Reperfusion Treatments in Disabling Versus Nondisabling Mild Stroke due to Anterior Circulation Vessel Occlusion.

BACKGROUND: The benefit of distinguishing between disabling versus nondisabling deficit in mild acute ischemic stroke due to endovascular thrombectomy-targetable vessel occlusion (EVT-tVO; including anterior circulation large and medium-vessel occlusion) is unknown. We compared safety and efficacy of acute reperfusion treatments in disabling versus nondisabling mild EVT-tVO. METHODS: From the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register, we included consecutive acute ischemic stroke patients (2015-2021) treated within 4.5 hours, with full NIHSS items availability and score ≤5, evidence of intracranial internal carotid artery, M1, A1-2, or M2-3 occlusion. After propensity score matching, we compared efficacy (3-month modified Rankin Scale score of 0-1, modified Rankin Scale score of 0-2, and early neurological improvement) and safety (nonhemorrhagic early neurological deterioration, any intracerebral or subarachnoid hemorrhage, symptomatic intracranial hemorrhage, and death at 3-month) outcomes in disabling versus nondisabling patients-adopting an available definition. RESULTS: We included 1459 patients. Propensity score matched analysis of disabling versus nondisabling EVT-tVO (n=336 per group) found no significant differences in efficacy (modified Rankin Scale score 0-1: 67.4% versus 71.5%, P=0.336; modified Rankin Scale score 0-2: 77.1% versus 77.6%, P=0.895; early neurological improvement: 38.3% versus 44.4%, P=0.132) and safety (nonhemorrhagic early neurological deterioration: 8.5% versus 8.0%, P=0.830; any intracerebral hemorrhage or subarachnoid hemorrhage: 12.5% versus 13.3%, P=0.792; symptomatic intracranial hemorrhage: 2.6% versus 3.4%, P=0.598; and 3-month death: 9.8% versus 9.2%, P=0.844) outcomes. CONCLUSIONS: We found similar safety and efficacy outcomes after acute reperfusion treatment in disabling versus nondisabling mild EVT-tVO; our findings suggest to adopt similar acute treatment approaches in the 2 groups. Randomized data are needed to clarify the best reperfusion treatment in mild EVT-tVO.

Association of the careggi collateral score with radiological outcomes after thrombectomy for stroke with an occlusion of the middle cerebral artery.

We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24 h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24 h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion.

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

OBJECTIVE: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19). METHODS: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period. RESULTS: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, p = 0.009) on admission. CONCLUSIONS: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

An Interoperability Platform Enabling Reuse of Electronic Health Records for Signal Verification Studies.

Depending mostly on voluntarily sent spontaneous reports, pharmacovigilance studies are hampered by low quantity and quality of patient data. Our objective is to improve postmarket safety studies by enabling safety analysts to seamlessly access a wide range of EHR sources for collecting deidentified medical data sets of selected patient populations and tracing the reported incidents back to original EHRs. We have developed an ontological framework where EHR sources and target clinical research systems can continue using their own local data models, interfaces, and terminology systems, while structural interoperability and Semantic Interoperability are handled through rule-based reasoning on formal representations of different models and terminology systems maintained in the SALUS Semantic Resource Set. SALUS Common Information Model at the core of this set acts as the common mediator. We demonstrate the capabilities of our framework through one of the SALUS safety analysis tools, namely, the Case Series Characterization Tool, which have been deployed on top of regional EHR Data Warehouse of the Lombardy Region containing about 1 billion records from 16 million patients and validated by several pharmacovigilance researchers with real-life cases. The results confirm significant improvements in signal detection and evaluation compared to traditional methods with the missing background information.

Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies.

Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR) data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases.

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study.

BACKGROUND AND PURPOSE: The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. METHODS: ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0-2) or unfavorable (score of 3-6). Safety outcomes were death and any intracranial bleeding. RESULTS: Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03-3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36-3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87-58.71; P=0.068) in the cases than in the controls. CONCLUSIONS: In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Prognostic value of multimodal evoked potentials in multiple sclerosis: the EP score.

Evoked potentials (EPs) have long been used as diagnostic tools in multiple sclerosis (MS), although their importance decreased as magnetic resonance imaging (MRI) became available. However, the prognostic value of EPs in MS has not been completely established. The aim of the study was to analyze the prognostic significance of EPs in a cohort of MS cases. From the Verona University Hospital MS Clinic database we retrospectively identified 80 MS patients who underwent a complete neurophysiological evaluation, including visual, brain stem, somatosensory and motor EPs and who were followed for at least 5 years after the study. EPs abnormalities were quantified through an index of global EPs alteration (EP score). The relationship between EP score and disability in terms of Expanded Disability Status Scale (EDSS) was analyzed by the Kaplan-Meier survival method and Spearman ρ correlation coefficient. ROC curves were used to determine the best EP score cut off to predict different EDSS endpoints. For each endpoint, sensitivity, specificity, positive and negative predictive value of EP score were calculated. We found a significant correlation (p < 0.001) between EP score and EDSS score at the time of neurophysiological study and at 1, 3 and 5 years of follow-up, particularly for motor and somatosensory EPs. Kaplan-Meier curves confirmed an increased risk of disability in those patients with EP score higher than the median value. EP score of 8 or 9 showed the highest sensitivity and specificity in predicting EDSS 4.0 and 6.0. EPs are reliable procedures to predict disability in MS patients. The correlation between EPs abnormalities and EDSS is higher than between conventional MRI and EDSS.

Azathioprine in multiple sclerosis.

Azathioprine is an immunosuppressive and steroid-sparing purine analogue, used in the treatment of several autoimmune diseases. In multiple sclerosis, available evidence suggests that oral azathioprine reduces relapse rates, provides a slight benefit on disability, and reduces new inflammatory lesions. Here, we focus on molecular mechanisms of Azathioprine and on its usefulness in multiple sclerosis.

Aspirin desensitization in patients undergoing percutaneous coronary interventions with stent implantation.

The aim of this study was to test the safety and efficacy of a novel rapid desensitization procedure in patients with acetylsalicylic acid sensitivity and coronary artery disease who underwent cardiac catheterization and coronary stent implantation. Aspirin plays a key role in the secondary prevention of atherothrombotic events and thrombotic complications after stent implantation. Aspirin sensitivity not only limits patients to benefit from the long-term use of this antiplatelet agent but is also often an impediment to the implantation of bare-metal and drug-eluting coronary stents. Of 1,014 patients admitted for cardiac catheterization, 26 (2.6%) had histories of aspirin sensitivity characterized by respiratory or cutaneous manifestations (none had previous anaphylactic reactions); of these, 61.5% presented with acute coronary syndromes. All patients underwent a novel rapid desensitization challenge procedure before cardiac catheterization, except for those presenting with ST-elevation myocardial infarctions (n = 4), who underwent desensitization before hospital discharge. The desensitization procedure involved the oral administration of 6 sequential doses of aspirin (1, 5, 10, 20, 40, and 100 mg) over 5.5 hours without the use of corticosteroids or antihistamines. Patients were followed for 1 year to assess compliance with aspirin therapy and adverse events. The desensitization procedure was successful in 23 patients (88.5%). Percutaneous coronary intervention with stent implantation was performed in 22 patients (1.8 stents/patient). Drug-eluting stents were used in all patients except those who underwent primary percutaneous coronary intervention (n = 3), in whom bare-metal stents were used. Multivessel percutaneous coronary intervention was performed in 30.7% of patients. At follow-up, all patients who successfully responded to the desensitization procedure tolerated aspirin well, without developing allergic reactions. Aspirin was withdrawn in only 1 patient, because of a peptic ulcer. In conclusion, rapid desensitization is safe and highly effective in patients with aspirin sensitivity and coronary artery disease who undergo coronary stent implantation, including those who receive drug-eluting stents.