Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

<p>Abstract</p> <p>Background</p> <p>Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models.</p> <p>Results</p> <p>This study examined the suitability of a murine model (CT26/Balb/C) of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO)-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver), invasion (invasion front), and immune response (invasion front and liver). Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%.</p> <p>Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver) whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%). However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0%) despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments.</p> <p>Conclusion</p> <p>In summary, cross-species comparison on a global gene expression scale suggests the validity of an animal model representing the human situation. The actual yield of potential target genes depends on several variables including the animal model, choice of inclusion criteria, inherent species differences and histologic assessment.</p

Endovascular Treatment of Intracranial Vein and Venous Sinus Thrombosis-A Systematic Review.

BACKGROUND Cerebral venous sinus or vein thromboses (SVT) are treated with heparin followed by oral anticoagulation. Even after receiving the best medical treatment, numerous patients experience neurological deterioration, intracerebral hemorrhage or brain edema. Debate regarding whether endovascular treatment (EVT) is beneficial in such severe cases remains ongoing. This systematic review summarizes the current evidence supporting the use of EVT for SVT on the basis of case presentations, with a focus on patient selection, treatment strategies and the effects of the COVID-19 pandemic. METHODS This systemic literature review included randomized controlled trials (RCTs) and retrospective observational data analyzing five or more patients. Follow-up information (modified Rankin scale (mRS)) was required to be provided (individual patient data). RESULTS 21 records (n = 405 patients; 1 RCT, 20 observational studies) were identified. EVT was found to be feasible and safe in a highly selected patient cohort but was not associated with an increase in good functional outcomes (mRS 0-2) in RCT data. In observational data, good functional outcomes were frequently observed despite an anticipated poor prognosis. CONCLUSION The current evidence does not support the routine incorporation of EVT in SVT treatment. However, in a patient cohort prone to poor prognosis, EVT might be a reasonable therapeutic option. Further studies determining the patients at risk, choice of methods and devices, and timing of treatment initiation are warranted

Functional Outcome and Safety of Intracranial Thrombectomy After Emergent Extracranial Stenting in Acute Ischemic Stroke Due to Tandem Occlusions

Background and Purpose: Various endovascular approaches to treat acute ischemic stroke caused by extra- intracranial tandem occlusions (TO) exist: percutaneous transluminal angioplasty with or without emergent extracranial carotid stenting (ECS) due to high-grade stenosis preceded or followed by intracranial mechanical and/or aspiration thrombectomy (MT). Which treatment strategy to use is still a matter of debate.Methods: From our ongoing prospective stroke registry we retrospectively analyzed 1,071 patients with anterior circulation stroke getting endovascular treatment within 6 h of symptom onset. ECS prior to intracranial MT for TO (n = 222) was compared to MT as standard of care (control group; acute intracranial vessel occlusion without concomitant ipsilateral ICA-occlusion or high-grade stenosis [C; n = 849]). Good functional outcome (mRS ≤ 2 at 3 months), mortality rates, frequencies of symptomatic intracranial hemorrhage (sICH) and successful recanalization (Thrombolysis in Cerebral Infarction Score [TICI] 2b or 3) were assessed. In subgroup analyses we tried to detect possible influences of stroke etiology, dual inhibition of platelet aggregation (IPA; clopidogrel [CLO]: n = 83; ticagrelor [TIC]: n = 137; in combination with Aspirin) and intravenous thrombolysis (IVT).Results: Functional outcome was superior in TO (mRS 0–2: 44.6%) when compared with controls (36.0%; OR [95% CI]: 3.49 [1.59–7.67]; p = 0.002). There was no difference in all-cause mortality at 3 months (TO: 21.6%; C: 27.7%; 0.78 [0.47–1.29]; p = 0.324), in-hospital mortality (0.76 [0.45–1.30]; p = 0.324), sICH (TO: 3.2%; C: 5.0%; 0.70 [0.30–1.59]; p = 0.389), and TICI 2b/3 (TO: 89.1%; C: 88.3%; p = 0.813). In subgroup-analysis, TIC and CLO did not differ in functional outcome (TIC: 45.3%; CLO: 44.6%; 1.04 [0.51–2.09]; p = 0.920) and mortality rates (all-cause mortality: TIC: 23.4%; CLO: 16.9%; 0.75 [0.27–2.13]; p = 0.594). sICH was more frequent in TIC (n = 7 [5.1%]) vs. CLO (n = 0; p = 0.048).Conclusion: In our pre-selected cohort, ECS prior to intracranial MT in TO allowed for a good functional outcome that was superior compared to a control population. Mortality rates did not differ. Despite a dual IPA in TO, there was no increase in sICH. CLO and TIC for dual IPA did not differ in terms out outcome and mortality rates. A significant increase in sICH was observed after initial loading with TIC

First-Pass Reperfusion by Mechanical Thrombectomy in Acute M1 Occlusion: The Size of Retriever Matters

Introduction: Single-pass complete reperfusion using stent retrievers has been shown to improve functional outcome in patients with large vessel occlusion strokes. The aim of this study was to investigate the optimal size of stent retrievers to achieve one-pass complete reperfusion by mechanical thrombectomy.Methods: The study evaluated the results of aspiration-assisted mechanical thrombectomy of acute isolated occlusion of the middle cerebral artery in the M1 segment with a novel 5 × 40-mm stent retriever compared to the usual 4 × 20-mm device. Reperfusion status was quantified using the Thrombolysis In Cerebral Infarction (TICI) scale. We hypothesized that thrombectomy of M1 occlusions with 5 × 40-mm stent retriever yields higher rates of complete first-pass reperfusion (FP) (TICI ≥2c after one pass) and successful or modified FP (mFP) (TICI ≥2b after one pass) than thrombectomy with 4 × 20. We included isolated M1 occlusions treated with pRESET 5 × 40 (phenox) as first-choice device for thrombectomy and compared with M1 occlusions treated with pRESET 4 × 20. We excluded patients with additional occlusions or tandem stenosis or who received an intracranial stent or angioplasty as a part of the endovascular treatment.Results: One hundred thirteen patients were included in the 4 × 20 group and 57 patients in the 5 × 40 group. The 5 × 40 group achieved higher FP compared to 4 × 20 group [61.4% (35 of 57 patients) vs. 40.7% (46 of 113), respectively; adjusted odds ratio (OR) and 95% confidence interval (95% CI) = 2.20 (1.08–4.48), p = 0.030] and a higher mFP [68.4%, 39 of 57 patients vs. 48.7%, 55 of 113; adjusted OR (95% CI) = 2.11 (1.04–4.28), p = 0.037]. Frequency of successful reperfusion (TICI ≥2b) was similar in both groups (100 vs. 97.3%), but frequency of complete reperfusion (TICI ≥2c) was higher in the 5 × 40 group [82.5 vs. 61.9%, adjusted OR (95% CI) = 2.47 (1.01–6.04), p = 0.047]. Number of passes to achieve reperfusion was lower in the 5 × 40 group than in the 4 × 20 group [1.6 ± 1.1 vs. 2 ± 1.4, p = 0.033; adjusted incidence rate ratio (95% CI) = 0.84 (0.69–1.03), p = 0.096]. Modified Rankin scale at 90 days was similar in 5 × 40 and 4 × 20 groups.Conclusions: The size of stent retriever matters in acute M1 occlusions treated with aspiration-assisted mechanical thrombectomy. A longer stent retriever with a larger nominal diameter achieves a higher complete and successful FP and higher successful reperfusion compared to a shorter stent retriever

The Combined Use of Intraluminal and Intrasaccular Flow Diversion for the Treatment of Intracranial Aneurysms: Report of 25 Cases

PurposeThe Medina Embolic Device (MED) is a new intrasaccular device with promising early results. Previously we documented our initial experience of this device both alone and in combination with other devices including flow diverter stents (FDS). We sought to determine the effect of the MED + FDS strategy for the treatment of selected aneurysms.Materials and MethodsWe performed a retrospective analysis of prospectively collected data to identify all patients with aneurysms treated using both the MED and intraluminal FDS. We present our technical success rate, early and mid-term angiographic follow-up, and clinical outcome data.ResultsWe identified 25 non-consecutive patients. The treatment was staged in 9 patients and in a single session 16 patients. The average age was 61±12.8 years (range 40–82). The average fundus height was 11±3.6 mm and average fundus width was 10.1±3.4 mm. In the staged cohort (n=9) at delayed angiography (mean 10 mths) 8 aneurysms (89%) showed complete exclusion (mRRC 1) and in one patient there was a parent vessel occlusion. In the simultaneous cohort delayed angiography (n=10, mean 8.1 months) demonstrated complete occlusion (mRRC 1) in 6 aneurysms (60%), 3 neck remnants (mRRC 2) (30%) and 1 patient (10%) showed persistent aneurysmal filling (mRRC 3a). There were 5 complications with permanent morbidity (mRS >2) in two patients. There were no mortalities.ConclusionThe MED can be successfully used in combination with intraluminal FDS and in selected aneurysms this may represent an alternative to FDS and adjunctive coiling

Flow Diversion for Reconstruction of Intradural Vertebral Artery Dissecting Aneurysms Causing Subarachnoid Hemorrhage—A Retrospective Study From Four Neurovascular Centers

Objective: Dissecting aneurysms (DAs) of the vertebrobasilar territory manifesting with subarachnoid hemorrhage (SAH) are associated with significant morbi-mortality, especially in the case of re-hemorrhage. Sufficient reconstruction of the affected vessel is paramount, in particular, if a dominant vertebral artery (VA) is impacted. Reconstructive options include stent-assisted coiling and flow diversion (FD). The latter is technically less challenging and does not require catheterization of the fragile aneurysm. Our study aims to report a multicentric experience with FD for reconstruction of DA in acute SAH. Materials and Methods: This retrospective study investigated 31 patients (age: 30–78 years, mean 55.5 years) who had suffered from SAH due to a DA of the dominant VA. The patients were treated between 2010 and 2020 in one of the following German neurovascular centers: University Hospital Leipzig, Katharinenhospital Stuttgart, BG Hospital Bergmannstrost Halle/Saale, and Heinrich-Braun-Klinikum Zwickau. Clinical history, imaging, implanted devices, and outcomes were reviewed for the study. Results: Reconstruction with flow-diverting stents was performed in all cases. The p64 was implanted in 14 patients; one of them required an additional balloon expandable stent to reconstruct severe stenosis in the target segment. One case demanded additional liquid embolization after procedural rupture, and in one case, p64 was combined with a PED. Further 13 patients were treated exclusively with the PED. The p48MW-HPC was used in two patients, one in combination with two additional Silk Vista Baby (SVB). Moreover, one patient was treated with a single SVB, one with a SILK+. Six patients died [Glasgow Outcome Scale (GOS) 1]. Causes of death were periprocedural re-hemorrhage, thrombotic occlusion of the main pulmonary artery, and delayed parenchymal hemorrhage. The remaining three patients died in the acute–subacute phase related to the severity of the initial hemorrhage and associated comorbidities. One patient became apallic (GOS 2), whereas two patients had severe disability (GOS 3) and four had moderate disability (GOS 4). Eighteen patients showed a complete recovery (GOS 5). Conclusion: Reconstruction of VA-DA in acute SAH with flow-diverting stents is a promising approach. However, the severity of the condition is reflected by high overall morbi-mortality, even despite technically successful endovascular treatment

The Use of Flow Diverting Stents to Treat Para-Ophthalmic Aneurysms

Background and purposeFew publications have dealt exclusively with the use of flow diverter stents for the treatment of para-ophthalmic aneurysms. We sought to determine the efficacy of flow diverting stents (FDSs) to treat aneurysms in this specific location.MethodsWe retrospectively reviewed our database of prospectively collected information for all patients treated with flow diversion for an unruptured saccular para-ophthalmic aneurysm between September 2009 and January 2016. The aneurysm fundus size, neck size, number and type of FDS, complications, and follow-up data were recorded.ResultsWe identified 74 patients that matched our inclusion criteria. Of these patients, 18 patients were male (24.3%). The average fundus size was 4.8 mm, 11 aneurysms had previous coil occlusions and 63 were treated solely with flow diversion. At an initial angiographic follow-up (mean avg. 3.2 months), 71.8% of the aneurysms were occluded, and at the last follow-up (mean avg. 31.8 months), 88.9% of aneurysms were occluded. One patient suffered permanent morbidity (1.36%) secondary to interruption of the antiplatelet medication and another died (1.36%) secondary to in-stent thrombosis that was also due to an interruption in the antiplatelet medication.ConclusionTreatment of saccular para-ophthalmic aneurysms with FDS is feasible and carries a high degree of technical success with low complication rates and excellent rates of aneurysm exclusion

Carotid Artery Stenting in Patients with Symptomatic and Asymptomatic Stenosis: In-Hospital Clinical Outcomes at a Single Neurovascular Center

Background: Carotid artery stenting (CAS) is a minimally invasive and proven percutaneous procedure that is widely used to treat patients with symptomatic and asymptomatic carotid artery stenosis. The purpose of this study was to characterize the in-hospital outcomes of symptomatic and asymptomatic patients undergoing CAS at a single neurovascular center. Methods: The study was conducted as a retrospective analysis of 1158 patients (asymptomatic, n = 636; symptomatic, n = 522; male, n = 816; median age, 71 years; NASCET method, 70-99% stenosis, n = 830) who underwent CAS between May 2009 and December 2020. In-hospital neurological outcomes, adverse reactions to iodinated contrast media, acute myocardial infarction, intraprocedural complications, and access-site issues were evaluated. The primary endpoints were disabling stroke (including disabling cerebral hyperperfusion syndrome [CHS]) and all in-hospital deaths. Results: A carotid stent could not be deployed in one patient due to calcified plaques (technical failure rate of 0.09%). Four patients (0.3%) experienced in-hospital, stroke-associated death, while five patients (0.4%) died from non-stroke-related causes. All stroke-associated deaths occurred in the symptomatic group and were due to CHS. The disabling stroke rate was 0.9% overall (n = 10; 0.5% versus 1.3% in asymptomatic versus symptomatic patients, respectively). Nineteen patients (1.6%) reached the in-hospital primary endpoint. More patients in the symptomatic group achieved this endpoint than in the asymptomatic group (2.5% versus 0.9%, respectively; p = 0.060). Conclusions: An evaluation was conducted on the in-hospital outcomes of 1158 patients at a single center who underwent CAS and was performed by trained physicians who were supervised by a senior neurovascular interventionist with over 20 years of experience, confirming the excellent safety profile of this procedure with a low rate of complications

The p48 Flow Modulation Device with Hydrophilic Polymer Coating (HPC) for the Treatment of Acutely Ruptured Aneurysms: Early Clinical Experience Using Single Antiplatelet Therapy

Background Flow diversion (FD) remains a potential treatment option following aneurysmal subarachnoid hemorrhage (aSAH) when standard options may not be feasible. However, it should not be considered a first-line treatment due to the need for dual antiplatelet therapy (DAPT). The hydrophilic polymer coating on the p48MW flow diverter (HPC, phenox) is a surface modification that inhibits platelet adhesion. This study aims to report on our early single-center experience using the p48MW HPC (phenox) flow diverter with single antiplatelet therapy (SAPT) following an aSAH. Materials and Methods We retrospectively identified all patients who had been treated with the p48MW HPC for aSAH under SAPT. All patients treated within 30 days following an aSAH were included. Any occurrence of thromboembolic and hemorrhagic complications was recorded alongside angiographic and clinical follow-up details. Results Eight patients were identified. The mean interval between aSAH and FD was 6 days. Of the eight ruptured aneurysms, one was blister-like, one saccular, one mycotic, and the remaining five were dissecting aneurysms. Intraprocedural transient thrombus formation was observed in four patients (50%). Stent thrombosis was observed in one patient (12.5%) on day 3 with spontaneous recanalization after being switched onto DAPT. None of the aneurysms rebled after treatment. Two patients died due to cerebral vasospasm. Complete aneurysm occlusion had been achieved in all but one patient at angiographic follow-up (average 6 months). Conclusions This small series highlights the possibility and limitations of using the p48MW HPC with SAPT in ruptured aneurysms. Randomized trials with longer follow-up in larger cohorts are underway

Use of the pCONus HPC as an adjunct to coil occlusion of acutely ruptured aneurysms: early clinical experience using single antiplatelet therapy

Background Coil occlusion has become the standard treatment for many ruptured aneurysms. However, specific aneurysm structures pose technical difficulties and may require the use of adjunctive neck-bridging devices, which necessitate the use of dual antiplatelet therapy. The hydrophilic polymer coating (pHPC, phenox) is a surface modification that inhibits platelet adhesion. Objective To present initial experience with the pCONUS HPC device as an adjunct to coil embolization for ruptured aneurysms using single antiplatelet therapy (SAPT). Methods All patients who were treated with the pCONUS HPC for ruptured aneurysms using SAPT were retrospectively identified. The occurrence of thromboembolic and hemorrhagic complications was recorded together with the angiographic and clinical follow-up details. Results Fifteen patients were identified (nine female) with a median age of 54 years (range 27-81). Six aneurysms were located at the anterior communicating artery, five at the middle cerebral artery bifurcation, two at the basilar artery bifurcation, one at the posterior communicating artery, and one involving the intradural internal carotid artery. Ten patients (66.6%) achieved modified Raymond-Roy classification I or II at post-treatment angiography, with 45.5% of patients having adequate occlusion (defined as complete occlusion or neck remnant) at follow-up. All patients received acetylsalicylic acid (ASA) as SAPT before and after the procedure. Intraprocedural thrombus formation was seen in three patients (20%), resolving in two patients after a bolus dose of eptifibatide, and one treated with mechanical aspiration. No clinical or radiological consequences were seen. There were no recurrent aneurysm ruptures. One patient died owing to cerebral vasospasm. Conclusion This initial clinical experience highlights the possibility and limitations of using the pCONUS HPC device in the treatment of complex ruptured aneurysm with ASA as SAPT. Randomized trials with longer follow-up in larger cohorts are underway