Oral Antiplatelet Therapy for Secondary Prevention of Non-Cardioembolic Ischemic Cerebrovascular Events

Stroke is the leading cause of disability and mortality worldwide. After an acute cerebrovascular ischemia, recurrent vascular events, including recurrent stroke or transient ischemic accidents (TIA), occur in around 20% of cases within the first 3 months. In order to minimize this percentage, antiplatelet therapy may play a key role in the management of non-cardioembolic cerebrovascular events. This review will focus on the current evidence of antiplatelet therapies most commonly discussed in practice guidelines and used in clinical practice for the treatment of stroke/TIA complications. The antiplatelet therapies most commonly used and discussed are as follows: aspirin, clopidogrel, and ticagrelor

Safety and efficacy of Rotigotine in hospedalized patients with Vascular Parkinsonism aged 75 and older. Effects on movement, praxis capacities, time-space orientation, quality of life and adherence to medical therapy

In hospitals without stroke unit Department, the patients with acute ischemic stroke are stabilized in First Aid and sent to the Department of Internal Medicine. During the hospedalization period the patients undergo medical therapy for the stabilization of hemodynamic parameters and instrumental examinations for the determination of cardiovascular risk and thromboembolic evaluation. All patients are subjected to multidimensional evaluation of cognitive, praxis capacities, spatial-temporal orientation, quality of life and adherence to medical therapy. The aim of this study is evaluate the effect of Rotigotine patch on the impairment of neuro-cognitive capacity throught a continuous dopaminergic stimulation with transdermal administration. We have observed 19 patients (10 male and 9 female with range age 75-92 yrs) with Acute Ischemic Stroke stabilized in First Aid Depatment. The outcomes were the neurological changes from the baseline to 7 days in the clinical summury score on MMSE (on a scale from 0 to 30, with higher scores indicating fewer symtoms and lower physical limitations), Morinsky scale (on scale from 0 to 8, indicating adherence to therapy) and swallowing test (acts/minute). During the first week the patients were undergone to treatment with rotigotine 2 mg/24 hours. At the end of the treatment we obtained a statistically significant correlation about improvement of MMSE, Morinsky scale and swallowing test from a basal value. Rotigotine transdermal patches could be a new useful approach in the treatment of elderly hospetalized patients with acute ischaemic stroke correlated with cognitive impairment. Data shown that low dose of rotigotine patch could improves cognitive and praxis functions and therefore the quality of life of the hospitalized elderly patients. Rotigotine was effective and well-tolerated when used in routine clinical practice. Our data gave comfortable results but further evaluation are needed to have conclusive results

Switch Strategy from Direct Aspiration First Pass Technique to Solumbra Improves Technical Outcome in Endovascularly Treated Stroke

Background: The major endovascular mechanic thrombectomy (MT) techniques are: Stent-Retriever (SR), aspiration first pass technique (ADAPT) and Solumbra (Aspiration + SR), which are interchangeable (defined as switching strategy (SS)). The purpose of this study is to report the added value of switching from ADAPT to Solumbra in unsuccessful revascularization stroke patients. Methods: This is a retrospective, single center, pragmatic, cohort study. From December 2017 to November 2019, 935 consecutive patients were admitted to the Stroke Unit and 176/935 (18.8%) were eligible for MT. In 135/176 (76.7%) patients, ADAPT was used as the first-line strategy. SS was defined as the difference between first technique adopted and the final technique. Revascularization was evaluated with modified Thrombolysis In Cerebral Infarction (TICI) with success defined as mTICI ≥ 2b. Procedural time (PT) and time to reperfusion (TTR) were recorded. Results: Stroke involved: Anterior circulation in 121/135 (89.6%) patients and posterior circulation in 14/135 (10.4%) patients. ADAPT was the most common first-line technique vs. both SR and Solumbra (135/176 (76.7%) vs. 10/176 (5.7%) vs. 31/176 (17.6%), respectively). In 28/135 (20.7%) patients, the mTICI was ≤ 2a requiring switch to Solumbra. The vessel’s diameter positively predicted SS result (odd ratio (OR) 1.12, confidence of interval (CI) 95% 1.03–1.22; p = 0.006). The mean number of passes before SS was 2.0 ± 1.2. ADAPT to Solumbra improved successful revascularization by 13.3% (107/135 (79.3%) vs. 125/135 (92.6%)). PT was superior for SS comparing with ADAPT (71.1 min (CI 95% 53.2–109.0) vs. 40.0 min (CI 95% 35.0–45.2); p = 0.0004), although, TTR was similar (324.1 min (CI 95% 311.4–387.0) vs. 311.4 min (CI 95% 285.5–338.7); p = 0.23). Conclusion: Successful revascularization was improved by 13.3% after switching form ADAPT to Solumbra (final mTICI ≥ 2b was 92.6%). Vessel’s diameter positively predicted recourse to SS

The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma

Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as follows: 1) treatment-naïve, frail ≥65y, or unfit ≥85y; and 2) relapsed/refractory (R/R) ≥55y. Data were prospectively collected from six Italian centres and compared for efficacy to two reference groups, treated with established iv Rituximab-CHT in 1st and 2nd line respectively. Results from April-2011 to March-2018, 17/51(33%) naïve, 21/51(41%) refractory and 13/51(25.5%) relapsed patients started DEVEC; 39/51(76.5%) were de-novo DLBCL; 10/51(19.6%) transformed-DLBCL and 2/51(3.9%) unclassifiable-DLBCL/classical-Hodgkin-lymphoma. The median age was 85y (range=77-93) and 78y (range=57-91) in naïve and R/R respectively and overall the DEVEC patients had very poor features compared to the reference. The rate of grade≥3 haematological-AEs was 43%(95CI=29-58%): G3-neutropenia was the most frequent; grade≥3 extra-haematological-AEs was 13.7% (95%CI=5.4-25.9%), the most frequent was infection. One-year OS and PFS were 67% and 61% for naive, 60% and 50% for reference-naïve respectively; Cox proportional hazard ratio (Cox-PH-ratio) for OS and PFS were 0.69 (95%CI=0.27-1.76;p=.441) and 0.68 (95%CI=0.28-1.62;p=.381) respectively. One-year OS and PFS were 48% and 39% in the R/R, 36% and 17% in the reference-R/R respectively; Cox-PH-ratio for OS and PFS, were 0.76 (95%CI=0.42-1.40; p=.386) and 0.48 (95%CI=0.28-0.82; p=.007) respectively. Conclusion The favourable activity of DEVEC compared to a real-life series and the convenience of an oral administration, may possibly lay the groundwork for a paradigm-shift in the treatment of elderly DLBCL

Correction: Bocci et al. Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma. <i>J. Clin. Med.</i> 2022, <i>11</i>, 7162

In the original publication [...

Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma

The upfront treatment of very elderly and frail patients with diffuse large B-cell lymphoma (DLBCL) is still a matter of debate. Herein, we report results of the metronomic all-oral DEVEC [prednisolone/deltacortene®, vinorelbine (VNR), etoposide (ETO), cyclophosphamide] combined with i.v. rituximab (R). This schedule was administered as a first line therapy in 22 elderly/frail DLBCL subjects (median age = 84.5 years). In 17/22 (77%) patients, the Elderly-IPI-score was high. After a median follow-up of 24 months, 15 patients had died: seven (50%) for causes unrelated to DLBCL or its treatment, six (40%) for progression, and two (13%) for multiorgan failure. Six treatment-pertinent serious-adverse-events occurred. At the end of induction, 14/22 (64%) achieved complete remission; overall survival and event-free survival at 24 months were both 54% (95% CI = 32–72%), while the time to progression was 74% (95% CI = 48–88%). Furthermore, antiproliferative and proapoptotic assays were performed on DLBCL/OCI-LY3 cell-line using metronomic VNR and ETO and their combination. Both metronomic VNR and ETO had concentration-dependent antiproliferative (IC50 = 0.036 ± 0.01 nM and 7.9 ± 3.6 nM, respectively), and proapoptotic activities in DLBCL cells. Co-administration of the two drugs showed a strong synergism (combination index 1) against cell proliferation and survival. This low-dose schedule seems to compare favourably with intravenous-CHEMO protocols used in the same subset. Indeed, the high synergism shown by metronomic VRN+ETO in in vitro studies, explains the remarkable clinical responses and it allows significant dose reductions

Cluster analysis of weather and pollution features and its role in predicting acute cardiac or cerebrovascular events

Background: Despite mounting evidence, the impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events. Methods: Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from 3 tertiary care center from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for enviromental protection, and from the Metereological Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rate of acute cardiac and cerebrovascular events with Poisson models. Results: As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated 4 separate clusters: mostly winter days with low temperatures and high ozone concentrations (cluster 1, n=60, 5.1%), days with moderately high temperatures and low pollutants concentrations (cluster 2, n=419, 35.8%), mostly summer and spring days with high temperatures and high ozone concentrations (cluster 3, n=673, 57.6%), and mostly winter days with low temperatures and low ozone concentrations (cluster 4, n=17, 1.5%). Overall cluster-wise comparisons showed significant overall differences in adverse cardiac and cerebrovascular events (p&lt;0.001), as well as in cerebrovascular events (p&lt;0.001) and strokes (p=0.001). Between-cluster comparisons showed that Cluster 1 was associated with an increased risk of any event, cerebrovascular events, and strokes in comparison to Cluster 2, Cluster 3 and Cluster 4 (all p&lt;0.05), as well as AMI in comparison to Cluster 3 (p=0.047). In addition, Cluster 2 was associated with a higher risk of strokes in comparison to Cluster 4 (p=0.030). Analysis adjusting for season confirmed the increased risk of any event, cerebrovascular events and strokes for Cluster 1 and Cluster 2. Conclusions: Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increases risk of acute cardiovascular events, especially cerebrovascular events. These findings may improve collective and individual risk prediction and prevention

Impact of weather and pollution on the rate of cerebrovascular events in a large metropolitan area

BACKGROUND: Despite mounting evidence, there is uncertainty on the impact of the interplay between weather and pollution features on the risk of acute cerebrovascular events (CVE). We aimed at appraising role of weather and pollution on the daily risk of CVE.METHODS: Anonymized data from a hub CVE center in a large metropolitan area were collected and analyzed according to weather (temperature. pressure. humidity, and rainfall) and pollution (carbon monoxide [CO]. nitrogen dioxide [NO2], nitrogen oxides [NOX], ozone [O-3], and particulate matter [PM]) on the same and the preceding days. Poisson regression and time series analyses were used to appraise the association between environmental features and daily CVE, distinguishing also several subtypes of events.RESULTS: We included a total of 2534 days, with 1363 days having ?1 CVE, from 2012 to 2017. Average daily rate was 1.56 (95% confidence interval: 1.49; 1.63) for CVE, with other event rates ranging between 1.42 for stroke and 0.01 for ruptured intracranial aneurysm. Significant associations were found between CVE and temperature, pressure, CO, NO2,NOX, O-3, and PM &lt;10 mu m (all P&lt;0.05), whereas less stringent associations were found for humidity, rainfall, and PM &lt;2.5 mu m. Time series analysis exploring lag suggested that associations were stronger at same-day analysis (lag 0), but even environmental features predating several days or weeks were significantly associated with events. Multivariable analysis suggested that CO (point estimate 1.362 [1.011; 1.836], P=0.042) and NO2 (1.011 [1.005; 1.016], P&lt;0.001) were the strongest independent predictors of CVE.CONCLUSIONS: Environmental features are significantly associated with CVE, even several days before the actual event. Levels of CO and NO2 can be potentially leveraged for population-level interventions to reduce the burden of CVE