Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results.

AIM: To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. METHODS AND RESULTS: One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ 1, 2, 4, and 6 h after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 h after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N = 32) as compared with patients not receiving morphine (N = 98; PRU = 187 [70-217]) vs. 73 [7-187]; P = 0.012). In patients with morphine, 1-h PRU values were similar between study groups (192 [114-236] vs. 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-h PRU values were not significantly different between study groups (69 [8-152] vs. 110 [6-193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4, and 6 h after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. CONCLUSIONS: There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.

Recanalisation theraphy for acute ischemic stroke in cancer patients.

To date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42-20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.

Hyposmia and Dysgeusia in COVID-19: Indication to Swab Test and Clue of CNS Involvement.

OBJECTIVE: To evaluate the prevalence of hyposmia and dysgeusia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their temporal relationship with the onset of other symptoms. METHODS: We performed a retrospective analysis of patients admitted during the month of March 2020 to the nonintensive COVID unit of Udine University Hospital on the basis of a positive swab test and/or of clinical-radiologic signs of SARS-CoV-2 infection. Patients were interviewed with a standardized questionnaire. Clinical and laboratory data were collected. Data were analyzed with descriptive statistics, and results expressed as point estimates and 95% confidence intervals (CIs). RESULTS: Of 141 patients admitted, 93 were interviewed. Hyposmia and dysgeusia were present in 58 cases (62.4%). In 22.4% of them, olfactory and gustatory impairment clearly preceded systemic symptoms. The presence of active smoking was very limited in both groups: 8.6% in hyposmic vs 2.9% in normosmic patients (odds ratio 3.2; 95% CI 0.3-28.6). Moreover, total leukocytes and neutrophils count were respectively 23% (effect estimate 1.23; 95% CI 1.06-1.42) and 29% (effect estimate 1.29; 95% CI 1.07-1.54) lower in the hyposmic cohort. No difference was found for other inflammatory biomarkers. CONCLUSIONS: Hyposmia and dysgeusia are common in SARS-CoV-2 infection and can precede systemic symptoms. They should be actively searched and prompt close monitoring and isolation until infection is confirmed or disproven. The lower number of total leukocytes and neutrophils in hyposmic patients might indicate an early-phase virus-induced cytopenia.

Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review.

OBJECTIVE: To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs). METHODS: Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, 59%; p < 0.001). Anti-programmed cell death protein 1/programmed cell death ligand 1 was more frequent in myasthenic syndromes (50/58, 86%; p = 0.005) and less common in meningitis (2/13, 15%; p < 0.001) and cranial neuropathies (13/31, 42%; p = 0.005). Anti-cytotoxic T-lymphocyte antigen-4 ICIs were more frequent in meningitis (8/13, 62%; p < 0.001) and less common in encephalitis (2/56, 4%; p = 0.009) and myositis (12/136, 9%; p = 0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; p = 0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; p = 0.003) and less common in encephalitis (19/56, 34%; p = 0.001). The highest mortality rate was reached in myasthenic syndromes (28%). CONCLUSION: Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.

Epidemiology of paraneoplastic neurological syndromes: a population-based study.

BACKGROUND: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy. METHODS: We performed a 9-year (2009-2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated. RESULTS: We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26-90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009-2011), 0.81/100,000 person-years (2012-2014) to 1.22/100,000 person-years (2015-2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001). CONCLUSIONS: This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.

Stroke-Like Presentation of Paraneoplastic Cerebellar Degeneration: a Single-Center Experience and Review of the Literature.

Paraneoplastic cerebellar degeneration (PCD) is usually thought to have a subacute progression over several weeks. We report herein incidence and clinical features of hyperacute onset PCD, a vertebrobasilar stroke mimic. We performed a retrospective analysis of all suspected PCD cases referred to the Udine University Hospital between 2009 and 2017. Our center provides the only neuroimmunology laboratory for three provinces of the Friuli-Venezia Giulia region, Italy (983,190 people as of January 1, 2017). Inclusion criteria were (1) abrupt onset of neurological symptoms; (2) initial consideration of a vascular etiology; (3) final diagnosis of "definite PCD." We also carried out a systematic review of the literature in order to identify previous stroke-like PCD cases. Between 2009 and 2017, 24 patients received a final diagnosis of PCD. The age-standardized incidence rate of PCD was 0.22/100,000 person-years. Two cases (8.3%) had a stroke-like onset, with an incidence of 0.02/100,000 person-years. Additionally, 10 previously reported stroke-like PCD cases were identified. Among all cases (n = 12), 67% were female; median age was 51 years (range, 22-69). An associated cancer was discovered in all cases. Brain imaging was normal in most (75%) of the patients. Cerebrospinal fluid (CSF) analysis showed inflammatory alterations in 73% of the cases. Cancer treatment was more effective than immunotherapy in improving the neurological syndrome. Typical patients with hyperacute PCD are middle-aged women with normal brain imaging, inflammatory markers in CSF, and cancer. Surgery of the underlying cancer is probably the best treatment. PCD must be considered in the differential diagnosis of acute-onset ataxia and/or vertigo.