Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds.

PrP Sc , a misfolded, aggregation-prone isoform of the cellular prion protein (PrP C ), is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals. PrP Sc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, posing challenges for the development of effective therapies. Since PrP C is the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity, it represents an attractive therapeutic target for prion diseases. In this minireview, we briefly outline the approaches to target PrP C and discuss our recent identification of Zn(II)-BnPyP, a PrP C -targeting porphyrin with an unprecedented bimodal mechanism of action. We argue that in-depth understanding of the molecular mechanism by which Zn(II)-BnPyP targets PrP C may lead toward the development of a new class of dual mechanism anti-prion compounds.

Gallium-doped zirconia coatings modulate microbiological outcomes in dental implant surfaces.

Despite the significant recent advances in manufacturing materials supporting advanced dental therapies, peri-implantitis still represents a severe complication in dental implantology. Herein, a sol-gel process is proposed to easily deposit antibacterial zirconia coatings onto bulk zirconia, material, which is becoming very popular for the manufacturing of abutments. The coatings' physicochemical properties were analyzed through x-ray diffraction and scanning electron microscopy-energy-dispersive x-ray spectroscopy investigations, while their stability and wettability were assessed by microscratch testing and static contact angle measurements. Uniform gallium-doped tetragonal zirconia coatings were obtained, featuring optimal mechanical stability and a hydrophilic behavior. The biological investigations pointed out that gallium-doped zirconia coatings: (i) displayed full cytocompatibility toward human gingival fibroblasts; (ii) exhibited significant antimicrobial activity against the Aggregatibacter actinomycetemcomitans pathogen; (iii) were able to preserve the commensal Streptococcus salivarius. Furthermore, the proteomic analyses revealed that the presence of Ga did not impair the normal oral microbiota. Still, interestingly, it decreased by 17% the presence of Fusobacterium nucleatum, a gram-negative, strictly anaerobic bacteria that is naturally present in the gastrointestinal tract. Therefore, this work can provide a valuable starting point for the development of coatings aimed at easily improving zirconia dental implants' performance.

Midterm outcomes of "wide neck" abdominal aortic aneurysm after open or endovascular repair in two European centers: a propensity score matching analysis.

BACKGROUND: The aim of this study was to compare mid-term clinical and morphological outcomes in patients undergoing open (OR) and endovascular aortic repair (EVAR) with a proximal wide neck abdominal aortic aneurysm (WN-AAA). METHODS: Between 2009 and 2014 data of all patients undergoing OR at IRCCS San Raffaele Hospital and EVAR at German Aortic Center Hamburg were retrospectively analyzed. Primary endpoints were aneurysm-related mortality at 5 years, reintervention, and overall mortality. Secondary endpoint was proximal neck enlargement. A 1:1 propensity score matching (PSM) was performed. Survival and freedom from AAA-related reintervention were investigated in matched OR and EVAR group by Kaplan-Meier analysis. RESULTS: Of all OR performed at IRCCS San Raffaele Hospital 70 were found to have a proximal neck >28 mm (mean age: 69.8±7.2 years, 67 [95.71%] male); of all consecutive EVAR performed at German Aortic Center Hamburg, 52 required an endograft size of at least 32 mm (mean age of 73.1±8.7 years, 49 [94.2%] male). After PSM, the study cohort consisted of 30 OR and EVAR. One early mortality was registered in both groups (P=NS). Mid-term freedom from reintervention compared in OR and EVAR, with no statistically significant differences (P=0.979). Eight (15.4%) patients treated with EVAR developed a significant proximal diameter enlargement (≥3 mm) while only 1 (1.4%) patient in the OR group had the same evolution (P<0.01). CONCLUSIONS: In WN-AAA neck enlargement is observed more frequently in patients undergoing EVAR, but reintervention rate was similar in the 2 groups, demonstrating that both options were safe and effective.

Functionalized magnesium alloys obtained by superplastic forming process retain osteoinductive and antibacterial properties: An in-vitro study.

OBJECTIVES: This study aimed to investigate the biocompatibility, osteogenic and antibacterial activity of biomedical devices based on Magnesium (Mg) Alloys manufactured by Superplastic Forming process (SPF) and subjected to Hydrothermal (HT) and Sol-Gel Treatment (Sol-Gel). METHODS: Mg-SPF devices subjected to Hydrothermal (Mg-SPF+HT) and Sol-Gel Treatment (Mg-SPF+Sol-Gel) were investigated. The biocompatibility of Mg-SPF+Sol-Gel and Mg-SPF+HT devices was observed by indirect and direct cytotoxicity assays, whereas the colonization of sample surfaces was assessed by confocal microscopy. qRT-PCR analysis and microbial growth curve analyses were employed to evaluate the osteogenic and antibacterial activity of both SPF-Mg treated devices, respectively. RESULTS: Mg-SPF+HT and Mg-SPF+Sol-Gel showed a high degree of biocompatibility. Analysis of mRNA expression of osteogenic genes in cells cultured on Mg-treated devices revealed a significant upregulation of the expression levels of BMP2 and Runx-2. Furthermore, the bacterial growth in strains developed in contact with both the Mg-SPF+HT and Mg-SPF+Sol-Gel devices was lower than that observed in the control. SIGNIFICANCE: Hydrothermal and Sol-Gel Treatments of Mg alloys obtained through the SPF process demonstrated bioactive, osteogenic and antibacterial activity, offering a promising alternative to conventional Mg-based devices. The obtained Mg-based materials may have the potential to enhance the tunability of temporary devices in maxillary reconstruction, eliminating the need for second surgeries, and ensuring a good bone reconstruction and a reduced implant failure rate due to bacterial infections.

Association of Impedance Aggregometry-Measured Platelet Aggregation With Thromboembolic Events in Patients Who Undergo Carotid Endarterectomy: A Pilot Study.

OBJECTIVES: The aim of the current study was to assess the relationship among thrombin receptor activator peptide 6 (TRAP test), adenosine-5'-diphosphate (ADP test), arachidonic acid (ASPI test), and stroke/transient ischemic attack (TIA), using the multiple electrode aggregometry (Multiplate) in patients undergoing carotid thromboendarterectomy (CEA). DESIGN: A retrospective study. SETTING: Vascular surgery operating rooms of a university hospital. PARTICIPANTS: One hundred thirty-one out of 474 patients undergoing CEA between November 2020 and October 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A preoperative blood sample of all enrolled patients was analyzed using the Multiplate analyzer. Receiver operating characteristics curves, were generated to test the ability of TRAP, ADP, and ASPI in discriminating perioperative thromboembolic stroke/TIA. A logistic LASSO regression model was used to identify factors independently associated with stroke/TIA. Eight patients experienced a perioperative stroke/TIA. Although all the platelet functional assays showed excellent predictive performance, an ADP value exceeding 72 U showed the highest specificity (87%) and sensitivity (68%) in discriminating patients who had a perioperative thromboembolic stroke/TIA, with a negative predictive value of 99% and a positive predictive value of 15%. After LASSO regression, an ADP >72 U and the need for a shunt during CEA were the only 2 variables independently associated with perioperative stroke/TIA. CONCLUSION: Because the ADP test was independently associated with perioperative stroke/TIA, the assessment of platelet reactivity using Multiplate may offer potential utility in monitoring patients undergoing CEA.

Acute kidney injury in patients undergoing endovascular or open repair of juxtarenal or pararenal aortic aneurysms.

BACKGROUND: The aim of this cohort study was to report the proportion of patients who develop periprocedural acute kidney injury (AKI) after endovascular repair (ER) and open surgery (OS) in patients with juxta/pararenal abdominal aortic aneurysm and to assess potential risk factors for AKI. The study also aimed to report the short- and long-term outcomes of patients with and without AKI. METHODS: This was a multicenter cohort study of five European academic high-volume centers (>50 OS or 50 ER infrarenal AAA repairs, plus >15 complex AAA repairs per year). All consecutively treated patients were extracted from a prospective vascular surgical registry and the data were scrutinized retrospectively. The primary end point for this study was the development of AKI. AKI was diagnosed when there is a two-fold increase of serum creatinine or decrease of glomerular filtration rate of >50% within 1 week of AAA repair. Secondary end points included long-term mortality and end-stage renal disease (ESRD). RESULTS: AKI occurred in 16.6% of patients in the ER group vs 30.3% in the OS group (P < .001). The 30-day mortality rate was higher among patients with AKI in both ER (15.4% vs 3.1%; P = .006) and OS (13.2% vs 5.3%; P = .001) groups. Age, chronic kidney disease, presence of significant thrombus burden in the pararenal region, >1000 mL blood loss in ER group were associated with development of AKI. Age, diabetes mellitus, chronic kidney disease, presence of significant thrombus burden in the pararenal region, and a proximal clamping time of >30 minutes in the OS group were associated with the development of AKI, whereas renal perfusion during clamping was the protective factor against AKI development. After a median follow-up of 91 months, AKI was associated with higher mortality rates in both the ER group (58.9% vs 29.7%; P < .001) and the OS group (61.5% vs 27.3%; P < .001). After the same follow-up period, AKI was associated with a higher incidence of ESRD in both the ER group (12.8% vs 3.6%; P = .009) and the OS group (9.9% vs 2.9%; P < .001). CONCLUSIONS: The current study identified important pre and postoperative factors associated with AKI after juxta/pararenal abdominal aortic aneurysm repair. Patients with postoperative AKI had significantly higher short- and long term mortality and higher incidence of ESRD than patients without AKI.

Endovascular treatment of chronic ilio-femoral vein obstruction with extension below the inguinal ligament in patients with post-thrombotic syndrome.

OBJECTIVE: This study aimed to evaluate postoperative outcomes of patients with chronic iliofemoral venous outflow obstruction and post-thrombotic syndrome (PTS) who underwent endovascular recanalization and stenting across the inguinal ligament. METHODS: All consecutive patients with chronic iliofemoral venous outflow obstruction and PTS were included in the analysis, from January 2018 and February 2022. Preoperative, intraoperative, and postoperative outcomes were assessed. Primary endpoints analyzed were major adverse events (MAEs) at 30 days and primary patency rate at 2 years of follow-up. Secondary endpoints assessed were secondary patency rate, target vessel revascularization, and clinical improvement evaluated with the Venous Clinical Severity Score (VCSS) classification, Villalta scale, and visual analog scale (VAS), respectively. RESULTS: A total of 63 patients (mean age, 48.1 ± 15.5 years; female, 61.9%) were evaluated. No intraoperative and 30-day postoperative complications were documented. The technical success rate was achieved at 100%. Overall, one in-stent occlusion and five in-stent restenosis were detected during follow-up. The primary patency rate was 93.7% (95% confidence interval [CI], 87.8%-99.9%) and 92.1% (95% CI, 85.6%-99%), at 1- and 2-year follow-up, respectively (Kaplan-Meier analysis). Target vessel revascularization was conducted in two cases, resulting in a secondary patency of 98.4% (95% CI, 95.4%-100%) at 2 years of follow-up. Stent fracture and/or migration were not observed during follow-up. A significant clinical improvement in the patient's quality of life was documented. The median improvement of VCSS and Villalta scores were 4 (interquartile range, 2-7; P = .001), and 3 (interquartile range, 1.5-5; P = .001) vs baseline at the last follow-up. Overall, pain reduction of 17 mm on the VAS scale was documented at 2 years of follow-up. At multivariate analysis, presence of trabeculation into the femoral vein and deep femoral vein (odds ratio, 1.89; 95% CI, 0.15-6.11; P = .043), and Villalta scale >15 points at admission (odds ratio, 1.89; 95% CI, 0.15-6.11; P = .043) were predictive for in-stent occlusion during the follow-up. CONCLUSIONS: The use of a dedicated venous stent across the inguinal ligament was safe and effective for the treatment of symptomatic iliofemoral venous disease with acceptable primary and secondary patency rates at 2 years of follow-up.

Factors influencing recurrent varicose vein formation after radiofrequency thermal ablation for truncal reflux performed in two high-volume venous centers.

OBJECTIVE: Recanalization of the saphenous vein trunk after endovenous radiofrequency ablation (RFA) is often associated with recurrent varicose veins (RVVs) or recanalization. This study aimed to assess the long-term results of RFA of the great saphenous vein (GSV) and identify the risk factors for GSV recanalization and RVVs during follow-up for patients presenting to dedicated outpatient vein centers. METHODS: All consecutive patients with incompetent GSVs who underwent RFA between 2009 and 2019 were retrospectively analyzed. The primary study end points were freedom from GSV recanalization and the RVV rate during follow-up. The secondary study end points were the postoperative complication rate and the risk factors for GSV recanalization and RVVs. Univariate and multivariate analyses were performed to identify the potential risk factors for GSV recanalization and RVVs. RESULTS: During the study period, 1568 limbs were treated in 1300 consecutive patients (mean age, 53.5 ± 12.9 years; 71.9% women; CEAP [clinical, etiology, anatomy, pathophysiology] C2-C6; venous clinical severity score >5). Technical success was achieved in 99.7% of cases. At a mean follow-up of 57.2 ± 25.4 months, the GSV occlusion and freedom from reintervention rates were 100% and 100% within 1 week, 97% and 95.7% at 1 year, 95.2% and 93.1% at 3 years, and 92.4% and 92.8% at 5 years, respectively. The recurrence rate was 10% (n = 158) during the follow-up period. On multivariate analysis, a direct confluence of the accessory saphenous vein into the saphenofemoral junction (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.0-7.04; P = .032), a history of pregnancy >2 (OR, 3.68; 95% CI, 1.19-11.36; P = .023), C4 (OR, 6.41; 95% CI, 1.36-30.28; P = .019), and preoperative GSV diameter >10 mm (OR, 1.82; 95% CI, 1.65-4.03; P = .043) were risk factors for GSV recanalization. Moreover, age >70 years (OR, 1.04; 95% CI, 1.01-1.06; P = .014) and incompetent perforator veins (OR, 1.17; 95% CI, 0.65-2.03; P = .018) were also risk factors for RVVs. CONCLUSIONS: RFA is a safe technique to ablate the GSV with a low complication rate and durability during 5 years of follow-up. However, patients with a high clinical score and those with direct confluence of the accessory saphenous vein into the saphenofemoral junction experienced higher long-term GSV recanalization and RVV rates.

Five-factors Modified Frailty Index role as predictors of outcomes after proximal abdominal aortic aneurysms.

BACKGROUND: The aim of the study was to evaluate the correlation between frailty, measured by the Five-Factor Modified Frailty Index (mFI-5) and mortality and all major adverse events (MAE) in patients who underwent proximal abdominal aortic aneurysm (p-AAA) open surgery (OS). METHODS: Data of all elective patients submitted to p-AAA OS from 2010 to 2021 were recorded. Primary endpoints were 30-day mortality and mid-term survival and secondary endpoints included postoperative acute kidney injury (AKI), freedom from aortic reintervention and any MAE. The impact of frailty was assessed by univariate and multivariate analysis; mid-term overall survival were estimated using Kaplan-Meier method (log-rank test). RESULTS: Two-hundred twenty-one patients (197 male, 24 female; aged 72.2±7.4) were included. Thirty-seven (16.4%) were octogenarians (>80 years). The mFI-5 was assessed in the entire group: mean mFI-5 was 0.29±0.12. One-hundred patients (100/221, 45.25%, 91:9 male-to-female ratio) were defined "frail" considering the mFI-5 cut-off >0.25. At univariate analysis a correlation was found between mFI-5>0.25 and mid-term mortality (Pearson correlation [r] 0.280, P<0.001) and AKI (r=0.146, P=0.030). No correlation with 30-day mortality was found (P not significant). At multivariate analysis mFI-5>0.25 increased the risk for midterm mortality (odds ratio 3.32, P=0.021) and postoperative AKI (OR 2.09, P<0.001). The effect of mFI-5>0.25 on mid-term mortality persisted after adjustment for age (P<0.001). Survival was estimated with Kaplan-Meyer method (mean follow-up of 52.7 months, 95% CI: 48.6-56.8); 68 (30.7%) deaths were recorded: 23 among non-frail patients (19.0%) and 45 among frail patients (45/100, 45%, P<0.001). CONCLUSIONS: These findings suggest that mFI-5 is a tool capable to identify "frail" patients, who appear to be at increased risk of postoperative AKI and mid-term mortality, but not 30-day mortality. Five-factor modified Frailty Index assessment is simple, fast and can be widely applied in surgical practice to perform appropriate risk stratifications.

Silver acetate and Triclosan Antimicrobial Graft Evaluation for surgical Repair of aortic disease (STAGER Study).

BACKGROUND: The aim of this study was to assess perioperative and late performance of a silver acetate and triclosan impregnated antimicrobial vascular graft (Intergard Synergy, Intervascular SAS, La Ciotat, France) during open surgical repair of abdominal aortic aneurysms (AAA), and to compare it with standard polyester grafts ones. METHODS: This retrospective single-centre study (STAGER Study, clinicaltrials.gov: NCT04557254) included patients undergone non-infectious AAA surgical repair between 2012 and 2019, divided into two groups according to the implanted aortic prosthesis: standard polyester graft (PolyG) and silver-triclosan graft (SynG). Early primary endpoints were 30-day mortality, major adverse events (MAEs), and reintervention rates; late primary endpoints were overall and aortic-related survival, reintervention-free survival, and graft infection rate at a mean follow-up (FU) of 49.4±26.8 months. RESULTS: Five hundred forty-seven patients were included [PolyG 49%, and SynG 51%]. Both groups were substantially homogeneous in risk factors and demographics. Two patients died within 30 days. In-hospital MAE rate [PolyG 14.2% vs. SynG 10.7%; P=.248] and 30-day reintervention rate were not significantly different [PolyG 2.6% vs. SynG 1.4%; P=.374]. At 5 years, overall survival in the PolyG and SynG groups were 85% and 84%, respectively. Reintervention-free survival was 82% for both groups. Aortic-related survival was 95% and 96%, respectively. Graft infection was observed in 8 (3.3%) PolyG patients and 5 (1.8%) SynG patients. CONCLUSIONS: Silver acetate and triclosan impregnated grafts demonstrated good early and mid-term results, being considered safe and durable for AAA open repair. Similar graft infection and related death rates were observed compared to polyester standard grafts, supporting non-superiority of one graft over the other.

Erratum: A tetracationic porphyrin with dual anti-prion activity.

[This corrects the article DOI: 10.1016/j.isci.2023.107480.].

Open and endovascular reinterventions after Candy Plug false lumen embolization of type B aortic dissection.

OBJECTIVE: In the majority of patients with chronic type B aortic dissection, there is persistent retrograde flow in the false lumen (FL) through distal re-entry tears. Among several endovascular techniques proposed for FL management, the "Candy Plug" (CP) technique has gained acceptance with good early results. The aim of this study is to report the types and outcomes of open and endovascular reinterventions and identify mechanisms of procedure failure as well as other causes for reinterventions. METHODS: All patients with type B aortic dissection submitted to thoracic endovascular aneurysm repair and CP implantation for FL embolization from January 2016 to December 2022 at our institution were included in this study. The preoperative, intraoperative, and postoperative data of the primary intervention and secondary reinterventions, when performed, were prospectively collected and retrospectively analyzed. Preoperative and postoperative computed tomography angiography were also analyzed. RESULTS: During the study period, 33 patients were submitted to thoracic endovascular aneurysm repair and CP implantation. Twenty-three patients (69.7%) showed thoracic FL complete thrombosis with aortic stability or positive remodeling at a mean follow-up of 45 ± 23.1 months. Ten patients (30.3%) underwent aortic reinterventions (male, n = 9; mean age, 60.5 ± 7.6 years). Of these 10 patients, in four patients, complete thrombosis of the FL was never achieved, leading to ongoing perfusion of the FL, defined as "primary failure." The other six patients underwent reinterventions for different causes: two patients, after initial sealing, showed a progressive enlargement of the abdominal FL leading to distal degeneration. One patient showed proximal degeneration, two patients showed a type II thoracoabdominal aortic aneurysm and CP implantation was used as a planned procedure to reduce the extent of the surgical procedure, and one patient had recurrent, intractable back pain despite complete thrombosis of the FL. Reinterventions were open in five cases and endovascular in five. One in-hospital death (postoperative day 27) after a type II thoracoabdominal aortic aneurysm open repair was recorded. In addition, two cases of delayed spinal cord ischemia after open reintervention were recorded: one resulting in permanent paraplegia and one transitory with complete recovery. CONCLUSIONS: The CP technique was safe and effective; however, a significant rate of aortic-related reintervention was observed. Several mechanisms led to reinterventions either in terms of "primary failure" of the CP or subsequent aneurysmal degeneration. Complex reinterventions were often necessary, with a high rate of major complications in case of open repair. Life-long and closer surveillance might be required in these patients.

A tetracationic porphyrin with dual anti-prion activity.

Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in vitro, in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance.

Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms.

OBJECTIVE: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs). BACKGROUND: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described. METHODS: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair. RESULTS: A total of 2603 patients (69% males; mean age 72±10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P <0.001) and rates of MAEs (34% vs 20%, P <0.001). Median follow-up was 15 months (interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50±4% vs 70±1% and 21±3% vs 7±1%, P <0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality (hazard ratio, 1.92; 95% CI] 1.50-2.44; P <0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P <0.001). CONCLUSIONS: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.

Transatlantic multicenter study on the use of a modified preloaded delivery system for fenestrated endovascular aortic repair.

OBJECTIVE: Analyze the outcomes of endovascular complex abdominal and thoracoabdominal aortic aneurysm repair using the Cook fenestrated device with the modified preloaded delivery system (MPDS) with a biport handle and preloaded catheters. METHODS: A multicenter retrospective single arm cohort study was performed, including all consecutive patients with complex abdominal aortic aneurysm repair and thoracoabdominal aortic aneurysms treated with the MPDS fenestrated device (Cook Medical). Patient clinical characteristics, anatomy, and indications for device use were collected. Outcomes, classified according to the Society for Vascular Surgery reporting standards, were collected at discharge, 30 days, 6 months, and annually thereafter. RESULTS: Overall, 712 patients (median age, 73 years; interquartile range [IQR], 68-78 years; 83% male) from 16 centers in Europe and the United States treated electively were included: 35.4% (n = 252) presented with thoracoabdominal aortic aneurysms and 64.6% (n = 460) with complex abdominal aortic aneurysm repair. Overall, 2755 target vessels were included (mean ,3.9 per patient). Of these, 1628 were incorporated via ipsilateral preloads using the MPDS (1440 accessed from the biport handle and 188 from above). The mean size of the contralateral femoral sheath during target vessel catheterization was 15F ± 4, and in 41 patients (6.7%) the sheath size was ≤8F. Technical success was 96.1%. Median procedural time was 209 minutes (IQR, 161-270 minutes), contrast volume was 100 mL (IQR, 70-150mL), fluoroscopy time was 63.9 minutes (IQR, 49.7-80.4 minutes) and median cumulative air kerma radiation dose was 2630 mGy (IQR, 838-5251 mGy). Thirty-day mortality was 4.8% (n = 34). Access complications occurred in 6.8% (n = 48) and 30-day reintervention in 7% (n = 50; 18 branch related). Follow-up of >30 days was available for 628 patients (88%), with a median follow-up of 19 months (IQR, 8-39 months). Branch-related endoleaks (type Ic/IIIc) were observed in 15 patients (2.6%) and aneurysm growth of >5 mm was observed in 54 (9.5%). Freedom from reintervention at 12 and 24 months was 87.1% (standard error [SE],1.5%) and 79.2% (SE, 2.0%), respectively. Overall target vessel patency at 12 and 24 months was 98.6% (SE, 0.3%) and 96.8% (SE, 0.4%), respectively, and was 97.9% (SE, 0.4%) and 95.3% (SE, 0.8%) for arteries stented from below using the MPDS, respectively. CONCLUSIONS: The MPDS is safe and effective. Overall benefits include a decrease in contralateral sheath size in the treatment of complex anatomies with favorable results.

Outcomes following Management of Complex Thoracoabdominal Aneurysm by an Open Approach.

BACKGROUND: In the last decade, advances in surgical techniques, and the introduction of adjuncts for organ protection, have modified the approach for thoracoabdominal aortic aneurysm (TAAA) surgical repair. The aim of this study is to determine whether the contemporary approach influenced the outcomes. METHODS: From 1989 to 2022, patients who had received elective open surgical repair (OSR) for TAAA at our institution were retrospectively analyzed. This series has been divided in two groups: Group 1 (1989-2009), and Group 2 (2010-2022). Patients included in Group 1 were those treated with a selective use of adjuncts, and Group 2 included patients treated with the systematic use of adjuncts. RESULTS: A total of 1107 patients were treated (Group 1: 455; Group 2: 652). The surgical management was significantly different between the two groups. The in-hospital mortality was significantly different between the two groups (Group 1: 13.4%, Group 2: 8.1%; p 0.004), as was the rate of permanent spinal cord ischemia (Group 1: 11.9%, Group 2: 7.8%; p 0.023). Renal and respiratory failure were reduced in Group 2, but not significantly. CONCLUSIONS: The use of the adjuncts enabled the achievement of improvement in mortality and SCI prevention in TAAA OSR. Although a refined surgical technique, mortality and morbidity are still noteworthy in this complex aortic field.

Fate of target visceral vessels in fenestrated and branched complex endovascular aortic repair.

OBJECTIVE: To assess branch vessel outcomes after endovascular repair of complex aortic aneurysms analyzing possible factors influencing early and long-term results. METHODS: The Italian Multicentre Fenestrated and Branched registry enrolled 596 consecutive patients treated with fenestrated and branched endografts for complex aortic disease from January 2008 to December 2019 by four Italian academic centers. The primary end points of the study were technical success (defined as target visceral vessel [TVV] patency and absence of bridging device-related endoleak at final intraoperative control), and freedom from TVV instability (defined as the combined results of type IC/IIIC endoleaks and patency loss) during follow-up. Secondary end points were overall survival and TVV-related reinterventions. RESULTS: We excluded 591 patients (3 patients with a surgical debranching and 2 patients who died before completion from the study cohort) were treated for a total of 1991 visceral vessels targeted by either a directional branch or a fenestration. The overall technical success rate was 98.4%. Failure was related to the use of an off-the-shelf (OTS) device (custom-made device vs OTS, HR, 0.220; P = .007) and a preoperative TVV stenosis of >50% (HR, 12.460; P < .001). The mean follow-up time was 25.1 months (interquartile range, 3-39 months). The overall estimated survival rates were 87%, 77.4%, and 67.8% at 1, 3, and 5 years, respectively (standard error [SE], 0.015, 0.022, and 0.032). During follow-up, TVV branch instability was observed in 91 vessels (5%): 48 type IC/IIIC endoleaks (2.6%) and 43 stenoses-thromboses (2.4%). The extent of aneurysm disease (thoracoabdominal aortic aneurysm [TAAA] types I-III vs TAAA type IV/juxtarenal aortic aneurysm/pararenal aortic aneurysm) was the only independent predictor for developing a TVV-related type IC/IIIC endoleak (HR, 3.899; 95% confidence interval [CI]:, 1.924-7.900; P < .001). Risk of patency loss was independently associated with branch configuration (HR, 8.883; P < .001; 95% CI, 3.750-21.043) and renal arteries (HR, 2.848; P = .030; 95% CI, 1.108-7.319). Estimated rates at 1, 3, and 5 years of freedom from TVV instability and freedom from TVV-related reintervention were 96.6%, 93.8%, and 90% (SE, 0.005, 0.007, and 0.014) and 97.4%, 95.0%, and 91.6% (SE, 0.004, 0.007, and 0.013), respectively. CONCLUSIONS: Intraoperative failure to bridge a TVV was associated with a preoperative TVV stenosis of >50% and the use of OTS devices. Midterm outcomes were satisfying, with an estimated 5-year freedom from TVV instability and reintervention of 90.0% and 91.6%, respectively. During follow-up, the larger extent of aneurysm disease was associated with an increased risk of TVV-related endoleaks, whereas a branch configuration and renal arteries were more prone to patency loss.

Electrophoretic deposition of gentamicin and chitosan into titanium nanotubes to target periprosthetic joint infection.

Periprosthetic joint infection (PJI) occurs in 1%-2% of primary total hip and knee arthroplasties; the rate can reach 20% in individuals at risk. Due to the low local bioavailability of systemic antibiotics and possible off-target effects, localized drug delivery systems are of great importance. Our aim was the electrophoretic deposition (EPD) of gentamicin and chitosan in Titanium (Ti) nanotubes to establish a local, prolonged antibiotic delivery. Nanotubes were created on Ti wire with a two-step anodization process. For drug deposition, EPD and the air-dry methods were compared. For a prolonged drug release, gentamicin and crosslinked chitosan were deposited in a two-step EPD process. Drug release was quantified by fractional volume sampling. The Ti wires were tested against Staphylococcus aureus by agar dilution and liquid culture methods. MC3T3-E1 osteoblastic cell viability was determined with trypan blue. Nanotubes were characterized by a 100 nm diameter and 7 µm length. EPD allowed a higher amount of gentamicin deposited than the air-dry method. Drug deposition was controllable by adjusting the voltage and duration of the EPD process. The crosslinked chitosan layer allowed diffusion-driven release kinetics for up to 3 days. Gentamicin-loaded Ti wires significantly inhibited bacterial growth and resulted in a larger inhibition zone compared to unloaded wires. Twenty-four hours of incubation with loaded wires did not have a significant effect on osteoblast viability. Gentamicin-loaded Ti nanotubes represent a promising approach for PJI prevention, as well as a valuable preclinical tool for the investigation of localized drug delivery systems created on Ti surface.

In-hospital cost-effectiveness analysis of open versus staged fenestrated/branched endovascular elective repair of thoracoabdominal aneurysms.

OBJECTIVE: To compare costs and effectiveness of elective open (OR) vs fenestrated/branched endovascular (ER) repair of thoracoabdominal aneurysms (TAAAs) in a high-volume center. METHODS: This single-center retrospective observational study (PRO-ENDO TAAA Study, NCT05266781) was designed as part of a larger health technology assessment analysis. All electively treated TAAAs between 2013 and 2021 were analyzed and propensity-matched. End points were clinical success, major adverse events (MAEs), hospital direct costs, and freedom from all causes and aneurysm-related mortality and reinterventions. Risk factors and outcomes were homogeneously classified according to the Society of Vascular Surgery reporting standards. Cost-effectiveness value and incremental cost-effectiveness ratio were calculated, considering the absence of MAEs as a measure of effectiveness. RESULTS: Propensity matching identified 102 pairs of patients out of 789 TAAAs. Mortality, MAE, permanent spinal cord ischemia rates, respiratory complications, cardiac complications, and renal injury were higher for OR (13% vs 5%, P = .048; 60% vs 17%, P < .001; 10% vs 3%, P = .045; 91% vs 18%, P < .001; 16% vs 6%, P = .024; 27% vs 6%, P < .001, respectively). Access complication rate (6% vs 27%; P < .001) was higher in the ER group. Intensive care unit stay was longer (P < .001) for OR, and ER patients were discharged home more frequently (3% vs 94%; P < .001). No differences in midterm end points were observed at 2 years. Despite ER reducing all the hospital cost items (-42% to -88%, P < .001), the higher expenses (P < .001) of the endovascular devices increased the overall cost of ER by 80%. Cost-effectiveness value for ER was favorable to OR (56,365 vs 64,903 €/patient) with an incremental cost-effectiveness ratio of 48,409 € per MAE saved. CONCLUSIONS: ER of TAAA reduces perioperative mortality and morbidity compared with OR, with no differences in reinterventions and survival rates at midterm follow-up. Despite the expenses for endovascular grafts, ER was found to be more cost-effective in preventing MAEs.