Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype.

OBJECTIVE: Primary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor can affect nNO levels and thus could play a role in the susceptibility to respiratory infections. We assessed the impact of these polymorphisms on nNO production and Pseudomonas aeruginosa (P.a.) infections in different PCD genotypes. METHODS: Prospective, longitudinal, single-centre study in patients with PCD with known genotype and one of three TAS2R38 haplotypes evaluated for up to 10 years. We related nNO values to TAS2R38 haplotypes in all patients, and in the three most frequent genotypes (CCDC39/CCDC40, DNAH5, DNAH11). In the genetic group(s) with different mean trends of nNO in relation to the polymorphism, we evaluated longitudinal lung function as a clinical outcome measure. We also studied any associations between the prevalence of chronic P.a. infection and PAV alleles. Linear mixed-effects models were used to evaluate longitudinal associations. RESULTS: 119 patients with PCD underwent 1116 study visits. Only in the DNAH11 mutations group was there a mean trend of nNO production which was significantly higher in PAV/PAV than AVI/AVI haplotype (p=0.033), with a better trend in spirometric and plethysmographic parameters. In patients with DNAH11 mutations the PAV allele was also associated with a significantly reduced prevalence of chronic P.a. CONCLUSION: TAS2R38 may be a modifier gene for PCD severity, but only in mild phenotype disease. Further study of TAS2R38 polymorphisms might enable new management strategies to prevent chronic P.a.

Effect of narrow paravisceral aorta on target vessel instability after fenestrated and branched endovascular aortic repair.

OBJECTIVE: To investigate the effect of narrow paravisceral aorta (NPA) on target vessel instability (TVI) after fenestrated-branched endovascular aortic repair. METHODS: We conducted a single-center retrospective study (2014-2023) of patients treated by fenestrated-branched endovascular aortic repair for thoracoabdominal aortic aneurysms (TAAA) or pararenal aortic aneurysms. The paravisceral aorta was defined as the aortic segment limited by the diaphragmatic hiatus proximally and the emergence of lower renal artery distally, and was considered "narrow" in case of a minimum inner diameter of <25 mm. The minimum aortic diameter, location, longitudinal extension, angulation, calcification, and thrombus thickness of NPA were evaluated at the preoperative computed tomography angiogram. End points were 30-day technical success and freedom from TVI. RESULTS: There were 142 patients with JRAA/pararenal aortic aneurysm (n = 85 [59%]) and extent IV (n = 24 [17%]) or extent I-III (n = 33 [23%]) TAAA, with 513 target arteries successfully incorporated through a fenestration (n = 294 [57%]) or directional branch (n = 219 [43%]). A NPA was present in 95 patients (70%), 73 (86%) treated by fenestrated endovascular aortic repair (FEVAR) and 22 (39%) by branched endovascular aortic repair (BEVAR). The overall 30-day mortality was 2% and technical success was 99%, without differences between NPA and non-NPA (P = .99). Kaplan-Meier estimated freedom from TVI at 4 years was 82%, 81% (95% CI, 75-95) in patients with a NPA and 80% (95% CI, 68-94) and in those without NPA (P = .220). The result was maintained for both FEVAR (NPA: 81% [95% CI, 62-88]; non-NPA: 76% [95% CI, 60-99]; P = .870) and BEVAR (NPA: 77% [95% CI, 69-99]; non-NPA: 80% [95% confidence interval (CI) 66-99]; P = .100). After multivariate analysis, the concomitant presence of a NPA <20 mm and angulation of >30° was significantly associated with TVI in FEVAR (HR, 3.21; 95% CI, 1.03-48.70; P = .036), being the result mostly driven by target vessel occlusion. In BEVAR, a NPA diameter of <25 mm was not associated with TVI (HR, 2.02; 95% CI, 0.59-5.23; P = .948); after multivariate analysis, the use of outer branches in case of a NPA longitudinal extension of >25 mm (hazard ratio [HR], 3.02; 95% CI, 1.01-36.33; P = .040) and NPA severe calcification (HR, 1.70; 95% CI, 1.00-22.42; P = .048) were associated with a higher chance for TVI. CONCLUSIONS: FEVAR and BEVAR are both feasible in cases of NPA and provide satisfactory target vessels durability. The use of outer branches should be avoided in cases with an inner aortic diameter of <25 mm with a longitudinal extension of >25 mm or moderate to severe NPA calcifications. In FEVAR, bridging stent patency may be negatively influenced by NPA of <20 mm in association with aortic angulation of >30°.

Fate of primary determinate and indeterminate target vessel endoleaks after fenestrated-branched endovascular aortic repair.

OBJECTIVE: The aim of this study was to investigate the outcomes of primary determinate and indeterminate target vessel endoleaks (TVELs) after fenestrated-branched endovascular aortic repair (F-BEVAR). METHODS: We conducted a single-center retrospective study (2014-2023) on F-BEVAR for thoracoabdominal (TAAAs) or pararenal aortic aneurysms (PRAAs). TVELs were classified as "primary" if present at the first postoperative computed tomography angiogram. Endoleaks were defined "determinate" (dELs) if the cause (type Ic or IIIc) and implicated target vessel were identifiable and "indeterminate" (iELs) if contrast enhancement was detectable at the level of fenestrations/branches without any evident source. Endoleaks involving multiple inflows (type II and target vessels) were defined as "complex" (cELs). Endpoints were endoleak spontaneous resolution, 1-year aneurysm sac failure to regress (>5 mm diameter decrease), and 4-year endoleak-related secondary interventions. Kaplan-Meier estimates and Cox regression were used for the analysis. RESULTS: There were 142 patients with JRAAs/PRAAs (n = 85; 60%) or TAAAs (n = 57; 40%), with 513 target arteries incorporated through a fenestration (n = 294; 57%) or directional branch (n = 219; 43%). Fifty-nine primary TVELs (12%) were identified in 35 patients (25%), a dEL in 20 patients (14%) and iEL in 15 (11%); 22 (15%) had a determinate or indeterminate cEL. Overall spontaneous resolution rate was 75% (95% confidence interval [CI], 51%-87%) at 4 years. cELs (odds ratio [OR], 5.00; 95% CI, 1.10-49.4; P < .001) and iELs after BEVAR (OR, 9.43; 95% CI, 3.41-56.4; P = .002) were more likely to persist >6 months, and persistent forms were associated with sac failure to regress at 1 year (OR, 1.72; 95% CI, 1.03-12.59; P = .040). Overall freedom from endoleak-related reinterventions was 85% (95% CI, 79%-92%) at 4 years, 92% (95% CI, 87%-97%) for those without primary TVELs and 62% (95% CI, 46%-84%) for those with any primary TVEL (P < .001). In particular, cELs (hazard ratio, 1.94; 95% CI, 1.4-18.81; P = .020) were associated with an increased need for reintervention. In case a secondary intervention was needed, iEL or cEL had an increased risk for multiple secondary procedures (hazard ratio, 2.67; 95% CI, 1.22-10.34; P = .034). CONCLUSIONS: Primary TVELs are frequent after F-BEVAR, and a clear characterization of the endoleak source by computed tomography angiogram is not possible in 40% of patients. Most primary TVELs spontaneously resolve, but during follow-up, patients with any primary TVEL experience a worsened freedom from endoleak-related reinterventions that is mostly driven by persistence of cELs and post-BEVAR iELs. Multiple secondary procedures may be required in case of iELs or cELs.

Role of intravascular ultrasound for the technical assessment of endovascular reconstruction of the aortic bifurcation.

OBJECTIVE: The aim of this study was to evaluate the role of intravascular ultrasound (IVUS) for the technical assessment of kissing stents (KSs) and covered endovascular reconstruction of the aortic bifurcation (CERAB) in the treatment of aortoiliac obstructive disease involving the aortic bifurcation. METHODS: We conducted a single-center retrospective review of patients undergoing endovascular treatment of severe aorto-iliac obstructive disease (2019-2023). IVUS was performed in patients treated by KSs or CERAB according to preoperative indications, in cases of moderate/severe calcifications, mural thrombus, total occlusions, and lesion extension towards the proximity of renal or hypogastric arteries. Indications for IVUS-guided intraoperative revisions were residual stenosis or compression >30%, incomplete stent-to-wall apposition, or flow-limiting dissection at the landing site. Follow-up assessment was performed at 6 and 12 months, and then yearly. Thirty-day outcomes and 2-year patency rates were evaluated. Logistic regression was used to identify factors associated with significant technical defects detected by IVUS needing intraoperative revision. RESULTS: IVUS was used for the technical assessment of 102 patients treated by KSs (n = 57; 56%) or CERAB (n = 45; 44%) presenting with severe intermittent claudication (39%), rest pain (39%), or ischemic tissue loss (25%). Twenty-nine significant technical defects were identified by IVUS in 25 patients (25%) who then had successful intraoperative correction by additional ballooning (n = 23; 80%) or stenting (n = 6; 20%). Patients with a severely calcified chronic total occlusion (odds ratio, 1.85; 95% confidence interval, 1.01-5.27; P = .044) or severely calcified narrow aortic bifurcation with <12 mm diameter (odds ratio, 2.34; 95% confidence interval, 1.10-8.64; P = .032) were at increased risk for IVUS-guided intraoperative revision. There were no postoperative deaths and no major adverse events. Two-year primary patency was 100%. CONCLUSIONS: IVUS was used for the technical assessment of KSs/CERAB in a selected cohort of patients with severe aorto-iliac obstructive disease. This allowed the identification and intraoperative correction of a significant technical defect not detected by completion angiogram in one-quarter of patients, achieving optimal 2-year results. IVUS assessment of KSs/CERAB may be considered especially in patients with a calcified total occlusion or narrow aortic bifurcation.

Outcomes of off-the-shelf preloaded inner branch device for urgent endovascular thoraco-abdominal aortic repair in the ItaliaN Branched Registry of E-nside EnDograft.

OBJECTIVE: The aim of this study was to report the outcomes of endovascular urgent thoracoabdominal aortic (TAAA) repair, using an off-the-shelf preloaded inner branch device (E-nside; Artivion). METHODS: Data from a physician-initiated national multicenter registry, including patients treated with E-nside endograft (INBREED) were prospectively collected (2020-2024); only urgent cases were included in this study. Primary outcomes were technical success and mortality at 30 days. Secondary outcomes were spinal cord ischemia rate, stroke rate, major adverse events (MAE) as also branch instability at 12 months. RESULTS: Of 185 patients enrolled in the INBREED, 64 (34.5%) were treated in a urgent setting and were included in the study. Reason for urgent repair was presence of aneurysm-related symptoms in 31 patients (48.4%), a contained rupture in eight (12.5%), and a large aneurysm >80 mm in 25 (39.1%). Extent of repair was I to III in 32 patients (50%) and IV in 32 (50%); 18 (28%) had a narrow (<25 mm) paravisceral aortic lumen. An adjunctive proximal thoracic endograft was deployed in 29 patients (45.3%); a distal bifurcated abdominal endograft was used in 33 (51.5%). Two hundred forty-nine target vessels (97.2%) were successfully incorporated through an inner branch from an upper arm (81.2%) or femoral (18.8%) access. A balloon expandable stent was used in 184 (75.7%) target vessels, a self-expandable stent in 59 (24.3%). Mean time for target vessel bridging was 39.9 ± 28.4 minutes per target vessel. Thirty-day cumulative major adverse event (MAE) rate was 28%, and mortality occurred in five patients (9.1%). There was one postoperative stroke (1.6%), and the spinal cord ischemia (SCI) rate was 8% (n = 5). For the 249 target vessels successfully incorporated through an inner branch, 1-year freedom from target vessel instability was 93% ± 3% after 1 year. CONCLUSIONS: The E-nside represents a valid solution for the urgent treatment of TAAAs, including symptomatic and ruptured TAAAs, as well as large asymptomatic TAAAs that cannot wait for a custom-made device. The preloaded inner branches and available proximal and distal graft diameters might be useful in urgent settings and provided satisfactory early and 1-year results, in terms of both endograft and target vessel stability. Further studies are required to assess the clinical role of E-nside for urgent TAAA repair.

A systematic review and meta-analysis on the outcomes of carotid endarterectomy after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: Intravenous thrombolysis (IVT) is the mainstay of treatment for patients presenting with acute ischemic stroke, whereas carotid endarterectomy (CEA) is indicated in patients with symptomatic carotid stenosis. However, the impact of prior IVT on the outcomes of CEA (IVT-CEA) is not clear. The aim of this study was to determine whether IVT may create additional stroke and death risk for CEA, compared with CEA performed in the absence of a history of recent IVT, and to determine the optimal timing for CEA after IVT. METHODS: We conducted a systematic review and meta-analysis of studies comparing the outcomes of IVT-CEA vs CEA, using the Medline, Embase, and Cochrane databases. RESULTS: We included 11 retrospective comparative studies, in which 135,644 patients underwent CEA and 2070 underwent IVT-CEA. The pooled rate of perioperative stroke was 4.2% in the IVT-CEA group and 1.3% in the CEA group (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.12-1.58; P = .21), with a high heterogenicity (I2 = 93%). The rate of stroke/death was 5.9% in patients undergoing IVT-CEA 1.9% in those receiving CEA only (OR, 0.42; 95% CI, 0.15-1.14; I2 = 92%; P = .09); after exclusion of studies including TIA as presenting symptom, stroke/death risk was 3.6% in IVT-CEA and 3.0% in CEA (OR, 1.42; 95% CI, 0.80-2.53; I2 = 50%; P = .11). The risk of stoke decreased with a delay in the performance of CEA (P = .268). Using results of the metaregression, the calculated delay of CEA that allows for a <6% risk was 4.6 days. Compared with CEA, patients undergoing IVT-CEA had a significantly higher risk of intracranial hemorrhage (2.5% vs 0.1%; OR, 0.11; 95% CI, 0.06-0.21; I2 = 28%; P < .001) and neck hematoma requiring reintervention (3.6% vs 2.3%; OR, 0.61; 95% CI, 0.43-0.85; I2 = 0%; P = .003). CONCLUSIONS: In patients presenting with an acute ischemic stroke, CEA can be safely performed after a prior endovenous thrombolysis, maintaining a stroke/death risk of <6%. After IVT, CEA should be deferred for ≥5 days to minimize the risk for intracranial hemorrhage and neck bleeding.

Intravascular Ultrasound in the Detection of Bridging Stent Graft Instability During Fenestrated and Branched Endovascular Aneurysm Repair Procedures: A Multicentre Study on 274 Target Vessels.

OBJECTIVE: The use of intravascular ultrasound (IVUS) reduces contrast medium use and radiation exposure during conventional endovascular aneurysm repair (EVAR). The aim of this study was to evaluate the safety and efficacy of IVUS in detecting bridging stent graft (bSG) instability during fenestrated and branched EVAR (F/B-EVAR). METHODS: This was a prospective observational multicentre study. The following outcomes were evaluated: (1) technical success of the IVUS in each bSG, (2) IVUS findings compared with intra-operative angiography, (3) incidence of post-operative computed tomography angiography (CTA) findings not detected with IVUS, and (4) absence of IVUS related adverse events. Target visceral vessel (TVV) instability was defined as any branch or fenestration issues requiring an additional manoeuvre or re-intervention. Any IVUS assessment that detected stenosis, kinking, or any geometric TVV issue was considered to be branch instability. All procedures were performed in ad hoc hybrid rooms. RESULTS: Eighty patients (69% males; median age 72 years; interquartile range 59, 77 years) from four aortic centres treated with F/B-EVAR between January 2019 and September 2021 were included: 70 BEVAR (21 off the shelf; 49 custom made), eight FEVAR (custom made), and two F/B-EVAR (custom made), for a total of 300 potential TVVs. Two TVVs (0.7%) were left unstented and excluded from the analysis. The TVVs could not be accessed with the IVUS catheter in seven cases (2.3%). Furthermore, 17 (5.7%) TVVs could not be examined due to a malfunction of the IVUS catheter. The technical success of the IVUS assessment was 91.9% (274/298), with no IVUS related adverse events. Seven TVVs (2.5%) showed signs of bSG instability by means of IVUS, leading to immediate revisions. The first post-operative CTA at least 30 days after the index procedure was available in 268 of the 274 TVVs originally assessed by IVUS. In seven of the 268 TVVs (2.6%) a re-intervention became necessary due to bSG instability. CONCLUSION: This study suggests that IVUS is a safe and potentially valuable adjunctive imaging technology for intra-operative detection of TVV instability. Further long term investigations on larger cohorts are required to validate these promising results and to compare IVUS with alternative technologies in terms of efficiency, radiation exposure, procedure time, and costs.

Editor's Choice - Outcomes of Off the Shelf Outer Branched Versus Inner Branched Endografts in the Treatment of Thoraco-Abdominal Aortic Aneurysm in the B.R.I.O. (BRanched Inner - Outer) Study Group.

OBJECTIVE: This study aimed to compare two commercially available off the shelf branched endografts for thoraco-abdominal aortic aneurysm (TAAA) repair, namely the E-nside (Artivion) and Zenith t-Branch (Cook Medical) devices. METHODS: This multicentre retrospective study (2020 - 2023) included patients treated by branched endovascular aortic repair (BEVAR) for TAAA using the inner branched E-nside or the outer branched t-Branch. Endpoints were 30 day technical success and major adverse events (MAEs) as well as one year freedom from target vessel instability and main endograft instability. RESULTS: The study included 163 patients: 79 (307 target vessels) treated with E-nside and 84 (325 target vessels) with t-branch. Aneurysm extent was I - III in 91 patients (55.8%; 47% of E-nside and 66% of t-Branch) and IV in 72 patients (44.2%; 53% of E-nside and 34% of t-Branch) (p = .011). An adjunctive proximal thoracic endograft was used in 43% of E-nside vs. 69% of t-Branch (p < .001), with less frequent thoracic endografting (14% vs. 76%; p < .001) and shorter length of coverage (p = .024) in extent IV TAAA treated by E-nside. E-nside cases had shorter renal artery bridging lengths (66 ± 17 mm vs. 76 ± 20 mm; p < .010) and less frequent use of a distal bifurcated endograft (53% vs. 80%; p < .001). Comparing 30 day results, the mortality rate was 1% vs. 2% (p = .62), any MAE occurred in 18% vs. 21% (p = .55), the stroke rate was 3% vs. 0% (p = .23), and the elective spinal cord ischaemia rate was 5% vs. 8% (p = .40) for E-nside and t-Branch, respectively. At one year, freedom from target vessel instability was 96 ± 3% for E-nside and 95 ± 3% for t-Branch (p = .58), and freedom from endograft instability was 98 ± 2% vs. 97 ± 3% (p = .46), respectively. CONCLUSION: Both off the shelf devices provided excellent early and one year results. The E-nside may require shorter thoracic aortic coverage and bridging length for the renal arteries, and less frequent implantation of a concomitant proximal thoracic or distal abdominal bifurcated endograft. However, these aspects did not determine significant differences in clinical outcomes.

Addressing global health disparities in the management of RSV infection in infants and children: Strategies for preventing bronchiolitis and post-bronchiolitis recurrent wheezing.

Background: The topic of equitable access to health care and its impact on exacerbating worldwide inequities in child health not only strikes at the heart of our health-care delivery systems but also deeply resonates with our collective social consciences. Nowhere is this better seen on a global scale than in the burden of illness caused by respiratory syncytial virus (RSV) infection, which extracts the most severe morbidity and mortality in infants and children in low- and middle-income countries (LMIC). This report addresses global health disparities that exist in the management of RSV infection in infants and children, and offers strategies for preventing bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Methods: A systematic literature review was conducted across the PubMed data bases of RSV infection and the socioeconomic impact of bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Results: The results of the present study address the many issues that deal with the question if prevention of RSV bronchiolitis can mitigate recurrent wheezing episodes and links RSV risks, downstream effects, prevention, malnutrition, and socioeconomic restraints of developing countries with a call for possible global action. Conclusion: The present study stresses the importance of considering the linkage between malnutrition and disease susceptibility because of the known relationships between undernutrition and greater vulnerability to infectious diseases, including RSV infection. These complex interactions between infectious disease and undernutrition also raise issues on the longer-term sequelae of postbronchiolitis recurrent wheezing. This prompts a discussion on whether industrialized countries should prioritize the provision of newly developed monoclonal antibodies and RSV vaccines to LMICs or whether vital nutritional needs should be a first focus. The resolution of these issues will require research and greater international discourse.

Impact of Carotid Stent Design on Embolic Filter Debris Load During Carotid Artery Stenting.

BACKGROUND: The carotid stent design may influence the risk of embolization during carotid artery stenting. The aim of the study was to assess this risk by comparing the quantity of embolized material captured by filters during carotid artery stenting, using different stent designs. METHODS: We conducted a single-center retrospective study of patients undergoing carotid artery stenting for asymptomatic carotid stenosis >70% (2010-2022) in a tertiary academic hospital (Padua University Hospital, Italy). Carotid stents were classified according to their design as open-cell (OCS), closed-cell (CCS), or micromesh stents (MMS). A distal filter protection was used in all patients, and the amount of captured embolized particles was semiautomatically analyzed using a dedicated software (Image-Pro Plus, Media Cybernetics). Primary end point was embolic filter debris (EFD) load, defined as the ratio of the filter area covered by particulate material to the total filter area. Secondary end points were 30 days major stroke and death. RESULTS: Four-hundred-eighty-one carotid artery stentings were included; 171 (35%) using an OCS, 68 (14%) a CCS, and 242 (50%) a MMS. Thirty-days mortality was 0.2% (n=1) and major stroke rate was 0.2% (P=0.987). Filters of patients receiving MMS were more likely to be free from embolized material (OCS, 30%; CCS, 13%; MMS, 41%; P<0.001) and had a lower EFD load (OCS, 9.1±14.5%; CCS, 7.9±14.0%; MMS, 5.0±9.1%; P<0.001) compared with other stent designs. After stratification by plaque characteristics, MMS had a lower EFD load in cases of hypoechogenic plaque (OCS, 13.4±9.9%; CCS, 10.9±8.7%; MMS, 6.5±13.1%; P<0.001), plaque length>15 mm (OC, 10.2±15.3; CC, 8.6±12.4; MM, 8.2±13.6; P<0.001), and preoperative ipsilateral asymptomatic ischemic cerebral lesion (OCS, 12.9±16.8%; CCS, 8.7±19.5%; MMS, 5.4±9.7%; P<0.001). After multivariate linear regression, use of MMS was associated with lower EFD load (P=0.038). CONCLUSIONS: The use of MMS seems to be associated with a lower embolization rate and EFD load, especially in hypoechogenic and long plaques and in patients with a preoperative evidence of asymptomatic ischemic cerebral lesion.