Pulmonary embolism post-Covid-19 infection. Physiopathological mechanisms and vascular damage biomarkers

Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index. Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2)

Cohort analysis of novel SPAST variants in SPG4 patients and implementation of in vitro and in vivo studies to identify the pathogenic mechanism caused by splicing mutations

Introduction: Pure hereditary spastic paraplegia (SPG) type 4 (SPG4) is caused by mutations of SPAST gene. This study aimed to analyze SPAST variants in SPG4 patients to highlight the occurrence of splicingmutations and combine functional studies to assess the relevance of these variants in the molecular mechanisms of the disease. Methods: We performed an NGS panel in 105 patients, in silico analysis for splicing mutations, and in vitro minigene assay. Results and discussion: The NGS panel was applied to screen 105 patients carrying a clinical phenotype corresponding to upper motor neuron syndrome (UMNS), selectively affecting motor control of lower limbs. Pathogenic mutations in SPAST were identified in 12 patients (11.42%), 5 missense, 3 frameshift, and 4 splicing variants. Then, we focused on the patients carrying splicing variants using a combined approach of in silico and in vitro analysis through minigene assay and RNA, if available. For two splicing variants (i.e., c.1245+1G>A and c.1414-2A>T), functional assays confirm the types of molecular alterations suggested by the in silico analysis (loss of exon 9 and exon 12). In contrast, the splicing variant c.1005- 1delG differed from what was predicted (skipping exon 7), and the functional study indicates the loss of frame and formation of a premature stop codon. The present study evidenced the high splice variants in SPG4 patients and indicated the relevance of functional assays added to in silico analysis to decipher the pathogenic mechanism

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Guida all’allenamento & nozioni di Primo Soccorso

prontuario per l'allenamento dei ragazzi con nozioni di primo soccorso sul campo da gioco e istruzioni per una immediata Basic Life SupportCenni sull'almentazione dello sportiv

Empirical antimicrobial therapy and qtc interval prolongation in emergency medicine

Background: QTc prolongation is a common though dangerous clinical condition, associated with increased risk of life-threatening arrhythmia torsades de pointes. The goal of this short communication is to evaluate the principal causes of risk of QTc prolongation that are observed in an emergency department and discuss the differences between drug- and non-drug-associated factors. Methods: The retrospective analysis is carried out on 130 patients that presented a QTc prolongation (>480 ms for man and >470 for female, respectively), admitted to the emergency department of a single Italian hospital. Patients with pace-maker (22) were excluded from this study. For each patients a minimum of 3 ECGs (12 leads) were recorded. Attention is paid on electrolytes disturbances and to the pharmacotherapy, with a particular emphasis to the use of antibiotics. Results: Mean age of the patients was 79.6 years (SD=11.3) and female and man were almost equally present (46.6 % F, 53.7 % M). The average QTc value is 492.2 ms (493.3 ms F, 492.8 M). The patients were divided in those with electrolytes disturbances (24.0 %), antimicrobial therapy (35.2%), both antimicrobial therapy and electrolytes disturbances (24.1 %), and other causes of QTc prolongation (16.7 %). Conclusions: This analysis shows the relevance of the empirical therapy established at the admission, in particular for infective diseases, as an important risk factor for the prolongation of QTc. Other factors that can increase the risk are electrolytes alterations, advanced age, cardiovascular diseases, drug-drug interaction

The accident and emergency department as monitoring centre of human mobility: the Bangladesh experience

Departments (A&E-D) are privileged eyewitnesses of thehealth needs of a population that resides or transits in a given area. Through the experience acquired in Rome’s Umberto 1° Policlinico’s A&E, we report the experience gained the study results of admissions of citizens from Bangladesh are reported. Materials and Methods: we conducted a retrospective study of patients that attended the A&E-D from 2000 to 2014. We isolated records of patients from Bangladesh, noting age, gender, reason for admission and the final diagnosis. Results: data analysis showed 16,420 admittances due to of Bangladeshi citizens. With regard to considering the conditions that led Bangladeshi migrants to visit the A&E-D, it was noted that the diagnostic group mainly represented was “Injury and poisoning”, “Symptoms, signs and ill-defined morbid conditions”, “Diseases of the nervous system and sensory organs”, “Factors influencing the state of health and recourse to health services” and “Diseases of the respiratory system”. The group that presented highly interesting characteristics was the one relating to cardiovascular disease and among these, Coronary Syndromes. Its peculiarity lies in the fact that in the 130 cases considered the average age was 42 years +/- 8, much lower than usual in European countries. Discussion: the results on the types of diseases presented by Bangladeshi patients were discussed, and in particular the genetic causes, environmental interaction and the lifestyles that can justify the precocity of coronary disease in this population, according to studies reported in the literature. The results could have an impact on the organization of health care systems

Cardiac complications in a patient affected by systemic mastocytosis and primitive myelofibrosis: a case report

Systemic mastocytosis with associated primitive myelofibrosis is a rare and com- plex disease with a difficult therapeutic management. The release of several in- flammation mediators can trigger acute cardiovascular events