Design, evolution, and experience with the candy plug device for endovascular false lumen occlusion of chronic aortic dissections.

INTRODUCTION: The management of the false lumen (FL) when dealing with aortic dissection is a crucial aspect since inducing its thrombosis is necessary in order to achieve aortic remodeling. One of the pitfalls of endovascular treatment of aortic dissection (AD) is retrograde distal FL perfusion and pressurization, which prevents FL thrombosis and thus aortic remodeling, while being associated with aneurysmal degeneration of the FL and poor long-term outcomes. AREAS COVERED: Currently, there is no CE/FDA approved device for FL closure, however different techniques and devices have been proposed to overcome this challenge, the most known of which is the Candy Plug (CP). This review aims to describe the CP device, its implantation technique, and the available data in the literature (PubMed, Cochrane, and EMBASE databases; last queried, December 31, 2023). EXPERT OPINIONS: While the treatment of AD remains technically challenging, the use of the CP technique to close any distal FL reperfusion proved to be feasible and safe with excellent rates of both technical and clinical success. Furthermore, recent studies have shown a quick learning curve with this technique.

Unintended Exchange of Target Vessels for Celiac Trunk and Superior Mesenteric Artery Branches in Complex Endovascular Aortic Repair.

PURPOSE: The treatment of thoracoabdominal aortic aneurysms (TAAAs) using branched endovascular aortic repair (BEVAR) is safe and effective. During deployment, the superior mesenteric artery (SMA) branch can unintentionally open into the celiac trunk (CT) ostium and switched catheterization of the SMA from the CT branch and the CT from the SMA branch can be used as an alternative technique in these cases. This study aimed to investigate the outcome of exchanging the intended target vessels (TVs) for the CT and SMA branches during BEVAR. MATERIALS AND METHODS: A single-center retrospective analysis of patients with TAAAs who underwent BEVAR, using off-the-shelf or custom-made devices (CMDs), with an unintended exchange of TVs for the CT and SMA branches was performed. RESULTS: Between 2014 and 2023, 397 patients were treated with BEVAR for TAAA. Eighteen (4.5%) of those patients were treated with an exchange of TVs for the CT and SMA branches. T-branch was used in 9 cases (50%) and the remaining patients were treated with CMDs. Twelve patients were treated electively, 3 were symptomatic and 3 presented with rupture. Of 36 mesenteric TVs in those 18 patients, 34 (94%) were catheterized successfully, including all 18 SMAs and 16 of the 18 CTs. No branch stenosis or occlusion of the switched mesenteric TVs was detected during follow-up. During 30-day follow-up, 3 patients died and during a median follow-up of 3 (interquartile range [IQR]: 1-15) months 3 more patients died. None of the deaths or the 2 unintended reinterventions was induced by the mesenteric TV exchange. The median hospital stay was 14 (IQR: 9-22) days with a median of 4 (IQR: 2-11) days at the intensive care unit. CONCLUSION: The exchange of the mesenteric TVs for the CT and SMA branches during BEVAR with off-the-shelf and CMD endografts is feasible with good TV patency and freedom from TV-related reinterventions. This alternative technique should be considered in selected cases when direct catheterization via the intended branch is deemed more time-consuming or not feasible. CLINICAL IMPACT: This is the first description of using an exchange of target vessels for the celiac trunk and the superior mesenteric artery branches in patients with thoracoabdominal aortic aneurysms undergoing BEVAR, using off-the-shelf or custom-made devices. The high success rate as well as the good clinical results without any branch stenosis or occlusion during follow-up highlight the feasibility of this alternative technique. It could help in challenging cases when catheterization of the intended target vessels is not possible or too time consuming, resulting in higher success rates of BEVAR and better clinical results.

Dilated Internal Iliac Artery Confers a Higher Risk of Endoleak in Iliac Branch Devices in a Single Centre Retrospective Experience.

OBJECTIVE: Iliac branch devices (IBDs) have shown good results but there is little evidence for the risk of internal iliac artery (IIA) endoleak, so there are no clear recommendations on the maximum diameter it should be. Based on limited evidence, it was hypothesised that an IIA of ≥ 11 mm in diameter presents an increased risk of type Ic endoleak. METHODS: This was a single centre, retrospective case control study. Patients undergoing an IBD with the main trunk of the IIA as the target vessel, between 2015 and 2021, were identified. Two groups were created: those with a main trunk diameter of < 11 mm; and those with a diameter of ≥ 11 mm. Technical success, freedom from type Ic endoleak, and re-intervention rates were compared. A receiver operating characteristic (ROC) curve was performed to show a cutoff IIA diameter value for risk of type Ic endoleak. Multivariate analysis was performed to assess the risk of type Ic endoleak and the presence of calcification, stenosis, and landing zone length in the IIA. RESULTS: There were 182 IBDs identified. The dilated IIA group (54 IBDs) had significantly lower technical success (91% vs. 98.4%; p = .002), lower freedom from type Ic endoleak (77% vs. 97.1% at 24 months; p = .001), and lower freedom from re-interventions (70% vs. 92.4% at 24 months; p = .002). The ROC curve showed that 10.5 mm was the cutoff diameter for type Ic endoleak. Moderate or severe calcification as well as landing zone length < 5 mm also correlated with type Ic endoleak. CONCLUSION: IBDs have a statistically significantly higher rate of technical failure, lower freedom from type Ic endoleak, and lower freedom from re-intervention when the IIA is ≥ 11 mm in diameter.

Genetic determinants of complement activation in the general population.

Complement is a fundamental innate immune response component. Its alterations are associated with severe systemic diseases. To illuminate the complement's genetic underpinnings, we conduct genome-wide association studies of the functional activity of the classical (CP), lectin (LP), and alternative (AP) complement pathways in the Cooperative Health Research in South Tyrol study (n = 4,990). We identify seven loci, encompassing 13 independent, pathway-specific variants located in or near complement genes (CFHR4, C7, C2, MBL2) and non-complement genes (PDE3A, TNXB, ABO), explaining up to 74% of complement pathways' genetic heritability and implicating long-range haplotypes associated with LP at MBL2. Two-sample Mendelian randomization analyses, supported by transcriptome- and proteome-wide colocalization, confirm known causal pathways, establish within-complement feedback loops, and implicate causality of ABO on LP and of CFHR2 and C7 on AP. LP causally influences collectin-11 and KAAG1 levels and the risk of mouth ulcers. These results build a comprehensive resource to investigate the role of complement in human health.

Transfemoral Access to Implant Iliac Branch Devices After Previous Aortic Grafts.

OBJECTIVE: To report on the outcomes of patients undergoing an iliac branch device implantation after previous open or endovascular aorto-biliac repair, using exclusively femoral access for catheterization and delivery of the covering stent to the hypogastric artery. METHODS: Single-center retrospective study in which all patients in whom an iliac branch device was implanted after previous open or endovascular aorto-biliac repair were identified. Patients in whom the hypogastric artery catheterization and delivery of the bridging cover stent were achieved via exclusive femoral access were included. Different techniques were used based on surgeon preference. Technical success and access-related complications, as well as iliac branch device endoleak or occlusions during follow-up, were evaluated. RESULTS: From 2015 to 2021, 28 patients with a prior open or endovascular aorto-biliac repair underwent 34 iliac branch device implantations. Most (71%) had juxtarenal or thoracoabdominal aortic aneurysms, 82% had common iliac artery aneurysms, and 25% had hypogastric artery aneurysms. Bilateral iliac branch device implantations were performed in 21% of the patients, and in 26% of cases, landing in the superior gluteal artery was obtained. An "up-and-over" technique from the contralateral groin was used in 65% of the cases, and a steerable sheath in 35%. Technical success was 94%, with no complications related to access or technique to catheterize and deliver the stents in the hypogastric artery. The cohort had 20% of major complications, with 3 perioperative deaths. Kaplan-Meier estimated an iliac branch device freedom from occlusion and endoleak was 92% and 83% at 2 years. CONCLUSIONS: The implantation of an iliac branch device over previous aortic or open endografts involving the aortic bifurcation is feasible and safe. We suggest using a femoral approach as the primary access of choice. CLINICAL IMPACT: In this study we present 28 patients with previous aortoiliac grafts in which iliac branch devices were performed as a subsequent step.We demonstrated the feasibility of the technique despite the difficulty of crossing a neobifurcation, with a steep angle, without complications associated with the technique. Based on our experience, we recommend transfemoral access as the first option for bypassing the hypogastric artery stent, preserving upper extremity access and its possible complications.

Ascending Aorta Nose-Cone Loop Technique as Bail Out for Precise Branched Endovascular Aortic Arch Endograft Delivery Without Valve Re-Crossing.

PURPOSE: To describe a right carotid-femoral through-and-through (T&T) guidewire technique during branched thoracic endovascular aortic arch repair (B-TEVAR) to facilitate endograft delivery in a very tortuous aortic anatomy for a type Ia endoleak (EL) of a previous aortic endograft implantation. TECHNIQUE: AT&T guidewire was established between the right common carotid artery and the right common femoral artery to facilitate a difficult endograft delivery. Once in the aortic arch, a loop in the ascending aorta was formed to allow the endograft to reach the desired position without losing tension on the guidewire. This maneuver allowed the T&T guidewire to be kept in place until the desired position was reached. The nose-tip of the endograft was curved over the looped guidewire pointing toward the innominate artery without crossing the valve. After endograft deployment, the T&T guidewire was released, and the branches were bridged in a standard fashion. Completion angiography documented correct deployment of the endograft and no sign of type I/III EL. The 1-month computed tomography angiography confirmed the correct deployment. CONCLUSION: Carotid-femoral T&T guidewire to facilitate endograft delivery in difficult anatomies can be feasible even in B-TEVAR. Possible bailout maneuvers are available if the aortic valve needs to be crossed after endograft delivery. CLINICAL IMPACT: Endovascular arch repair gains popularity as a valuable alternative, especially in patients considered unfit for open repair. A through-and-through (T&T) guidewire for endovascular arch repair with a landing zone in zone 0 according to Ishimaru is usually performed through the externalization of the femoral guidewire through a transapical access, but this may not always be feasible in frail patients. A right carotid-femoral though-and-through guidewire with a loop formation in the ascending aorta is proposed to achieve the support of a T&T wire to pass tortuous aortoiliac anatomies and access the ascending aorta without the need for aortic valve crossing.

Transvenous Access for Emergent Thoracic and Thoracoabdominal Aortic Aneurysm Repair in Patients Without Femoral Access.

PURPOSE: To describe the technique of transvenous access for emergent endovascular repair of thoracic and thoracoabdominal aneurysms exemplified with 2 cases. TECHNIQUE: Transvenous access to the aorta is described as an alternative access method to deliver aortic endografts in emergency situations. A 68-year-old female patient with severely compromised iliac and subclavian artery access was treated for a ruptured extent V thoraco-abdominal aortic aneurysm with a t-Branch (Cook Medical, Bjaeverskov, Denmark) delivered through a transcaval access. To avoid severe aortocaval shunting a balloon-expandable covered stent was deployed through a carotid access due to severe bilateral subclavian ostial stenosis. A 71-year-old man with an acute type B aortic dissection and bilateral narrow long-segment stenting of the iliac arteries was treated with a physician-modified thoracic endovascular aortic repair using an arteriovenous fenestration created at the level of the common iliac artery. We describe the access creation by fenestration using a transseptal needle. CONCLUSION: Transvenous access for thoracic and thoraco-abdominal aortic aneurysm repair is safe and feasible in selected emergent cases. CLINICAL IMPACT: A transvenous approach may be helpful in selected patients when an endovascular repair needs to be performed but no arterial femoral access is available. This approach proved to be feasible even with large-bore introducer sheaths, taking its place in the armamentarium of the vascular surgeon for emergent complex endovascular aortic repairs.

Risk Prediction Models for Peri-Operative Mortality in Patients Undergoing Major Vascular Surgery with Particular Focus on Ruptured Abdominal Aortic Aneurysms: A Scoping Review.

PURPOSE: The present scoping review aims to describe and analyze available clinical data on the most commonly reported risk prediction indices in vascular surgery for perioperative mortality, with a particular focus on ruptured abdominal aortic aneurysm (rAAA). MATERIALS AND METHODS: A scoping review following the PRISMA Protocols Extension for Scoping Reviews was performed. Available full-text studies published in English in PubMed, Cochrane and EMBASE databases (last queried, 30 March 2023) were systematically reviewed and analyzed. The Population, Intervention, Comparison, Outcome (PICO) framework used to construct the search strings was the following: in patients with aortic pathologies, in particular rAAA (population), undergoing open or endovascular surgery (intervention), what different risk prediction models exist (comparison), and how well do they predict post-operative mortality (outcomes)? RESULTS: The literature search and screening of all relevant abstracts revealed a total of 56 studies in the final qualitative synthesis. The main findings of the scoping review, grouped by the risk score that was investigated in the original studies, were synthetized without performing any formal meta-analysis. A total of nine risk scores for major vascular surgery or elective AAA, and 10 scores focusing on rAAA, were identified. Whilst there were several validation studies suggesting that most risk scores performed adequately in the setting of rAAA, none reached 100% accuracy. The Glasgow aneurysm score, ERAS and Vancouver score risk scores were more frequently included in validation studies and were more often used in secondary studies. Unfortunately, the published literature presents a heterogenicity of results in the validation studies comparing the different risk scores. To date, no risk score has been endorsed by any of the vascular surgery societies. CONCLUSIONS: The use of risk scores in any complex surgery can have multiple advantages, especially when dealing with emergent cases, since they can inform perioperative decision making, patient and family discussions, and post hoc case-mix adjustments. Although a variety of different rAAA risk prediction tools have been published to date, none are superior to others based on this review. The heterogeneity of the variables used in the different scores impairs comparative analysis which represents a major limitation to understanding which risk score may be the "best" in contemporary practice. Future developments in artificial intelligence may further assist surgical decision making in predicting post-operative adverse events.

Emergent endovascular treatment options for thoracoabdominal aortic aneurysm.

For a long time, parallel grafting, physician-modified endografts, and, more recently, in situ fenestration were the only go-to endovascular options for ruptured thoracoabdominal aortic aneurysm, offered mixed results, and depended mainly on the operator's and center's experience. As custom-made devices have become an established endovascular treatment option for elective thoracoabdominal aortic aneurysm, they are not a viable option in the emergency setting, as endograft production can take up to 4 months. The development of off-the-shelf (OTS) multibranched devices with a standardized configuration has allowed the treatment of ruptured thoracoabdominal aortic aneurysm with emergent branched endovascular procedures. The Zenith t-Branch device (Cook Medical) was the first readily available graft outside the United States to receive the CE mark (in 2012) and is currently the most studied device for those indications. A new device, the E-nside thoracoabdominal branch endoprosthesis OTS multibranched endograft (Artivion), has been made commercially available, and the GORE EXCLUDER thoracoabdominal branch endoprosthesis OTS multibranched endograft (W. L. Gore and Associates) is expected to be released in 2023. Due to the lack of guidelines on ruptured thoracoabdominal aortic aneurysm, this review summarizes the available treatment options (ie, parallel grafts, physician-modified endografts, in situ fenestrations, and OTS multibranched devices), compares the indications and contraindications, and points out the evidence gaps that should be filled in the next decade.

Endovascular Options for the Ascending Aorta and Aortic Arch: A Scoping Review.

The gold standard for aneurysmal repair of the ascending aorta and the aortic arch has been open surgery with an established track record of good results in suitable patients. In recent years, with innovations in the endovascular field alternative endovascular solutions for pathologies of the aortic arch and ascending aorta became available. At first reserved only for highly selected patients unfit for open surgery, endovascular aortic arch repair is now being offered to patients with suitable anatomy in high-volume referral centers after discussion in an interdisciplinary team. The present scoping review aims at providing an overview on indications, available devices, technical aspects, and feasibility studies of endovascular arch repair both in elective and emergent situations, including also experiences and considerations from our center.

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.

European Multicentric Experience With Fenestrated-branched ENDOvascular Stent Grafting After Previous FAILed Infrarenal Aortic Repair: The EU-FBENDO-FAIL Registry.

OBJECTIVE: To report the mid-term outcomes of fenestrated-branched endovascular aneurysm repair (F-BEVAR) following a failed previous endovascular aneurysm repair (pEVAR) or previous open aneurysm repair (pOAR). METHODS: Data from consecutive patients who underwent F-BEVAR for pEVAR or pOAR from 2006 to 2021 from 17 European vascular centers were analyzed. Endpoints included technical success, major adverse events, 30-day mortality, and 5-year estimates of survival, target vessel primary patency, freedom from reinterventions, type I/III endoleaks, and sac growth >5 mm. BACKGROUND: Treatment of a failed previous abdominal aortic aneurysm repair is a complex undertaking. F-BEVAR is becoming an increasingly attractive option, although comparative data are limited regarding associated risk factors, indications for treatment, and various outcomes. RESULTS: There were 526 patients included, 268 pOAR and 258 pEVAR. The median time from previous repair to F-BEVAR was 7 (interquartile range, 4-12) years, 5 (3-8) for pEVAR, and 10 (6-14) for pOAR, P <0.001. Predominant indication for treatment was type Ia endoleak for pEVAR and progression of the disease for pOAR. Technical success was 92.8%, pOAR (92.2%), and pEVAR (93.4%), P =0.58. The 30-day mortality was 6.5% overall, 6.7% for pOAR, and 6.2% for pEVAR, P =0.81. There were 1853 treated target vessels with 5-year estimates of primary patency of 94.4%, pEVAR (95.2%), and pOAR (94.4%), P =0.03. Five-year estimates for freedom from type I/III endoleaks were similar between groups; freedom from reintervention was lower for pEVAR (38.3%) than for pOAR (56.0%), P =0.004. The most common indication for reinterventions was for type I/III endoleaks (37.5%). CONCLUSIONS: Repair of a failed pEVAR or pOARis safe and feasible with comparable technical success and survival rates. While successful treatment can be achieved, significant rates of reintervention should be anticipated, particularly for issues related to instability of target vessels/bridging stents.

A scoping review on the approaches for cannulation of reno-visceral target vessels during complex endovascular aortic repair.

OBJECTIVES: The aim of this study was to assess the approaches to reno-visceral target vessels (TVs) cannulation during branched-fenestrated endovascular aortic repair, determine the evidence base that links these approaches to clinical outcomes and identify literature gaps. METHODS: A scoping review following the PRISMA Protocols Extension for Scoping Reviews was performed. Available full-text studies published in English (PubMed, Cochrane and EMBASE databases; last queried, 31 June 2022) were systematically reviewed and analysed. Data were reported as descriptive narrative or tables, without any statistical analysis nor quality assessment. RESULTS: Fourteen retrospective articles were included. Seven articles studied the use of upper extremity access (UEA) during branched-fenestrated endovascular aortic repair, 3 studied the use of steerable sheaths and 4 included both approaches. A left UEA was used in 757 patients (technical success: 99%, stroke rate: 1-3%) and a right UEA in 215 patients (technical success: 92-98%, stroke rate: 0-13%). Seven studies (1066 patients) described a surgical access only (technical success: 80-99%, stroke rate: 0-13%), while 3 studies (146 patients) described a percutaneous access only (technical success: 83-90%, stroke rate: 3%) and lastly 4 studies compared UEA versus use of steerable sheaths from the transfemoral approach (TFA) (UEA: 563 patients, technical success: 95-98%, stroke rate: 1-8%; TFA: 209 patients, technical success: 98-100%, stroke rate: 0-1%). CONCLUSIONS: Both UEA and TFA as cannulation approaches were associated with high technical success and low perioperative complications. Currently, there is a paucity of high-quality data to provide definitive indication. Optimal UEA in terms of side (left versus right) and approach (surgical versus percutaneous) needs further study.

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Ten years of dynamic consent in the CHRIS study: informed consent as a dynamic process.

The Cooperative Health Research in South Tyrol (CHRIS) is a longitudinal study in Northern Italy, using dynamic consent since its inception in 2011. The CHRIS study collects health data and biosamples for research, and foresees regular follow-ups over time. We describe the experience with the CHRIS study dynamic consent, providing an overview of its conceptualization and implementation, and of the participant-centered strategies used to assess and improve the process, directly linked to participation and communication. In order to comply with high ethical standards and to allow broadness in the areas of research, CHRIS dynamic consent was conceived as an interactive process: based on a strong governance and an ongoing tailored communication with participants, it aims to promote autonomy and to develop a trust-based engaged relationship with participants, also relevant for retention. Built within an online platform, the consent allows granular choices, which can be changed over time. In a process of co-production, participants views have been investigated and kept into account in policy development. Participants showed a high degree of participation, thus enabling the consolidation of the CHRIS resources. Even though a low change rate was reported in the baseline, participants valued the possibility of changing their informed consent choices. Communication (language-tailored, ongoing, multimedia) was important for participants, and for participation and retention. In our experience, dynamic consent was proven to be a flexible consent model, which allowed to meet ethical and legal standards for participation in research, and to accommodate participants' and researchers' needs.

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.

Prospective epidemiological, molecular, and genetic characterization of a novel coronavirus disease in the Val Venosta/Vinschgau: the CHRIS COVID-19 study protocol.

The COVID-19 pandemic has been threatening the healthcare and socioeconomic systems of entire nations. While population-based surveys to assess the distribution of SARS-CoV-2 infection have become a priority, pre-existing longitudinal studies are ideally suited to assess the determinants of COVID-19 onset and severity.The Cooperative Health Research In South Tyrol (CHRIS) study completed the baseline recruitment of 13,393 adults from the Venosta/Vinschgau rural district in 2018, collecting extensive phenotypic and biomarker data, metabolomic data, densely imputed genotype and whole-exome sequencing data.Based on CHRIS, we designed a prospective study, called CHRIS COVID-19, aimed at: 1) estimating the incidence of SARS-CoV-2 infections; 2) screening for and investigating the determinants of incident infection among CHRIS participants and their household members; 3) monitoring the immune response of infected participants prospectively.An online screening questionnaire was sent to all CHRIS participants and their household members. A random sample of 1450 participants representative of the district population was invited to assess active (nasopharyngeal swab) or past (serum antibody test) infections. We prospectively invited for complete SARS-CoV-2 testing all questionnaire completers gauged as possible cases of past infection and their household members. In positive tested individuals, antibody response is monitored quarterly for one year. Untested and negative participants receive the screening questionnaire every four weeks until gauged as possible incident cases or till the study end.Originated from a collaboration between researchers and community stakeholders, the CHRIS COVID-19 study aims at generating knowledge about the epidemiological, molecular, and genetic characterization of COVID-19 and its long-term sequelae.

Early and mid-term outcomes of open popliteal artery aneurysm repair with prosthetic grafts.

OBJECTIVE: The aim of the present study was to assess the early and mid-term outcomes of open surgical repair (OSR) for popliteal artery aneurysms (PAAs) with prosthetic grafts. METHODS: The pre-, intra-, and postoperative data for all the patients who had undergone OSR for PAAs with prosthetic grafts at our Institution between January 2009 and July 2019 were included in a prospectively maintained database, which was retrospectively analyzed. Primary patency was defined as uninterrupted flow (<50% stenosis) in the graft with no additional procedures performed. Secondary patency was defined as the restoration of graft patency. RESULTS: A total of 82 patients had undergone OSR for 104 PAAs (median age, 71 years; interquartile range [IQR], 67-78 years; 82 men) with prosthetic grafts. Of the 104 PAAs, 72 (68%) had been asymptomatic. The median diameter was 30 mm (IQR, 24-37 mm). A medial approach was used for 35 PAAs (34%) and a posterior approach for 69 (65%). The repairs consisted of aneurysmectomy or aneurysm ligation without removal with an interposition graft placed and end-to-end anastomoses. The median operative time was 120 minutes (IQR, 103-142 minutes). The estimated blood loss was 281 mL (IQR, 150-281 mL). Only one patient treated with a posterior approach sustained a permanent peroneal nerve lesion. A second patient also treated via the posterior approach had required surgical revision for bleeding on postoperative day 2. No temporary lesions were recorded. No early amputations were required, and no perioperative deaths occurred. The median length of stay was 3 days (IQR, 3-4 days). An expanded polytetrafluoroethylene graft was used in 92 cases (88%) and a Dacron graft in 12 cases (12%). An 8-mm graft was used in 64 cases (62%). The median follow-up was 34.6 months (IQR, 8.5-62.7 months). No related mortality occurred. Of the 104 PAAs, 19 had required reintervention, with primary and secondary patency of 78% and 88% at 3 years, respectively. The median interval to reintervention was 28.3 months. CONCLUSIONS: OSR of PAAs with prosthetic grafts is safe and feasible, with good mid-term results and satisfactory primary and secondary patency at 3 years.

Prevalence and determinants of serum antibodies to SARS-CoV-2 in the general population of the Gardena valley.

Estimating the spread of SARS-CoV-2 infection in communities is critical. We surveyed 2244 stratified random sample community members of the Gardena valley, a winter touristic area, amidst the first expansion phase of the COVID-19 pandemic in Europe. We measured agreement between Diasorin and Abbott serum bioassay outputs and the Abbott optimal discriminant threshold of serum neutralisation titres with recursive receiver operating characteristic curve. We analytically adjusted serum antibody tests for unbiased seroprevalence estimate and analysed the determinants of infection with non-response weighted multiple logistic regression. SARS-CoV-2 seroprevalence was 26.9% (95% CI 25.2-28.6) by June 2020. The bioassays had a modest agreement with each other. At a lower threshold than the manufacturer's recommended level, the Abbott assay reflected greater discrimination of serum neutralisation capacity. Seropositivity was associated with place and economic activity, not with sex or age. Symptoms like fever and weakness were age-dependent. SARS-CoV-2 mitigation strategies should account for context in high prevalence areas.