Alpha 1-acid glycoprotein is upregulated in severe COVID-19 patients and decreases neutrophil NETs in SARS-CoV-2 infection.

Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19.

Isolation and primary culture of human abdominal aorta smooth muscle cells from brain-dead donors: an experimental model for vascular diseases.

Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was standardized. Ten abdominal aorta samples were obtained from patients diagnosed with brain death who were organ and tissue donors with family consent. After surgical ablation to capture the aorta, the aortic tissue was removed, immersed in a Custodiol® solution, and kept between 2 and 8 °C. In the laboratory, in a sterile environment, the tissue was fragmented and incubated in culture plates containing an enriched culture medium (DMEM/G/10% fetal bovine serum, L-glutamine, antibiotics and antifungals) and kept in an oven at 37 °C and 5% CO2. The aorta was removed after 24 h of incubation, and the culture medium was changed every six days for twenty days. Cell growth was confirmed through morphological analysis using an inverted optical microscope (Nikon®) and immunofluorescence for smooth muscle alpha-actin and nuclei. The development of the VSMCs was observed, and from the twelfth day, differentiation, long cytoplasmic projections, and adjacent cell connections occurred. On the twentieth day, the morphology of the VSMCs was confirmed by actin fiber immunofluorescence, which is a typical characteristic of VSMCs. The standardization allowed VSMC growth and the replicability of the in vitro test, providing a protocol that mimics natural physiological environments for a better understanding of the cardiovascular system. Its use is intended for investigation, tissue bioengineering, and pharmacological treatments.

Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

PURPOSE: We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). METHODS: From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. RESULTS: Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). CONCLUSION: The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Adequacy of venous thromboembolism risk stratification and prophylaxis in a tertiary university hospital.

Background: Venous thromboembolism is the third most common cardiovascular disease and the main cause of preventable death in hospitalized patients. Prophylaxis is still underused, despite well-established guidelines in the literature. Studies show a worldwide prophylaxis adequacy rate close to 50%. Objectives: To assess the adequacy of risk stratification and prophylactic measures for venous thromboembolism in a tertiary university hospital. Methods: A cross-sectional observational study was carried out, collecting data from medical records. Adult patients hospitalized by different specialties were enrolled and divided into surgical and clinical groups. The risk stratification of venous thromboembolism performed by the attending physicians was compared with stratification based on recent guidelines performed by the research physicians. Prophylaxis measures prescribed by the attending physicians were compared with guideline recommendations, thus obtaining the prophylaxis adequacy rate. Results: 400 patients were analyzed, 169 (42.3%) surgical and 231 (57.7%) clinical. The overall stratification adequacy rate was 50.8%. Adequacy rates were 39.1% and 59.3% in the surgical and clinical groups respectively (P < 0.0001). The overall prophylaxis adequacy rate was 71.5%, with 78.1% in the surgical group and 66.7% in the clinical group (P=0.0137). Conclusions: Risk stratification adequacy is low, demonstrating a low awareness among prescribing physicians of the need for adequate stratification for prescription of prophylaxis. However, the prophylaxis prescription adequacy rates are higher than those in global data.

Prospective Assessment of a Protocol Using Neuromonitoring, Early Limb Reperfusion, and Selective Temporary Aneurysm Sac Perfusion to Prevent Spinal Cord Injury During Fenestrated-branched Endovascular Aortic Repair.

OBJECTIVE: The aim of this study was to analyze the outcomes of a standardized protocol using routine CSFD, neuromonitoring, LL reperfusion, and selective TASP to prevent SCI during F-BEVAR. BACKGROUND: SCI is to be the most devastating complication for the patient, family, and surgeon, with impact on patient's quality of life and long-term prognosis. An optimal standardized protocol may be used to improve outcomes. METHODS: Patients enrolled in a prospective, nonrandomized single-center study between 2013 and 2018. A SCI prevention protocol was used for TAAAS or complex abdominal aneurysms with ≥5-cm supraceliac coverage including CSFD, neuromonitoring, LL reperfusion, and selective TASP. Endpoints included mortality and rates of SCI. RESULTS: SCI prevention protocol was used in 170 of 232 patients (73%) treated by F-BEVAR. Ninety-one patients (55%) had changes in neuromonitoring, which improved with maneuvers in all except for 9 patients (10%) who had TASP. There was one 30-day or in-hospital mortality (0.4%). Ten patients (4%) developed SCIs including in 1% (1/79) of patients with normal neuromonitoring and 10% (9/91) of those who had decline in neuromonitoring ( P = 0.02). Permanent paraplegia occurred in 2 patients (1%). Factors associated with SCI included total operating time (odds ratio 1.5, 95% confidence interval 1.1-2.2, P = 0.02) and persistent changes in neuromonitoring requiring TASP (odds ratio 15.7, 95% confidence interval 2.9-86.2, P = 0.001). CONCLUSION: This prospective nonrandomized study using a standardized strategy to prevent SCI was associated with low incidence of the SCI during F-BEVAR. Permanent paraplegia occurred in 1%.

Short-Term Outcomes of Transfemoral Carotid Artery Stenting and Carotid Endarterectomy in Symptomatic Patients: Data from a Multicentric Prospective Registry in Brazil.

BACKGROUND: Transfemoral carotid artery stenting (TF-CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. Because their main objective is to prevent future ischemic events, regular reassessment of the outcomes is mandatory for providing the best therapy. The purpose of this study was to describe the practice and the outcomes of TF-CAS and CEA in symptomatic patients in public university hospitals in Brazil, using data from a prospective multicentric registry. METHODS: A prospective 8-year observational study of patients with symptomatic carotid artery atherosclerotic disease that underwent TF-CAS and CEA in 5 public university hospitals affiliated with the RHEUNI (Registry Project of Vascular Disease in the Public University Hospitals of São Paulo). All consecutive procedures were included. The indications for the procedures were determined by each surgeon's individual discretion, in accordance with a preoperative risk evaluation. The outcome measures were any 30-day follow-up death, stroke, myocardial infarction (MI), and their combined outcome (major adverse cardiovascular events [MACE]). The registration of the study was made at clinicaltrials.gov NCT02538276. RESULTS: From January 2012 through December 2019, 376 consecutive and symptomatic patients were included in the study records. There were 152 TF-CAS procedures (40.4%) and 224 CEA procedures (59.5%). All completed the 30-day follow-up period. Occurrence of death (TF-CAS: 0.66% × CEA: 0.66%, P = 0.99), stroke (TF-CAS: 4.61% × CEA: 4.46%, P = 0.99), and MI (TF-CAS: 0.66% × CEA: 0%, P = 0.403) were similar in both groups, without statistically significant differences. MACE rate did not differ in both groups (TF-CAS: 5.92% × CEA: 4.46%, P = 0.633). CONCLUSIONS: Data from a prospective registry of 5 Brazilian university hospitals showed that TF-CAS and CEA in symptomatic patients had similar 30-day perioperative rates of death, stroke, and MI and their combination.

Inpatient consultations with the vascular and endovascular surgery team at an academic tertiary hospital.

Background: Inpatient consultations are a fundamental component of practice in tertiary care centers. However, such consultations demand resources, generating a significant workload. Objectives: To investigate the profile of inpatient consultations requested by other specialties and provided by the Vascular and Endovascular Surgery team at an academic tertiary hospital. Methods: Prospective observational study. Results: From May 2017 to May 2018, 223 consultations were provided, representing 2.2% of the workload. Most consultations were requested by Oncology (16.6%), Hematology (9.9%), Nephrology (9.0%), and Cardiology (6.3%). The leading reasons for inpatient consultation were: need for vascular access (51.1%) and requests to evaluate a vascular disease (48.9%). Acute venous diseases accounted for 19.3% of consultations, chronic arterial diseases for 14.8%, acute arterial diseases for 7.2%, diabetic feet for 5.4%, and chronic venous diseases accounted for 2.2%. Surgical treatment was performed in 57.0%, either conventional (43.9%) or endovascular (13.0%). Almost all (98.2%) patients' issues were resolved. Conclusions: Inpatient consultations with the Vascular and Endovascular Surgery team in a tertiary academic hospital accounted for 2.2% of the team's entire workload. Most patients were elective and underwent low-complexity elective surgical procedures. There may be an opportunity to improve healthcare, redirecting these patients to the outpatient flow.

Introdução: Interconsultas são um componente fundamental da prática clínica em centros de atendimento terciários. No entanto, esse tipo de consulta requer recursos, resultando em uma alta carga de trabalho. Objetivo: Investigar o perfil das interconsultas solicitadas por outros departamentos e realizadas pela equipe de Cirurgia Vascular e Endovascular em um hospital universitário terciário. Métodos: Estudo observacional prospectivo. Resultados: De maio de 2017 a maio de 2018, foram realizadas 223 consultas, correspondendo a 2,2% da carga de trabalho. A maioria das consultas foram solicitadas pelos departamentos de Oncologia (16,6%), Hematologia (9,9%), Nefrologia (9,0%) e Cardiologia (6,3%). As principais razões das interconsultas foram a necessidade de acesso vascular (51,1%) e de avaliação de doenças vasculares (48,9%). As doenças venosas agudas corresponderam a 19,3% das avaliações; as doenças arteriais crônicas, a 14,8%; as doenças arteriais agudas, a 7,2%; o pé diabético, a 5,4%; e as doenças venosas crônicas corresponderam a 2,2%. Foi realizado tratamento cirúrgico em 57,0% dos casos, tanto convencional (43,9%) quanto endovascular (13,0%). Foram resolvidos os problemas de quase todos os pacientes (98,2%). Conclusão: As interconsultas realizadas pela equipe de Cirurgia Vascular e Endovascular em um hospital universitário terciário corresponderam a 2,2% da carga de trabalho total. A maioria dos pacientes eram eletivos e foram submetidos a procedimentos cirúrgicos eletivos de baixa complexidade. O redirecionamento desses pacientes para o atendimento ambulatorial poderia auxiliar na melhoria dos serviços de saúde.

Microstates in complex and dynamical environments: Unraveling situational awareness in critical helicopter landing maneuvers.

Understanding decision-making in complex and dynamic environments is relevant for designing strategies targeting safety improvements and error rate reductions. However, studies evaluating brain dynamics in realistic situations are scarce in the literature. Given the evidence that specific microstates may be associated with perception and attention, in this work we explored for the first time the application of the microstate model in an ecological, dynamic and complex scenario. More specifically, we evaluated elite helicopter pilots during engine-failure missions in the vicinity of the so called "dead man's curve," which establishes the operational limits for a safe landing after the execution of a recovery maneuver (autorotation). Pilots from the Brazilian Air Force flew a AS-350 helicopter in a certified aerodrome and physiological sensor data were synchronized with the aircraft's flight test instrumentation. We assessed these neural correlates during maneuver execution, by comparing their modulations and source reconstructed activity with baseline epochs before and after flights. We show that the topographies of our microstate templates with 4, 5, and 6 classes resemble the literature, and that a distinct modulation characterizes decision-making intervals. Moreover, the source reconstruction result points to a differential activity in the medial prefrontal cortex, which is associated to emotional regulation circuits in the brain. Our results suggest that microstates are promising neural correlates to evaluate realistic situations, even in a challenging and intrinsically noisy environment. Furthermore, it strengthens their usage and expands their application for studying cognition under more realistic conditions.

Contemporary Management of Arterial Thoracic Outlet Syndrome.

BACKGROUND: Arterial thoracic outlet syndrome (aTOS) is characterized by compression of the subclavian artery as it exits the thoracic girdle. Chronic and repetitive compression leads to several degrees of arterial wall damage. The treatment is varied and depends on the presentation severity. This study aimed to describe the contemporary experience in managing arterial thoracic outlet syndrome at a large tertiary hospital. METHODS: We conducted a single-institution retrospective review of aTOS cases from January 2009 to January 2020. Demographic data, clinical presentation, medical images, operative notes, and outcomes were assessed. RESULTS: Thirteen aTOS cases were identified. The mean age was 43 ± 10 years, and 11 (85%) were women. Both sides were equally affected: right (7 cases, 54%) and left (6 cases, 46%). The most common clinical presentation was arm claudication (7 cases, 54%). Other presentations were: acute arm ischemia, pulsatile neck mass and distal embolization. Cervical ribs were identified by plain X-rays in most cases. All patients were submitted to surgical decompression through the supraclavicular approach. Patients with early disease stages were not submitted to arterial reconstruction and were followed with duplex scan. Arterial reconstruction was done in advanced disease stages (5 cases, 38%): end-to-end anastomosis, interposition graft, and bypass graft. The mean follow-up duration was 32,6 ± 25 months. In all patients, the subclavian artery/graft was patent, and the vascular symptoms were entirely resolved. There were no deaths or amputations. CONCLUSIONS: Arterial thoracic outlet syndrome has a varied clinical presentation. Cervical ribs are the most common anatomic abnormalities. The diagnosis was based on history, physical examination, and imaging exams. Surgery consisted of supraclavicular decompression, arterial resection, and vascular reconstruction, according to the disease stage. The outcomes were excellent.

Paraquat degradation by photocatalysis: experimental desing and optimization.

This study describes the experimental design and optimization of application TiO2 catalysts doped with 0.5, 1, 1.5, 2.0% of Fe. The catalysts were prepared using the impregnation method applied in Paraquat herbicide degradation. The catalysts were characterized by the following techniques: specific surface area and volume, mean pore diameter (BET method), scanning electron microscopy and photoacoustic spectroscopy. The characterization presented results indicating that both calcination temperature and the increase nominal metallic load affected by the structure of catalysts, changing the textural properties, as well as the band gap. The catalyst that presented the best herbicide removal percentage was TiO2 calcined at 773 K with removal of 90.2%. However, according to the experimental design and optimization, both variables (calcination temperature and Fe percentage) are significant in the process. In addition, a positive effect was found in the interaction between the two variables. The values show that a third order kinetic model better described the Paraquat photocatalytic degradation.

Surgical treatment of cervical rib-associated arterial thoracic outlet syndrome.

The arterial form of thoracic outlet syndrome is rare and is associated with anatomic anomalies, generally a cervical rib. It has a varied range of manifestations. The aim of this article is to describe two cases with different clinical presentations: microembolization and aneurysm. A cervical rib was present in both cases. Diagnosis was made on the basis of history, physical examination, postural maneuvers, and X-rays. Computed tomography angiography provided the anatomic detail necessary to plan surgery. Surgical treatment was performed via supraclavicular access, successfully, in both cases.

Carbon-Coated Stent and the Role of the Kallikrein-Kinin System in Peripheral Angioplasty.

OBJECTIVE: The purpose of this study was to investigate the clinical evolution of patients treated with carbon-coated stent, as well as its patency and the inflammatory response triggered by this process through the quantification of serum elements of the kallikrein-kinin system (KKS). METHODS: This was a single-center prospective study with 27 patients with peripheral artery disease (PAD) who required percutaneous transluminal angioplasty and stenting of the iliacofemoropopliteal segment using carbon-coated stent grafts (carbostents). The blood concentrations of the total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein levels were assessed by the colorimetric method and tissue kallikrein levels were evaluated by the spectrophotometric method. The activity of kininase II was measured by -fluorometric analysis. RESULTS: Of the 27 patients who completed the 6 months of the study (11 iliac territory, 16 femoropopliteal territory), only one experienced restenosis (3.7%) (femoropopliteal segment) and no patient had occlusion (96.3% of patency). In 1 year, four patients were lost to follow-up and all 23 patients evaluated maintained stent patency, except for the patient who had restenosis throughout the first 6 months. We report complete (100%) member salvage in 12 months of follow-up. The activity levels of high- and low-molecular-weight kininogens decreased significantly over time (before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.001, and before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.001; 24 h vs. 6 months, p < 0.001, respectively). Patients also had significantly lower levels of plasma and tissue kallikrein (before vs. 24 h, p < 0.001; before vs. 6 months, p < 0.001, and before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.05, respectively). There was a significant increase in the enzymatic activity of kininase II at 24 h and after 6 months compared to the pre-treatment control (p < 0.001). CONCLUSION: Our early experience shows that the use of carbon-coated stents in PAD appears to be safe, with low rates of early restenosis (3.7% in the first 6 months and 5% in the 12 months of follow-up). We concluded that KKS was involved in the inflammatory response caused by the placement of carbon-coated stents.

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. METHODS: This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation. RESULTS: Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts. CONCLUSIONS: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.

Endovascular treatment of left internal thoracic artery aneurysm.

Aneurysm of the internal thoracic artery is a rare entity, with variable presentation and a potential risk of fatal rupture. Angiotomography is the diagnostic test of choice and is useful for planning treatment. Considering the morbidity of thoracic access for a direct approach and the unpredictable risk of rupture, an endovascular procedure is the treatment modality of choice for this type of aneurysm. We describe the case of an internal thoracic artery aneurysm discovered incidentally during investigation of syncope and treated by embolization with low-profile and controlled-release microcoils.

Impact of aortic wall thrombus on late changes in renal function among patients treated by fenestrated-branched endografts.

OBJECTIVE: Renal function deterioration is an important determinant of mortality in patients treated for complex aortic aneurysms. We have previously determined that catheter and guidewire manipulation in diseased aortas during fenestrated-branched endovascular aneurysm repair (F-BEVAR) is associated with risk of renal function deterioration. The aim of this study was to describe the impact of atherothrombotic aortic wall thrombus (AWT) on renal function deterioration among patients treated by F-BEVAR for pararenal and extent IV thoracoabdominal aortic aneurysms. METHODS: Clinical data of 212 patients treated for complex aortic aneurysms with F-BEVAR were entered into a prospectively maintained database (2007-2015). AWT was evaluated by computed tomography angiography using volumetric measurements in nonaneurysmal aortic segments. AWT was classified as mild, moderate, or severe using objective assessment of the number of affected segments, thrombus type, thickness, area, and circumference. Acute kidney injury (AKI) was defined using Risk, Injury, Failure, Loss of kidney function, and End-stage renal disease (RIFLE) criteria, and renal function deterioration was defined by a decline in estimated glomerular filtration rate (eGFR) >30% from baseline. Patient survival and renal outcomes were assessed at dismissal, at 6 to 8 weeks, at 6 months, and annually, including AKI, serum creatinine concentration, eGFR, chronic kidney disease stage, need for renal replacement therapy, and presence of kidney infarction. RESULTS: There were 169 male (80%) and 43 female (20%) patients with a mean age of 75 ± 7 years. Aneurysm extent was pararenal in 157 patients and extent IV thoracoabdominal aortic aneurysm in 55 patients. A total of 700 renal-mesenteric arteries were incorporated (3.1 ± 1 vessels/patient). AWT was classified as mild in 98 patients (46%), moderate in 75 (35%), and severe in 39 (19%). At 30 days, 45 patients (21%) developed AKI. Decline in eGFR and kidney infarction were associated with higher AWT volume index and severe AWT classification (P < .05). There was no association of AWT with 30-day mortality, which was 0.5% for the entire cohort. Mean follow-up was 29 ± 23 months. Freedom from renal function deterioration was 73% ± 6% for mild, 81% ± 6% for moderate, and 66% ± 8% for severe AWT patients at 3 years (P = .012) and 46% ± 9% and 82% ± 4% for those with or without AKI after the initial procedure (P < .001). Overall, 41 patients (19%) had progression of chronic kidney disease stage, but none of the patients required renal replacement therapy. Survival was 73% ± 5% for mild, 72% ± 6% for moderate, and 69% ± 10% for severe AWT patients at 3 years (P = .67). CONCLUSIONS: AWT is a significant predictor of AKI and continued decline in renal function after the initial F-BEVAR procedure. Longer follow-up time is needed to determine the actual impact of AWT on survival.

Evolution from physician-modified to company-manufactured fenestrated-branched endografts to treat pararenal and thoracoabdominal aortic aneurysms.

OBJECTIVE: The purpose of this study was to review treatment trends and outcomes of patients who underwent fenestrated-branched endovascular aneurysm repair (F-BEVAR) of pararenal aneurysms (PRAs) or thoracoabdominal aortic aneurysms (TAAAs) using physician-modified endografts (PMEGs) or company-manufactured devices (CMDs). METHODS: We reviewed the clinical data of 316 consecutive patients (242 male patients; mean age, 75 ± 8 years) who underwent F-BEVAR between 2007 and 2016. F-BEVAR was performed under two prospective investigational device exemption protocols since 2013. End points were mortality, major adverse events (MAEs), patient survival, reintervention, branch instability, aneurysm-related mortality, renal function deterioration, and target vessel patency. RESULTS: There were 145 patients (46%) treated by PMEGs (84 PRAs, 26 extent IV and 35 extent I-III TAAAs) and 171 patients (54%) who had CMDs (88 PRAs, 42 extent IV and 41 extent I-III TAAAs). Choice of endograft evolved from PMEGs in 131 patients (83%) treated in the first half of experience to CMDs in 144 patients (91%) treated in the second half of experience (P < .001). Patients treated by PMEGs had significantly (P < .05) larger aneurysms, more chronic pulmonary and kidney disease, and higher comorbidity severity scores. A total of 1081 renal-mesenteric arteries were targeted in both groups. Technical success was lower for PMEGs (98% vs 99.5%; P = .02). Thirty-day mortality was 5.5% for PMEGs (PRAs, 1.2%; extent IV 3.8% and extent I-III, 17.1%) and 0% for CMDs (P = .0018). Patients treated by PMEGs had significantly more (P < .001) MAEs (48% vs 23%) and longer hospital stay (9 ± 10 days vs 6 ± 6 days; P = .001). Mean follow-up was significantly longer for patients treated by PMEGs (38 ± 26 months vs 14 ± 12 months; P < .001). At 3 years, patient survival (68% ± 4% vs 67% ± 8%; P = .11), freedom from reintervention (68% ± 4% vs 68% ± 8%; P = .17), primary (94% ± 2% vs 92% ± 2%; P = .64) and secondary target vessel patency (98% ± 1% vs 98% ± 1%; P = .89), and freedom from renal function deterioration (75% ± 4% vs 65% ± 6%; P = .24) were similar for patients treated by PMEGs or CMDs, respectively. CONCLUSIONS: Choice of F-BEVAR evolved from PMEGs to almost exclusively CMDs under physician-sponsored investigational device exemption protocols. PMEG patients had more comorbidities and larger aneurysms. CMDs were performed with higher technical success, no mortality, and fewer MAEs.

A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. METHODS: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared. RESULTS: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years). CONCLUSIONS: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.

Hesperidin-Loaded Solid Lipid Nanoparticles: Development and Physicochemical Properties Evaluation.

Although nanocarrier systems have been investigated to function as therapeutic delivery agents to specific sites of the body, the drug encapsulation method is not always well elucidated. In this work, solid lipid nanoparticles (SLN) composed by stearic acid or cetostearyl alcohol were prepared by a hot homogenization method using poly(vinyl alcohol) or polysorbate as surfactant and loaded with hesperidin, a bioflavonoid that possesses many pharmacological properties. The obtained SLN were characterized by several physicochemical techniques to identify interactions between the constituents and to evaluate the drug incorporation into the nanoparticles. According to scanning electron microscopy and dynamic light scattering the hesperidin-loaded and unloaded SLN have spherical shapes, sizes ranging from 300 to 600 nm, zeta potentials varying from -35 to -20 mV, polydispersity indexes between 0.240 and 0.445, and entrapment efficiencies higher than 88%. X-ray diffraction showed the hesperidin amorphization due to its encapsulation in SLN, and also showed crystallization degree and polymorphic modification of the lipids after the SLN preparation. FTIR, Raman and Photoacoustic spectroscopy revealed no chemical reactions between drug and lipids, however, these results indicated that the drug was incorporated differently into nanoparticles based on the SLN composition. The analysis showed that stearic acid-based SLN prepared with polysorbate were more efficient to enclosure the hesperidin while the glycosydic part of the hesperidin was not entrapped in the cetostearyl alcohol-based SLN; instead, the hesperidin remained on the SLN surface due to lipid crystallization. The physicochemical characterization allowed identifying different types of hesperidin incorporation into the SLN, which can interact in a varied manner as targeted drug delivery systems.

The Role of Interleukins and Inflammatory Markers in the Early Restenosis of Covered Stents in the Femoropopliteal Arterial Segment.

BACKGROUND: The objective of this study was to evaluate the relationship between inflammatory markers, such as interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß), and highly sensitive C-reactive protein, and the development of arterial restenosis 6 months after femoropopliteal percutaneous transluminal angioplasty (PTA) with covered stent implantation. METHODS: We recruited 27 patients of a tertiary hospital in Brazil who were treated with covered stents for atherosclerotic peripheral arterial disease. Serum samples were collected before stent implantation, then 24 hr later, and 6 months after the procedure. RESULTS: At 6-month follow-up, 4 patients (15%) presented restenosis. IL1- ß, IL-6, IL-8, and TNF-α levels showed a statistically significant reduction after both 24 hr and 6 months compared with pretreatment levels (P < 0.01). There were increased levels of IL-10 and TGF-ß both 24 hr and 6 months after PTA and stenting compared with pretreatment levels (P < 0.01). None of the cytokines studied were correlated with restenosis. CONCLUSIONS: This study demonstrated a significant increase in anti-inflammatory TGF-ß and IL-10 and a decrease in proinflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α 6 months after the procedure, but no inflammatory marker was independently identified as a risk factor for in-stent restenosis.