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Competing Interests: Funding Support and Author Disclosures Prof Vola is a clinical consultant for Affluent Medical. Prof Salizzoni is a surgical proctor for Epygon. Dr Vairo is an echocardiography proctor for Epygon. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Treatment of malignant melanoma has improved in the last few years owing to early detection and new therapeutic options. Still, management of advanced disease remains a challenge because it requires systemic treatment. In such cases, dacarbazine-based chemotherapy has been widely used, despite low efficacy. Neoadjuvant therapies emerge as alternative options that could help chemotherapy to achieve increased benefit. In this work, we evaluate LVR01, an attenuated Salmonella enterica serovar typhimurium, as neoadjuvant intralesional therapy in combination with dacarbazine in a preclinical melanoma model. B16F1 melanoma‒bearing mice received intraperitoneal administration of dacarbazine for 3 consecutive days. LVR01 treatment, consisting of one single intratumoral injection, was applied 1 day before chemotherapy began. This therapeutic approach retarded tumor growth and prolonged overall survival, revealing a strong synergistic antitumor effect. Dacarbazine induced a drastic reduction of secondary lymphoid organ cellularity, which was partially restored by Salmonella, particularly potentiating activated cytotoxic cell compartments. Systemic immune reactivation could be a consequence of the intense inflammatory tumor microenvironment induced by LVR01. We propose that the use of LVR01 as neoadjuvant intralesional therapy could be considered as an interesting strategy with close clinical application to boost chemotherapy effect in patients with melanoma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Health-related quality of life (HRQOL) is an increasingly important issue in assessing the consequences of any surgical or medical intervention. Our study aimed to evaluate change in HRQOL 6 months after elective cardiac operations and to identify specific predictors of poor HRQOL., Methods: In this prospective, single-center study, HRQOL was evaluated before and 6 months after the operation using the Medical Outcome Study 36-Item Short Form Health Survey questionnaire and its two components: the Physical Component Summary and the Mental Component Summary. We distinguished patients with worsening of HRQOL according to the minimal clinically important difference. All consecutive adult patients undergoing cardiac operations were included., Results: The preoperative and postoperative 36-Item Short Form Health Survey questionnaires were completed by 326 patients, and 24 patients died before completing follow-up questionnaires. On the basis of the definition used, clinically significant deterioration of HRQOL was observed in 93 patients (26.6%) for the Physical Component Summary and in 99 patients (28.2%) for the Mental Component Summary. Renal replacement for acute renal failure and mechanical ventilation for longer than 48 hours were independent risk factors for Physical Component Summary and Mental Component Summary worsening or death., Conclusions: Although our study showed overall improvement of quality of life after cardiac operations, more than one-quarter of the patients manifested deterioration of HRQOL at 6 months postoperatively. The findings from this study should help clinicians to inform patients about their likely postoperative functional status and quality of life., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous coronary intervention (PCI) for bifurcation lesions (BL) using 2 stents technique is known to be associated with high rates of procedural failure especially on the side branch (SB) mainly due to stent incomplete apposition. Stent deployment at very high pressure (SDHP) may lead to better stent expansion and apposition. However, SDHP may also be at the origin of deeper wall injury resulting into major cardiac adverse events. No data are available on evaluation of SDHP in BL treated by a mini-crush stent technique., Methods: One hundred and thirteen consecutive patients underwent PCI for BL (Medina 1, 1, 1) using a mini-crush stent technique with SDHP defined as ≥20atm. An angiographic follow-up was performed at 6 month and clinical follow-up was obtained at a median of 3 years., Results: Stent deployment mean pressures were 20±1.4atm (range 20-25) in the main vessel (MV) and 20±1.5atm (range 20-25) in SB. Simultaneous final kissing balloon was used in 92% of cases. PCI was successful in 100%. Angiographic follow-up was obtained in 83% of patients. Restenosis rate was 13% (12% restenosis in the SB) with only one case (0.8%) of SB probable thrombosis. Another case of late stent thrombosis occurred at a 3 years clinical follow-up., Conclusion: Compared with previously published studies in which stents were deployed at lower pressure, SDHP does not increase the restenosis rate in BL using mini-crush stent technique but seems to reduce the rate of stent thrombosis., (Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Ischemic mitral regurgitation (IMR) is a common complication of coronary artery disease and represents an independent predictor of mortality. In the IMR the pattern of mitral valve annular dilatation is asymmetrical: this can explain the long-term incidence of recurrent mitral regurgitation after surgical annular size reduction with a symmetrical ring. The aim of this study is to analyze early and mid-term results of mitral valve repair (MVR) with the CMA IMR ETlogix ring, specifically developed for the surgical correction of IMR., Methods: Retrospectively, we studied 157 consecutive patients who underwent MVR with the CMA ETlogix ring for the treatment of grade ≥2 IMR in our center between June 2006 and December 2012. We reported clinical and echocardiographic early and mid-term results of this surgical technique., Results: Postoperative 30days mortality was 6.3%. Postoperative echocardiography evaluation at discharge revealed the absence of residual MR in 70%, mild MR in 26.5% and moderate MR in 3.5% of patients respectively. Median echographic follow-up time was 28 (3-84) months: survival rate was 92.1% at 32months; free from mitral valve reoperation rate was 97.5% and grade >2 MR recurrence free survival rate was 96.6%., Conclusion: There are a few reports in the literature concerning the mid-term results of IMR surgical correction with CMA Etlogix ring. Our study, taking into account a large series of patients and an important follow-up period, demonstrates the effectiveness of this surgical repair technique reporting a low mid-term incidence of recurrent MR., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Totally endoscopic cardiac operations for coronary procedures and atrial septal defect repair have demonstrated improved quality of life, but they have required longer cross-clamp times compared with open operations. Although transcatheter valve implantation remains appropriate for inoperable patients, the totally endoscopic approach could be an effective treatment for lower risk patients, including complete removal of the stenotic aortic valve, while minimizing surgical chest wall trauma, and providing excellent early quality of life. Totally endoscopic aortic valve replacement procedures were previously performed with the 3f Enable bioprosthesis. We present the first case, to our knowledge, of Sorin Perceval implantation., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Although hundreds of samples obtained from ascending thoracic aortic aneurysms (ATAA) of patients undergoing elective surgical repair have already been characterized biomechanically, their rupture properties were always derived from uniaxial tensile tests. Due to their bulge shape, ATAAs are stretched biaxially in vivo. In order to understand the biaxial rupture of ATAAs, our group developed a novel methodology based on bulge inflation and full-field optical measurements. The objective of the current paper is threefold. Firstly, we will review the failure properties (maximum stress, maximum stretch) obtained by bulge inflation testing on a cohort of 31 patients and compare them with failure properties obtained by uniaxial tension in a previously published study. Secondly, we will investigate the relationship between the failure properties and the age of patients, showing that patients below 55years of age display significantly higher strength. Thirdly, we will define a rupture risk based on the extensibility of the tissue and we will show that this rupture risk is strongly correlated with the physiological elastic modulus of the tissue independently of the age, ATAA diameter or the aortic valve phenotype of the patient., Statement of Significance: Despite their medical importance, rupture properties of ascending thoracic aortic aneurysms (ATAA) subjected to biaxial tension were inexistent in the literature. In order to address this lack, our group developed a novel methodology based on bulge inflation and full-field optical measurements. Here we report rupture properties obtained with this methodology on 31 patients. It is shown for the first time that rupture occurs when the stretch applied to ATAAs reaches the maximum extensibility of the tissue and that this maximum extensibility correlates strongly with the elastic properties. The outcome is a better detection of at-risk individuals for elective surgical repair., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Our case reports the first migration of a stent already deployed at high pressure in the main vessel during a 2-stent strategy for a bifurcation lesion using T and protrusion technique. The Kissing balloon was not optimal and could have led to an insufficient strut/cell opening and then to LAD stent pulled back into the artery tree. This case report highlights the importance of an optimal Kissing Balloon in two stent bifurcation technique., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Minimally invasive aortic valve replacement has so far required a minithoracotomy or a ministernotomy. We present here the first series of totally endoscopic aortic valve replacement (TEAVR)., Methods: Between June 2013 and April 2015, 14 consecutive patients (12 males, mean age=76 ± 5.4 years) with a mean EuroSCORE II of 2.72 ± 0.03% underwent TEAVR. A five trocar setting was used in all patients: after ablation of the native valve, a Nitinol stented sutureless 3f Enable Medtronic valve, compressed into the main working trocar, was introduced into the thorax and then expanded in the aortic root., Results: Among the 14 patients, a thoracoscopic approach was successful in 13 (92.8%) and conversion into an open surgery using the right anterior minithoracotomy was necessary to close the aortotomy in one case. Mean cross-clamping and cardiopulmonary (CPB) times were 112 ± 18 and 161 ± 31 min, respectively. All patients left the surgical unit within 8 days after the operation without any paravalvular leakage. There was no paravalvular regurgitation, conductive block or any major adverse event at a mean follow-up of 10 ± 4 months (range 2-16)., Conclusions: TEAVR is feasible and safe in a selected subset of patients. Closed chest surgery has the potential to become the future approach of the isolated aortic valve replacement in low risk patients but further technical refinement and larger studies are necessary to reduce operative durations and enhance reproducibility., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: In this article we present a consecutive single-center experience of implantation of the Medtronic 3f Enable aortic valve (Medtronic Inc, Minneapolis, MN)., Methods: Between March 2011 and October 2014, 200 consecutive patients (mean age, 76.4 ± 5.9 years; logistic EuroScore, 7.8% ± 7.0%) in our unit received the 3f Enable valve. This is a retrospective analysis of this prospective monocentric cohort., Results: The 3f Enable valve could be implanted in all the scheduled 141 isolated aortic valve replacement (AVR) procedures (14 full sternotomies, 73 ministernotomies, 44 minithoracotomies, and 10 thoracoscopic approaches) and 59 combined procedures (all using full sternotomy). Reclamping was necessary in 7 (3.5%) patients (paravalvular leakage [PVL] was ≥ grade 1 because of undersizing or prosthetic misalignment); mean cross-clamp and cardiopulmonary bypass (CPB) times were 65 ± 31 and 91 ± 39 minutes, respectively. Sixteen (8%) patients required early implantation of a pacemaker (PM). At a mean follow-up of 12.6 ± 8.1 months, mean transvalvular gradient and effective orifice area (EOA) were 9.8 ± 4.4 mm Hg and 1.87 ± 0.6 cm(2), respectively. Mild PVL was present in 7 (3.5%) patients and moderate PVL was present in 5 (2.5%) patients. No device migration was registered, and no moderate PVL was detected in the last 100 patients of the cohort. Overall, 3-year survival was 78%., Conclusions: The 3f Enable valve shows excellent results regarding PVL but in our experience required a learning curve and a refinement of the technique of implantation. Use of the prosthesis was possible in various less invasive approaches., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the case of a 61-year-old man who underwent a Bentall procedure with a BioValsalva conduit for an acute type A aortic dissection. Two years later the patient presented at our institution with severe aortic regurgitation caused by the rupture of one cusp of the bioprosthesis (Elan valve) included in the conduit. A transcatheter valve-in-valve option was discussed by the heart team but was dismissed in favor of a sutureless 3f Enable valve implantation into the failing bioprosthesis after leaflet removal. This strategy simplified the surgical procedure and provided excellent postoperative hemodynamics at follow-up., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recently, sutureless aortic bioprostheses have been increasingly adopted to facilitate minimally invasive aortic valve replacement. We aimed at evaluating the impact of the transition from conventional bioprostheses to the routine use of the 3f Enable prosthesis (Medtronic ATS Medical, Minneapolis, MN) for aortic valve replacement through ministernotomy., Methods: Between November 2009 and November 2012, 83 consecutive minimally invasive aortic valve replacement procedures were performed in our institution by the same surgeon through an upper T-shaped ministernotomy. The earliest 42 patients (group A) received a conventional bioprosthesis, and the later 41 patients (group B) received the sutureless 3f Enable valve. Aortic clamping and cardiopulmonary bypass times, early outcomes, and valve hemodynamics were compared., Results: There was no statistical intergroup difference in baseline characteristics. In-hospital mortality was 1% (a single nonvalve-related death). Average aortic clamping times in group A and group B were, respectively, 85 ± 17 and 47 ± 11 minutes (p < 0.0001); the cardiopulmonary bypass time was 108 ± 21 and 69 ± 15 minutes, respectively (p < 0.0001). There were three paravalvular leakages in group A (grade I) and four in group B (two grade I, and two grade II); three pacemaker implantations occurred in group B (p = 0.07); mean transvalvular gradient at discharge was 16.9 ± 9.1 mm Hg in group A and 11.4 ± 4.3 mm Hg in group B (p = 0.0007). During follow-up (average 25.5 ± 12.9 months), one structural valve deterioration was registered in group A, and was treated with a valve-in-valve procedure., Conclusions: In our initial experience, the sutureless 3f Enable technology significantly reduced the clamping and cardiopulmonary bypass times, as well as the mean transvalvular gradient in aortic valve replacement through ministernotomy., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the first case of a successful transapical transcatheter treatment of a giant pseudoaneurysm originating from a rupture of the mitroaortic fibrosa that occurred 3 months after a Bentall procedure in a 81-year-old male patient. Because of the age of the patient and the location of the leak at the mitroaortic fibrosa, the risk of a conventional ascending aorta reoperation was considered too high, and a transcatheter approach was chosen. A transapical puncture was performed with a left minithoracotomy followed by a catheterization of the pseudoaneurysm neck and an 8-mm Amplatzer (St. Jude Medical, Saint Paul, MN, USA) device was delivered, resulting in a successful complete endovascular exclusion of the pseudo-aneurysmal sac., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 33-year-old man underwent urgent coronary artery de-obstruction for acute thrombotic occlusion of the left descending coronary artery. After 10 days of antiplatelet and heparin therapy, ventriculographic and echocardiographic control revealed a giant thrombus in the left ventricle, an ejection fraction of 40%, and severe mitral regurgitation. Heparin-induced thrombocytopenia was diagnosed. After urgent mitral valve annuloplasty and left ventricular thrombectomy, the patient was discharged. In the literature, several cases of right atrial and ventricular thrombi have been described; however, to the best of our knowledge, this is the first report of giant left ventricular thrombus during heparin-induced thrombocytopenia., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The consequences of inhibition of cortisol synthesis by a single dose of etomidate on subsequent vasopressor drug usage and the duration of relative adrenal insufficiency (RAI) after cardiac surgery are not known., Methods: This was a prospective, randomized, double-blinded controlled trial of 100 patients undergoing elective cardiac surgery and receiving either etomidate or propofol at induction of anaesthesia. A short corticotropin test was performed 12, 24, and 48 h after anaesthesia induction. RAI was defined as a response <250 nmol litre(-1)., Results: The mean (sd) norepinephrine infusion rate during the first 48 postoperative hours was 0.11 (0.01) and 0.11 (0.01) µg kg(-1) min(-1) in the etomidate and propofol groups, respectively (P=0.89). Time to norepinephrine withdrawal was similar between the groups. The incidence of RAI was higher in the etomidate group at 12 h (100% vs 41%, P<0.001) and 24 h (85% vs 25%, P<0.001)., Conclusions: A single bolus of etomidate blunts the hypothalamic-pituitary-adrenal axis response for more than 24 h in patients undergoing elective cardiac surgery, but this was not associated with an increase in vasopressor requirements.

Objectives: To study the evolution of antibiotic resistance in isolates of Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) obtained in Uruguay between the years 1976 and 2000, and to determine the incidence of class 1 and 2 integrons in the multi-resistant isolates., Methods: We studied 258 strains of Salmonella Typhimurium from various sources, isolated between 1976 and 2000. We determined the evolution of antibiotic resistance and the distribution of class 1 and 2 integrons in all isolates by means of disk diffusion assays and PCR., Results: During the period 1989-2000 resistance to streptomycin was 56.8%, tetracycline 13.6%, sulfonamides 11.2%, and ampicillin 7.2%. Resistance to gentamicin, kanamycin, chloramphenicol, and nalidixic acid were lower than 5%; no resistance was detected to fluoroquinolones, oxyiminocephalosporins, and amikacin. These results show a dramatic decrease with respect to values found in the period 1976-1988. In this period, resistance to streptomycin was 63.2%, tetracycline 36.8%, sulfonamides 32.3%, and ampicillin 27.8%. Throughout the two periods, 29 multi-resistant Salmonella Typhimurium strains were isolated harboring some class of integron: 15 strains had only intI2, 11 strains presented both intI1 and intI2, and three isolates only intI1., Conclusions: Our results show a marked decrease in resistance throughout these years, along with a correlation between resistance to different antibiotics and the presence of integrons.

We report the initial experience of two cardiovascular surgery centers in the treatment of descending thoracic aorta lesions with covered stent grafts in high-surgical risk patients. From April 1999 to November 2004, 54 patients, mean age 64 years (range 16-83), were treated by stent graft for a lesion of the descending aorta (degenerative aneurysms n = 22, aortic dissections n = 12, chronic post traumatic aneurysms n = 5, anastomotic false aneurysms n = 2, penetrating ulcers n = 4, intramural hematomas n = 5, traumatic rupture n = 4), with 42.6% treated on an emergency basis. Three devices were used: Talent (n = 49), Excluder (n = 4), and Zenith (n = 1). In three patients, combined surgery of the proximal aorta was performed. Prior bypass of the left supra-aortic arteries was performed in four patients. The follow-up was clinical and radiological (plain chest film and computed tomographic scan) at 1, 3, 6, 12, 18, and 24 months and yearly thereafter. The stent graft was successfully deployed in all cases. Two early deaths related to the stent graft (one migration and aortic rupture and one stroke) and one related to adult respiratory distress syndrome occurred. Morbidity was 16.6% (iliac access damage n = 4, groin reintervention n = 3, transient ischemic attack n = 1, tamponade n = 1). The follow-up was 100% complete (mean 22.8 months, range 3-51). Fifteen primary endoleaks (type I n = 6, type II n = 8, type III n = 1) and one secondary endoleak were reported. They were treated by additional stent graft (n = 7) and elective surgical conversion (n = 1). Six endoleaks resolved spontaneously at 6 months, and two are being monitored. Twelve endoleaks (75%) occurred in patients treated for degenerative aneurysms. Freedom from secondary reintervention was 81.3% at 3 years. Two transient paraparesias were observed at 3 and 18 months. Of the 13 deaths observed during the follow-up, only one was related to the stent graft. Actuarial survival at 12 and 24 months was 90.0% and 75.4%, respectively. Mortality results are encouraging in this specific cohort of high-surgical risk patients. A new kind of morbidity is observed, related to endoleaks, whose necessary management could hinder the durability of the technique.

Background: The aim of this study was to evaluate the late results in adult patients who underwent surgery of the abdominal aorta as children., Methods: During a 17-year period, eight children underwent surgery for lesions of the abdominal aorta. There were 6 boys and 2 girls, with an average age of 10 years. The presenting symptom that led to diagnosis of abdominal aortic lesions was hypertension in five cases and lower-limb claudication in three. The underlying disease was middle aortic syndrome in three cases, infrarenal aortic hypoplasia in two, infrarenal aortic aneurysm in two, and Takayasu's disease in one. Five children had associated renal artery lesions, including four with bilateral lesions and one with a unilateral lesion. Aortic bypass was used in all cases. A straight tube graft was placed between the distal descending thoracic or supraceliac aorta and the infrarenal aorta in six cases, and a bifurcated bypass was placed between the infrarenal aorta and the iliac arteries in two. Renal artery revascularization procedures (n = 9) included ex vivo repair with renal autotransplantation in five cases, direct reimplantation on the arch of Riolan in two, and direct reimplantation of the renal artery onto the aortic graft in two., Results: One patient died on postoperative day 1. The remaining seven patients recovered uneventfully. Mean follow-up was 10.2 years. No patient was lost to follow-up. Further surgical intervention was required in three patients. The indications for additional surgery were fibrosis of a renal artery reimplanted onto the graft at 3 years, deterioration of the aortoaortic graft at 5 years, and false iliac aneurysm at 20 years. All seven patients had normal physical development. The average increase in height and weight were 28.5 cm and 26.2 kg, respectively. All patients had normal sexual function, and two are parents. All patients are currently asymptomatic. Short Form 36 scores for quality-of-life parameters were 78% to 83%., Conclusions: Late results of abdominal aortic surgery in children, in our experience, are encouraging. Quality of life in adulthood was excellent. Insofar as possible, correction should be deferred until the child is 8 to 10 years old so that a prosthesis of sufficient diameter can be used.

Long-term success of endovascular treatment of infrarenal abdominal aortic aneurysms (AAA) depends on secure "attachment" of the stent to the proximal and distal necks of the aneurysm. The purpose of this retrospective study was to detect changes in the proximal neck early after endovascular treatment of infrarenal AAA. Between November 1997 and December 1998, we performed endovascular treatment of infrarenal AAA in 43 patients. A bifurcated modular stent (AneuRx by Medtronic) was used in all patients. An oversized stent with a diameter 10% greater than the preoperative diameter of the proximal neck of the AAA was used in all cases. Follow-up examinations were carried out at 1, 6, and 12 months using plain roentgenography, color Doppler ultrasound, and CT scan with contrast injection. Statistical analysis was performed using the Student's t-test. Deterioration of the aortic neck is the result of a variety of mechanisms. The natural history of the infrarenal neck of AAA following endovascular repair (as well as conventional open repair) is progressive enlargement. Stenting could be an added risk factor for expansion. Strict follow-up is essential for early detection of this complication.