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Maintenance of genome stability relies on functional centromeres for correct chromosome segregation and faithful inheritance of the genetic information. The human centromere is the primary constriction within mitotic chromosomes made up of repetitive alpha-satellite DNA hierarchically organized in megabase-long arrays of near-identical higher order repeats (HORs). Centromeres are epigenetically specified by the presence of the centromere-specific histone H3 variant, CENP-A, which enables the assembly of the kinetochore for microtubule attachment. Notably, centromeric DNA is faithfully inherited as intact haplotypes from the parents to the offspring without intervening recombination, yet, outside of meiosis, centromeres are akin to common fragile sites (CFSs), manifesting crossing-overs and ongoing sequence instability. Consequences of DNA changes within the centromere are just starting to emerge, with unclear effects on intra- and inter-generational inheritance driven by centromere's essential role in kinetochore assembly. Here, we review evidence of meiotic selection operating to mitigate centromere drive, as well as recent reports on centromere damage, recombination and repair during the mitotic cell division. We propose an antagonistic pleiotropy interpretation to reconcile centromere DNA instability as both driver of aneuploidy that underlies degenerative diseases, while also potentially necessary for the maintenance of homogenized HORs for centromere function. We attempt to provide a framework for this conceptual leap taking into consideration the structural interface of centromere-kinetochore interaction and present case scenarios for its malfunctioning. Finally, we offer an integrated working model to connect DNA instability, chromatin, and structural changes with functional consequences on chromosome integrity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

The human centromere comprises large arrays of repetitive α-satellite DNA at the primary constriction of mitotic chromosomes. In addition, centromeres are epigenetically specified by the centromere-specific histone H3 variant CENP-A that supports kinetochore assembly to enable chromosome segregation. Because CENP-A is bound to only a fraction of the α-satellite elements within the megabase-sized centromere DNA, correlating the three-dimensional (3D) organization of α-satellite DNA and CENP-A remains elusive. To visualize centromere organization within a single chromatid, we used a combination of the centromere chromosome orientation fluorescence in situ hybridization (Cen-CO-FISH) technique together with structured illumination microscopy. Cen-CO-FISH allows the differential labeling of the sister chromatids without the denaturation step used in conventional FISH that may affect DNA structure. Our data indicate that α-satellite DNA is arranged in a ring-like organization within prometaphase chromosomes, in the presence or absence of spindle's microtubules. Using expansion microscopy, we found that CENP-A organization within mitotic chromosomes follows a rounded pattern similar to that of α-satellite DNA, often visible as a ring thicker at the outer surface oriented toward the kinetochore-microtubule interface. Collectively, our data provide a 3D reconstruction of α-satellite DNA along with CENP-A clusters that outlines the overall architecture of the mitotic centromere.

Objectives: No reliable scores are available to predict mortality following surgery for type A acute aortic dissection (TAAAD). Recently, the German Registry of Acute Aortic Dissection Type A (GERAADA) score has been developed. We aim to compare how the GERAADA score performs in predicting operative mortality for TAAAD to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II., Methods: We calculated the GERAADA score and EuroSCORE II in patients who underwent TAAAD repair at the Bristol Heart Institute. As there are no precise criteria to calculate the GERAADA score, we used 2 methods: a Clinical-GERAADA score, which evaluated malperfusion with clinical and radiological evidence, and a Radiological-GERAADA score, where malperfusion was assessed by computed tomography scan alone., Results: 207 consecutive patients had surgery for TAAAD, and the observed 30-day mortality was 15%. The Clinical-GERAADA score showed the strongest discriminative power with an area under the curve (AUC) of 0.80 [95% confidence interval (CI) 0.71-0.89], while the Radiological-GERAADA score had an AUC of 0.77 (95% CI 0.67-0.87). EuroSCORE II showed acceptable discriminative power with an AUC of 0.77 (95% CI 0.67-0.87)., Conclusions: Clinical GERAADA score performed better than the other scores and it is specific and easy to use in the context of a TAAAD. Further validation of the new criteria for malperfusion is needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer. Here, we describe KaryoCreate (karyotype CRISPR-engineered aneuploidy technology), a system that enables the generation of chromosome-specific aneuploidies by co-expression of an sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to mutant KNL1. We design unique and highly specific sgRNAs for 19 of the 24 chromosomes. Expression of these constructs leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny, with an average efficiency of 8% for gains and 12% for losses (up to 20%) validated across 10 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, frequent in gastrointestinal cancers, promotes resistance to TGF-β, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe an innovative technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond., Competing Interests: Declaration of interests T.D. is on the Scientific Advisory Board (SAB) of io9. S.M.L. is a co-founder of io9 and a member of Biological Dynamics, Inc. SAB. T.D. and N.B. are inventors on patent application no. 63/375,181., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Surgical treatment of primary lung T4 tumors is controversial especially when the cancer invades the mediastinal structures or the descending thoracic aorta. Conventional surgical treatment is associated with a high perioperative mortality and morbidity rate. Thoracic EndoVascular Aortic Repair has emerged as a valid off-label alternative to conventional surgery. We aimed to assess perioperative and midterm aortic-related outcome of patients who have undergone aortic stent-graft implantation, followed by en bloc surgical treatment of the involved aorta and lung cancer resection., Materials and Methods: From July 2017 to May 2020, we treated 5 patients diagnosed with a T4 lung cancer by the involvement of the descending thoracic aorta. When only the descending thoracic aorta is involved, a 2-stage procedure was considered, with aortic stent-graft implantation performed before tumor resection. One-stage strategy, with stent-graft implantation carried out before thoracotomy, was preferred for patients with the involvement of cardiac and/or other vascular mediastinal structures., Results: The mean age was 58.4 ± 6.2 years. All patients were affected by non-small cell lung cancer. All 5 patients required a single stent-graft to completely cover the involved segment of aorta. Four patients underwent a 2-stage procedure. One patient, with the involvement of the left inferior pulmonary vein, required a 1-stage en bloc resection of the left lower lobe, aortic wall adventitia, left inferior pulmonary vein, and reconstruction of the left atrial wall. Primary procedural success was achieved in all. At follow-up, no patient developed aortic-related complications. One patient died 2 years after surgery, due to local recurrence of the tumor., Conclusion: T4 lung resection combined with aortic stent-graft implantation can be safely performed. Endovascular surgery, by avoiding the use of cardiopulmonary bypass, aortic cross-clamping, and graft replacement, can reduce significant morbidity and mortality rate. Postoperative and long-term outcome of these patients treated with endovascular surgery is mainly related to pulmonary disease, not to aortic treatment.

Objectives: Female sex is considered a risk factor for mortality and morbidity following cardiac surgery. This study is the first to review the UK adult cardiac surgery national database to compare outcomes following surgical coronary revascularisation and valvular procedures between females and males., Methods: Using data from National Adult Cardiac Surgery Audit, we identified all elective and urgent, isolated coronary artery by-pass grafting (CABG), aortic valve replacement (AVR) and mitral valve replacement/repair (MVR) procedures from 2010 to 2018. We compared baseline data, operative data and outcomes of mortality, stroke, renal failure, deep sternal wound infection, return to theater for bleeding, and length of hospital stay. Multivariable mixed-effect logistical/linear regression models were used to assess relationships between sex and outcomes, adjusting for baseline characteristics., Results: Females, compared to males, had greater odds of experiencing 30-day mortality (CABG odd ratio [OR] 1.76, confidence interval [CI] 1.47-2.09, p < .001; AVR OR 1.59, CI 1.27-1.99, p < .001; MVR OR 1.37, CI 1.09-1.71, p = .006). After CABG, females also had higher rates of postoperative dialysis (OR 1.31, CI 1.12-1.52, p < .001), deep sternal wound infections (OR 1.43, CI 1.11-1.83, p = .005) and longer length of hospital stay (β 1.2, CI 1.0-1.4, p < .001) compared to males. Female sex was protective against returning to theater for postoperative bleeding following CABG (OR 0.76, CI 0.65-0.87, p < .001) and AVR (OR 0.72, CI 0.61-0.84, p < .001)., Conclusion: Females in the United Kingdom have an increased risk of short-term mortality after cardiac surgery compared to males. This highlights the need to focus on the understanding of the causes behind these disparities and implementation of strategies to improve outcomes in females., (© 2022 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Background: Hybrid coronary revascularization (HCR) combines the benefits of a left internal mammary artery to left anterior descending artery anastomosis, via a mini thoracotomy, with percutaneous coronary intervention (PCI) for other diseased coronaries., Aims: The aim of this meta-analysis is to compare the short- and long-term outcomes of HCR with those of coronary artery bypass grafting (CABG) for multi-vessel coronary artery disease (MCAD)., Methods: We performed a meta-analysis with a primary outcome of short-term mortality and secondary outcomes of mid-term survival, length of hospital stay, stroke, renal failure and mid-term MACE rate., Results: 3399 patients (HCR = 1164, CABG = 2235) were included, with no significant difference in short-term mortality between groups (OR = 1.50, 95% CI = [0.90,2.49], p = 0.11), although a higher mortality rate was seen in the HCR group (0.73% vs 0.64%). The average length of stay in intensive care unit was significantly shorter following HCR than CABG (mean difference = -15.52 h, CI = [-22.47,-8.59], p˂0.001) and overall hospital stay was also shorter in this group, although not statistically significant (mean difference = -3.15 days, 95% CI = [-6.55, 0.25], p = 0.07). HCR was associated with a reduced odds of blood transfusion (OR = 0.34, 95% CI = [0.22,0.54], p < 0.001). There was not a significant difference in mid-term survival (OR = 0.86, 95% CI = [0.62,1.21], p = 0.39) or MACE rate (OR = 0.82, 95% CI = [0.55,1.23], p = 0.34). No differences were found between HCR and CABG for post-operative stroke (OR = 1.36, 95% CI = [0.87, 2.13], p = 0.16) or renal failure (OR = 0.71, 95% CI = [0.43,1.16], p = 0.14)., Conclusions: HCR has a higher incidence of short-term mortality compared to CABG in patients with MCAD, although this difference is not statistically significant. Similar rates of mid-term survival and other short term post-operative complications were found between the two groups. HCR has a shorter ICU stays and reduced requirement for blood transfusion., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Ischemia and malperfusion are strong predictors of poor postoperative outcomes in type A acute aortic dissection (TAAAD). Serum lactate is an accurate surrogate point-of-care marker of malperfusion. The aim of this study is to investigate the correlation between lactate, in-hospital outcomes, and 1-year survival following TAAAD repair., Methods: One hundred and thirty-two patients underwent operative repair of TAAAD over a 4-year period at our institution 128 patients had serum lactate measurements at three stages peri-operatively-preoperatively, at the end of cardiopulmonary bypass (post-CPB) and 6 h postintensive care unit (ICU) admission. The primary outcomes were in-hospital mortality and 1-year survival. The secondary outcomes were the incidences of in-hospital morbidities., Results: Patients were divided into two groups: 88 (68.8%) with normal lactate and 40 (31.2%) with elevated lactate (>2.2 mmol/L). Lactate measured preoperatively (odds ratio 1.52, 95% confidence interval 1.17-2.07, p < .01), post-CPB (1.34, 1.14-1.64, p < .01) and 6 h post-ICU admission (1.29, 1.08-1.55, p < .01) was an independent predictor of in-hospital mortality. Following adjustment for the Penn Classification, lactate continued to have a significant correlation with in-hospital mortality at all three timepoints. There was a higher incidence of complications in the elevated lactate group and especially hemofiltration (20% vs. 9.1%, p = .08). 1-year survival was similar in both groups (p = .23)., Conclusions: There is a direct correlation between elevated serum lactate and postoperative mortality after TAAAD repair, which is independent of the Penn Classification status on admission., (© 2022 Wiley Periodicals LLC.)

Background: Coronary artery aneurysm represents a challenging and potentially fatal disease., Aim and Material Methods: We present the case of a giant right coronary artery aneurysm treated surgically after percutaneous intervention and fracture of the stent., Results and Discussion: The aneurism was opened and the coronary ligated proximally and distally. It was not possible to re-established continuity of the coronary artery or perform a bypass graft. An early surgical strategy would have re-established blood flow in the involved coronary artery and avoided chronic ischemia of the supplied myocardial territory., (© 2022 Wiley Periodicals LLC.)

Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system (CNS). The poor prognosis of GBM due to resistance to therapy has been associated with high chromosomal instability (CIN). Replication stress is a major cause of CIN that manifests as chromosome rearrangements, fragility, and breaks, including those cytologically expressed within specific chromosome regions named common fragile sites (CFSs). In this work, we characterized the expression of human CFSs in the glioblastoma U-251 MG cell line upon treatment with the inhibitor of DNA polymerase alpha aphidicolin (APH). We observed 52 gaps/breaks located within previously characterized CFSs. We found 17 to be CFSs in GBM cells upon treatment with APH, showing a frequency equal to at least 1% of the total gaps/breaks. We report that two CFSs localized to regions FRA2E (2p13/p12) and FRA2F (2q22) were only found in U-251 MG cells, but not lymphocytes or fibroblasts, after APH treatment. Notably, these glioblastoma-specific CFSs had a relatively high expression compared to the other CFSs with breakage frequency between ∼7 and 9%. Presence of long genes, incomplete replication, and delayed DNA synthesis during mitosis (MiDAS) after APH treatment suggest that an impaired replication process may contribute to this loci-specific fragility in U-251 MG cells. Altogether, our work offers a characterization of common fragile site expression in glioblastoma U-251 MG cells that may be further exploited for cytogenetic and clinical studies to advance our understanding of this incurable cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Balzano, Di Tommaso, Antoccia, Pelliccia and Giunta.)

Background: Despite advances in cardiac surgery, observational studies suggest that females have poorer post-operative outcomes than males. This study is the first to review sex related outcomes following both coronary artery bypass graft (CABG) and valve surgery with or without combined CABG., Methods: We identified 30 primary research articles reporting either short-term mortality (in-hospital/30 day), long-term mortality, and post-operative stroke, sternal wound infection and myocardial infarction (MI) in both sexes following CABG and valve surgery with or without combined CABG. Reported adjusted odds/hazard ratio were pooled using an inverse variance model., Results: Females undergoing CABG and combined valve and CABG surgery were at higher risk of short-term mortality (odds ratio (OR) 1.40; 95% confidence interval (CI) 1.32-1.49; I 2  = 79%) and post-operative stroke (OR 1.2; CI 1.07-1.34; I 2  = 90%) when compared to males. However, for isolated AVR, there was no difference found (OR 1.19; 95% CI 0.74-1.89). There was no increased risk in long-term mortality (OR 1.04; 95% CI: 0.93-1.16; I 2  = 82%), post-operative MI (OR 1.22; 95%CI: 0.89-1.67; I 2  = 60%) or deep sternal wound infection (OR 0.92; 95%CI: 0.65-1.03, I 2  = 87%). No evidence of publication bias or small study effect was found., Conclusion: Females are at a greater risk of short-term mortality and post-operative stroke than males following CABG and valve surgery combined with CABG. However, there is no difference for Isolated AVR. Long-term mortality is equivalent in both sexes. PROSPERO Registration: CRD42021244603., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Mitral valve (MV) repair has demonstrated excellent short- and long-term outcomes, however, its merit in the elderly population is still debated. We conducted a meta-analysis of studies that have compared the MV repair to replacement in the elderly population., Methods: A systematic literature search was conducted for any study published on MV surgery on elderly patients (≥75 years old). A pooled risk-ratio meta-analysis was done to evaluate short-term mortality, postoperative complications, surgical timings, and long-term survival rates., Results: A total of nine retrospective observational studies were included in the quantitative meta-analysis. Pooled meta-analysis showed a reduced risk of short-term mortality for the MV repair group (risk ratio [RR] = 0.41 [0.24-0.71], p-value = .005). Postoperative neurological complications were in favor of repair, although not significantly (RR = 0.49 [0.21-1.11], p-value = .07). Operative timings (cardiopulmonary bypass and crossclamp time) were not different between the groups although no data were available on the complexity of the repairs. Long-term survival rates were in favor of the repairs (pooled treatment effect of -0.47 [-0.64; -0.29], p = .005)., Conclusions: MV surgery is a safe and effective procedure for the elderly. MV repair demonstrated better short-term outcomes compared to replacement. Long-term survival rates are significantly better after repair., (© 2021 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Background: Aortic arch dissection is a catastrophic acute event involving the aorta. Its accurate diagnosis and treatment are mandatory to optimize patient outcome. We aimed to assess the efficacy and safety of endovascular treatment with transfemoral bare stents of isolated aortic arch dissection as a valid alternative in patients unsuitable for conventional surgery., Methods: In this case series, we report our experience with 3 patients affected by isolated aortic arch dissection treated with endovascular surgery from February 2019 to May 2019. All patients were associated with severe comorbidities emergently referred at our center. Vascular access was achieved by surgical exposure of the right common femoral artery performed under general anesthesia. All patients were observed for at least 3 months., Results: All patients were treated in a hybrid operative room with transfemoral implantation of a bare metal Jotec E-XL stent released in the aortic arch. The postoperative period was uneventful, and all 3 patients were discharged or transferred on the fourth postoperative day. At follow-up, computed tomography scans showed good results in all patients., Conclusions: A purely endovascular approach to located aortic arch dissections, with bare stents, remains challenging, although it has been proven to be a valid alternative treatment in some off-label cases., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The choice of ring for mitral valve repair is still largely left to the surgeon's preferences and there are no specific guidelines regulating this decision. Despite this previous researches have described important features appertaining to each of the different types of rings currently available. Particularly, the debate is still open in regards to the flexibility that these devices should or should not have. Later in this issue of the Journal, Panicker and colleagues have reported their results with flexible and rigid rings in mitral valve repair. The results are very interesting and once again are highlighting the importance of using the right ring for the right disease., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Objective: To ascertain whether body mass index (BMI) has a clinical effect on short- and long-term postoperative outcomes after surgical aortic valve replacement in patients with severe aortic stenosis., Design: Single-center, retrospective study., Setting: Tertiary referral hospital., Participants: The study comprised 1,561 patients who underwent isolated first-time aortic valve replacement between 2005 and 2012., Interventions: Fourteen underweight patients were removed from the analysis. The remaining patients were divided into the following 4 groups according to their BMI: 418 as normal weight (≥18.5 to <25 kg/m 2 ), 629 as overweight (≥25 to <30 kg/m 2 ), 342 as obese (≥30 to <35 kg/m 2 ), and 158 as very obese (≥35 kg/m 2 ). Early mortality and postoperative complications were compared, and long-term survival rates were investigated., Measurement and Main Results: Thirty-day mortality was higher in the normal weight group but did not reach statistical significance (p = 0.054), and the incidence of postoperative complications was not different for cerebrovascular accident (p = 0.70), re-sternotomy for bleeding (p = 0.17), sternal wound infection (p = 0.07), and dialysis (p = 0.07). With a mean follow-up time of 4.92 ± 2.82 years, survival rate was better in the overweight group. A Cox proportional hazard model found BMI inversely correlated with long-term mortality when analyzed in a univariable fashion (hazard ratio 0.95; p = 0.009), but this apparent protective effect disappeared when adjusted for preoperative covariates (hazard ratio 0.98, 95% confidence interval 0.96-1.004; p = 0.12)., Conclusion: Once adjusted for preoperative characteristics, obesity does not represent an independent predictor for long-term survival rates. There was a higher incidence of 30-day mortality in the normal weight group compared with the overweight and very obese groups. The incidence of deep sternal wound infection was higher in very obese patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We describe the rare case of a 61-year-old man admitted to our emergency department with visceral-organ and lower-limb malperfusion because of an unknown retroperitoneal high-grade undifferentiated pleomorphic sarcoma and a severe paraneoplastic obstruction of the descending thoracic aorta, treated with thoracic endovascular aortic repair. The postoperative period was uneventful, and the patient was discharged within 4 days. At 6-month follow-up, computed tomography showed complete patency of the descending thoracic aorta. This single case experience shows that thoracic endovascular aortic repair can be a less invasive and effective off-label alternative to exclude infiltrated or obstructed descending thoracic aorta, thus avoiding conventional surgery., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Here we evaluate the usefulness of transfemoral uncovered stent implantation to avoid secondary conventional surgery for residual type A aortic dissection (TAAD) of the aortic arch after ascending aorta replacement., Methods: From June 2009 to April 2015, 11 patients were treated with transfemoral implantation of uncovered stents in the aortic arch after surgical replacement of ascending aorta performed on average 4.7±2.3 years earlier. An enlarged dissected aortic arch or a dangerous median growth of more than 5 mm/yr or impending rupture presenting as chest pain were indications for treatment. The dissected aortic tracts diameter must not exceed 45 mm. Five patients (45.5%) were treated with Djumbodies Dissection System, 6 patients (54.5%) with Jotec E-XL aortic stent., Results: There were no perioperative deaths or permanent neurologic complications. Primary procedural success was obtained in all patients and the residual TAAD in aortic arch was obliterated, with disappearance of the false lumen. Median intensive care unit (ICU) stay was 24 hours; post-operative hospital stay was 5.2±1.4 days. One death, not aortic related, occurred during follow-up period (mean 5.2±1.9 years). Descending thoracic aorta diameter significantly increased in 3 patients (27.3%): one patient (9.0%) needed a secondary conventional surgery, the other 2 (18.2%) of a distal extension with PETTICOAT approach., Conclusions: Endovascular approach with uncovered metal bare stent is surely an evolving strategy to perform a purely endovascular treatment, indicated only for treatment of an aortic arch with a diameter of less than 40 or 45 mm, to avoid progressive thoracic aortic dilatation and/or rupture., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Late aneurysm formation in the proximal aorta or distal aortic arch is a recognized sequela of untreated stenosis of the aortic isthmus and is associated with substantial risk of aortic rupture. We describe the case of a 44-year-old man with untreated coarctation of the aorta who presented with a prestenotic dissecting thoracic aortic aneurysm. He declined surgery because he was a Jehovah's Witness. Instead, we performed emergency endovascular aortic repair in which 2 stent-grafts were placed in the descending aorta. Our experience suggests that this procedure is a useful and safe alternative to open surgery in patients who have aneurysms associated with coarctation of the aorta.

Objectives: The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency., Methods: Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10⁻⁵  M and 10⁻⁶ M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels., Results: At the end of the culture period, neointimal thickness was significantly (P = 0.001) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases., Conclusions: Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.

Background: To remark the feasibility of endovascular treatment of an aorto-caval fistula in a old high risk patient with "hostile" abdomen for previous surgeries., Methods: In September 2009 a 81-years-old patient was admitted in emergency at our department because of abdominal pain and massive oedema of the lower extremities associated to dyspnoea (New York Heart Association (NYHA) functional class III). A CT scan showed an aorto-caval fistula involving the abdominal aorta below the renal arteries. This abnormal communication was likely due to the previous abdominal surgeries, was complicated by occlusion of the inferior vena cava at the diaphragm and was responsible for the massive oedema of the lower extremities. Because of unstable conditions and hostile abdomen the patient was considered unfit for conventional surgery and an endovascular approach was planned. After unsuccessful attempt by positioning of an Amplatzer vascular ring into the fistula, a Medtronic covered stent-grafts were implanted from the renal arteries to the both common iliac arteries. The patient had an impressive improvement characterized by a 18 Kg weight loss and a complete restoration of the functional capacity (from NYHA class III to NYHA class I) associated to a complete resolution of the lower extremities oedema as confirmed at the a month-CT-scan., Conclusion: Endovascular surgery of aorto-caval fistula represents a good option in alternative to conventional surgery mostly in old high risk patient.

Background: Aortic pathology progression and/or procedure related complications following endovascular repair should always be considered mostly in older patients. We herein describe a hybrid procedure for treatment of rapidly expanding thoracoabdominal aneurysm following endovascular treatment of a descending thoracic aortic aneurysm in an older patient., Case Presentation: A 82-year-old man at 18 months after endovascular surgery for a contained rupture of descending thoracic aortic aneurysm revealed a type IV thoracoabdominal aneurysm with significant increase of the aortic diameters at superior mesenteric and renal artery levels. A hybrid approach consisting of preventive visceral vessel revascularization and endovascular repair of entire abdominal aorta was performed. Under general anaesthesia and by xyphopubic laparotomy, the infrarenal aneurysmatic aorta and common iliac arteries were replaced by a bifurcated woven prosthetic graf. From each of the prosthetic branches two reverse 14 x 7 mm bifurcated PTFE prosthetic grafts were anastomized to both renal arteries and to the celiac axis and superior mesenteric artery, respectively. Vessel ischemia was restricted to the time required for anastomosis. Three 10 cm Gore endovascular stent-grafts for a total length of 15 cm, were used. The overlapping of the stent-grafts was carried out from the bottom upwards, starting from the aorto-iliac prosthetic body up to the healthy segment of thoracic aorta, 40 mm from the previous stent-grafts.The patient was discharged on the 9th postoperative day., Conclusion: This technique offers the advantage of a less invasive treatment, reducing the risk of paraplegia, visceral ischaemia and pulmonary complications, mostly in older patients.