Antiplatelets and antithrombotics in neurointerventional procedures: guideline update

Antiplatelet and antithrombotic medication management before, during, and after neurointerventional procedures has significant practice variation. This document updates and builds upon the 2014 Society of NeuroInterventional Surgery (SNIS) Guideline 'Platelet function inhibitor and platelet function testing in neurointerventional procedures', providing updates based on the treatment of specific pathologies and for patients with specific comorbidities

Antiplatelets and antithrombotics in neurointerventional procedures: Guideline update.

BACKGROUND: Antiplatelet and antithrombotic medication management before, during, and after neurointerventional procedures has significant practice variation. This document updates and builds upon the 2014 Society of NeuroInterventional Surgery (SNIS) Guideline 'Platelet function inhibitor and platelet function testing in neurointerventional procedures', providing updates based on the treatment of specific pathologies and for patients with specific comorbidities. METHODS: We performed a structured literature review of studies that have become available since the 2014 SNIS Guideline. We graded the quality of the evidence. Recommendations were arrived at through a consensus conference of the authors, then with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: The management of antiplatelet and antithrombotic agents before, during, and after endovascular neurointerventional procedures continues to evolve. The following recommendations were agreed on. (1) It is reasonable to resume anticoagulation after a neurointerventional procedure or major bleeding episode as soon as the thrombotic risk exceeds the bleeding risk in an individual patient (Class I, Level C-EO). (2) Platelet testing can be useful to guide local practice, and specific approaches to using the numbers demonstrate marked local variability (Class IIa, Level B-NR). (3) For patients without comorbidities undergoing brain aneurysm treatment, there are no additional considerations for medication choice beyond the thrombotic risks of the catheterization procedure and aneurysm treatment devices (Class IIa, Level B-NR). (4) For patients undergoing neurointerventional brain aneurysm treatment who have had cardiac stents placed within the last 6-12 months, dual antiplatelet therapy (DAPT) is recommended (Class I, Level B-NR). (5) For patients being evaluated for neurointeventional brain aneurysm treatment who had venous thrombosis more than 3 months prior, discontinuation of oral anticoagulation (OAC) or vitamin K antagonists should be considered as weighed against the risk of delaying aneurysm treatment. For venous thrombosis less than 3 months in the past, delay of the neurointerventional procedure should be considered. If this is not possible, see atrial fibrillation recommendations (Class IIb, Level C-LD). (6) For patients with atrial fibrillation receiving OAC and in need of a neurointerventional procedure, the duration of TAT (triple antiplatelet/anticoagulation therapy=OAC plus DAPT) should be kept as short as possible or avoided in favor of OAC plus single antiplatelet therapy (SAPT) based on the individual's ischemic and bleeding risk profile (Class IIa, Level B-NR). (7) For patients with unruptured brain arteriovenous malformations there is no indication to change antiplatelet or anticoagulant management instituted for management of another disease (Class IIb, Level C-LD). (8) Patients with symptomatic intracranial atherosclerotic disease (ICAD) should continue DAPT following neurointerventional treatment for secondary stroke prevention (Class IIa, Level B-NR). (9) Following neurointerventional treatment for ICAD, DAPT should be continued for at least 3 months. In the absence of new stroke or transient ischemic attack symptoms, reversion to SAPT can be considered based on an individual patient's risk of hemorrhage versus ischemia (Class IIb, Level C-LD). (10) Patients undergoing carotid artery stenting (CAS) should receive DAPT before and for at least 3 months following their procedure (Class IIa, Level B-R). (11) In patients undergoing CAS during emergent large vessel occlusion ischemic stroke treatment, it may be reasonable to administer a loading dose of intravenous or oral glycoprotein IIb/IIIa or P2Y12 inhibitor followed by maintenance intravenous infusion or oral dosing to prevent stent thrombosis whether or not the patient has received thrombolytic therapy (Class IIb, C-LD). (12) For patients with cerebral venous sinus thrombosis, anticoagulation with heparin is front-line therapy; endovascular therapy may be considered particularly in cases of clinical deterioration despite medical therapy (Class IIa, Level B-R). CONCLUSIONS: Although the quality of evidence is lower than for coronary interventions due to a lower number of patients and procedures, neurointerventional antiplatelet and antithrombotic management shares several themes. Prospective and randomized studies are needed to strengthen the data supporting these recommendations.

Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies.

Breast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone. Artificial Intelligence (AI)-based tools can support cancer detection and classification in breast biopsies ensuring rapid, accurate, and objective diagnosis. We present here the development, external clinical validation, and deployment in routine use of an AI-based quality control solution for breast biopsy review. The underlying AI algorithm is trained to identify 51 different types of clinical and morphological features, and it achieves very high accuracy in a large, multi-site validation study. Specifically, the area under the receiver operating characteristic curves (AUC) for the detection of invasive carcinoma and of ductal carcinoma in situ (DCIS) are 0.99 (specificity and sensitivity of 93.57 and 95.51%, respectively) and 0.98 (specificity and sensitivity of 93.79 and 93.20% respectively), respectively. The AI algorithm differentiates well between subtypes of invasive and different grades of in situ carcinomas with an AUC of 0.97 for invasive ductal carcinoma (IDC) vs. invasive lobular carcinoma (ILC) and AUC of 0.92 for DCIS high grade vs. low grade/atypical ductal hyperplasia, respectively, as well as accurately identifies stromal tumor-infiltrating lymphocytes (TILs) with an AUC of 0.965. Deployment of this AI solution as a real-time quality control solution in clinical routine leads to the identification of cancers initially missed by the reviewing pathologist, demonstrating both clinical utility and accuracy in real-world clinical application.

P2Y12 inhibitors for the neurointerventionalist.

The use of antiplatelets is widespread in clinical practice. However, for neurointerventional procedures, protocols for antiplatelet use are scarce and practice varies between individuals and institutions. This is further complicated by the quantity of antiplatelet agents which differ in route of administration, dosage, onset of action, efficacy and ischemic and hemorrhagic complications. Clarifying the individual characteristics for each antiplatelet agent, and their associated risks, will increasingly become relevant as the practice of mechanical thrombectomy, stenting, coiling and flow diversion procedures grows. The aim of this review is to summarize the existing literature for the use of P2Y12 inhibitors in neurointerventional procedures, examine the quality of the evidence, and highlight areas in need of further research.

Glycoprotein IIb/IIIa inhibitors for the neurointerventionalist.

Antiplatelet therapies are commonly used in neurointerventional procedures. However, specific guidelines for their use in these settings is lacking and it can often be difficult to balance the potential risks and benefits of these medications. Considering the continued growth and adoption of neurointerventional procedures, it is crucial to understand the properties of these agents in order to use them safely. Large-scale clinical trials are still needed to clarify many of these aspects for this emerging field. However, the existing literature already provides insight into which antiplatelet drugs are of benefit to the neurointerventionalist as well as their associated risks of ischemic and hemorrhagic complications. Hence, this review focuses on the applications of GPIIb/IIIA inhibitors to neurointerventional procedures.

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy.

PURPOSE: There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. METHODS: We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement ≥ 70% for binary closed-ended questions/≥ 50% for closed-ended questions with > 2 response options. RESULTS: Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. CONCLUSION: Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.

Tumoral and pseusotumoral processes of the vagina in the pediatric population: A 26-YEAR retrospective study.

BACKGROUND: Vaginal lesions are rare and of various types in children. Clinical presentation is generally undifferenciated. Histological examination is fundamental to ascertain the nature of the lesion. Regarding tumoral lesions, histological subtypes encountered are radically different from those seen in adults, dominated by stromal benign lesions. OBJECTIVE: The aim of this retrospective study was to describe characteristics and pathological aspects of pediatric vaginal lesions, diagnosed in a single pediatric experienced center. STUDY DESIGN: A database analysis was performed on all vaginal samples of patients under 18 years old received in a pediatric-specialized pathology laboratory of an academic hospital, over a 26-year period. RESULTS: Among 36 vaginal tissue samples reported, a total of 15 tumoral or pseudotumoral processes was recorded. Primitive malignant tumors included embryonal rhabdomyosarcoma (n = 3) and germ-cell tumors, yolk-sac type (n = 2). Benign tumoral or pseudotumoral processes included inflammatory stromal polyps (n = 8), epidermic cyst (n = 1), and benign Müllerian papilloma (n = 1). DISCUSSION: Over 15 primitive vaginal tumors, 1/3 was malignant with embryonal rhabdomyosarcoma being the most common. The remaining 2/3 specimens were benign, with stromal inflammatory lesions being the most commonly observed. Fibro-epithelial polyp is a debated entity, which covers a wide histological spectrum, with varying inflammation and stromal cellularity, raising sometimes the question of the differential diagnosis with rhabdomyosarcoma. Stromal cells morphology along with their immunohistochemical profile suggest their reactive myofibroblastic nature. Pseudotumoral inflammatory lesions display very similar histological findings with these entities. A common pathogenesis beginning with an inflammatory process, potentially accelerated by chronic traumatic factors, could be discussed. CONCLUSION: We confirmed the rarity and the diversity of vaginal lesions in children. Vaginoscopy and biopsy sample should be systematic, given the non-specific presentation of tumoral processes. Myogenin immunostain must be systematic in case of vaginal polypoid mass, in order to rule out malignancy.

Chemosensitivity, tumor infiltrating lymphocytes (TILs), and survival of postpartum PABC patients treated by neoadjuvant chemotherapy.

BACKGROUND: Pregnancy-associated breast cancer (PABC) refers to breast cancers (BC) diagnosed during pregnancy or shortly after birth. Although the inflammatory environment of post-partum PABC cases (designed as PP-PABC) may be deleterious, so far PP-PABC have scarcely been distinguished from breast cancers diagnosed during pregnancy. Furthermore, whether PP-PABC cases have an enhanced immune infiltration remains unknown. We investigated chemosensitivity, immune infiltration and survival of PP-PABC patients treated by neoadjuvant chemotherapy (NAC) compared to non-PABC matched BC patients. MATERIALS AND METHODS: We identified PP-PABC cases among a cohort of 1199 invasive BC treated with NAC between 2002 and 2012. Each PP-PABC case was matched with 3 non-PABC controls, according to age and pathological breast cancer subtype. Microbiopsy specimens and paired surgical samples were evaluated for stromal lymphocyte infiltration. Association of clinical and pathological factors with pathological complete response (pCR) and disease-free survival (DFS) was assessed by univariate and multivariate analyses. RESULTS: Our final population study was composed of 116 patients (29 PP-PABC and 87 non-PABC). Median follow-up was of 49.0 and 29.3 months, respectively. After NAC, pCR rates (p = 0.64), post-NAC immune infiltration (stromal TILs: p = 0.67; intratumoral TILs: p = 0.14), and DFS rates (p = 0.17) were comparable between PP-PABC and non-PABC patients in global population. Similar results were found after stratification by pathological subtype. CONCLUSION: We observed similar patterns between postpartum PABC and control tumors in terms of chemosensitivity, immune infiltration, and prognostic. Our results enhance the idea that PP-PABC should receive the same standard of care treatment as other patients, including neoadjuvant chemotherapy.

Genetic Counselling Pitfall: Co-Occurrence of an 11.8-Mb Xp22 Duplication and an Xp21.2 Duplication Disrupting IL1RAPL1.

We report a 3-generation family in which 2 Xp copy number variations (CNVs) co-segregate. The proband presented with syndromic intellectual disability. The CNV had been revealed by conventional karyotyping, identifying a large Xp22 duplication causing an Xp functional disomy. Family studies found that this duplication was inherited from the proband's mother and was also present in one of his sisters. This sister had conventional karyotyping performed during pregnancy with a normal result. Postnatally, her child, the proband's nephew, presented with autism spectrum disorders. aCGH revealed a 339-kb IL1RAPL1 duplication. Overall, the proband, his mother, and one of his sisters all harboured both CNVs, while his other sister and the 2 sons of each sister only carried the IL1RAPL1 intragenic duplication. As seen in this family, we emphasise the importance of small CNV detection, the pathogenicity of IL1RAPL1 exonic duplications in male carriers, and the difficulties for genetic counselling with the risk of double diagnosis in a single patient.