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Arterial calcification is an actively regulated process, with different morphological manifestations. Micro-RNAs emerged as potential regulators of vascular calcification; they may become novel diagnostic tools and be used for a finest staging of the carotid plaque progression. The present study aimed at characterizing the different miRNA-mRNA axes in carotid plaques according to their histological patterns of calcification. Histopathological analysis was performed on 124 retrospective carotid plaques, with clinical data and preoperatory angio-CT. miRNA analysis was carried out with microfluidic cards. Real-time PCR was performed for selected miRNAs validation and for RUNX-2 and SOX-9 mRNA levels. CD31, CD68, SMA, and SOX-9 were analyzed by immunohistochemistry. miRNA levels on HUVEC cells were analyzed for confirming results under in vitro osteogenic conditions. Histopathological analysis revealed two main calcification subtypes of plaques: calcific cores (CC) and protruding nodules (PN). miRNA array and PCR validation of miR-1275, miR-30a-5p, and miR-30d indicated a significant upregulation of miR-30a-5p and miR-30d in the PN plaques. Likewise, the miRNA targets RUNX-2 and SOX-9 resulted poorly expressed in PN plaques. The inverse correlation between miRNA and RUNX-2 levels was confirmed on osteogenic-differentiated HUVEC. miR-30a-5p and miR-30d directly correlated with calcification extension and thickness at angio-CT imaging. Our study demonstrated the presence of two distinct morphological subtypes of calcification in carotid atheromatous plaques, supported by different miRNA signatures, and by different angio-CT features. These results shed the light on the use of miRNA as novel diagnostic markers, suggestive of plaque evolution.

Introduction. Cervical artery dissection (CAD) is a rare condition, being one of the leading causes of stroke in patients under the age of 45, with a reported prevalence of up to 20%. The management of CAD remains controversial due to its rarity and the lack of large-scale randomized controlled trials. The aim of this study was to report the long-term outcomes of CAD in a real-world setting. Methods. This retrospective, observational, single-center study included patients diagnosed with CAD between 2010 and 2019 (approval number: 153/2015/U/Oss/AOUBo). Clinical presentation, risk factors, and medical therapies were prospectively analyzed. Management strategies included both medical and interventional approaches. Follow-up consisted of annual clinical visits and carotid duplex ultrasound (DUS), with telephone interviews every six months. The primary endpoint was defined by the overall long-term stroke/death rate and in relation to the type of medical treatment, localization of the dissection and clinical manifestations. Results. A total of 62 patients were included, predominantly male (65%) with a mean age of 58 (±2) years. Thirteen dissections (21%) were trauma-related. CAD locations included the common carotid artery in 6 cases (10%), extracranial internal carotid artery in 29 (46%), intracranial internal carotid artery in 9 (14%), and vertebral artery in 16 (25%). One patient (2%) had dissections in both the extracranial internal carotid and vertebral arteries, and another (2%) in both the vertebral and basilar arteries. Bilateral dissections were observed in 5 patients (8%). Ischemic manifestations occurred in 43 patients (68%): 10 transient ischemic attacks (16%), 17 minor strokes (27%), and 16 major strokes (25%), with ischemic lesions on cerebral CT in 31 cases (72%). Fifty-eight (93%) patients were treated medically (anticoagulants and/or antiplatelets), while 4 patients (7%) underwent surgical or endovascular intervention. The mean follow-up was 81 ± 35 months. During this period, 2 patients (4%) experienced stroke and 15 (24%) died. The estimated 10-year survival rate was 71%, and the 10-year stroke/death-free survival rate was 70%. Among medically treated patients, the 10-year stroke/death-free survival was 86% for those on anticoagulation and 67% for those on antiplatelet therapy (p = 0.1). Patients presenting with ischemic symptoms had a lower estimated 10-year stroke/death-free survival rate compared to those with non-ischemic presentations (61% vs. 69%, p = 0.7). Patients with dissection of the common carotid artery had a significantly lower estimated 10-year stroke/death-free survival rate (25%), compared to dissections in other cervical arteries (p = 0.001). Conclusions. In this real-world, single-center experience, cervical artery dissection was associated with a favorable long-term prognosis in most cases, especially among patients managed conservatively with medical therapy. Stroke and mortality rates were relatively low during extended follow-up. Although no statistically significant difference was observed between anticoagulation and antiplatelet therapy, the trend favored anticoagulation for stroke/death-free survival. Patients with CCA dissections had significantly worse 10-year stroke/death-free survival compared to those with dissections in other cervical arteries.

Background Popliteal artery aneurysms (PAAs) need urgent treatment in case of acute thrombosis, distal embolization, or rupture. Few data are available in the literature about the treatment results in these scenarios. The aim of the present study was to evaluate an 11-year multicenter experience in the urgent treatment of PAAs. Methods All symptomatic PAAs surgically treated in two vascular centers between 2010 and 2021 were retrospectively analyzed. In the postoperative period periodical clinical and Duplex-Ultrasound evaluation were performed. The evaluated endpoint was the outcome of urgent PAAs treatment according to their clinical presentation. Statistical analysis was performed by Kaplan-Meier log-rank evaluation and multivariable Cox regression tests. Results Sixty-six PAAs needed an urgent repair. Twelve (18%) patients had a PAA rupture and 54 (82%) had an acute limb ischemia (ALI) due to either distal embolization or acute thrombosis. Patients with ALI underwent bypass surgery in 51 (95%) cases, which was associated with preoperative thrombolysis in 18 (31%) cases. A primary major amputation was performed in 3 (5%) cases. The mean follow-up was 52 ± 21 months with an overall 5-year limb salvage of 83 ± 6%. Limb salvage was influenced only by the number of patent tibial arteries (pTA) [5-years limb salvage 0%, 86 ± 10%, 92 ± 8% and 100% in case of 0, 1, 2 or 3 pTA, respectively ( P  = .001)]. An independent association of number of pTA and limb loss was found [hazard ratio (HR): 0.14 (95% confidence interval (CI) 0.03–0.6), P  = .001]. Overall 5-year survival was 71 ± 7%. Ruptured PAAs were associated with lower 5-year survival compared with the ALI group (48 ± 2% vs. 79 ± 7%, P  = .001). The number of pTA (33 ± 20%, 65 ± 10%, 84 ± 10% and 80 ± 10% for 0, 1, 2 and 3 pTA, respectively, P  = .001) and the thrombolysis (94 ± 6% vs. 62 ± 10%, P  = .03) were associated with higher survival in patients with ALI. There was an independent association of number of pTA and long-term survival [HR 0.15 (95% CI 0.03–0.8), P  = .03]. Conclusions PAA rupture is the cause of urgent PAA treatment in almost one fifth of cases, and it is associated with lower long-term survival. ALI can benefit from thrombolysis, and long-term limb salvage and survival are associated with the number of pTA.

Background and aims In order to systematically review the latest evidence on anesthesia, intraoperative neurologic monitoring, postoperative heparin reversal, and postoperative blood pressure management for carotid endarterectomy. The present review is based on a single chapter of the Italian Health Institute Guidelines for diagnosis and treatment of extracranial carotid stenosis and stroke prevention. Methods and results A systematic article review focused on the previously cited topics published between January 2016 and October 2020 has been performed; we looked for both primary and secondary studies in the extensive archive of Medline/PubMed and Cochrane library databases. We selected 14 systematic reviews and meta-analyses, 13 randomized controlled trials, 8 observational studies, and 1 narrative review. Based on this analysis, syntheses of the available evidence were shared and recommendations were indicated complying with the GRADE-SIGN version methodology. Conclusions From this up-to-date analysis, it has emerged that any type of anesthesia and neurological monitoring method is related to a better outcome after carotid endarterectomy. In addition, insufficient evidence was found to justify reversal or no-reversal of heparin at the end of surgery. Furthermore, despite a low evidence level, a suggestion for blood pressure monitoring in the postoperative period was formulated.

Background/Objectives: Carbon dioxide digital-subtraction angiography (CO2-DSA) is an increasingly adopted technique in endovascular aortic repair (EVAR) and fenestrated/branched EVAR (F/B-EVAR); it is used to reduce the amount of iodinate contrast medium (ICM) and prevent postoperative renal function worsening (PO-RFW). Our aim is to report results from the literature on EVAR and F/B-EVAR procedures using CO2-DSA, together with wider applications in aortic endovascular treatment. Methods: We performed a literature review by searching electronic databases for published data on CO2-DSA during EVAR and F/B-EVAR procedures. The endpoints were postoperative renal function worsening (PO-RFW) and efficacy of intraoperative arterial visualization. Further, applications of CO2 for thoracic endovascular aortic repair (TEVAR) were described. Results: Seventeen studies reporting results on CO2-DSA in EVAR (644 patients) were retrieved. Overall, 372 (58%) procedures were performed with CO2 alone, and 272 (42%) were performed with CO2+ICM. Eight studies analyzed the effect of CO2-DSA angiography on PO-RFW; four studies showed a significantly lower rate of PO-RFW compared to ICM. Five studies (153 patients) analyzed intraoperative arterial visualization with CO2-DSA; renal and hypogastric arteries were effectively visualized in 69% and 99% of cases, respectively. The use of CO2-DSA in F/B-EVAR has not been widely investigated. The largest series reported that PO-RFW was lower in the CO2 vs. ICM group. Conclusions: Carbon dioxide is widely applied in modern aortic endovascular treatment. CO2-DSA for EVAR and F/B-EVAR is an efficient technique for reducing PO-RFW while allowing acceptable arterial intraoperative visualization.

: Carbon dioxide digital-subtraction angiography (CO -DSA) is an increasingly adopted technique in endovascular aortic repair (EVAR) and fenestrated/branched EVAR (F/B-EVAR); it is used to reduce the amount of iodinate contrast medium (ICM) and prevent postoperative renal function worsening (PO-RFW). Our aim is to report results from the literature on EVAR and F/B-EVAR procedures using CO -DSA, together with wider applications in aortic endovascular treatment. : We performed a literature review by searching electronic databases for published data on CO -DSA during EVAR and F/B-EVAR procedures. The endpoints were postoperative renal function worsening (PO-RFW) and efficacy of intraoperative arterial visualization. Further, applications of CO for thoracic endovascular aortic repair (TEVAR) were described. : Seventeen studies reporting results on CO -DSA in EVAR (644 patients) were retrieved. Overall, 372 (58%) procedures were performed with CO alone, and 272 (42%) were performed with CO +ICM. Eight studies analyzed the effect of CO -DSA angiography on PO-RFW; four studies showed a significantly lower rate of PO-RFW compared to ICM. Five studies (153 patients) analyzed intraoperative arterial visualization with CO -DSA; renal and hypogastric arteries were effectively visualized in 69% and 99% of cases, respectively. The use of CO -DSA in F/B-EVAR has not been widely investigated. The largest series reported that PO-RFW was lower in the CO vs. ICM group. : Carbon dioxide is widely applied in modern aortic endovascular treatment. CO -DSA for EVAR and F/B-EVAR is an efficient technique for reducing PO-RFW while allowing acceptable arterial intraoperative visualization.

Introduction. Iodinated contrast media completion angiography (ICM-A) may underestimate the presence of type II endoleak (ELII) after endovascular aortic repair (EVAR), particularly if they are at low flow. Contrast-enhanced ultrasound (CEUS) has been proposed as the gold standard in ELII detection during EVAR follow-up. Intraprocedural carbon dioxide (CO2) angiography has been shown to be useful in this setting; however no comparative studies including these three techniques are currently available. Our aim was to investigate the accuracy of a new automated CO2 angiographic (CO2-A) system in the detection of ELII, by comparing it with ICM-A and CEUS. Methods. A series of consecutive patients undergoing EVAR for abdominal aortic aneurysm (AAA) were enrolled and submitted to ICM-A and CO2-A during the procedure. The iodinated contrast media were delivered through an automatic injector connected to a pigtail catheter in the suprarenal aorta. CO2 was delivered through a recently available automatic injector connected to a 10 F sheath positioned in the external iliac artery. All patients were blindly evaluated by CEUS within postoperative day 1. The ICM-A and CO2-A ability to detect ELII was compared with that of CEUS through Cohen’s concordance Index (K). Results. Twenty-one patients were enrolled in the study. One (5%), seven (33%), and four (19%) ELII were detected by ICM-A, CO2-A, and CEUS, respectively. The only ELII detected by ICM-A was also detected by CO2-A and CEUS. Three cases of ELII detected by CO2-A were not detected by CEUS. All ELII detected by CEUS were visualized by CO2-A. CEUS and ICM-A showed a poor agreement (Cohen’s K: 0.35) while CEUS and CO2-A showed a substantial agreement (Cohen’s K: 0.65) for ELII detection. Conclusion. CO2-A is safe and effective method for ELII detection in EVAR, with a significantly higher agreement with CEUS if compared with ICM-A. This trial is registered with 155/2015/U/Oss.

AimsPoly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays.MethodsA total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen’s (dual) and Fleiss (triple) κ coefficients.ResultsIn-house BRCA1/2 molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%.ConclusionsIn-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays.

BackgroundEndometrial cancers with more than one molecular feature—POLE mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)—are called ‘multiple classifiers’.ObjectiveTo describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them.MethodsMultiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification.ResultsAmong 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. TP53 sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%.ConclusionsThe characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and TP53 sequencing.

Endometrial cancers with more than one molecular feature-POLE mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)-are called 'multiple classifiers'. To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them. Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification. Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. TP53 sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%. The characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and TP53 sequencing.