The anti-COVID-19 vaccine unveils latent systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune connective disease characterized by extensive fibrosis of the skin, vasculature, and internal organs. The lung, heart, and kidney are frequently involved. The early clinical manifestation is the Raynaud’s phenomenon (RP), but diagnosis may be delayed for years, when systemic involvement is evident or even irreversible. The early identification of SSc could enable prompt treatment and improve prognosis of these patients. A variety of autoimmune conditions after SARS-CoV-2 vaccination have been reported, following which the term “autoimmune post-COVID vaccine syndrome” has been proposed. We present a case of latent diffused SSc with lung involvement in a 40-year-old woman with a history of RP, which became apparent after receiving the first dose of an anti- SARS-CoV-2 vaccine. Case Report: A young non-smoking woman, 40 years old, came for an outpatient cardiological evaluation in October 2021 referred by a pulmonologist who recorded the persistence of tachycardia, chest pain, and dyspnea, suspecting post- SARS-CoV-2 vaccine pericarditis, in June 2021. Echocardiography and laboratory analyses led us to exclude a pathological framework related to the vaccine and we hypothesized a systemic autoimmune disease, e.g., systemic sclerosis. A diagnosis of scleroderma was subsequently confirmed via pulmonary computed tomography and laboratory test. Conclusions Side effects often attributed to the Covid-19 vaccine might not always be caused by it, which can be actually the trigger that unmasks an underlying connective tissue disease. In this case, SARS-CoV-2 vaccination unleashed a latent SSc allowing for an early diagnosis and therefore influencing favorably the prognosis

Antiviral activity and metal ion-binding properties of some 2-hydroxy-3-methoxyphenyl acylhydrazones

Here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and African Green monkey kidney cells). Interesting antiviral EC50 values are obtained against herpes simplex virus-1 and vaccinia virus. The biological activity of acylhydrazones is often attributed to their metal coordinating abilities, so potentiometric and microcalorimetric studies are here discussed to unravel the behavior of the three 2-hydroxy-3-methoxyphenyl compounds in solution. It is worth of note that the acylhydrazone with the higher affinity for Cu(II) ions shows the best antiviral activity against herpes simplex and vaccinia virus (EC50 ~ 1.5 µM, minimal cytotoxic concentration = 60 µM, selectivity index = 40).status: publishe

Metal-chelating properties and antiviral activity of some 2-hydroxyphenyl amides

Influenza virus is an hot topic in medicinal chemistry and great efforts are ongoing for the discover of new antivirals able to overcome problems related to resistant strains and adverse side effects of current drugs. Influenza virus endonuclease is an attractive target for antiviral drug development and in particular the strategy to chelate the metal ion(s) within the active site proved to be an efficient mode to inhibit enzymatic activity. Our previous findings revealed that 2-hydroxyamide derivatives are able to chelate Mg2+ ions, forming complexes with different stoichiometric ratios. Here we report on the activity of the three ligands N-(4-fluorobenzyl)-2-hydroxybenzamide, N-(4-fluorobenzyl)-2,3-dihydroxybenzamide, and N1,N3-bis(4-fluorobenzyl)-2-hydroxyisophthalamide, containing the salicylic group, and their Mg2+ complexes (7)-(9), evaluated by means of virus yield assay in influenza virus-infected MDCK cells and vRNP reconstitution assay in HEK293T cells. In some cases, promising anti-influenza activity with EC50 values in the low micromolar range were found. As a contribute to clarify the activity in cells of the ligands, here we also present a study on the their coordinating properties towards the other essential metal ion Cu(II), carried out by potentiometric and calorimetric measurements.status: publishe

Spontaneous coronary artery dissection: an Italian single centre experience

Aims: Spontaneous coronary artery dissection (SCAD) is an emerging cause of acute myocardial infarction (AMI) in young women without a typical cardiovascular risk profile. Knowledge on SCAD is based on observational studies and is still scarce. The aim of this monocentric observational study was to evaluate the predisposing factors, clinical features and prognosis of SCAD patients. Methods: Between 2013 and 2020, 58 patients with angiographic diagnosis of SCAD were identified in our centre with an overall prevalence of 0.9% among patients admitted for AMI (58 of 6414 patients). Results: The mean age was 54 ± 11 years and the majority were women (n = 50, 86%) with one or fewer cardiovascular risk factors (n = 35, 60%). The prevalence of Fibromuscolar Dysplasia (FMD) was 39% (7 of 18 screened patients). The rate of major adverse cardiovascular and cerebrovascular events (MACCEs) was used to assess the prognosis. Out-of-hospital cardiac arrest because of ventricular fibrillation was observed in four (7%) patients. The majority of patients (n = 51, 88%) were treated conservatively without revascularization. The in-hospital and 30-day clinical course was uneventful in most patients (n = 54, 93%) with two cardiac deaths. During a median follow-up of 12 months, there were no further deaths. The global rate of SCAD recurrence was significant (n = 8, 14%) but predictors have not been identified. Conclusion: Although overall survival seems good, SCAD is a potentially malignant, not rare disease, which can present with sudden cardiac death and not uncommon recurrence. Prognostic stratification and optimal management of SCAD patients remain to be defined

Left atrial appendage occlusion in patients with atrial fibrillation and large prevalence of prior intracranial bleeding

Abstract Background: Left atrial appendage occlusion (LAAO) represents an alternative approach for the prevention of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF) and contraindication for oral anticoagulation (OAC). The aim of our study was to analyse the outcomes in patients treated with LAAO, with a focus on cases with previous intracranial bleeding. Methods: Sixty patients with NVAF underwent LAAO (75.4 ± 9 years); mean CHA2DS2-VASc was 4.4 ± 1.7, mean HAS-BLED 3.2 ± 0.9. Thirty-two patients (53.3%) reported previous intracranial bleeding. Ischaemic and bleeding events recorded during follow-up were compared with expected event rates according to CHA2DS2-VASc and HAS-BLED scores. Results: Device implantation was successful in 58 patients (96.7%). The antiplatelet therapy was tailored according to patients' bleeding risk. During follow-up (2.32 ± 1.5 years) 3 ischaemic strokes and 1 transient ischaemic attack occurred, versus 13 total expected thromboembolic events (P = 0.033); 5 major bleedings were observed, versus 7 expected ones, if the patients were under OAC. Considering the combined endpoint (thromboembolic and major bleeding events) 9 events were observed versus 20 expected major events (P = 0.031). In the prespecified subgroup of patients with previous intracranial bleeding, two ischaemic strokes and one transient ischaemic attack were observed during follow-up versus six total expected thromboembolic events; no intracranial bleeding recurrence was recorded. Regarding the combined endpoint four major events were recorded versus nine expected ones. Conclusion: LAAO is an efficient and safe option for the prevention of cardioembolic stroke in patients with NVAF, high thromboembolic risk and contraindication to OAC, particularly in patients with previous intracranial bleeding

Same-day transfer for the invasive strategy of patients with non-ST-segment elevation acute coronary syndrome admitted to spoke hospitals: Data from the Emilia-Romagna Regional Network

Background: The service strategy (same-day transfer between spoke hospital and hub centre with catheterisation laboratory (cath-lab) facility to perform invasive procedures) has been suggested to improve the management of patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) admitted to spoke hospitals. We used data from a large prospective Italian registry to describe application, performance and outcome of the service strategy in the daily clinical practice. Methods: This study was based on an observational, post-hoc analysis of all consecutive NSTEACS patients admitted to spoke non-invasive hospitals of the Emilia-Romagna regional network and receiving coronary artery angiography (CAA)percutaneous coronary intervention (PCI). We evaluated: application of service strategy, time to cath-lab access, hospital stay length, 30-days occurrence of adverse events. Results: From January 2011-December 2012, 2952 NSTEACS consecutive patients were admitted to spoke non-invasive hospitals and received CAA. Overall, 1765 (60%) patients were managed with a service strategy. After multivariable analysis, service strategy emerged as independent predictor of faster access to cath-lab (within 72 h: hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.9-2.7, p<0.0001; within 24 h: HR 2.8, 95% CI 2.2-3.3, p<0.0001, respectively). Service strategy significantly reduced hospital stay length (-5.5 days, p<0.0001). We estimated a mean of Euro1590 saved for each patient managed with service strategy. Thirty-day occurrence of adverse events did not differ between patients managed with or without a service strategy. Conclusions: In our daily clinical practice, a service strategy seems to be an effective approach to optimise the invasive management of NSTEACS patients admitted to spoke hospitals

SEX-RELATED DIFFERENCES IN LONG COVID-19 SYNDROME

Background: Sex-differences have been demonstrated in the acute phase of COVID-19. Females (F) were found to be less prone to develop a severe disease than males (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Aim and Results: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, females reported the following symptoms more frequently than males: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia - all without significant differences in breathlessness, cough, and sleep disturbance. After a mean follow-up time of 5 months after the acute phase, females were significantly more likely than males to report dyspnoea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnoea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough and sleep disturbance were not influenced by sex. Conclusion: We demonstrated that females were more symptomatic than males not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in females, such as dyspnoea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex-perspective in order to implement early preventive and personalized therapeutic strategies