Midterm results on a new self-expandable covered stent combined with branched stent grafts: Insights from a multicenter Italian registry

Objective: To investigate the technical periprocedural and midterm outcomes of endovascular repairs with multibranched endovascular repair or iliac branch devices combined with a new self-expanding covered stent. Methods: The COvera in BRAnch registry is a physician-initiated, multicenter, ambispective, observational registry (ClinicalTrials.gov Identifier: NCT04598802) enrolling patients receiving a multibranched endovascular repair or iliac branch devices procedure mated with Bard Covera Plus (Tempe, AZ) covered stent, designed to evaluate the outcomes of the covered stent mated with patient-specific and off-the-shelf branched stent graft. Primary end points were technical success, branch instability, and freedom from aortic and branch-related reintervention within 30 days and at follow-up. Preoperative characteristics, comorbidities, and outcomes definitions were graded according to the Society for Vascular Surgery reporting standards. Results: Two hundred eighty-four patients (76 years; range, 70-80 years; 79% males) in 24 centers were enrolled for a total of 708 target vessels treated. The covered stents were mated with an off-the-shelf graft in 556 vessels (79%) and a custom-made graft in 152 (21%). Three hundred seven adjunctive relining stents in 277 vessels (39%) were deployed, of which 116 (38%) were proximal, 66 (21%) intrastent, and 125 (41%) distal. Adjunctive relining stent placement was more frequent when landing in a vessel branch instead of the main trunk (59% vs 39%; P = .031), performing a percutaneous access (49% vs 35%; P < .001), using a stent with a diameter of 8 mm or greater (44% vs 36%; P = .032) and a length of 80 mm or greater (65% vs 55%; P = .005), when a post-dilatation was not performed (45% vs 29%; P < .001) and when an inner branch configuration was used (55% vs 35%; P < .001). Perioperative technical bridging success was 98%. Eight patients (3%) died in the perioperative period. Two deaths (1%) were associated with renal branch occlusion followed by acute kidney injury and paraplegia. Follow-up data were available for 638 vessels (90%) at a median of 32 months (Q1, Q3, 21, 46). Branch instability was reported in 1% of branches. Forty-six patients (17%) died during follow-up, nine (3%) of them owing to aortic-related causes. Primary patency rates at 1, 2, and 3 years were 99% (581/587), 99% (404/411), and 97% (272/279), respectively. Branch instability was associated with patient-specific devices (9% vs 4%; P = .014) and intrastent adjunctive stent placement (12% vs 2%; P = .003), especially when a bare metal balloon-expandable stent was used (25% vs 3%; P < .001). Conclusions: The use of this new self-expanding covered stent mated with branched endografts proved to be safe and feasible with high technical procedural success rates. Low rates of branch instability were observed at midterm follow-up. Comparative studies with other commercially available covered stents are warranted

A cross-sectional study evaluating hospitalization rates for chronic limb-threatening ischemia during the COVID-19 outbreak in Campania, Italy

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 +/- 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32-0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p &lt; 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions

How the First Year of the COVID-19 Pandemic Impacted Patients’ Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p &lt; 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p &lt; 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

LentiRILES, a miRNA-ON Sensor System for Monitoring the Functionality of miRNA in Cancer Biology and Therapy

International audienceA major unresolved challenge in miRNA biology is the capacity to monitor the spatiotemporal activity of miRNAs expressed in animal disease models. We recently reported that the miRNA-ON monitoring system called RILES (RNAi-inducible expression Luciferase system) implanted in lentivirus expression system (LentiRILES) offers opportunity to decipher the kinetics of miRNA activity in vitro, in relation with their intracellular trafficking in glioblastoma cells. In this study we describe in detail the method for production of LentiRILES stable cell lines and employed it in several applications in the field of miRNA biology and therapy. We show that LentiRILES is a robust, highly specific and sensitive miRNA sensor system that can be used in vitro as a single-cell miRNA monitoring method, cell-based screening platform for miRNA therapeutics and as a tool to analyze the structurefunction relationship of the miRNA duplex. Furthermore, we report the kinetic of miRNA activity upon the intracranial delivery of miRNA mimics in an orthotopic animal model of glioblastoma. This information is exploited to evaluate the tumor suppressive function of miRNA-200c as locoregional therapeutic modality to treat glioblastoma. Our data provide evidence that LentiRILES is a robust system, well-suited to resolve the activity of endogenous and exogenously expressed miRNAs for basic research to gene and cell therapy

Le Pouvoir et ses écritures

Dans la réflexion sur les relations entre l’art et la réalité, la question des écritures du pouvoir se situe à un point de croisement fécond. C’est du pouvoir politique qu’il s’agit principalement dans ce volume, dans l’appréciation des œuvres qu’il suscite. Apparaissent des hommes qui exercent le pouvoir et qui prennent la plume, décrivent leur situation, leur condition, leurs fonctions. Certains sont des créateurs avant d’avoir eu une situation politique. Quelle relation leur œuvre entretient-elle avec leur action ? Viennent aussi et surtout les hommes de l’art qui s’intéressent au pouvoir. Comment représentent-ils cette position dominante de personnages de premier plan, voire de personnages collectifs, de groupes au pouvoir ou de masses ? Comment la création rend-elle compte, non pas seulement de la figure du grand homme, mais de la forme du pouvoir, de la configuration de son exercice ? Quelle est la nature de l’engagement de l’artiste, si tant est que l’écriture en suppose un ? D’une position à l’autre, de celle de l’homme politique à celle de l’artiste, et inversement, se révèlent en effet des interactions, s’illustrent des fonctions particulières de la littérature et des arts, des corollaires nécessaires à l’exercice du pouvoir ou une part même de cet exercice. Pour approcher de ces interférences, le champ d’investigation qu’adopte ce volume est large, de l’Antiquité à l’époque contemporaine, sans limitation géographique, avec un croisement des approches disciplinaires, ce qui permet de relativiser, de percevoir des continuités sur la longue durée, d’établir de fécondes comparaisons. Le fil qui est suivi est celui qui transversalement infléchit une certaine idée du pouvoir. D’abord, les visions et les positions euphorisées, idéalisation du prince dans le conseil ou dans son éducation, célébrations du pouvoir, pour atteindre à ces situations stables ou moins stables de l’écriture dans l’exercice du pouvoir. Puis, les visions contrastées ou même ambiguës du pouvoir, et, plus appuyées, les critiques et les contestations, avant que n’arrive l’oscillation ou le choix clair entre l’emprise et la déprise. De là, enfin, des contre-pouvoirs ou d’autres pouvoirs peuvent surgir sur des horizons de fuite

Mid-term results on a new self-expandable covered stent combined with branched stent-grafts: insights from a multicenter Italian registry

Objective: To investigate the technical periprocedural and mid-term outcomes of endovascular repairs with multibranched (BEVAR) or iliac-branch devices (IBD) combined with a new self-expanding covered stent. Methods: The COBRA (COvera in BRAnch) registry is a physician-initiated, multicenter, ambispective, observational registry (ClinicalTrials.gov Identifier: NCT04598802) enrolling patients receiving a BEVAR or IBD procedure mated with Bard Covera Plus (Tempe, Arizona, USA) covered stent, designed to evaluate the outcomes of the covered stent mated with patient-specific and off-the-shelf branched stent-graft. Primary endpoints were technical success, branch instability, and freedom from aortic and branch-related reintervention within 30 days and at follow-up. Preoperative characteristics, comorbidities, and outcomes definition were graded according to the Society for Vascular Surgery reporting standards. Results: Two hundred eighty-four patients [76 years (70-80); 79% males] in 24 centers were enrolled for a total of 708 target vessels treated. The CSs were mated with an off-the-shelf graft in 556 vessels (79%) and a custom-made graft in 152 (21%). Three-hundred-seven adjunctive relining stents in 277 vessels (39%) were deployed, of which 116 (38%) proximal, 66 (21%) intrastent and 125 (41%) distal. Adjunctive relining stent placement was more frequent when landing in a vessel branch instead of the main trunk (59%vs39%, p=.031), performing a percutaneous access (49%vs35%, p<.001), using a stent with a diameter ≥8mm (44%vs36%, p=.032) and a length ≥80mm (65%vs55%, p=.005), when a post-dilatation was not performed (45%vs29%, p<.001) and when an inner-branch configuration was used (55%vs35%, p<.001). Perioperative technical bridging success was 98%. Eight patients (3%) died in the perioperative period. Two deaths (1%) were associated with renal branch occlusion followed by acute kidney injury and paraplegia. Follow-up data were available for 638 vessels (90%) at a median of 32 months (Q1, Q3: 21,46). A branch instability was reported in 1% of branches. Forty-six (17%) patients died during follow-up, nine (3%) of them due to aortic-related causes. Primary patency rates at one year, two and three years were 99% (581/587), 99% (404/411), and 97% (272/279) respectively. Branch instability was associated with patient-specific devices (9% vs 4%, p=.014) and intrastent adjunctive stent placement (12% vs 2%, p=.003), especially when a bare metal balloon-expandable stent was used (25%vs3%, p<.001). Conclusions: The use of this new self-expanding covered stent mated with branched endografts proved to be safe and feasible with high technical procedural success rates. Low rates of branch instability were observed at mid-term follow-up. Comparative studies with other commercially available covered stents are warranted

The role of genetic breast cancer susceptibility variants as prognostic factors

Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P<0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers=1.21; 95% CI: 1.09-1.35, P=0.0002 and HR=1.29; 95% CI: 1.12-1.47, P=0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility. © The Author 2012. Published by Oxford University Press. All rights reserved

The role of genetic breast cancer susceptibility variants as prognostic factors

Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P<0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers=1.21; 95% CI: 1.09–1.35, P=0.0002 and HR=1.29; 95% CI: 1.12–1.47, P=0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility