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- Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapyPublication . Ribeiro, Sónia; Simões, Ana Rita; Rocha, Filipe; Vala, Inês Sofia; Pinto, Ana Teresa; Ministro, Augusto; Poli, Maria Esmeralda; Diegues, Isabel Maria; Pina, Maria Filomena; Benadjaoud, Mohamed Amine; Flamant, Stephane; Tamarat, Radia; Osório, Hugo; Pais, Diogo; Casal, Diogo; Pinto, Fausto J.; Matthiesen, Rune; Fiuza, Manuela; Santos, Susana Constantino RosaThe contribution of radiotherapy, per se, to late cardiotoxicity remains controversial. To clarify its impact on the development of early cardiac dysfunction, we developed an experimental model in which the hearts of rats were exposed, in a fractionated plan, to clinically relevant doses of ionizing radiation for oncological patients that undergo thoracic radiotherapy. Rat hearts were exposed to daily doses of 0.04, 0.3, and 1.2 Gy for 23 days, achieving cumulative doses of 0.92, 6.9, and 27.6 Gy, respectively. We demonstrate that myocardial deformation, assessed by global longitudinal strain, was impaired (a relative percentage reduction of >15% from baseline) in a dose-dependent manner at 18 months. Moreover, by scanning electron microscopy, the microvascular density in the cardiac apex was significantly decreased exclusively at 27.6 Gy dosage. Before GLS impairment detection, several tools (qRT-PCR, mass spectrometry, and western blot) were used to assess molecular changes in the cardiac tissue. The number/expression of several genes, proteins, and KEGG pathways, related to inflammation, fibrosis, and cardiac muscle contraction, were differently expressed in the cardiac tissue according to the cumulative dose. Subclinical cardiac dysfunction occurs in a dose-dependent manner as detected by molecular changes in cardiac tissue, a predictor of the severity of global longitudinal strain impairment. Moreover, there was no dose threshold below which no myocardial deformation impairment was detected. Our findings i) contribute to developing new markers and exploring non-invasive magnetic resonance imaging to assess cardiac tissue changes as an early predictor of cardiac dysfunction; ii) should raise red flags, since there is no dose threshold below which no myocardial deformation impairment was detected and should be considered in radiation-based imaging and -guided therapeutic cardiac procedures; and iii) highlights the need for personalized clinical approaches.
- A catastrophic seronegative anti-phospholipid syndrome: case and literature reviewPublication . Pinto, Vanda; Ministro, Augusto; Carreira, Nuno; Cardoso, Ana; Gonçalves, Catarina Sousa; Henriques, Mickael; Rato, João; Silva, Emanuel; Pedro, Luís MBackground: Antiphospholipid Syndrome (APS) is a multisystemic autoimmune disease characterized by arterial and venous thrombosis and / or obstetric morbidity in the presence of at least one circulating anti-phospholipid antibody. The spectrum of vascular events varies from deep venous thrombosis to catastrophic APS, a rare form characterized by acute multiorgan thrombosis and high mortality. Case report: We present the case of a 32-week pregnant woman arriving in the hospital emergency room with bilateral acute lower limb ischemia. In the obstetric evaluation, fetal death was declared. Computerized Tomography angiography showed pulmonary embolism of both pulmonary arteries, areas of splenic and right renal infarction and multiple arterial and venous thrombosis. The patient underwent urgent caesarean section and axillary-bifemoral bypass. No events registered. In the postoperative period, in an intensive care unit, treatment with rituximab and plasmapheresis were added to anticoagulant therapy. The laboratorial investigation was negative for thrombophilia and autoimmune diseases. Conclusion: Catastrophic APS develops quickly, with multiorgan involvement and high mortality rate. The presented case poses a multidisciplinary challenge, with the surgical approach of extra-anatomical revascularization being less invasive and guaranteeing immediate perfusion of the lower limbs. Although the serological tests were negative for anti-phospholipid antibodies, this case hardly fits into another diagnosis. Therefore, it was treated as a catastrophic APS, having shown a favorable evolution.
- Clinical aspects and present challenges of the seat belt aortaPublication . Melo, Ryan; Amorim, Pedro; Soares, Tony; Fernandes E Fernandes, Ruy; Ministro, Augusto; Garrido, Pedro; Fernandes e Fernandes, José; Pedro, Luís MObjective: Seat belt aorta is rare and difficult to manage. The lack of data and follow-up increases the complexity of treating such patients. We aimed to create a decision algorithm by reviewing our current experience and analyzing the presentation and management of our patients. Methods: We performed a descriptive case series based on retrospective analysis of all consecutive patients admitted with the diagnosis of seat belt aorta from 2008 to 2018. Seat belt aorta was defined as any blunt abdominal aortic lesion resulting from a seat belt compression mechanism after a car accident. Results: Nine consecutive patients were admitted with the diagnosis of seat belt aorta, all of whom developed lesions in the infrarenal aorta. Eight patients were assessed in the acute phase and one patient presented with late-onset symptoms. Associated injuries were present in all acute patients, and seat belt sign and small bowel injury were present in 88%. One patient presented with a small intimal tear and was treated conservatively. All other patients diagnosed with large intimal flaps (seven patients) and pseudoaneurysm (one patient) underwent open repair in five cases and endovascular repair in three cases. In-hospital mortality for the acute cases was 38%, with no mortality seen during follow-up. Two patients submitted to endovascular repair required reinterventions. Conclusions: Seat belt aorta is a deadly condition, frequently associated with blunt thoracoabdominal trauma with concomitant injuries; the presence of a seat belt sign or lower limb ischemia must lead to a high diagnostic suspicion. Management must take into account the other concomitant injuries. Follow-up is crucial as most patients are young; they may develop complications and subsequently require further intervention.
- Early impairment of paracrine and phenotypic features in resident cardiac mesenchymal stromal cells after thoracic radiotherapyPublication . Picchio, Vittorio; Gaetani, Roberto; Pagano, Francesca; Derevyanchuk, Yuriy; Pagliarosi, Olivia; Floris, Erica; Cozzolino, Claudia; Bernava, Giacomo; Bordin, Antonella; Rocha, Filipe; Pereira, Ana; Ministro, Augusto; Pinto, Ana; De Falco, Elena; Serino, Gianpaolo; Massai, Diana; Tamarat, Radia; Pesce, Maurizio; Santos, Susana Constantino Rosa; Messina, Elisa; Chimenti, IsottaRadiotherapy-induced cardiac toxicity and consequent diseases still represent potential severe late complications for many cancer survivors who undergo therapeutic thoracic irradiation. We aimed to assess the phenotypic and paracrine features of resident cardiac mesenchymal stromal cells (CMSCs) at early follow-up after the end of thoracic irradiation of the heart as an early sign and/or mechanism of cardiac toxicity anticipating late organ dysfunction. Resident CMSCs were isolated from a rat model of fractionated thoracic irradiation with accurate and clinically relevant heart dosimetry that developed delayed dose-dependent cardiac dysfunction after 1 year. Cells were isolated 6 and 12 weeks after the end of radiotherapy and fully characterized at the transcriptional, paracrine, and functional levels. CMSCs displayed several altered features in a dose- and time-dependent trend, with the most impaired characteristics observed in those exposed in situ to the highest radiation dose with time. In particular, altered features included impaired cell migration and 3D growth and a and significant association of transcriptomic data with GO terms related to altered cytokine and growth factor signaling. Indeed, the altered paracrine profile of CMSCs derived from the group at the highest dose at the 12-week follow-up gave significantly reduced angiogenic support to endothelial cells and polarized macrophages toward a pro-inflammatory profile. Data collected in a clinically relevant rat model of heart irradiation simulating thoracic radiotherapy suggest that early paracrine and transcriptional alterations of the cardiac stroma may represent a dose- and time-dependent biological substrate for the delayed cardiac dysfunction phenotype observed in vivo.
- Clinical outcomes of aortic arch hybrid repair in a real-world single-center experiencePublication . Soares, Tony; Melo, Ryan; Amorim, Pedro; Ministro, Augusto; Sobrinho, Gonçalo; Silvestre, Luís; Fernandes E Fernandes, Ruy; Martins, Carlos; Fernandes e Fernandes, José; Pedro, Luís MObjective: Aortic arch aneurysmal disease remains a therapeutic challenge. For patients unsuitable for standard open surgery, hybrid repair with debranching of the supra-aortic arteries followed by thoracic endovascular grafting has been shown to be an effective solution. The aim of this study was to report the clinical outcomes of a single-institution experience using hybrid aortic arch repair. Methods: The cases of all consecutive patients submitted to hybrid aortic arch repair between January 2010 and June 2018 were prospectively collected and retrospectively analyzed. The outcomes of the study were 30-day mortality, perioperative complications, 2-year survival, endoleak, and reintervention rates. Results: A total of 35 patients with a median age of 71 years (interquartile range, 62-77 years) were submitted to hybrid aortic arch repair, with a median follow-up of 26.9 months (interquartile range, 2.4-63.6 months). Ten procedures (28.6%) were performed urgently for contained rupture. The most common etiology was degenerative (n ¼ 14 [40.0%]). The proximal landing zones according to the Ishimaru classification were zone 2 in 20 patients (57.1%), zone 1 in 12 patients (34.3%), and zone 0 in 3 patients (8.6%). Early endoleaks were observed in six patients (17.1%), equally distributed between type I and type II. Late endoleaks were identified in 4 of 24 patients (16.7%; type I, n ¼ 2 [8.3%]; type II, n ¼ 1 [4.2%]; and type III, n ¼ 1 [4.2%]). Thirty-day mortality rate was 14.3% (n ¼ 5) with an early death rate of 8.7% (2/23) in elective cases and 30.0% (3/10) in urgent cases (odds ratio [OR], 4.93; confidence interval [CI], 0.68-35.67; P ¼ .128). Except in one patient, 30-day mortality was associated with landing zone 0 or zone 1 (26.7% vs 5.0%; OR, 6.91; CI, 0.68-69.86; P ¼ .141). Three patients (8.6%) suffered a postoperative stroke, and no episodes of spinal cord ischemia were observed. Two-year survival rate was 67.8% (CI, 49.4%- 80.8%). Survival rates were significantly lower with increasing age (hazard ratio [HR], 1.10; CI, 1.03-1.18; P ¼ .004), urgent procedure (HR, 4.80; CI, 1.56-14.80; P ¼ .003), zone 0 or zone 1 (HR, 6.34; CI, 1.73-23.18; P ¼ .001), presence of arrhythmia (HR, 3.76; CI, 1.22-11.62; P ¼ .013), and cerebrovascular disease (HR, 4.12; CI, 1.38-12.35; P ¼ .006). A multivariate analysis identified age (HR, 1.11; P ¼ .047) and zone 0 or zone 1 (HR, 4.93; P ¼ .033) as the only predictors for overall mortality. Conclusions: Hybrid aortic arch repair seems to be an alternative for higher risk patients not suitable for open repair, but selection of patients is crucial and may benefit from further refinement. In this study, worse outcomes were seen in older patients and those who required more proximal landing zones.
- The evolution of management of type B aortic dissection in a series of 100 consecutive cases in a tertiary centerPublication . Lopes, Alice; Pedro, Luís M; Melo, Ryan; Moutinho, Mariana; Sobrinho, Gonçalo; Amorim, Pedro; Silvestre, Luís; Fernandes E Fernandes, Ruy; Ministro, Augusto; Martins, Carlos; Almeida, Ana G.; Nobre, Angelo; Pinto, Fausto J.; Fernandes E Fernandes, JoseIntroduction and objectives: Management of aortic dissection is rapidly evolving. The present study aims to assess paradigm shifts in type B aortic dissection (TBAD) treatment modalities and their outcomes according to clinical presentation and type of treatment. We also aim to assess the impact of endovascular technology in TBAD management in order to define organizational strategies to provide an integrated cardiovascular approach. Methods: We performed a retrospective review with descriptive analysis of the last 100 consecutive patients with TBAD admitted to the Vascular Surgery Department of Centro Hospitalar Universitário Lisboa Norte over a 16-year period. Results were stratified according to treatment modality and stage of the disease. The study was further divided into two time periods, 2003-2010 and 2011-2019, respectively before and after the introduction of a dedicated endovascular program for aortic dissections. Results: A total of 100 patients (83% male; mean age 60 years) were included, of whom 59 were admitted in the acute stage (50.8% with complicated dissections). The other 41 patients were admitted for chronic dissections, most of them for surgical treatment of aneurysmal degeneration. Temporal analysis demonstrated an increase in the number of patients operated for aortic dissection, mainly due to an increase in chronic patients (33.3% in 2003-2010 vs. 64.4% in 2011-2019) and a clear shift toward endovascular treatment from 2015 onward. Overall in-hospital mortality was 14% and was significantly higher in the chronic phase (acute 5.1% vs. chronic 26.8%; OR 5.30, 95% CI 1.71-16.39; p=0.003) and in patients with aneurysmal degeneration, regardless of the temporal phase. Only one death was recorded in the endovascular group. Conclusion: Management of TABD carried an overall mortality of 14% during a 16-year period, but the appropriate use of endovascular technology has substantially reduced in-hospital mortality.
- Adaptations in the Vascular Surgery Department of the CHULN during the COVID-19 pandemic and impact on overall activityPublication . Duarte, António; Melo, Ryan; Lopes, Alice; Rato, João; Rodrigues, Marta; Henriques, Mickael; Gomes, Miguel; Pinto, Vanda; Ribeiro, Karla; Silva, Emanuel; Moutinho, Mariana; Garrido, Pedro; Manuel, Viviana; Ministro, Augusto; Sobrinho, Gonçalo; Silvestre, Luís; Amorim, Pedro; Fernandes E Fernandes, Ruy; Meireles, Nuno; Martins, Carlos; Pedro, Luís MWith the onset of the SARS-CoV-2 pandemic in early 2020, health services and personnel adapted their resources to mitigate and control the outbreak. These needs inevitably led to adaptations in most medical and surgical departments, including in our Vascular Surgery department. As we are facing a second outbreak of this pandemic, with unpredictable outcomes and repercussions in health services, it is crucial to learn from previous experiences and share strategies to perform the best care to our patients, despite the restrictions that have been imposed. Through this paper, we review the adaptations in Centro Hospitalar Universitário Lisboa Norte and particularly in our department to overcome the pandemic. We also assess the impact of these changes in our activity and compare with the experience of other fellow surgeons. With an upcoming second outbreak, it is crucial to learn from this and other departments’ experiences to overcome a potential health crisis.