miR-632 Induces DNAJB6 Inhibition Stimulating Endothelial-to-Mesenchymal Transition and Fibrosis in Marfan Syndrome Aortopathy.

Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 gene mutations leading to TGF-ß signaling hyperactivation, vascular wall weakness, and thoracic aortic aneurysms (TAAs). The pathogenetic mechanisms are not completely understood and patients undergo early vascular surgery to prevent TAA ruptures. We previously reported miR-632 upregulation in MFS TAA tissues compared with non-genetic TAA tissues. DNAJB6 is a gene target of miR-632 in cancer and plays a critical role in blocking epithelial-to-mesenchymal transition by inhibiting the Wnt/ß catenin pathway. TGF-ß signaling also activates Wnt/ß catenin signaling and induces endothelial-to-mesenchymal transition (End-Mt) and fibrosis. We documented that miR-632 upregulation correlated with DNAJB6 expression in both the endothelium and the tunica media of MFS TAA (p < 0.01). Wnt/ß catenin signaling, End-Mt, and fibrosis markers were also upregulated in MFS TAA tissues (p < 0.05, p < 0.01 and p < 0.001). Moreover, miR-632 overexpression inhibited DNAJB6, inducing Wnt/ß catenin signaling, as well as End-Mt and fibrosis exacerbation (p < 0.05 and p < 0.01). TGF-ß1 treatment also determined miR-632 upregulation (p < 0.01 and p < 0.001), with the consequent activation of the aforementioned processes. Our study provides new insights about the pathogenetic mechanisms in MFS aortopathy. Moreover, the high disease specificity of miR-632 and DNAJB6 suggests new potential prognostic factors and/or therapeutic targets in the progression of MFS aortopathy.

The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study.

The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-ß-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

Circulating Levels of Ferritin, RDW, PTLs as Predictive Biomarkers of Postoperative Atrial Fibrillation Risk after Cardiac Surgery in Extracorporeal Circulation.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haematological parameters as POAF risk biomarkers in patients subjected to cardiac surgery. We enrolled 105 patients (mean age = 70.1 ± 7.1 years; 70 men and 35 females) with diverse heart pathologies and who were subjected to cardiothoracic surgery. Their blood samples were collected and used to determine hematological parameters. Electrocardiographic and echocardiographic parameters were also evaluated. The data obtained demonstrated significantly higher levels of serum ferritin, red cell distribution width (RDW), and platelets (PLTs) in POAF patients. However, the serum ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥148.5 ng/mL, identifies the subjects at the highest POAF risk, and with abnormal ECG atrial parameters, such as PW indices, and altered structural heart disease variables. Serum ferritin, RDW, and PTLs represent predictive biomarkers of POAF after cardiothoracic surgery in CECC; particularly, serum ferritin combined with anormal PW indices and structural heart disease variables can represent an optimal tool for predicting not only POAF, but also the eventual stroke onset.

Correlation between the DNA fragmentation index (DFI) and sperm morphology of infertile patients.

PURPOSE: To evaluate the correlation between the DNA Fragmentation Index (DFI) and sperm morphology in patients undergoing ICSI, as a predictive parameter in reproductive outcomes. METHODS: A retrospective study was conducted on 125 infertile patients enrolled in a fertility clinic. Seminal characteristics were measured following the WHO guidelines (2010) for the examination of the seminal fluid. After collecting motile sperm population by pellet swim up, DFI was calculated and simultaneously associated with sperm morphology using in situ TUNEL assay and an image analyzer software in at least 250 spermatozoa for each patient. RESULTS: All subjects were divided into two groups according to a cutoff established, by choice, of the sperm DFI (15%): group A (< 15%) consisting of 65 patients and group B (≥ 15%) of 60 patients. Data were analyzed using non-parametric statistical methods. The results demonstrate that there is no statistical difference between the two groups in seminal characteristics. The collective data show a high significant correlation, suggesting that spermatozoa with abnormal morphology are the best candidates to contain DNA damage (p < 0.001). Also, when group A is compared with group B, an increased percentage of morphologically normal spermatozoa with fragmented DNA was observed in patients, with DFI values ≥ 15% (p < 0.001). CONCLUSION: These results are aimed at providing an exact value of DFI in morphologically normal spermatozoa, which will be helpful to the embryologist in evaluating the risk of transferring, during the ICSI procedure, a spermatozoon whit normal morphology but fragmented DNA.

Specific miRNA and Gene Deregulation Characterize the Increased Angiogenic Remodeling of Thoracic Aneurysmatic Aortopathy in Marfan Syndrome.

Marfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene, leading to alterations in the extracellular matrix microfibril assembly and the early formation of thoracic aorta aneurysms (TAAs). Non-genetic TAAs share many clinico-pathological aspects with MFS and deregulation of some microRNAs (miRNAs) has been demonstrated to be involved in the progression of TAA. In this study, 40 patients undergoing elective ascending aorta surgery were enrolled to compare TAA histomorphological features, miRNA profile and related target genes in order to find specific alterations that may explain the earlier and more severe clinical outcomes in MFS patients. Histomorphological, ultrastructural and in vitro studies were performed in order to compare aortic wall features of MFS and non-MFS TAA. MFS displayed greater glycosaminoglycan accumulation and loss/fragmentation of elastic fibers compared to non-MFS TAA. Immunohistochemistry revealed increased CD133+ angiogenic remodeling, greater MMP-2 expression, inflammation and smooth muscle cell (SMC) turnover in MFS TAA. Cultured SMCs from MFS confirmed higher turnover and α-smooth muscle actin expression compared with non-MFS TAA. Moreover, twenty-five miRNAs, including miR-26a, miR-29, miR-143 and miR-145, were found to be downregulated and only miR-632 was upregulated in MFS TAA in vivo. Bioinformatics analysis revealed that some deregulated miRNAs in MFS TAA are implicated in cell proliferation, extracellular matrix structure/function and TGFß signaling. Finally, gene analysis showed 28 upregulated and seven downregulated genes in MFS TAA, some of them belonging to the CDH1/APC and CCNA2/TP53 signaling pathways. Specific miRNA and gene deregulation characterized the aortopathy of MFS and this was associated with increased angiogenic remodeling, likely favoring the early and more severe clinical outcomes, compared to non-MFS TAA. Our findings provide new insights concerning the pathogenetic mechanisms of MFS TAA; further investigation is needed to confirm if these newly identified specific deregulated miRNAs may represent potential therapeutic targets to counteract the rapid progression of MFS aortopathy.

DNA fragmentation index, pAKT and pERK1/2 in cumulus cells are related to oocyte competence in patients undergoing in vitro fertilization programme.

Activated pERK1/2 and pAKT are key players in supporting cell survival and proliferation pathways. Translocation of pERK1/2 into the nucleus, where it interacts with transcription factors and DNA itself, is instrumental in exerting an anti-apoptotic effect. In this study, pAKT levels, pERK1/2 nuclear localization and DNA fragmentation index (DFI) in cumulus cells of single cumulus-oocyte complexes of patients undergoing in vitro fertilization programmes were evaluated and correlated with the clinical outcome of the related embryos. For a positive clinical outcome of blastocyst development, pERK1/2 nuclear localization and DFI value had a significant inverse relationship, whereas the former and the intracellular accumulation of pAKT had a significant direct relationship. This relationship was not observed for the negative clinical outcome of the arrested embryos. Moreover, intracellular accumulation of pAKT and DFI value had a significant inverse relationship in all samples examined. The obtained data suggest that the intranuclear relocation of pERK1/2, along with an enhanced intracellular accumulation of pAKT, may exert a survival effect and increase cell viability, therefore providing a novel marker tool to choose the best oocyte to be fertilized and submitted to an intracytoplasmic sperm injection cycle.

Gelatinolytic activity in gingival crevicular fluid and saliva of growing patients with Marfan syndrome: a case-control study.

BACKGROUND: Aim of the study was to evaluate the gelatinolytic activity in the saliva and gingival crevicular fluid from a sample group of subjects with Marfan syndrome. METHODS: Two groups were analyzed in this case-control study. A group of 28 subjects with Marfan syndrome (MG) was recruited from the Centre for Rare Disease, Marfan Clinic of Tor Vergata University Hospital. The second sample, 23 subjects, with the same characteristics and without any syndrome, was the control group (CG). Saliva and gingival crevicular fluid were collected and transferred to a sterile test tube and stored frozen at - 20 °C until analysis at the Medical Chemistry Laboratory. Gelatin substrate zymography was used for the evaluation and characterization of saliva and crevicular fluid proteinases. Correlation test and Student's t-test have been used to analyze data. RESULTS: In all samples different gelatin-degrading activities were observed. Two bands, which are related to the molecular weights of pro-MMP-9 and active MMP-9, respectively, were detectable in 100% of Marfan and control samples. MMP-2 activity was higher in Marfan group. Additional bands (55/48 kDa), corresponding to the activated forms of collagenase (MMP-13), were observed in saliva samples of both groups. CONCLUSIONS: The association of an enhanced activity by MMP-13 with an increased amount of active MMP-9 might be an important biomarker for the diagnosis of Marfan syndrome.

Mitral Valve Repair with a Semi-Rigid C-Band Annuloplasty Ring in Ischemic Mitral Regurgitation: Still a Viable Surgical Option?

BACKGROUND: Ischemic mitral valve regurgitation (IMR) develops in approximately 10% of patients after myocardial infarction. Surgical management of IMR is controversial, as many series have failed to demonstrate the superiority of mitral valve repair (MVRep) over mitral valve replacement (MVR) in IMR. Moreover, in the setting of MVRep, the choice of ring type is the subject of much debate. The study aim was to evaluate the results of MVRep in IMR with the use of a semi-rigid incomplete C-ring. METHODS: Between January 2006 and May 2014, a total of 105 patients (79 males, 26 females; mean age 69 ± 8 years) underwent surgical MVRep using a semi-rigid incomplete ring (median size 30 mm) during coronary artery bypass grafting (CABG) to treat IMR. The patients' mean logistic EuroSCORE was 14 ± 12, and the preoperative left ventricular ejection fraction was 43 ± 11%. The mean duration of follow up was 48 ± 31 months, and was 100% complete. RESULTS: In-hospital mortality was 6.6% (n = 7). The main predictor of in-hospital mortality was cardiopulmonary bypass time (p <0.05). Echocardiography performed at discharge showed moderate mitral regurgitation (MR) in only one patient, and significant reductions in left ventricular end-diastolic diameter (p <0.0001) and MR grade (p <0.0001). After seven years, freedom from all-cause death was 73 ± 9%, while freedoms from recurrence of MR grade ≥2 and NYHA class >II were 95 ± 3% and 89 ± 4%, respectively. Freedom from reintervention was 100%. CONCLUSIONS: Despite the adverse prognosis of IMR, the present study demonstrated the effectiveness and durability of mitral valve repair with the use of a semi-rigid ring, as a concomitant procedure to CABG, showing good results in terms of recurrence of MR and event-free survival at mid-term follow up.

Toll-like receptor-4 signaling pathway in aorta aging and diseases: "its double nature".

Recent advances in the field of innate immunity have revealed a complex role of innate immune signaling pathways in both tissue homeostasis and disease. Among them, the Toll-like receptor 4 (TLR-4) pathways has been linked to various pathophysiological conditions, such as cardiovascular diseases (CVDs). This has been interrogated by developing multiple laboratory tools that have shown in animal models and clinical conditions, the involvement of the TLR-4 signaling pathway in the pathophysiology of different CVDs, such as atherosclerosis, ischemic heart disease, heart failure, ischemia-reperfusion injury and aorta aneurysm. Among these, aorta aneurysm, a very complex pathological condition with uncertain etiology and fatal complications (i.e. dissection and rupture), has been associated with the occurrence of high risk cardiovascular conditions, including thrombosis and embolism. In this review, we discuss the possible role of TLR-4 signaling pathway in the development of aorta aneurysm, considering the emerging evidence from ongoing investigations. Our message is that emphasizing the role of TLR-4 signaling pathway in aorta aneurysm may serve as a starting point for future studies, leading to a better understanding of the pathophysiological basis and perhaps the effective treatment of this difficult human disease.

Gene Expression and Apoptosis Levels in Cumulus Cells of Patients with Polymorphisms of FSHR and LHB Undergoing in Vitro Fertilization Program.

BACKGROUND/AIMS: FSH receptor (FSHR) Ala307Thr and Asn680Ser and LHß chain (LHB) Trp28Arg and Ile35Thr polymorphisms affect the response to pharmacological ovarian stimulation with r-FSH in women undergoing assisted reproductive treatment (ART). Here, we evaluated the expression level of selected genes involved in follicle maturation and the possible onset of apoptosis in cumulus cells of patients with single and double FSHR and LHB polymorphisms, as potential markers of oocyte competence. METHODS: Cumulus cells from 36 stimulated patients were collected and SNP genotyping performed by PCR. Gene expression was evaluated through real-time PCR, and apoptosis estimated via TUNEL assay, and cleaved caspase-3 and pAKT immunostaining. RESULTS: The cumulative data show significant correlations indicating that the genetic alteration of FSHR and/or LHB genes may lead to perturbations of the signaling network programmed to granulosa cell survival and follicle development. Notably, when double heterozygotes were compared to the rest of the patients, a higher level of apoptosis in terms of both DNA fragmentation index and amount of active caspase-3 was observed in cumulus cells. CONCLUSIONS: These results may help to define personalized stimulation protocols in ART programs, to increase the success rate of ICSI procedures in accordance with the polymorphic condition of the individual patient.

Long-Term Results of Aortic Root Surgery in Marfan Syndrome Patients: A Single-Center Experience.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare long-term results of Marfan syndrome (MFS) patients affected by aortic root disease undergoing aortic root replacement with the Bentall or David operation. METHODS: Since 1994, a total of 59 patients has been followed at the authors' Marfan Center, having undergone either a Bentall operation (Bentall group, n = 30) or a David operation (David group, n = 29). RESULTS: No operative mortality was recorded. After 20 years (mean follow up 97 ± 82 months; range 1 to 369 months) no prosthesis-related major bleeding or thromboembolic events had been observed; the 20-year survival was 94 ± 6% in the Bentall group, and 100% in the David group (p = 0.32). Freedom from reintervention for aortic valve dysfunction was 100% in the Bentall group, and 75 ± 13% in the David group (p = 0.04). This inter-group difference became relevant after the first eight-year period of follow-up, and was mainly associated with a particular familiar genetic phenotype involving three out of four reoperated patients. Freedom from all-cause death, myocardial infarction, stroke, prosthetic valve-related complications, and reintervention on any aortic segment was 69 ± 12% in the Bentall group, and 67 ± 14% in the David group (p = 0.33). CONCLUSIONS: The Bentall and David operations are both associated with satisfactory long-term results in MFS patients. The low rate of valve prosthesis-related complications suggested that the Bentall operation would continue to be a standard surgical treatment. The reimplantation technique, adopted for less-dilated aortas, provides satisfactory freedom from reoperation. Careful attention should be paid to the reimplantation technique in patients affected by a serious familiar genetic phenotype.

Cardiovascular Disease in Ageing: An Overview on Thoracic Aortic Aneurysm as an Emerging Inflammatory Disease.

Medial degeneration associated with thoracic aortic aneurysm and acute aortic dissection was originally described by Erdheim as a noninflammatory lesion related to the loss of smooth muscle cells and elastic fibre fragmentation in the media. Recent evidences propose the strong role of a chronic immune/inflammatory process in aneurysm evocation and progression. The coexistence of inflammatory cells with markers of apoptotic vascular cell death in the media of ascending aorta with aneurysms and type A dissections raises the possibility that activated T cells and macrophages may contribute to the elimination of smooth muscle cells and degradation of the matrix. On the other hand, several inflammatory pathways (including TGF-ß, TLR-4 interferon-γ, chemokines, and interferon-γ) seem to be involved in the medial degeneration related to aged and dilated aorta. This is an overview on thoracic aortic aneurysm as an emerging inflammatory disease.

Relationship between apoptosis and survival molecules in human cumulus cells as markers of oocyte competence.

To select from a single patient the best oocytes able to reach the blastocyst stage, we searched for valuable markers for oocytes competence. We evaluated the DNA fragmentation index (DFI) and the level of some survival molecules, such as AKT, pAKT and pERK1/2, in individual cumulus cell-oocyte complexes (COC). The study included normo-responder women. The average age of the patients was 34.3. DFI in cumulus cells was evaluated using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labelling (TUNEL) assay in situ. AKT, pAKT and pERK1/2 were measured by immunological assay and densitometric analysis of fluorescent signals using NIS-Elements BR 3.10 image software. Statistical analysis was performed using STATA SE/14.1. The study focused on 53 patients involved after informed consent. Out of 255 MII oocytes, 197 were fertilized and the derived embryos had the following evolution: 117 completed the development to blastocyst and were transferred to uterus; 57 were vitrified at the blastocyst stage; and 23 were arrested during in vitro culture at different stages of cleavage. We found a significant statistical difference between the DFI of cumulus cells of the arrested embryos and the transferred blastocysts (P = 0.004), confirming that DFI could be considered as a valuable marker of oocyte competence. In addition, the pAKT/DFI ratio was higher in cumulus cells of oocytes able to produce blastocysts, indicating that DFI is significantly lower when pAKT is higher (P = 0.043). This study demonstrates for the first time that the relationship between apoptosis and survival molecules can be used as a marker to select the best oocytes.

Transcatheter aortic valve replacement for a bicuspid aortic valve following replacement of the ascending aorta.

A normally functioning bicuspid aortic valve that is spared during replacement of the ascending aorta may ultimately require replacement due to structural deterioration. We report the use of transcatheter aortic valve replacement to replace a stenotic BAV 17 years following replacement of the ascending aorta.

Matrix Metalloproteinases (MMPs), Their Genetic Variants and miRNA in Mitral Valve Diseases: Potential Biomarker Tools and Targets for Personalized Treatments.

Mitral valve diseases (MVD)s, comprising congenital and acquired forms, are characterized by a diverse etiology, pathophysiology, prevalence, and incidence. In industrialized countries, the acquired forms represent 2.5% of all cardiovascular diseases, with a marked augmentation after the age of 65 years. In addition, all forms of MVDs (i.e., degenerative forms) have a difficult clinical management. The major challenge is 'the early diagnosis', and echocardiographic analysis has been shown inappropriate for diagnosing MVD in moderate forms. Thus, there is a strong need to identify more appropriate biomarker tools to diagnose MVDs at early clinical stage before complications occur and worsen the prognosis. Innovative biomarker tools may particularly be appropriate for the complex treatment of elderly patients, the clinical management of which is very difficult due to the high risk of surgical interventions and no clear benefits in terms of life expectancy or quality of life compared to younger patients. These biomarker tools may be identified as genetic factors and/or components of cellular and molecular pathways related to the mechanisms of MDV pathophysiology. In this review, emphasis is placed on the possibility of proposing matrix metalloproteinase (MMP) pathways, their genetic variants and microRNA as promising predictive, diagnostic and prognostic biomarkers and targets for personalized treatments. Evidence is also provided of the lack of any consistent evidence which actually hampers their clinical application. Thus, criticisms and concerns are underlined, as well as suggestions to close the existing gaps.

Acute Type A Aortic Dissection: Beyond the Diameter.

Aortic dissection is a life-threatening condition in which early diagnosis, treatment and close follow up are critical for survival. Between 60% and 70% of patients with acute aortic dissection are affected at the ascending aorta, classified as Stanford type A (TAD). Preventive surgery of the aorta in asymptomatic patients on the basis of aortic size alone remains controversial among patient populations without known risk factors for aortic dissection. In fact, many dissection patients do not appear to have markedly dilated aortas at the time of presentation. In contrast, previous studies have indicated that the incidence of aortic dissection did not decrease, regardless of elective aortic replacement therapy. An increased aortic size as a follow up parameter is not sufficient to predict aortic dissection and rupture. Here, published evidence is reported regarding the limited role of aortic size in the genesis of TAD. Currently, a need exists to develop new markers to prevent aortic complications, especially in patients with sporadic ascending aneurysms (S-TAAs). It is important to emphasize this interesting aspect to the scientific cardiothoracic surgery forum in an attempt to improve guidelines for this disease.

Impact of Prosthesis-Patient Mismatch after Mitral Valve Replacement.

BACKGROUND: The study aim was to determine the impact of prosthesis-patient mismatch (PPM) on early and late clinical outcomes, left atrial and ventricular remodeling, late tricuspid valve regurgitation and pulmonary hypertension (PH) in patients after mitral valve replacement (MVR). METHODS: A total of 46 patients (mean age 66 ± 9.3 years) with mitral valve diseases and undergoing isolated MVR was enrolled in the study. The mitral valve effective orifice area (EOA) was determined using the continuity equation and indexed for the patient's body surface area (EOAi). PPM was defined as EOAi ≤1.2 cm2/m2. PH was defined as a systolic pulmonary artery pressure (sPAP) >40 mmHg. Both, clinical and echocardiographic follow up were performed. RESULTS: PPM was identified in 25% of patients, but no significant differences were observed in baseline and operative characteristics when comparing patients with and without PPM. The NYHA class was improved in most cases after surgery. Indeed, significant decreases in mean transvalvular gradient (from 8.6 ± 2.8 mmHg to 5 ± 1.3 mmHg, p = 0.001), left atrial dimension (LAD) (from 31.9 ±9.8 mm to 29.5 ± 7 mm, p = 0.011), left ventricular end-systolic diameter (from 42.6 ± 18.1 mm to 35.5 ± 6.6 mm, p = 0.044) and left ventricular end-diastolic diameter (from 55.8 ± 19.2 mm to 48.7 ± 6.1 mm, p = 0.024) were observed over time when comparing preoperative and postoperative echocardiographic data. In addition, at follow up (mean 6.9 ± 1.8 years) there were significant decreases in LAD (from 31.9 ± 9.8 mm to 28 ± 11.1 mm, p = 0.001), left ventricular enddiastolic volume (from 106.9 ± 32.9 ml to 92.3 ± 21.9 ml, p = 0.024), tricuspid regurgitation (TR) (from 87% to 27%, p = 0.002) and PH (from 78.3% to 58.7%, p = 0.043) in all patients. No significant differences were observed in hemodynamic, clinical outcome and atrial natriuretic peptide levels of patients with and without PPM. CONCLUSIONS: Mitral PPM does not appear to have any negative effect on ventricular and atrial remodeling, TR and PH during the early and late postoperative periods.

Partially anaortic clampless off-pump coronary artery bypass prevents neurologic injury compared to on-pump coronary surgery: a propensity score-matched study on 286 patients.

Anaortic coronary artery bypass proved to prevent early neurologic injury compared to on-pump CABG. The Cardica PAS-Port(®) is a fully automated device that might be able to perform proximal aorto-venous anastomoses without an increased embolic risk. We evaluated early post-operative neurologic outcome in a matched population following clampless OPCAB (CCAB: either "all-arterial" or with automatically anastomosed venous grafts) or on-pump CABG. 366 consecutive patients were submitted to isolated coronary bypass by a single surgeon experienced in both off and on-pump procedures between January 2009 and December 2013. Of these patients, 223 underwent a clampless off-pump revascularization. After propensity score matching, 143 pairs were selected, who received either off-pump or on-pump surgery. In the off-pump group, CCAB was performed with an all-arterial approach (n = 33) or with automated proximal anastomosis of the venous graft(s) by means of the Cardica PAS-Port(®) connector (n = 110). Neurologic injury was defined as non-reversible (NRNI: lethal coma or stroke) or reversible (RNI: TIA or delirium). Operative mortality was 2.4 % (CCAB 1.4 %; CABG 3.5 %; p = 0.14). The global rate of early neurologic injury was 5.6 % (CCAB 2.1 vs. CABG 9.1 %; p = 0.006). Incidence was 1.4 % for NRNI (CCAB 0 vs. CABG 2.8 %; p = 0.04) and 4.2 % for RNI (CCAB 2.1 vs. CABG 6.3 %; p = 0.06). No differences were found among other major perioperative outcomes. CCAB prevents both early post-operative RNI and NRNI. This result can be achieved with a totally anaortic strategy and also with the aid of a fully automated device for proximal aorto-venous anastomoses.

Penn classification in acute aortic dissection patients.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of the Penn classification in predicting in-hospital mortality after surgery in acute type A aortic dissection patients. METHODS: We evaluated 58 patients (42 men and 16 women; mean age 62.17 ± 10.6 years) who underwent emergency surgery for acute type A aortic dissection between September 2003 and June 2010 in our department. We investigated the correlation between the pre-operative malperfusion and in-hospital outcome after surgery. RESULTS: Twenty-eight patients (48%) were Penn class Aa (absence of branch vessel malperfusion or circulatory collapse), 11 (19%) were Penn class Ab (branch vessel malperfusion with ischaemia), 5 (9%) were Penn class Ac (circulatory collapse with or without cardiac involvement) and 14 (24%) were Penn class Abc (both branch vessel malperfusion and circulatory collapse). The number of patients with localized or generalized ischaemia or both, Penn class non-Aa, was 30 (52%). In-hospital mortality was 24%. In-hospital mortality was significantly higher in Penn class Abc and Penn class non-Aa. Intensive unit care stay, hospital ward stay and overall hospital stay was longer in Penn class non-Aa vs Penn class Aa. De Bakey type I dissection and type II diabetes mellitus were associated with in-hospital mortality. CONCLUSION: Preoperative malperfusion is important for the evaluation of patients with acute aortic type A dissection. The Penn classification is a simple and quick method to apply and predict in-hospital mortality and outcomes.