Alzheimer’s disease (AD) is the most common type of dementia, affecting 24 million individuals. Clinical and epidemiological studies have found several links between vascular risk factors (VRF), neurovascular unit dysfunction (NVUd), blood-brain barrier breakdown (BBBb) and AD onset and progression in adulthood, suggesting a pathogenetic continuum between AD and vascular dementia. Shared pathways between AD, VRF, and NVUd/BBB have also been found at the molecular level, underlining the strength of this association. The present paper reviewed the literature describing commonly shared molecular pathways between adult-onset AD, VRF, and NVUd/BBBb. Current evidence suggests that VRF and NVUd/BBBb are involved in AD neurovascular and neurodegenerative pathology and share several molecular pathways. This is strongly supportive of the hypothesis that the presence of VRF can at least facilitate AD onset and progression through several mechanisms, including NVUd/BBBb. Moreover, vascular disease and several comorbidities may have a cumulative effect on VRF and worsen the clinical manifestations of AD. Early detection and correction of VRF and vascular disease by improving NVUd/BBBd could be a potential target to reduce the overall incidence and delay cognitive impairment in AD.

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.

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.

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.

The Emergency Heart Failure Mortality Risk Grade (EHMRG) can predict short-term mortality in patients admitted for acute heart failure (AHF) in the emergency department (ED). This paper aimed to evaluate if TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can improve in-hospital death prediction in patients at moderate-to-high risk, according to EHMRG score classification. From 1 January 2018 to 30 December 2019, we retrospectively enrolled all the consecutive subjects admitted to our Internal Medicine Department for AHF from the ED. We performed bedside echocardiography within the first 24 h of admission. We evaluated EHMRG and NYHA in the ED, days of admission in Internal Medicine, and in-hospital mortality. We assessed cutoffs with ROC curve analysis and survival with Kaplan–Meier and Cox regression. We obtained a cohort of 439 subjects; 10.3% underwent in-hospital death. Patients with normal TAPSE/PASp in EHMRG Classes 4, 5a, and 5b had higher survival rates (100%, 100%, and 94.3%, respectively), while subjects with pathologic TAPSE/PASp had lower survival rates (81.8%, 78.3%, and 43.4%, respectively) (p < 0.0001, log-rank test). TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can further stratify the risk of in-hospital death evaluated by EHMRG.

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.