is associated with low expression of alpha-Gal and high production of clusterin and CD59.

BACKGROUND: Porcine Sertoli cells have an inherent resistance to human xenoreactive antibody and complement-mediated lysis, however, the mechanisms of protection are still unclear. METHODS: Neonatal porcine Sertoli cells (NPSCs) were isolated from testes of 10 to 15-day-old piglets. Immortalized porcine aortic endothelial cells (iPECs) were used as control cells. An in vitro humoral injury model was used to assess whether NPSCs could resist human xenoantibody and complement-mediated lysis. Expressions of alpha-Gal, clusterin, CD59, CD46, and CD55 were examined to investigate the possible mechanisms of the immunoprotection of NPSCs. RESULTS: Compared with iPECs, NPSCs significantly resisted human natural antibody and complement-mediated lysis when incubated with 20% normal human serum (NHS) in vitro (24.38 +/- 0.50 vs. 53.13 +/- 14.53%, P < 0.01). Mechanistically, NPSCs expressed lower level of alpha-Gal (Gmean: 41.78 +/- 2.39 vs. 95.17 +/- 2.39, P < 0.01), which was correlated with decreased binding of human xenoreactive IgG and IgM. Additionally, NPSCs expressed higher level of clusterin measured by both Western blot and fluorescence-activated cell sorter analysis and expressed more CD59 mRNA detected by reverse-transcription polymerase chain reaction. CONCLUSIONS: These data demonstrate that the resistance of NPSCs to human xenoantibody and complement-mediated lysis is associated with low expression of xenoantigen alpha-Gal and high production of the complement inhibitors clusterin and CD59.

IL-5 overexpression attenuates aortic dissection by reducing inflammation and smooth muscle cell apoptosis.

BACKGROUND: As an inflammation-related cytokine, interleukin (IL)-5 has been reported to be involved in the development of cardiovascular diseases, such as chronic heart failure and atherosclerosis. However, the role of IL-5 in acute aortic dissection (AAD) has barely been explored. METHODS: Aortic tissue samples from normal donors and patients with AAD were collected, and the expression and localization of IL-5 in aortic tissue were analyzed. In addition, a mouse AAD model was established by administering angiotensin II (Ang II) to ß-aminopropionitrile (BAPN)-treated mice. Morphological examinations and histopathologic analyses were performed to evaluate the effects of IL-5 overexpression on the occurrence of AAD. RESULTS: IL-5 expression was significantly decreased in aorta samples from AAD patients compared to those from donors, and macrophages were the main source of IL-5. In addition, IL-5 expression was decreased in plasma and aortic tissue samples from AAD mice. IL-5 overexpression markedly attenuated the occurrence of AAD in mice and produced corresponding decreases in the inflammatory response and cell apoptosis. In cocultures of macrophages and smooth muscle cells (SMCs), IL-5 overexpression in the macrophages significantly reduced Ang II-induced SMC apoptosis. CONCLUSION: IL-5 overexpression suppresses the development of AAD by reducing inflammation and SMC apoptosis. These results suggest that IL-5 is a potential therapeutic target in AAD.

When Behcet's disease meets Stanford type A aortic dissection, heart transplantation is a reliable treatment.

Behcet's disease (BD) is an immune system disease characterized by multi-system vascular inflammation. Its occurrence in patients who experience a Stanford type A aortic dissection (AD) is very rare, but extremely dangerous. A 44-year-old male patient was diagnosed with an acute Stanford type A AD and underwent a standard Bentall procedure and total aortic arch replacement plus descending aortic stented elephant trunk implantation. Aortic valve leakage and an aortic root pseudoaneurysm developed 3 months after surgery. At this time, we suspected that this patient had BD. After immunosuppressive treatment, we performed modified Bentall again; however, the heart failure occurred shortly after the second operation. Finally, we successfully treated this patient with a heart transplant. This is the first report of a heart transplant to treat BD with acute Stanford type A AD. In the diagnosis and treatment of acute Stanford type A AD, in addition to the traditional pathogenic factors, we need to be alert to BD, and heart transplantation may be a good way to treat such patients.

Robustness of the Comparative Observational Evidence Supporting Class I and II Cardiac Surgery Procedures.

Background Current cardiac surgery guidelines give Class I and II recommendations to valve-sparing root replacement over the Bentall procedure, mitral valve (MV) repair over replacement, and multiple arterial grafting with bilateral internal thoracic artery based on observational evidence. We evaluated the robustness of the observational studies supporting these recommendations using the E value, an index of unmeasured confounding. Methods and Results Observational studies cited in the guidelines and in the 3 largest meta-analyses comparing the procedures were evaluated for statistically significant effect measures. Two E values were calculated: 1 for the effect-size estimate and 1 for the lower limit of the 95% CI. Thirty-one observational studies were identified, and E values were computed for 75 effect estimates. The observed effect estimates for improved clinical outcomes with valve-sparing root replacement versus the Bentall procedure, MV repair versus replacement, and grafting with bilateral internal thoracic artery versus single internal thoracic artery could be explained by an unmeasured confounder that was associated with both the treatment and outcome by a risk ratio of more than 16.77, 4.32, and 3.14, respectively. For MV repair versus replacement and grafting with bilateral internal thoracic artery versus single internal thoracic artery, the average E values were lower than the effect sizes of the other measured confounders in 33.3% and 60.9% of the studies, respectively. For valve-sparing root replacement versus the Bentall procedure, no study reported effect sizes for associations of other covariates with outcomes. Conclusions The E values for observational evidence supporting the use of valve-sparing root replacement, MV repair, and grafting with bilateral internal thoracic artery over the Bentall procedure, MV replacement, and grafting with single internal thoracic artery are relatively low. This suggests that small-to-moderate unmeasured confounding could explain most of the observed associations for these procedures.

Effect of atrial pacing on post-operative atrial fibrillation following coronary artery bypass grafting: Pairwise and network meta-analyses.

BACKGROUND: To determine the effect of atrial pacing on the rate of post-operative atrial fibrillation (POAF) following coronary artery bypass grafting. METHODS: After a systematic literature search, randomized clinical trials (RCTs) comparing any combination of no pacing (NP), bi-atrial (BiA) pacing, left-atrial (LA) pacing and right-atrial (RA) pacing were included. Pairwise and network meta-analyses were performed using the generic inverse variance method. The primary outcome was POAF incidence. Secondary outcomes were postoperative bleeding, infection, and operative mortality. Leave-one-out and meta-regression were done. RESULTS: Fourteen RCTs were included with a total of 1727 patients. Compared with NP, any form of atrial pacing was significantly associated with lower incidence of POAF (odds ratio [OR]: 0.49; 95% confidence interval [CI]: 0.35-0.69). BiA pacing was associated with the larger risk reduction (OR: 0.36; 95% CI: 0.20-0.64 vs. 0.59; 95% CI: 0.34-1.02 for LA and 0.64; 95% CI: 0.38-1.07 for RA). Secondary outcomes were similar between the no pacing and pacing groups. On meta-regression, age and the use of continuous monitoring were associated with lower reduction of the incidence of POAF. In the network meta-analysis, BiA pacing ranked the best strategy for the prevention of POAF (OR: 0.34; 95% CI: 0.21-0.55). CONCLUSIONS: Compared to other pacing modalities, BiA pacing is associated with lower rates of POAF following CABG.