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Objectives: Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color. ‘White’ clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy. Materials and methods: Seventy five ‘white’ thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. Results: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). ‘White’ clots contained significantly more platelets/other (p

Supplemental material, sj-pdf-1-eso-10.1177_23969873211024777 for Correlation between acute ischaemic stroke clot length before mechanical thrombectomy and extracted clot area: Impact of thrombus size on number of passes for clot removal and final recanalization by Rosanna Rossi, Seán Fitzgerald, Sara M Gil, Oana M Mereuta, Andrew Douglas, Abhay Pandit, Paul Brennan, Sarah Power, Jack Alderson, Alan O’Hare, Michael Gilvarry, Ray McCarthy, Klearchos Psychogios, Georgios Magoufis, Georgios Tsivgoulis, István Szikora, Katarina Jood, Petra Redfors, Annika Nordanstig, Erik Ceder, Turgut Tatlisumak, Alexandros Rentzos, John Thornton and Karen M Doyle in European Stroke Journal

Supplemental material, sj-pdf-2-eso-10.1177_23969873211024777 for Correlation between acute ischaemic stroke clot length before mechanical thrombectomy and extracted clot area: Impact of thrombus size on number of passes for clot removal and final recanalization by Rosanna Rossi, Seán Fitzgerald, Sara M Gil, Oana M Mereuta, Andrew Douglas, Abhay Pandit, Paul Brennan, Sarah Power, Jack Alderson, Alan O’Hare, Michael Gilvarry, Ray McCarthy, Klearchos Psychogios, Georgios Magoufis, Georgios Tsivgoulis, István Szikora, Katarina Jood, Petra Redfors, Annika Nordanstig, Erik Ceder, Turgut Tatlisumak, Alexandros Rentzos, John Thornton and Karen M Doyle in European Stroke Journal

Introduction: We assessed the correlation between thrombus size before and after mechanical thrombectomy, measured as length by Computed Tomography Angiography/Non-Contrast Computed Tomography (CTA/NCCT) and Extracted Clot Area, ECA, respectively. We also assessed the influence of thrombus size on the number of passes required for clot removal and final recanalization outcome. Materials and methods: Acute ischaemic stroke (AIS) thrombi retrieved by mechanical thrombectomy from 500 patients and data of clot length by CTA/NCCT were collected from three hospitals in Europe. ECA was obtained by measuring the area of the extracted clot. Non-parametric tests were used for data analysis. Results: A strong positive correlation was found between clot length on CTA/NCCT and ECA (rho = 0.619,N = 500, P < 0.0001*). Vessel size influences clot length on CTA/NCCT (H2 = 98.6, P < 0.0001*) and ECA (H2 = 105.6,P < 0.0001*), but the significant correlation between CTA/NCCT length and ECA was evident in all vessels. Poorer revascularisation outcome was associated with more passes (H5 = 73.1, P < 0.0001*). More passes were required to remove longer clots (CTA/NCCT; H4 = 31.4, P < 0.0001*; ECA; H4 = 50.2, P < 0.0001*). There was no significant main association between recanalization outcome and length on CTA/NCCT or ECA, but medium sized clots (ECA 20-40 mm(2)) were associated with least passes and highest revascularisation outcome (N = 500, X-2 = 16.2, P < 0.0001*). Conclusion: Clot length on CTA/NCCT strongly correlates with ECA. Occlusion location influences clot size. More passes are associated with poorer revascularisation outcome and bigger clots. The relationship between size and revascularisation outcome is more complex. Clots of medium ECA take less passes to remove and are associated with better recanalization outcome than both smaller and larger clots.

Background Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots. Objective To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass. Methods As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated. Results Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1-3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes. Conclusion LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.

Purpose Our purpose was to assess the impact of occlusion location in patients suffering from Acute Ischemic Stroke (AIS) on the total number of passes (attempts) necessary to retrieve the clot and on final revascularization outcome. Moreover, we analysed the impact of bridging-therapy, i.e. the concomitant use of IV tPA (intravenous tissue plasminogen activator) and mechanical thrombectomy (MT) on the different categories of occlusion locations. Methods 550 mechanically extracted thrombi were collected from four partner hospitals: Beaumont (Dublin) Sahlgrenska (Gothenburg), National Institute of Clinical Neurosciences (Budapest) and Metropolitan Hospital (Piraeus). In the vast majority of the cases (311 patients, 56.5%) the thrombus was located in the Middle Cerebral Artery (MCA), followed by Carotid Terminus/Internal Carotid Artery (ICA) in 89 cases (16.2%) and by vertebral/basilar artery (45 patients, 8.2%). In 65 cases (11.8%) a tandem occlusion, i.e. the occlusion of both ICA and MCA was found, while a dual occlusion occurred in 26 cases (4.7%). 248 patients (45.1%) underwent bridging-therapy, while 291 patients (52.9%) were treated with MT alone. For 11 patients (2%) we have no information whether tPA was administered or not. Recanalization rate was defined by using the modified Thrombolysis In Cerebral Infarction (mTICI) score. Non-parametric Kruskal-Wallis test using IBM SPSS-25 software was used for statistical analysis. Results Occlusion location had a significant impact on the total number of passes required to retrieve the clot as well as on final revascularization outcome. The cases with tandem and dual occlusion showed higher number of procedural passes and lower percentage of complete revascularizations (mTICI=3, Table 1). Bridging-therapy did not significantly reduce the total number of passes or improve the recanalization rates for patients with singular occlusion. On the other hand, bridging-therapy significantly lowered the total number of passes to remove the clot in patients with dual and tandem occlusion (N=87, mean for MT+tPA= 2.63±1.73, MT alone=3.80±2.14, H1=7.608, p=0.006*), but had no statistically significant effect on the final mTICI score (N=87, H1=0.266, p=0.606). Conclusion This study suggests that occlusion location significantly influences the total number of procedural passes in MT procedures as well as the final revascularization outcome. Furthermore, bridging-therapy lowers the number of procedural passes in cases of tandem and dual occlusion without having significant effect on final mTICI score. Funding: Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus. Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus. non-peer-reviewed

Both intravenous thrombolysis with tissue plasminogen activator (IV-rtPA) and mechanical thrombectomy (MT) increase recanalization rates. We assessed if bridging-therapy (the concomitant use of rtPA and MT) could increase the recanalization rates and reduce the number of procedural passes in patients suffering from acute ischemic stroke (AIS) when compared to MT alone. Analysis of type of device used, stentriever or aspiration catheter, is also reported. 334 mechanically extracted thrombi were collected from two partner hospitals: Beaumont (Dublin) and Sahlgrenska (Gothenburg). 158 patients (47.3%) were treated with bridging-therapy, while 176 (52.7%) underwent MT alone. Recanalization rate was defined by using the modified Thrombolysis In Cerebral Infarction (mTICI) score. Non-parametric Kruskal-Wallis test was used for statistical analysis. Bridging-therapy reduced the total number of passes to remove the clot (mean for MT+rtPA=2.27±2.10, MT alone=2.63±1.88, H1=4.376, p=0.036*). Analysing the device, rtPA lowered the overall number of passes using stentriever devices (mean for MT+rtPA=1.57±1.12, MT alone=2.36±1.48, H1=8.303, p=0.004*), but not for aspiration (mean for MT+rt-PA=1.78±1.22, MT alone=2.03±1.47, for H1=0.795, p=0.372). Also, when using both devices no significant reduction of number of passes was observed (mean for MT+rtPA=3.29±2.90, MT alone=3.83±2.20, H1=3.027, p=0.082). There was no significant effect on final mTICI score using bridging-therapy when compared to MT alone (H1=1.163, p=0.281). This small study suggests that bridging-therapy lowers the number of procedural passes in MT procedures, specifically when using stentriever devices. However, this did not have a significant effect on final mTICI score. Funding: Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus. Funding: Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus. non-peer-reviewed

Introduction: Lipid accumulation and inflammation are considered hallmarks of the unstable atherosclerotic plaque. In particular, adipocyte fatty acid binding protein (FABP4) expression within the plaque is associated with its progression and vulnerability. The aim of this study was to investigate the histopathology of thrombi collected from acute ischaemic stroke patients who underwent mechanical thrombectomy focusing on the presence of FABP4 and other atherosclerotic plaque components, including collagen and dystrophic calcification. Methods: 250 mechanically extracted thrombi were collected from three partner hospitals: Beaumont Hospital (Dublin, Ireland), Sahlgrenska University Hospital (Gothenburg, Sweden) and Mayo Clinic (Rochester, Minnesota, USA). Clots were immediately formalin-fixed and embedded in paraffin. 3-µm thickness serial sections were cut and stained with Martius Scarlett Blue to identify erythrocytes, fibrin, white blood cells and platelets/other. Masson s and von Kossa stains were performed to identify collagen and calcification, respectively. The expression of FABP4 was assessed by immunofluorescence. Results: FABP4 expression by adipocytes was confirmed in eight of 250 clots (3.2%). Adipocytes represented the main component in one white clot. Collagen was associated in two cases whereas von Kossa staining showed calcification in one case. Conclusions: The expression of potentially atherogenic components in these clots suggests that they may have originated from large vessel occlusions. Further studies are required to confirm the atherosclerotic aetiology. Our findings have implications for neurointervention and therapeutic strategies to reduce atherosclerotic plaque progression and stroke recurrence. Science Foundation Ireland (Grant Number 13/RC/2073) and Cerenovus. non-peer-reviewed

Introduction: Advances in mechanical thrombectomy have created the unique opportunity to study the acute ischemic stroke clot material. However, there is a lack of uniformity in the histopathologic characterization of thrombi. Many clots are mainly red in colour and predominantly composed of Red Blood Cells and Fibrin. In this context, white clots represent a less common entity and their histological composition is largely unknown. We investigated the histopathological features of 21 white clots retrieved by thrombectomy. To our knowledge, this is the first series reported to date. Methods: Twenty one mechanically extracted white thrombi were collected from two partner hospitals: Beaumont Hospital and Sahlgrenska University Hospital. Clots were immediately formalin-fixed and subsequently embedded in paraffin. For each case, serial sections of 3-µm thickness were cut and stained with Hematoxylin & Eosin and Martius Scarlett Blue (MSB) for the identification of main clot components. The MSB-stained slide underwent whole slide scanning (Olympus VS120) and histologic quantification was performed using Orbit Image Analysis Software (Orbit Image Analysis, Idorsia Ltd.). Von Kossa staining was performed to confirm calcification when suspected. The presence of specific components was assessed by immunostaining for platelets (CD42b), von Willebrand Factor (vWF) and fatty-acid binding protein (FABP4) for adipocytes. Results: The quantification identified the Platelets as the major component in white clots accounting for up to 90% of their composition. The main components showed mean values of 75.67% for Platelets, 13.36% for Fibrin, 5.07% for Red Blood cells and 3.75% for White Blood Cells Immunostaining confirmed the presence of CD42b and vWF in all cases. Collagen and calcification were present in one case. Interestingly, adipocytes represented the main component in two cases. Conclusions: Platelets are the key component of white clots . Calcification and adipocytes are also found occasionally. Increased levels of platelets and calcium confer resistance to thrombolysis and may render clots stiffer and less accessible for stent retrievers leading to low recanalization rates. The presence of adipocytes may represent a histological marker of fat embolism when suspected or a vulnerable atherosclerotic plaque, especially if associated with collagen. Science Foundation Ireland (Grant Number 13/RC/2073) and Industrial partners Cerenovus non-peer-reviewed

Guardando con distanza critica la storia dell’intervento di palazzo Abatellis, comprendiamo che attraverso quest’opera di restauro e rifunzionalizzazione è stato concepito un edificio pubblico, un museo, come un luogo di aggregazione e di possibile rigenerazione urbana. Fin da subito - come scrive Vigni nel 1954 - era stata prevista ‘anche la possibilità di un’attività culturale della Galleria, a mezzo di mostre temporanee, di mostre dei restauri via via compiuti, di apertura notturna con illuminazione artificiale, in modo che tale istituto entrasse a far parte della vita cittadina più completa possibile’. Lo stesso Vigni era consapevole che in quegli anni il panorama dei musei italiani doveva rinnovarsi con la ricostruzione postbellica e rispondere a una domanda alternativa d’uso e di fruizione del patrimonio artistico. L’esempio di rigenerazione ante litteram di Carlo Scarpa individua, nel mutamento di senso dell’esistente, l’innesco di un auspicabile atteggiamento virtuoso per il ‘riordino’ del costruito di prossimità e in una implementazione di beni e servizi di qualità, accessibili ad una moltitudine di consumatori/utenti, consapevoli della natura culturale e sociale, prima ancora che tecnologica, per rafforzare la qualità della vita i questi luoghi.

Il presente lavoro si basa sui risultati ottenuti dall’Università di Bologna sulle prime due annualità del piano triennale 2010/2012 di rilievo della fauna ittica ed applicazione dell’ISECI sui corpi idrici appenninici e di alta pianura dell’Emilia Romagna afferenti alla Rete Regionale delle acque superficiali monitorate da ARPA ER. I risultati ottenuti qualificano l’ISECI come uno strumento in grado di interpretare su scala di bacino i peggioramenti qualitativi che caratterizzano gli idrosistemi indagati al diminuire della quota altitudinale. L’ISECI sembra però, in situazioni localizzate, sovrastimare o sottostimare il reale stato ecologico delle comunità ittiche mostrando, quindi, la necessità di un’evoluzione della sua formulazione matematica e concettuale. In the present work are reported the results of the ISECI application on water bodies of the Apennine and high plains of Emilia Romagna. Data were collected by the University of Bologna on the ARPA-ER’s freshwater monitoring Regional Network from 2010 to 2012. On the basin scale ISECI described successfully the deterioration of the investigated hydro system with decreasing altitude. However, in localized areas, ISECI seemed to overestimate or underestimate the real ecological status of fish communities suggesting the need to modify and further develop its mathematical and conceptual formula.