Beyond RCTs: Short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack.

BACKGROUND AND PURPOSE: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs. METHODS: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment. RESULTS: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding. CONCLUSIONS: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.

Cutting-Edge Techniques and Drugs for the Treatment of Pulmonary Embolism: Current Knowledge and Future Perspectives.

Pulmonary embolism (PE) is a potentially life-threatening condition requiring prompt diagnosis and treatment. Recent advances have led to the development of newer techniques and drugs aimed at improving PE management, reducing its associated morbidity and mortality and the complications related to anticoagulation. This review provides an overview of the current knowledge and future perspectives on PE treatment. Anticoagulation represents the first-line treatment of hemodynamically stable PE, direct oral anticoagulants being a safe and effective alternative to traditional anticoagulation: these drugs have a rapid onset of action, predictable pharmacokinetics, and low bleeding risk. Systemic fibrinolysis is suggested in patients with cardiac arrest, refractory hypotension, or shock due to PE. With this narrative review, we aim to assess the state of the art of newer techniques and drugs that could radically improve PE management in the near future: (i) mechanical thrombectomy and pulmonary embolectomy are promising techniques reserved to patients with massive PE and contraindications or failure to systemic thrombolysis; (ii) catheter-directed thrombolysis is a minimally invasive approach that can be suggested for the treatment of massive or submassive PE, but the lack of large, randomized controlled trials represents a limitation to widespread use; (iii) novel pharmacological approaches, by agents inhibiting thrombin-activatable fibrinolysis inhibitor, factor Xia, and the complement cascade, are currently under investigation to improve PE-related outcomes in specific settings.

Impact of carotid stenosis on the outcome of stroke patients submitted to reperfusion treatments: a narrative review.

Intravenous thrombolysis (IT) and mechanical thrombectomy (MD) are the two interventional approaches that have changed the outcome of patients with acute ischemic stroke (AIS). Ipsilateral and contralateral carotid stenosis (ICS, CCS) play an important role in regulating cerebral hemodynamics, both in chronic and acute situations such as AIS. Several studies have explored their role in the incidence and severity of stroke, but very few have investigated the possible impact of ICS and CCS on the efficacy of interventional procedures. The purpose of this review was to I) highlight the incidence and prevalence of carotid stenosis (CS); II) assess the impact of ICS and CCS on cerebral hemodynamics; III) evaluate the effect of carotid stenosis on the efficacy of interventional therapies (IT and MT) for AIS; and IV) report therapeutic complications related to CS. We searched PubMed/Medline for case reports, reviews, and original research articles on English-language review topics during the period from January 1, 2000 to October 1, 2023. CS is associated with 15-20 % of the total number of AIS. ICS and CCS had a negative influence on both cerebral hemodynamics before AIS and outcome after interventional procedures (IT, MT alone or in bridging). Available data on cerebral hemodynamics and efficacy of interventional therapies for AIS suggest a negative role of CS. Therefore, early diagnosis of CS may be considered relevant to preventive and post-stroke treatment strategies.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.

INTRODUCTION: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities. METHODS: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates. RESULTS: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period. PRIMARY ENDPOINT: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason. CONCLUSION: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study.

OBJECTIVE/BACKGROUND: sleep alterations strongly influence migraine severity. Prophylactic therapies have a major impact on migraine frequency and associated symptoms. The study purpose was to compare the impact of oral drug therapies or gene-related anti-calcitonin monoclonal antibodies (anti-CGRP mAbs) on sleep alterations. We also evaluated which drug therapies are more effective on sleep quality and the different impact on migraine frequency and life quality. PATIENTS/METHODS: this is a multicenter, prospective study conducted in three specialized headache centers (Marche Polytechnic University, Ancona; University of Palermo, Palermo; Fondazione Policlinico Campus Bio-Medico, Rome). At baseline, we assigned migraine patients to preventive therapy with first-line drugs or anti-CGRP mAbs. The Pittsburgh Sleep Quality Index (PSQI) and Migraine Disability Assessment (MIDAS) scales were administered. After three months, we re-evaluated the patients with the same scales. RESULTS: 214 patients were enrolled. Any prophylaxis was significantly associated with a reduction in PSQI score (mean difference 1.841; 95%CI:1.413-2.269; p < 0.0001), most significantly in the anti-CGRP mAb group (mean difference 1.49; 95%CI:2.617-0.366; p = 0.010). Anti-CGRP mAbs resulted in significant improvement in migraine severity and MIDAS scores. Among oral therapies, calcium antagonists and antidepressants were the most effective in reducing PSQI score between T0 and T1 (p = 0.042; p = 0.049; p < 0.0001, respectively). CONCLUSIONS: anti-CGRP mAbs revitalized the management of migraine with stable and well-documented efficacy. Our data also suggest that anti-CGRP mAbs result in a positive effect on sleep quality, with a significant improvement in PSQI scores. Knowing the relevant impact of sleep disruption on migraine severity, these data could help for the management of migraine patients.

Effects of a Single Session of OnabotulinumtoxinA Therapy on Sleep Quality and Psychological Measures: Preliminary Findings in a Population of Chronic Migraineurs.

Chronic migraine is a burdensome condition, and onabotulinumtoxinA is revealed to be an effective therapy. Migraine shows a bidirectional relationship with sleep, but the effects of preventive therapies on sleep quality are poorly studied. This study aims to evaluate the effects of a single session of onabotulinumtoxinA on patients' sleep quality and correlates the results with measures of comorbid anxiety/depression. Patients completed self-administrable questionnaires about sleep quality (Pittsburgh Sleep Quality Index-PSQI) and psychological symptoms (Beck Depression Inventory, 2nd edition-BDI-II-and Hospital Anxiety and Depression Scale-HADS-subscales "a" and "d" for anxiety and depression, respectively), and reported migraine frequency at baseline and after 12 weeks. The 42 included patients showed a significant reduction in migraine days (from 20.6 ± 6.0 to 13.6 ± 6.2, p < 0.001), while no changes were observed in sleep quality (PSQI score from 11.0 ± 5.0 to 9.8 ± 4.6, p = 0.277) or psychological measures (BDI-II from 16.7 ± 10.2 to 15.7 ± 10.3, p = 0.678; HADS-a from 10.3 ± 4.8 to 9.3 ± 5.5, p = 0.492; and HADS-d from 7.2 ± 3.9 to 7.1 ± 5.0, p = 0.901). On the other hand, a strong correlation among PSQI, BDI-II, HADS-a, and HADS-d scores (p < 0.001, rho > 0.7) was found. Despite its efficacy in migraine prevention, a single session of onabotulinumtoxinA was not able to affect patients' sleep quality or their psychological symptoms.

The Relationship between Post-COVID Syndrome and the Burden of Comorbidities Assessed Using the Charlson Comorbidity Index.

Introduction: The post-COVID-19 syndrome is a clinical entity characterized by the manifestation of signs and symptoms that develop after the acute phase of COVID-19, which persist for a duration of more than 12 weeks and are not explained by any alternative diagnosis. It has been observed that individuals with pre-existing chronic diseases, including cardiovascular and pulmonary diseases, are at a greater risk of developing post-COVID-19 syndrome. The Charlson Comorbidity Index (CCI) is a useful tool employed to evaluate the burden of comorbidities and predict the prognosis of patients with post-COVID-19 syndrome. The present study aims to assess whether the burden of comorbidities, evaluated using the CCI, correlates with post-COVID-19 syndrome. Materials and Methods: Between 21 April 2020 and 15 May 2023, we enrolled all consecutive outpatients with previous COVID-19 admissions to a post-acute day-hospital service three months after a negative SARS-CoV-2 molecular test. We assessed age, sex, BMI, acute COVID-19 and post-COVID-19 signs, and symptoms and calculated CCI according to its current definition. Post-COVID-19 syndrome was defined as the persistence of at least one sign or symptom lasting more than 12 weeks after COVID-19 resolution and not explained by an alternative diagnosis. The relationship between post-COVID-19 and CCI was explored first with the chi-squared test, then with different binary logistic regression models. We considered significant values of p lower than 0.05. Results: We obtained a cohort of 3636 patients and observed a significant association between the number of post-COVID-19 symptoms and CCI. Patients developing post-COVID-19 were more commonly affected by a greater burden of comorbidities. Patients with at least one CCI point had an increased risk of post-COVID-19 syndrome (OR:2.961; 95%CI: 2.269-3.863; p < 0.0001), which increased further for CCI ≥ 4 (OR:6.062; 95%CI: 3.163-11.618; p < 0.0001). Conclusions: Patients affected by post-COVID-19 show a greater clinical complexity and a larger burden of comorbidities, synthesized by a higher CCI; moreover, a higher CCI seems to correlate with an increasing post-COVID-19 risk, being the presence of ≥1 or ≥4 CCI points associated with a 3-fold and 6-fold increased risk of post-COVID-19 syndrome, respectively.

Ipsilateral and contralateral carotid stenosis contribute to the outcome of reperfusion treatment for ischemic stroke.

Introduction: Ipsilateral and contralateral carotid stenosis (ICS, CCS) influence acute ischemic stroke (AIS) severity and prognosis. Few data are available about their impact on reperfusion therapies efficacy. Aim of this study was to evaluate the impact of ICS and CCS on the effect of intravenous thrombolysis (IT), mechanical thrombectomy (MT) or both and of antiplatelet therapy (AT). Methods: We enrolled all the consecutive patients admitted for AIS to our stroke unit and submitted to IT, MT, IT+MT, or AT. We established the presence of a significant ICS or CCS (≥70%) by ultrasound examination or brain angio-CT, or MRI. Clinical and instrumental information were collected; delta National Institutes of Health Stroke Scale (NIHSS) from pre-treatment to patients' discharge was employed as the main outcome measure. Results: In total, 460 subjects were enrolled, 86 with ICS and 38 with CCS. We observed a significant linear trend of delta (NIHSS) between carotid stenosis categories for patients undergoing IT (p = 0.011), MT (p = 0.046), and MT+IT (p = 0.040), but no significant trend among subjects receiving no reperfusion treatments was observed (p = 0.174). Discussion: According to our findings, ICS and CCS negatively influence AIS patients' outcome treated by interventional therapies. ICS might exert an unfavorable effect both by cerebral hypoperfusion and by continuous microembolization toward ischemic area, while CCS is probable involved in reducing the collateral circles effectiveness. The importance of early carotid stenosis detection and treatment should then be reevaluated not only to manage the prevention approaches but also to obtain insights about post-stroke treatment strategies efficacy.

Quantitative and Qualitative Pain Evaluation in Response to OnabotulinumtoxinA for Chronic Migraine: An Observational Real-Life Study.

(1) Background: Randomized controlled trials and real-life studies demonstrated the efficacy of OnabotulinumtoxinA (OBT-A) for CM prevention. However, no studies specifically addressed its effect on pain's quantitative intensity and qualitative characteristics. (2) Methods: This is an ambispective study: a post-hoc retrospective analysis of real-life prospectively collected data from two Italian headache centers on CM patients treated with OBT-A over one year (i.e., Cy1-4). The primary endpoint was the changes in pain intensity (Numeric Rating Scale, NRS; the Present Pain Intensity (PPI) scale, the 6-point Behavioral Rating Scale (BRS-6)) and quality scale (the short-form McGill Pain Questionnaire (SF-MPQ)) scores. We also assessed the relationship between changes in intensity and quality of pain and disability scale (MIDAS; HIT-6) scores, monthly headache days (MHDs), and monthly acute medication intake (MAMI) (3) Results: We retrieved 152 cases (51.5 years SD 11.3, 80.3% females). From baseline to Cy-4, MHDs, MAMI, NRS, PPI, and BRS-6 scores decreased (consistently p < 0.001). Only the throbbing (p = 0.004), splitting (p = 0.018), and sickening (p = 0.017) qualities of pain collected in the SF-MPQ were reduced. Score variations in MIDAS related to those in PPI scales (p = 0.035), in the BRS-6 (p = 0.001), and in the NRS (p = 0.003). Similarly, HIT-6 score changes related to PPI score modifications (p = 0.027), in BRS-6 (p = 0.001) and NRS (p = 0.006). Conversely, MAMI variation was not associated with qualitative or quantitative pain score modifications except BRS-6 (p = 0.018). (4) Conclusions: Our study shows that OBT-A alleviates migraine by reducing its impact on multiple aspects, such as frequency, disability, and pain intensity. The beneficial effect on pain intensity seems specific to pain characteristics related to C-fiber transmission and is associated with a reduction in migraine-related disability.

Divergence Between Clinical Trial Evidence and Actual Practice in Use of Dual Antiplatelet Therapy After Transient Ischemic Attack and Minor Stroke.

BACKGROUND: Randomized controlled trials (RCTs) proved that short-term (21-90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. METHODS: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. RESULTS: We evaluated 1070 patients, who had 72 (interquartile range, 62-79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <4 and 252 (74.7%) because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <6 and no symptomatic arterial stenosis. Additionally, 144 (13.5%) patients would have been excluded because of revascularization procedures. Three hundred forty-five patients (32.2%) did not follow the RCT procedures because of late (>24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. CONCLUSIONS: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05476081.

Stroke territory and atherosclerosis in ischemic stroke patients with a history of migraine with aura.

Introduction: The mechanisms subtending the increased stroke risk in migraine with aura (MA) are not fully understood. Our study aims to evaluate if the clinical profile in stroke patients with MA differentiates from those without MA. Methods: We retrieved the prospective registered electronic clinical dossiers of adult patients younger than 60 years with acute ischemic stroke admitted in four hospitals between January 2016 and June 2022. Patients were classified by the history of MA (MA+ and MA-). Results: We identified 851 stroke patients (59 MA+, 6.9%). Compared to MA-, MA+ patients were characterized by younger age (44.0 ± 10.6 vs 50.1 ± 8.2 years), female sex (59.3% vs 29.0%), and affected by cryptogenic (OR 2.594 95% CI 1.483-4.537), and cerebellar stroke (OR 3.218 95% CI 1.657-6.250; p ≤ 0.001 for all comparisons). After adjusting for age and sex, MA+ patients presented less frequently hypertension (OR 0.349 95% CI 0.167-0.470; p=0.005) and dyslipidemia (OR 0.523 95% CI 0.280-0.974; p = 0.041). After adjusting also for risk factors, the MA+ group had less frequently symptomatic large vessel stenosis (OR 0.126 95% CI 0.017-0,924; p = 0.042) and clinical atherosclerosis (OR 0.103 95% CI 0.014-0.761; p = 0.026), while intima-media thickness did not differ (p = 0.395). Discussion: Cryptogenic and cerebellar stroke and fewer vascular risk factors and clinical atherosclerosis seem to characterize stroke patients with MA.

Prevention and treatment of catheter-related venous thrombosis in long-term parenteral nutrition: A SINuC position statement.

The implementation of long-term parenteral nutrition (PN) often requires the placement of central venous access, a procedure that carries a considerable risk of catheter-related venous thrombosis (CRT). The occurrence of CRT represents a major event in the natural history of patients in PN since it can lead to central venous access loss and PN failure. Despite the importance of this topic in clinical nutrition, the prevention and treatment of CRT in PN represents one of the "gray areas" of the literature of the presence of few randomized controlled clinical trials and the generally low level of evidence of published scientific papers. Through a narrative review of the literature and a Delphi consensus, the Italian Society of Clinical Nutrition and Metabolism (SINuC) aimed to collect some practical recommendations regarding the current state-of-the-art in the prevention, diagnosis, and treatment of CRT in patients undergoing long-term PN.

Impact of Dimethylfumarate on Sleep in Multiple Sclerosis Patients: An Actigraphic Study.

BACKGROUND: Sleep disorders in multiple sclerosis (MS) patients are common. Dimethylfumarate is an oral disease-modifying drug (DMT), whose impact on sleep is unknown. OBJECTIVE: The aim of this study was to characterize actigraphic patterns in MS patients treated with dimethylfumarate. METHODS: Twenty relapsing-remitting MS patients with low to a mild disability, aged 20-50y, treated with dimethylfumarate for more than 6 months, were enrolled. All subjects had no history of sleep disorders. Actigraphy was used to study sleep patterns during a seven-day period. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Twenty healthy subjects served as controls. RESULTS: Our results showed statistically significant differences between some actigraphic patterns in MS patients treated with dimethylfumarate and healthy subjects, but the values for patients were still within normal limits. PSQI score was higher in MS patients compared to controls. CONCLUSION: Our findings suggest that dimethylfumarate, an oral DMT with a favourable benefit-risk profile, does not strongly alter sleep patterns in MS patients with low to mild disability and with no history of sleep disorders. Actigraphy is a simple diagnostic tool, able to support an objective measure of sleep parameters. The simplicity of application may allow considering its use for a screening of sleep disorders in MS patients.

Efficacy of Onabotulinum Toxin A on Obsessive-Compulsive Traits in a Population of Chronic Migraine Patients.

BACKGROUND: Drug addiction may play an important role in chronic migraine (CM) with medication-overuse headache (MOH). Psychiatric diseases are associated with CM, but data regarding obsessive-compulsive disorder (OCD) are lacking. We aimed to establish the prevalence of OCD traits in CM patients with MOH and the impact on onabotulinum toxin A (OBT-A) treatment. METHODS: A total of 75 patients with CM and MOH undergoing treatment with OBT-A in our Headache Centre were evaluated. At baseline and after four injection sessions, we assessed the migraine burden and the presence of OCD traits with the Obsessive-Compulsive Inventory-Revised (OCI-R) test. RESULTS: At baseline, 28% of patients had OCI-R scores compatible with borderline OCD aspects, while 22.7% were pathological. An improvement in headache was significantly associated with an increase in the number of subjects with a normal OCI-R score at T0 and T1, whereas patients with a pathological OCI-R score at T0 showed a significantly higher prevalence of CM at T1. CONCLUSIONS: Our data showed a significant rate of OCD traits at baseline, which could strengthen the hypothesis of an addictive disorder underlying CM with MOH. OCD traits seem to influence the OBT-A response. An OCD assessment could be useful in improving patients' selections before starting treatments.

Homocysteine, Cognitive Functions, and Degenerative Dementias: State of the Art.

There is strong evidence that homocysteine is a risk factor not only for cerebrovascular diseases but also for degenerative dementias. A recent consensus statement renewed the importance and the role of high levels of homocysteine in cognitive decline in several forms of degenerative dementia, such as Alzheimer's disease. Although the molecular mechanisms by which homocysteine causes cell dysfunction are known, both the impact of homocysteine on specific cognitive functions and the relationship between homocysteine level and non-Alzheimer dementias have been poorly investigated. Most of the studies addressing the impact of hyperhomocysteinemia on dementias have not examined the profile of performance across different cognitive domains, and have only relied on screening tests, which provide a very general and coarse-grained picture of the cognitive status of the patients. Yet, trying to understand whether hyperhomocysteinemia is associated with the impairment of specific cognitive functions would be crucial, as it would be, in parallel, learning whether some brain circuits are particularly susceptible to the damage caused by hyperhomocysteinemia. These steps would allow one to (i) understand the actual role of homocysteine in the pathogenesis of cognitive decline and (ii) improve the diagnostic accuracy, differential diagnosis and prognostic implications. This review is aimed at exploring and revising the state of the art of these two strictly related domains. Suggestions for future research are provided.

Clusters of Comorbidities in the Short-Term Prognosis of Acute Heart Failure among Elderly Patients: A Retrospective Cohort Study.

Background and Objectives: Elderly patients affected by acute heart failure (AHF) often show different patterns of comorbidities. In this paper, we aimed to evaluate how chronic comorbidities cluster and which pattern of comorbidities is more strongly related to in-hospital death in AHF. Materials and Methods: All patients admitted for AHF to an Internal Medicine Department (01/2015−01/2019) were retrospectively evaluated; the main outcome of this study was in-hospital death during an admission for AHF; age, sex, the Charlson comorbidity index (CCI), and 17 different chronic pathologies were investigated; the association between the comorbidities was studied with Pearson's bivariate test, considering a level of p ≤ 0.10 significant, and considering p < 0.05 strongly significant. Thus, we identified the clusters of comorbidities associated with the main outcome and tested the CCI and each cluster against in-hospital death with logistic regression analysis, assessing the accuracy of the prediction with ROC curve analysis. Results: A total of 459 consecutive patients (age: 83.9 ± 8.02 years; males: 56.6%). A total of 55 (12%) subjects reached the main outcome; the CCI and 16 clusters of comorbidities emerged as being associated with in-hospital death from AHF. Of these, CCI and six clusters showed an accurate prediction of in-hospital death. Conclusions: Both the CCI and specific clusters of comorbidities are associated with in-hospital death from AHF among elderly patients. Specific phenotypes show a greater association with a worse short-term prognosis than a more generic scale, such as the CCI.

Ditans: a new prospective for the therapy of migraine attack?

INTRODUCTION: Migraine attack is characterized by disabling pain and associated symptoms. Triptans represent the "gold standard" therapy, but cardiac subjects have significant limitations for this approach. New drug families are under consideration to expand therapeutic offerings, especially in the presence of contraindications or for non-responsive patients. This review aimed to analyze studies related to the category of "ditans," with a focus on lasmiditan, which is available for human use. MATERIALS AND METHODS: We consulted PubMed/MEDLINE, Web of Science, and www. CLINICALTRIALS: gov to find both original and review articles on the mechanism of action of 5-HT1F agonists in migraine, and for randomized, double-blind, placebo-controlled trials (RCTs) on the family of drugs called "ditans," with a focus on "lasmiditan," published in the time frame of 01-Jan-2010 to 31-Mar-2022. Only studies conducted in human subjects and published in English were included in this review. RESULTS: We retrieved four RCTs (named SAMURAI, SPARTAN, GLADIATOR, and CENTURION) and several studies that analyzed the efficacy and safety of lasmiditan. Lasmiditan at increasing doses showed significant improvement in pain and most other troublesome symptoms at 2 h. Adverse events were mild and mainly represented by dizziness, vertigo, drowsiness, and fatigue. No vasoconstrictive effects were described, suggesting the use of ditans as a safe option in chronic cardio- and cerebro-vascular disease. DISCUSSION: Lasmiditan could be a viable alternative to triptans, although further RCT studies and real-world evidence are needed to better understand its potential and possible adverse events in a larger population.

Gender differences in obsessive-compulsive disorder traits among chronic migraine patients.

BACKGROUND: Psychiatric illnesses are often associated with severe forms of headache as chronic migraine (CM) with medication overuse headaches (MOH). Few data are available about obsessive-compulsive disorders (OCD) in migraineurs. This study aimed to investigate OCD traits in CM with MOH patients of both sexes and the impact on migraine treatment. METHODS: We enrolled all consecutive patients with CM and MOH treated with onabotulinumtoxin-A (OBT-A) in our Headache Center. Each subject was submitted to the Obsessive-Compulsive Inventory-Revised (OCI-R) test at the start (T0) and after four OBT-A sessions (T1). Statistical analysis compared OCI-R results at T0 and T1 according to sex with the chi-square test. RESULTS: We analyzed a sample of 60 subjects (40 females, 66.7%). At T0, 25% of males and 37.5% of females had a normal profile while 60% of males and 22.5% of females presented pathologic OCD traits. At T1, 30% of males and 60% of females were normal, while 40% of males and 15% of females resulted frankly pathologic. The difference in the OCI-R distribution was significant at T0 (p = 0.024) and at T1 (p = 0.047). Both males and females underwent a significant increase in normalization rates at T1 (p < 0.05). CONCLUSION: We observed a significant OCD traits rate at baseline, moreover among men. Females showed a more significant improvement in OCD traits at T1. OBT-A confirmed its high efficacy on CM, with a migraine severity improvement in both genders and all the OCI-R classes. Psychological attitude in the management of migraine should be better investigated in future studies.

Implementation of EHMRG Risk Model in an Italian Population of Elderly Patients with Acute Heart Failure.

Acute heart failure (AHF) is a cardiac emergency with an increasing incidence, especially among elderly patients. The Emergency Heart failure Mortality Risk Grade (EHMRG) has been validated to assess the 7-days AHF mortality risk, suggesting the management of patients admitted to an emergency department (ED). EHMRG has never been implemented in Italian ED nor among elderly patients. We aimed to assess EHMRG score accuracy in predicting in-hospital death in a retrospective cohort of elderly subjects admitted for AHF from the ED to an Internal Medicine Department. We enrolled, in a 24-months timeframe, all the patients admitted to an Internal Medicine Department from ED for AHF. We calculated the EHMRG score, subdividing patients into six categories, and assessing in-hospital mortality and length of stay. We evaluated EHMRG accuracy with ROC curve analysis and survival with Kaplan−Meier and Cox models. We collected 439 subjects, with 45 in-hospital deaths (10.3%), observing a significant increase of in-hospital death along with EHMRG class, from 0% (class 1) to 7.7% (class 5b; p < 0.0001). EHMRG was fairly accurate in the whole cohort (AUC: 0.75; 95%CI: 0.68−0.83; p < 0.0001), with the best cutoff observed at >103 (Se: 71.1%; Sp: 72.8%; LR+: 2.62; LR-: 0.40; PPV: 23.0%; NPV: 95.7%), but performed better considering the events in the first seven days of admission (AUC: 0.83; 95%; CI: 0.75−0.91; p < 0.0001). In light of our observations, EHMRG can be useful also for the Italian emergency system to predict the risk of short-term mortality for AHF among elderly patients. EHMRG performance was better in the first seven days but remained acceptable when considering the whole period of hospitalization.