Creating hemodialysis autogenous access in children and adolescents.

OBJECTIVE: End-stage renal disease (ESRD) in childhood and adolescence is rare, with relatively few published reports of pediatric ESRD vascular access. This study analyzes a 10-year experience creating arteriovenous fistulas (AVFs) in children and adolescents. Our goal is to review our strategy for creating functional autogenous vascular access in younger patients and report our results. METHODS: We retrospectively reviewed data and outcomes for consecutive vascular access patients aged ≤19 years during a 10-year period. Each patient had preoperative vascular ultrasound mapping by the operating surgeon in addition to physical examination. A distal forearm radiocephalic AVF was the first access choice when feasible, and a proximal radial artery inflow AVF was the next option. Demographic data, inflow artery, venous outflow target, and required transposition vs direct AVFs were variables included in the analysis. Primary and cumulative patency were calculated by Kaplan-Meier analysis. RESULTS: Thirty-seven AVFs were created in 35 patients. No grafts were used. Ages were 6 to 19 years (mean, 15 years), and 20 were male. Causes of ESRD included glomerular disease (n = 18) and urinary obstruction or reflux (n = 7), among others. Three had previous AVFs, and 10 were obese. The proximal radial artery supplied AVF inflow in 25 patients and the brachial artery in only seven. Eleven individuals required a transposition and one a vein translocation to the contralateral arm. No patients developed hand ischemia, although two later required banding procedures for high flow. Eleven patients had successful transplants. A single patient died, unrelated to the vascular access. Five AVFs failed. Of these, two had new successful AVFs created, two regained renal function, one was transplanted, and one declined other procedures. Primary and cumulative patency rates were 75% and 85% at 12 months, 70% and 85% at 24 months, and 51% and 85% at 36 months, respectively. Median follow-up was 16 months. CONCLUSIONS: Creating an AVF for hemodialysis is a successful vascular access strategy for pediatric and adolescent patients. Proximal radial artery AVFs provided safe and functional access when a distal AVF was not feasible. Cumulative AVF patency was 85% at 36 months.

Effect of fenestration configuration on renal artery outcomes during fenestrated-branched endovascular aortic repair.

OBJECTIVE: The aim of this study was to evaluate the effect of fenestration configuration and fenestration gap on renal artery outcomes during fenestrated-branched endovascular aortic repair (F/BEVAR). METHODS: A retrospective multicenter analysis was performed, including patients with complex aortic aneurysms treated with F/BEVAR that incorporated at least one small fenestration to a renal artery. The renal fenestrations were divided into groups 1 (8 × 6 mm) and 2 (6 × 6 mm). Primary patency, target vessel instability (TVI), freedom from secondary interventions (SIs), occurrence of type IIIc endoleak, all related to the renal arteries, were analyzed at 30-day, 1-year, and 5-year landmarks. The fenestration gap (FG) distance was analyzed as a modifier, and clustering was addressed at the patient level. RESULTS: A total of 796 patients were included in this study, 71.7% male, with a mean age of 73.3 ± 8.1 years. The mean follow-up was 30.0 ± 20.6 months. Of the 1474 small renal fenestrations analyzed, 47.6% were 8 × 6 mm, and 52.4% were 6 × 6 mm. At the 30-day landmark, primary patency (99.9% vs 98.0%; P value < .001 for groups 1 and 2, respectively), freedom from TVI (99.6% vs 97.1%; P value < .001 for groups 1 and 2, respectively), and freedom from SI (99.8% vs 98.4%; P value = .022 for groups 1 and 2, respectively) were higher in 8 × 6 compared with 6 × 6 fenestrations, and the incidence of acute kidney injury was similar across the groups (92.6% vs 92.7%; P value = .953 for groups 1 and 2 respectively). The primary patency at 1 and 5 years was higher in 8 × 6 fenestrations (1-year: 98.8% vs 96.9%; 5-year: 97.8% vs 95.7%, for groups 1 and 2, respectively, P values = .010 and .021 for 1 and 5 year comparisons, respectively). The freedom from SIs was significantly higher among 6 × 6 fenestrations at 5 years (93.1% vs 96.4%, for groups 1 and 2, respectively, P value = .007). The groups were equally as likely to experience a type Ic endoleak (1.3% and 1.6% for 8 × 6 and 6 × 6mm fenestrations, respectively, P = .689). The 6 × 6 fenestrations were associated with higher risk of kidney function deterioration (17.8%) when compared with 8 × 6 fenestrations (7.6%) at 5 years (P < .001). The risk of type IIIc endoleak was significantly higher among 8 × 6 fenestrations at 5 years (4.9% and 2% for 8 × 6 and 6 × 6 mm fenestrations, respectively; P = .005). A FG ≥5 mm negatively impacted the cumulative 5-year freedom from TVI (group 1: FG ≥5 mm = 0.714, FG <5 mm = 0.857; P < .001; group 2: FG ≥5 mm = 0.761, FG <5 mm = 0.929; P < .001) and the cumulative 5-year freedom from type IIIc endoleak (group 1: FG ≥5 mm = 0.759, FG <5 mm = 0.921; P = .034; group 2: FG ≥5 mm = 0.853, FG <5 mm = 0.979; P < .001) in both groups and the cumulative 5-year patency in group 2 (group 1: FG ≥5 mm = 0.963, FG <5 mm = 0.948; P = .572; group 2: FG ≥5 mm = 0.905, FG <5 mm = 0.938; P = .036). CONCLUSIONS: Fenestration configuration for the renal arteries impacts outcomes. The 8 × 6 small fenestrations have better patency at 30 days, 1 year, and 5 years, whereas 6 × 6 small fenestrations are associated with lower rates of SIs, primarily due to a lower incidence of type IIIc endoleaks. FG ≥5 mm at the level of the renal arteries significantly impacts the freedom from TVI, freedom from type IIIc endoleak, and 5-year patency independently of the fenestration size or vessel diameter.

Trends and Outcomes in Management of Thoracic Aortic Injury in Children, Adolescent, and Mature Pediatric Patients Using Data from the National Trauma Data Bank.

BACKGROUND: Thoracic aortic injury (TAI) is rare in the pediatric population. Thoracic endovascular aortic repair (TEVAR) is the recommended standard of care for treatment in the adult population given its association with lower rates of mortality and morbidity than traditional open repairs for treatment of TAI. However, there are unique anatomic challenges in treating pediatric patients with TEVAR which may impact the outcomes and pediatric guidelines. We aimed to compare current management trends and outcomes between different pediatric age groups using data from the National Trauma Data Bank (NTDB). METHODS: We analyzed the NTDB from 2007 to 2019 using International Classification of Diseases (ICD)-9 and -10 codes to identify patients with a TAI. We excluded patients older than 21 years and any patients who died in the emergency department. The pediatric patients were stratified by age group: children (1-11 years), adolescent (12-17 years), and mature (18-21 years) patients. Patient characteristics compared included injury mechanism and severity, TAI intervention, and outcomes between the 3 groups using bivariate analysis (analysis of variance for parametric and Kruskal-Wallis for nonparametric variables). These characteristics and outcomes were also compared by TAI intervention and injury mechanism. ICD-9 and -10 procedural codes were used to identify patients who underwent TEVAR, open aortic repair (OAR), or both. The modified Poisson regression was performed with relative risk (RR) to evaluate our primary outcome measure-mortality during the trauma admission. RESULTS: A total of 2,431 pediatric TAI were identified in the NTDB that met the inclusion criteria. This included 134 children (5.5%), 733 adolescent (30.2%), and 1,564 mature (64.3%) patients. Children had significantly lower median Injury Severity Scores (34.1) than the adolescent (38) or mature population (36.1) (P = 0.001). The mechanism of injury differed between age groups. Children had higher rates of blunt trauma (90.3% children, 89.6% adolescent, and 86.8% mature patients) and mature patients had higher rates of penetrating trauma (6% children, 10.1% adolescent, and 12.5% mature patients) (P < 0.001). TAI management also differed significantly between pediatric age groups. Mature patients had significantly higher rates of TEVAR (3% children, 25.2% adolescent, and 29.2% mature patients) and children were most likely to be treated with nonoperative management (NOM) (94% children, 67.9% adolescent, and 64.8% mature patients) (P < 0.001). Patients who were treated with TEVAR were discharge home most frequently (31.8% NOM, 54.1% TEVAR, 44.3% OAR, 22.2% both TEVAR and OAR). Upon modified Poisson regression analysis, patient age was not associated with an increased risk of in-hospital mortality. Intervention with TEVAR (RR: 0.22, 95% CI: 0.15-0.33, P < 0.001) and OAR (RR: 0.58, 95% CI: 0.36-0.93, P = 0.024) were associated with a lower risk of mortality than NOM. CONCLUSIONS: TAI is less prevalent in children compared to adults. TEVAR for TAI is associated with lower risk of in-hospital mortality compared to both NOM and OAR without differences between pediatric subgroups. Further studies should be completed to determine the most appropriate management guidelines.

Outcome Analysis Comparing Asymptomatic Juxtarenal Aortic Aneurysms Treated with Custom-Manufactured Fenestrated-Branched Devices and the "Off-The-Shelf" Zenith p-Branch Device.

BACKGROUND: Numerous endovascular options have been used for the repair of juxtarenal aortic aneurysms (JRAAs) over the last 15 years. This study aims to compare the performance between the Zenith p-branch device and custom-manufactured fenestrated-branched devices (CMD) for the treatment of asymptomatic JRAA. METHODS: A single-center retrospective analysis of prospectively collected data was performed. Patients with a diagnosis of JRAA submitted to endovascular repair between July 2012 and November 2021 were included in the study, being divided into 2 groups: CMD and Zenith p-branch. The following variables were analyzed: preoperative information: demographics, comorbidities, and maximum aneurysm diameter; procedural data: contrast volume, fluoroscopy time, radiation dose, estimated blood loss, and technical success; and postoperative data: 30-day mortality, duration of intensive care unit and hospital stay, major adverse events, secondary interventions, target vessel instability, and long-term survival. RESULTS: From a total of 373 physician-sponsored investigational device exemption (Cook Medical devices) cases performed at our institution, 102 patients presented the diagnosis of JRAA. Of these, 14 patients were treated with the p-branch device (13.7%) and 88 (86.3%) with a CMD. Both groups presented similar demographic composition and maximum aneurysm diameter. All devices were successfully deployed, with no type I or III endoleaks observed at procedure completion. The contrast volume (P = 0.023) and radiation dose (P = 0.001) were significantly higher in the p-branch group. No significant difference was observed between the groups for the remaining intraoperative data. No paraplegia or ischemic colitis has been observed during the first 30 days after the surgical procedures. There was no 30-day mortality in either group. One major cardiac adverse event was registered in the CMD group. Early outcomes were similar in both groups. No significant difference was found between the groups with respect to the presence of type I or III endoleaks during the follow-up. From a total of 313 target vessels stented in the CMD group (mean of 3.55 per patient) and 56 in the p-branch group (mean of 4 per patient), 4.79% and 5.35% presented instability, respectively, with no difference observed between the groups (P = 0.743). Secondary interventions were required in 36.4% of the CMD cases and 50% of the p-branch group, but this was not statistically different (P = 0.382). In the p-branch cohort, 2 of 7 reinterventions (28.5%) were target vessel-related and in the CMD group, 10 of 32 secondary interventions (31.2%) were target vessel-related. CONCLUSIONS: Comparable perioperative outcomes were obtained when appropriately selected patients were treated with either the off-the-shelf p-branch or CMD for JRAA. The long-term target vessel instability does not appear impacted by the presence of pivot fenestrations in comparison to other target vessel configurations. Given these outcomes, delay in CMD production time should be considered when treating patients with large juxtarenal aneurysms.

A straightforward one-step strategy for SARS-CoV-2 diagnosis and screening of variants of concern: a multicentre study.

BACKGROUND: The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) has changed unevenly over time around the world. Although whole genome sequencing is the gold standard for virus characterisation, the discovery of alpha VOC causing spike gene target failure (SGTF) result, when tested using an reverse transcription real-time polymerase chain reaction (RT-qPCR) assay, has provided a simple tool for tracking the frequencies of variants. OBJECTIVES: The aim of this study was to investigate if a multiplex RT-qPCR assay (BioM 4Plex VOC) could be used to detect SARS-CoV-2 and to perform a VOC screening test in a single reaction tube. Here, we present the multicentre study evaluating this assay. METHODS: Twelve laboratories have participated in the multicentre study. The BioM 4Plex VOC was distributed to them with detailed instructions of how to perform the test. They were asked to test the BioM 4Plex VOC in parallel with their routine Commercial SARS-CoV-2 diagnostic assay. Additionally, they were requested to select SARS-CoV-2-positive samples with genome sequenced and lineage definition according to PANGO lineage classification. FINDINGS: The BioM 4Plex VOC and commercial RT-PCR assay are equally effective in detecting SARS-CoV-2. Results revealed a specificity of 96.5-100% [95% confidence interval (CI)], a sensitivity of 99.8-100% (95% CI), and an accuracy of 99.8-100% (95% CI). A 99% concordance rate was found between results from the BioM 4Plex VOC and that from available genome sequencing data. MAIN CONCLUSIONS: The BioM 4Plex VOC provides an effective solution to detect SARS-CoV-2 infections and screening for VOCs in a single reaction. It is a straightforward method to help us monitor the frequency and distribution of VOCs and develop strategies to better cope with the pandemics.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

Severe Acute Respiratory Syndrome Coronavirus 2 P.2 Lineage Associated with Reinfection Case, Brazil, June-October 2020.

A 37-year-old healthcare worker from the northeastern region of Brazil experienced 2 clinical episodes of coronavirus disease. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by reverse transcription PCR in samples collected 116 days apart. Whole-genome sequencing revealed that the 2 infections were caused by the most prevalent lineage in Brazil, B.1.1.33, and the emerging lineage P.2. The first infection occurred in June 2020; Bayesian analysis suggests reinfection at some point during September 14-October 11, 2020, a few days before the second episode of coronavirus disease. Of note, P.2 corresponds to an emergent viral lineage in Brazil that contains the mutation E484K in the spike protein. The P.2 lineage was initially detected in the state of Rio de Janeiro, and since then it has been found throughout the country. Our findings suggest not only a reinfection case but also geographic dissemination of the emerging Brazil clade P.2.

Performance of Viabahn balloon-expandable stent compared with self-expandable covered stents for branched endovascular aortic repair.

OBJECTIVE: The objective of this study was to compare the performance between the Viabahn balloon-expandable stent (VBX; Viabahn [W. L. Gore & Associates, Flagstaff, Ariz]) and a covered self-expandable stent (SES; Fluency [Bard Peripheral Vascular, Tempe, Ariz]) used as bridging stents for directional branches during fenestrated or branched endovascular aneurysm repair of complex aortic aneurysms. METHODS: Patients with thoracoabdominal aortic aneurysms (type I-IV) or pararenal aortic aneurysms either at high risk for open repair or unsuitable for endovascular repair with commercially available devices were prospectively enrolled in a physician-sponsored investigational device exemption trial. Descriptive statistics of the cohort included demographics, risk factors, and anatomic and device characteristics. Individual branches were grouped as either VBX or SES and had data analyzed for primary patency, branch-related type I or type III endoleaks, branch instability, branch-related secondary intervention, and branch-related aortic rupture or death. Categorical variables were expressed as total and percentage, and continuous variables were expressed as median (interquartile range). Kaplan-Meier curves were used to estimate long-term results. Groups were compared with the log-rank test. P value <.05 was considered statistically significant. RESULTS: During the period from July 2012 through June 2019, there were 263 patients treated for complex aortic aneurysm (thoracoabdominal aortic aneurysm) with fenestrated or branched endografts. The devices used were either custom-manufactured devices or off-the-shelf p-Branch or t-Branch (Cook Medical, Bloomington, Ind) devices. The median age was 71 years (interquartile range, 66-79 years); 70% were male, and 81% were white. The most common cardiac risk factors were smoking (92%), hypertension (91%), hyperlipidemia (78%), and chronic obstructive pulmonary disease (52%). The total number of vessels incorporated into the repair was 977, with branches representing 18.4% (179 branches). Among these 179 branches, the celiac artery, superior mesenteric artery, right renal artery, and left renal artery received 54 (30%), 56 (31%), 38 (21%), and 31 (18%) branches, respectively. VBX and SES groups represented 96 (54%) and 81 (46%) of the branches implanted. The celiac artery, superior mesenteric artery, right renal artery, and left renal artery received VBX as a bridging stent in 40%, 46.7%, 33.8%, and 32.2% respectively. The overall cohort survival rate was 78.5% at 24 months. There was no branch-related rupture or mortality. Primary patency at 24 months (VBX, 98.1%; SES, 98.6%; log-rank, P = .95), freedom from endoleak (VBX, 95.6%; SES, 98.6%; log-rank, P = .66), freedom from secondary intervention (VBX, 94.7%; SES, 98.1%; log-rank, P = .33), and freedom from branch instability (VBX, 95.6%; SES, 97.2%; log-rank, P = .77) were similar between groups. CONCLUSIONS: This initial experience with VBX stents demonstrated excellent primary patency and similarly low rates of branch-related complications and endoleaks, with no branch-related aortic rupture or death. Our results demonstrate that in a high-volume, experienced aortic center, the VBX stent is a safe and effective bridging stent option during branched endovascular aortic repair. Multicenter studies with a larger cohort and longer follow-up are necessary to validate these findings.

Fenestrated-branched endovascular aortic repair is a safe and effective option for octogenarians in treating complex aortic aneurysm compared with nonoctogenarians.

OBJECTIVE: Open repair of complex aortic aneurysms is frequently not an option for octogenarians because of prohibitive surgical risks. This study aimed to analyze the outcomes of fenestrated-branched endovascular aortic repair (F-BEVAR) in octogenarians (≥80 years old) compared with nonoctogenarians (<80 years old). METHODS: We reviewed 893 patients with pararenal or extent I to V thoracoabdominal aneurysms, enrolled in six prospective physician-sponsored investigational device exemption studies from 2012 to 2018. All patients were treated with either company-manufactured off-the-shelf or patient-specific F-BEVAR stent grafts. Data analyzed included demographics, cardiovascular risk factors, history of active cancer, American Society of Anesthesiologists classification, aortic anatomy characteristics, and procedural data. End points included mortality, major adverse events (all-cause mortality, stroke, paralysis, acute kidney injury [RIFLE criteria], dialysis, myocardial infarction, respiratory failure, and bowel ischemia), technical success, hospital length of stay, target artery instability (occlusion/stenosis, endoleak, rupture or death), and secondary interventions. RESULTS: During the study period, 195 octogenarian patients (22%) and 698 (78%) nonoctogenarian patients were treated with F-BEVAR. Octogenarians presented more frequently with a history of cancer (17% vs 11%; P = .01), whereas nonoctogenarians more frequently had hyperlipidemia (76% vs 65%; P = .003), chronic obstructive pulmonary disease (42% vs 33%; P = .04) and American Society of Anesthesiologists class III to V (78% vs 70%; P = .02). Male sex was similar between groups (68% [octogenarians] vs 70% [nonoctogenarians]; P = .62). Octogenarians had a larger mean aneurysm diameter (67 ± 1 mm vs 65 ± 1 mm; P = .002). The thoracoabdominal classification and the use of upper extremity access were similar between groups. Estimated blood loss was also similar (484 ± 454 mL [octogenarian] vs 416 ± 457 mL [nonoctogenarian]; P = .07). Octogenarians had an increased mean number of vessels incorporated into the repair (3.1 ± 1.4 vs 2.7 ± 1.7; P < .001). The technical success rate was 99% for octogenarians and 97% for nonoctogenarians (P = .19). The 30-day mortality rate was 0.5% for octogenarians and 1.3% for the nonoctogenarians (P = .70). Major adverse events (9.2% vs 9.7%), types I/III endoleak (4.6% vs 2.4%) access complication (3.1% vs 3.3%), and length of stay (8.2 ± 27 days vs 5.7 ± 6.3 days) were all similar between the groups. Freedom from target artery instability and freedom from secondary interventions at 3 years were similar between the groups. Octogenarian survival was lower at 3 years compared with nonoctogenarians on univariate analysis (log-rank P < .01) and on multivariable analysis after adjusting for history of active cancer, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: Despite small differences in demographics, anatomic factors, and procedural data, F-BEVAR was safe and effective with nearly identical early outcomes in octogenarians in these experienced aortic centers. More extensive clinical experience and longer follow-up are needed to better delineate factors impacting longer term mortality.

In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas.

OBJECTIVE: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. METHODS: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. RESULTS: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality. CONCLUSIONS: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10 months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population.

Contemporary Outcomes After Partial Resection of Infected Aortic Grafts.

INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection. METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed. RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01) CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.

Morphology and morphogenesis of SARS-CoV-2 in Vero-E6 cells.

BACKGROUND: The coronaviruses (CoVs) called the attention of the world for causing outbreaks of severe acute respiratory syndrome (SARS-CoV), in Asia in 2002-03, and respiratory disease in the Middle East (MERS-CoV), in 2012. In December 2019, yet again a new coronavirus (SARS-CoV-2) first identified in Wuhan, China, was associated with a severe respiratory infection, known today as COVID-19. This new virus quickly spread throughout China and 30 additional countries. As result, the World Health Organization (WHO) elevated the status of the COVID-19 outbreak from emergency of international concern to pandemic on March 11, 2020. The impact of COVID-19 on public health and economy fueled a worldwide race to approve therapeutic and prophylactic agents, but so far, there are no specific antiviral drugs or vaccines available. In current scenario, the development of in vitro systems for viral mass production and for testing antiviral and vaccine candidates proves to be an urgent matter. OBJECTIVE: The objective of this paper is study the biology of SARS-CoV-2 in Vero-E6 cells at the ultrastructural level. METHODS: In this study, we documented, by transmission electron microscopy and real-time reverse transcription polymerase chain reaction (RT-PCR), the infection of Vero-E6 cells with SARS-CoV-2 samples isolated from Brazilian patients. FINDINGS: The infected cells presented cytopathic effects and SARS-CoV-2 particles were observed attached to the cell surface and inside cytoplasmic vesicles. The entry of the virus into cells occurred through the endocytic pathway or by fusion of the viral envelope with the cell membrane. Assembled nucleocapsids were verified inside rough endoplasmic reticulum cisterns (RER). Viral maturation seemed to occur by budding of viral particles from the RER into smooth membrane vesicles. MAIN CONCLUSIONS: Therefore, the susceptibility of Vero-E6 cells to SARS-CoV-2 infection and the viral pathway inside the cells were demonstrated by ultrastructural analysis.

Outcomes of endovascular repair of chronic postdissection compared with degenerative thoracoabdominal aortic aneurysms using fenestrated-branched stent grafts.

OBJECTIVE: The objective of this study was to analyze outcomes of fenestrated-branched endovascular aneurysm repair (F/BEVAR) for treatment of postdissection and degenerative thoracoabdominal aortic aneurysms (TAAAs). METHODS: We reviewed the clinical data of 240 patients with extent I to extent III TAAAs enrolled in seven prospective physician-sponsored investigational device exemption studies from 2014 to 2017. All patients had manufactured off-the-shelf or patient-specific fenestrated-branched stent grafts used to target 888 renal-mesenteric arteries with a mean of 3.7 vessels per patient. End points included mortality, major adverse events (any-cause mortality, stroke, paralysis, dialysis, myocardial infarction, respiratory failure, bowel ischemia, and estimated blood loss >1 L), technical success, target artery patency, target artery instability, occlusion or stenosis, endoleak, rupture or death, reintervention, and renal function deterioration. RESULTS: There were 50 patients (21%) treated for postdissection TAAAs and 190 (79%) who had degenerative TAAAs. Postdissection TAAA patients were significantly younger (67 ± 9 years vs 74 ± 8 years; P < .001), were more often male (76% vs 52%; P = .002), and had more prior aortic repairs (84% vs 67%; P = .02) and larger renal (6.4 ± 1.2 mm vs 5.8 ± 0.9 mm; P < .001) and mesenteric (8.9 ± 1.7 mm vs 7.8 ± 1.4 mm; P < .001) target artery diameters. There was no difference in aneurysm diameter (66 ± 13 mm vs 67 ± 11 mm; P = .50), extent I or extent II TAAA classification (64% vs 56%; P = .33), and length of supraceliac coverage (22 ± 9.5 cm vs 20 ± 10 cm; P = .38) between postdissection and degenerative patients, respectively. Preloaded guidewire systems (66% vs 43%; P = .003) and fenestrations as opposed to directional branches (58% vs 24%; P < .001) were used more frequently to treat postdissection patients. Technical success was 100% for postdissection TAAAs and 99% for degenerative TAAAs (P = .14). At 30 days, there was no difference in mortality (2% postdissection, 3% degenerative), major adverse events (24% postdissection, 26% degenerative; P = .73), spinal cord injury (6% postdissection, 12% degenerative; P = .25), paraplegia (2% postdissection, 7% degenerative; P = .19), and dialysis (0% postdissection, 5% degenerative; P = .24). Mean follow-up was 14 ± 12 months. Endoleaks were significantly more frequent in patients with postdissection TAAAs (76%) compared with degenerative TAAAs (43%; P < .001). At 2 years, there was no difference in patient survival (84% ± 7% vs 72% ± 4%; P = .13), freedom from aorta-related death (98% ± 2% vs 94% ± 2%; P = .45), primary (95% ± 2% vs 97% ± 1%; P = .93) and secondary target artery patency (99% ± 1% vs 98% ± 1%; P = .48), target artery instability (89% ± 3% vs 91% ± 1%; P = .17), and freedom from reintervention (58% ± 10% vs 67% ± 5%; P = .23) for postdissection and degenerative TAAAs, respectively. CONCLUSIONS: Despite minor differences in demographics, anatomic factors, and stent graft design, F/BEVAR was safe and effective with nearly identical outcomes in patients with postdissection and degenerative TAAAs. Larger clinical experience and longer follow-up are needed to better evaluate differences in mortality, spinal cord injury, target artery instability, and reintervention.

Identification of SARS-CoV-2 and additional respiratory pathogens cases under the investigation of COVID-19 initial phase in a Brazilian reference laboratory.

Coronavirus disease 2019 (COVID-19) surveillance, in Brazil, initiated shortly after its description, in China. Our aim was to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and additional pathogens in samples from the initial phase of the outbreak in Brazil, from late February to late March. From 707 samples analysed, 29 (4.1%) were SARS-CoV-2 positive. Fever and cough were their most prevalent symptoms. Co-detection of rhinovirus was observed in 2 (6.9%) cases. Additional pathogens were identified in 66.1% of the SARS-CoV-2 negative cases, mainly rhinovirus and influenza A(H1N1)pdm09. Thus, we emphasise the importance of differential diagnosis in COVID-19 suspected cases.

An Inexpensive and Accurate Reverse Transcription-PCR-Melting Temperature Analysis Assay for Real-Time Influenza Virus B Lineage Discrimination.

In this work, we describe a SYBR-Green one-step reverse transcription-PCR protocol coupled with a melting temperature analysis (RT-PCR-Tm ), which allows the discrimination of influenza B lineages Yamagata and Victoria. The assay is performed using a regular real-time thermocycler and is based on differences in melting temperature (Tm ) of a 131-bp amplicon, obtained from a conserved region of hemagglutinin gene. A total of 410 samples collected during the 2004, 2008, and 2010-2017 influenza seasons in Brazil were tested, and the lineages were correctly characterized using their melting profiles. The temperature range is significantly different between both lineages throughout the time (Mann-Whitney test; P < 0.0001, confidence interval = 95%), and the Tm is not affected by viral load (Spearman correlation test; r = 0.287, P = 2.245 × 10-9). The simplicity and cost-effectiveness of this protocol make it an option for influenza B lineage surveillance worldwide.

The role of selective stenting for superior mesenteric artery scallops during fenestrated endovascular aneurysm repair.

OBJECTIVE: Stenting of small fenestrations of the Zenith fenestrated endograft (ZFEN; Cook Medical, Bloomington, Ind) is necessary during fenestrated endovascular aneurysm repair (FEVAR) of complex abdominal aortic aneurysms to avoid malalignment. However, stenting of superior mesenteric artery (SMA) scallops of ZFEN devices is optional according to the instructions for use. The objective of this study was to assess the early and midterm outcomes of selective use of stents in SMA scallops of ZFEN during FEVAR procedures. METHODS: This study is a single-institution retrospective review of prospectively enrolled patients treated at the University of North Carolina at Chapel Hill between July 2010 and August 2014. Only patients with SMA scallops were included for analysis. We compared results between patients grouped as stented or unstented SMA scallops. The scallops were stented when one or more of the following criteria were present: misalignment of scallop determined by balloon testing intraoperatively; configuration consisting of an SMA scallop and a single renal fenestration or stent; and pre-existing stenosis in the vessel adjacent to the graft scallop. The study was approved by the local Institutional Review Board. Primary outcomes addressed were mortality, vessel patency, early and late complications, and reintervention rates. Baseline characteristics of the patients and procedure data were also described. RESULTS: During the 48-month study period, 61 patients were treated for complex abdominal aortic aneurysms at the University of North Carolina with a mean age of 73 years, and 74.3% of patients were male. Thirty-nine of 61 patients (63.9%) had a device design with an SMA scallop and were included for analysis. Eleven of 39 patients (28%) had the SMA primarily stented and 28 (72%) were unstented. There was only one death (2.5%) during the 30-day postoperative period, with 100% technical success and branch patency. In the unstented group, there were three SMA complications during follow-up, two requiring reintervention; however, there were no associated deaths. Among the stented group, there was one branch-related complication that occurred during the procedure but no stent stenosis or occlusion during the long-term follow-up. During the mean follow-up period of 21.7 months, no SMA stent thrombosis occurred. There was no statistical difference in outcomes between groups. CONCLUSIONS: Single-wide SMA scallops of ZFEN during FEVAR procedures may be selectively stented using specific criteria and rigorous follow-up, without compromising the safety and efficacy of the SMA.

Comparison of commercially available versus customized branched-fenestrated devices in the treatment of complex aortic aneurysms.

OBJECTIVE: To evaluate and compare the early outcomes of patients treated for complex aortic aneurysms using a commercially available Zenith fenestrated endograft (ZFEN) or an advanced customized fenestrated-branched endovascular repair, which includes custom-made device or off-the-shelf p-branch devices available for use in a physician-sponsored investigational device exemption (PSIDE). METHODS: Between July 2012 and July 2015, patients who underwent to complex aortic aneurysms repair at University of North Carolina-Chapel Hill were retrospectively analyzed using data prospectively collected in electronically maintained aortic database. Patients were separated in two groups: ZFEN and PSIDE (custom-made device and p-branch). Demographics data, cardiac risk factors, comorbidities, computed tomography angiography anatomic measurements (aneurysm diameter, length of aortic coverage above the celiac artery), procedural data (operative time, estimated blood loss, intraoperative complications), and 30-day outcomes (mortality, major adverse cardiac events, stroke/transient ischemic attack, paraplegia, gastrointestinal complications, visceral branch complications, and endoleak) were analyzed. RESULTS: Among the 131 repairs for complex aortic aneurysms (juxtarenal or thoracoabdominal), there were 60 ZFEN and 71 PSIDE devices. Demographics and risk factors had similar distribution between groups, except that PSIDE patients more commonly had a history of previous aortic surgery (33% vs 5% [ZFEN]; P = .0001). PSIDE patients had a greater number of stented vessels (3.4 vs 2.2; P < .001) and length of aortic coverage (72 mm vs -13.4 mm) than ZFEN; however, no differences were seen in operative time, estimated blood loss or fluoroscopic time. Early outcomes were similar between groups, except for duration of hospital stay, which was significantly longer in PSIDE cohort (4.4 days vs 3.3 days; P = .05). CONCLUSIONS: More advanced fenestrated-branched endovascular repair does not seem to increase the complications associated with repair compared with patients receiving a ZFEN device in an experienced treatment center. Although mortality and morbidity were comparable between the groups, further studies evaluating long-term outcomes are needed.

Renal volumes and estimated glomerular filtration rate changes after fenestrated-branched endovascular aortic repair.

OBJECTIVE: To describe changes in renal volumes (RV) and renal function after fenestrated-branched endovascular repair (F-BEVAR) for complex aortic aneurysms. METHODS: The data from patients enrolled in a physician-sponsored investigational device exemption clinical trial for endovascular treatment of complex aortic aneurysms from July 2012 to April 2017 were retrospectively analyzed. Descriptive statistics were calculated using the mean ± standard deviation. The mean estimated glomerular filtration rate (eGFR) and RV were calculated at baseline and 6, 12, and 18 months after F-BEVAR. Variable distributions were evaluated for skewness, and all models required log-transformation. Linear models using generalized estimating equations were used to assess the association between the RV and eGFR over time after adjustment for relevant covariates. We used Kaplan-Meier life-table analysis to calculate survival and branch patency. RESULTS: A total of 139 patients were followed up for 18 months or until death. The mean age was 71 ± 8 years (70% male). The most common risk factor was hypertension (92%). Chronic kidney disease (CKD; eGFR <60 mL/min) was present in 56 patients (40%). Thirty-one patients (22%) had ≥1 accessory renal artery. Of these 31 accessory arteries, 27 (87%) were embolized or covered. On average, the eGFR had decreased over time compared with baseline, with a median change of -4.4 mL/min (interquartile range [IQR], -11.4 to 4.9 mL/min), -2.6 mL/min (IQR, -11.9 to 6.5 mL/min), and -3.4 mL/min (IQR, -11.9 to 5.5 mL/min) at 6, 12, and 18 months postoperatively, respectively. Similarly, the RV had decreased from baseline by 8% ± 17%, 10% ± 17%, and 11% ± 22% at 6, 12, and 18 months, respectively. An increase in the baseline patient age of 5 years was estimated to be associated with a 3% (95% confidence interval [CI], 0.2%-6.0%) decrease in the mean eGFR during the follow-up period, collapsing over time. This change is similar to the natural history of renal deterioration with age. We estimated that an increase in the log-RV of 1 U would be associated with an estimated 26% (95% CI, 3%-52%) increase in the mean eGFR. Preexisting CKD did not affect the average change in RV. Of the 56 patients with previous CKD, 9 (16.1%) showed improvement in the eGFR to >60 mL/min. The median follow-up period was 17.9 months (IQR, 6.3-24.8). The Kaplan-Meier survival rate at 1 and 2 years was 84.7% (95% CI, 78.3%-91.1%) and 78.8% (95% CI, 71.0%- 86.6%), respectively. CONCLUSIONS: The RV and eGFR decreased in patients undergoing repair at the rates expected for patients with complex aortic disease. The eGFR correlated with the RV. Most of the decline in renal function occurred within the first 6 months postoperatively, after which, the renal function had stabilized.

Stenting of superior mesenteric and celiac arteries does not increase complication rates after fenestrated-branched endovascular aneurysm repair.

OBJECTIVE: This study compared complications in patients undergoing fenestrated-branched endovascular aneurysm repair (F-BEVAR) without and with stenting of the superior mesenteric artery (SMA) or celiac artery (CA), with particular attention to the length of coverage above the CA. METHODS: A retrospective review was performed of a prospectively maintained database of patients treated with F-BEVAR for thoracoabdominal aortic aneurysms between July 2012 and May 2017. Data included demographics, risk factors, comorbidities, preoperative aneurysm characteristics, procedural data, and outcomes. Patients were grouped as follows: group 1, no SMA or CA stent; group 2, SMA or CA stent and <5 cm of coverage above the CA; and group 3, SMA or CA stent and ≥5 cm of coverage above the CA. Complications measured included death, myocardial infarction, respiratory failure, stroke or transient ischemic attack, paraplegia, acute kidney injury, mesenteric ischemia, and vascular complications. Individual and composite complications were compared between groups. RESULTS: There were 223 patients who had data analyzed (group 1, 53 [24%]; group 2, 101 [45%]; and group 3, 69 [31%]). Mean age was 72 years (76% male). There was no difference in patients' characteristics between groups, except for hypertension (less common in group 2) and history of previous aortic surgery (more common in group 3). Group 2 (15%) and group 3 (90%) had higher spinal drain use than group 1 (2%; P < .0001). Mean operative time was longer in groups 2 and 3 compared with group 1 (group 1, 224 minutes; group 2, 253 minutes; and group 3, 313 minutes; P < .0001). Group 1 had more intraoperative complications, without difference in the technical success and mortality rates. Failure to deliver a bridging stent occurred in only 3 of 695 vessels (0.4%) intended, without difference between groups (P = .79). The incidence of major complications (individually and composite analysis) was similar between groups. On 30-day computed tomography angiography, there was no difference in type I or type III endoleaks (2%, 3%, and 6%) and branch patency (98%, 99%, and 99%) for groups 1, 2, and 3, respectively. At 3 years of follow-up, there was no difference in survival, stent patency, and branch instability. Group 3 had a higher reintervention rate compared with groups 1 and 2 (P < .0001); however, there was no difference between groups 1 and 2 (P = .31). CONCLUSIONS: Patients who needed SMA or CA incorporation with stents during F-BEVAR for aortic repair had more complex procedures, as assessed by operative time, brachial access, number of vessels incorporated, and spinal drain use. However, the extension of the repair did not affect the outcomes, demonstrated by similar mortality and morbidity rates between groups.

Outcomes and complications after fenestrated-branched endovascular aortic repair.

OBJECTIVE: To report the outcomes of patients enrolled in a physician-sponsored investigational device exemption trial for endovascular treatment of complex thoracoabdominal aortic aneurysms with fenestrated and/or branched devices. METHODS: This study represents a retrospective analysis of a prospectively maintained database of patients enrolled in a physician-sponsored investigational device exemption trial for endovascular treatment of complex thoracoabdominal aneurysms between July 2012 and July 2017. Subjects included high-risk patients for open repair and patients with unsuitable anatomy for either standard endovascular aneurysm repair or Zenith (Cook Medical, Bloomington, Ind) fenestrated device. Aneurysm classification was based upon Crawford classification. We included the pararenal and paravisceral aneurysms in the type IV aneurysm group, because the repair of these aneurysms usually involved treatment of all four visceral branches. The endografts implanted were custom manufactured devices or off-the-shelf devices based on the Cook Zenith platform. Variables analyzed included preoperative demographics and comorbidities, anatomic aneurysmal characteristics, procedural details, and perioperative complications. RESULTS: One -hundred fifty patients with a mean age of 71 ± 7.9 years were treated; 69% were male. Tobacco use (93%) and hypertension (91%) were the most common risk factors. Fifty-seven patients (38%) had a history of previous aortic repair. The mean aneurysm diameter was 62 ± 12 mm and 14 (9%) aneurysms were associated with chronic dissection. A total of 573 visceral vessels were incorporated (celiac artery/superior mesenteric artery [287 vessels], renal arteries [275 vessels], and 11 additional vessels) and 539 were stented. The celiac artery/superior mesenteric artery received a fenestrated design in 76.1% of cases. Branch designs were used in the renal artery in 13.2%, with the remainder treated with fenestrations. Spinal cord drainage was used in 51% of patients (76/150). The mean operative time, fluoroscopy time, and estimated blood loss were 283 ± 89 minutes, 83 ± 38 minutes, and 417 ± 404 mL, respectively. There were five patients (3.3%) with intraoperative complications, resulting in one intraoperative death. The early mortality was 2.7% (4/150). Major complications included respiratory failure in 7% (10/150), stroke and myocardial infarction in 0.7% each (1/150), and paraplegia in 2.7% (4/150). Acute kidney injury occurred in 4.7% of patients (7/150), two of whom required temporary dialysis. Thirty-nine percent of patients experienced at least one complication. Early branch vessel patency was 99.8% (525/526). Survival, primary, and primary-assisted branch patency at 2 years of follow-up were 79%, 97%, and 99%, respectively. CONCLUSIONS: Endovascular repair of complex aneurysms is safe and effective when performed in a high-volume center experienced in aortic disease management. Branch vessels patency and the low incidence of paraplegia and mortality support expanded use to treat most complex thoracoabdominal aortic aneurysms.