The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the ...prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic.
This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines.
The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients (death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001).
An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients’ population.
•Scleroderma patients showed higher COVID-19 prevalence and mortality rate than general population.•Mortality remained stable comparing pre-/post-vaccine periods, despite net drop in general population.•It might be due to impaired vaccine immunogenicity, immunomodulating drugs, scleroderma lung fibrosis.•Monitoring of vaccine response is highly recommendable in the next pandemic phase.•Harmonization of immunomodulator cycles and vaccine booster is very advisable.
Mpox virus (MPXV) has recently spread outside of sub-Saharan Africa. This large multicentre study was conducted in Lombardy, the most densely populated Italian region accounting for more than 40% of ...Italian cases. The present study aims to: i) evaluate the presence and the shedding duration of MPXV DNA in different body compartments correlating the MPXV viability with the time to onset of symptoms; ii) provide evidence of MPXV persistence in different body compartment as a source of infection and iii) characterize the MPXV evolution by whole genome sequencing (WGS) during the outbreak occurred in Italy.
The study included 353 patients with a laboratory-confirmed diagnosis of MPXV infection screened in several clinical specimens in the period May 24th - September 1st, 2022. Viral isolation was attempted from different biological matrices and complete genome sequencing was performed for 61 MPXV strains.
MPXV DNA detection was more frequent in the skin (94.4%) with the longest median time of viral clearance (16 days). The actively-replicating virus in cell culture was obtained for 123/377 (32.6%) samples with a significant higher viral quantity on isolation positive samples (20 vs 31, p < 0.001). The phylogenetic analysis highlighted the high genetic identity of the MPXV strains collected, both globally and within the Lombardy region.
Skin lesion is gold standard material and the high viral load and the actively-replicating virus observed in genital sites confirms that sexual contact plays a key role in the viral transmission.
•MPXV detection was more frequent from the skin lesions (289 of 306, 94·4%).•The median clearance time of MPXV DNA was 16 days in the skin, 14 days in the oropharynx.•Higher isolation rate was observed in semen, urine, anogenital, urethral and skin samples.•Higher isolation rate was observed in samples collected between 0 and 7 days (65/158, 41.1%) from the onset of symptoms.•Our 61 genomes are distributed in 37 local subclusters of the outbreak clade.
The integration of endocytic routes is critical to regulate receptor signaling. A non-clathrin endocytic pathway (NCE) of the epidermal growth factor receptor (EGFR) is activated at high ligand ...concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)-resident protein reticulon-3 (RTN3), and a specific cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)–ER contact sites that were required for the formation/maturation of NCE invaginations. Ca
2+
release at these sites, triggered by IP3-dependent activation of ER Ca
2+
channels, was needed for the completion of EGFR internalization. Thus, we identified a mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca
2+
signaling.
Abstract Background The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May ...2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. Methods Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. Results The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors ( n = 681, median 58, range 12–92 years) were older than males ( n = 849, median 53, range 2–97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3 h (≥10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. Conclusions The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.
The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional ...treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit.
The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching.
Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in nontreated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission.
Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation.
Acute lower limb ischemia (ALLI) poses a major threat to limb survival. For many years, surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution ...to the management of ALLI. It seems that the newly designed endovascular thrombectomy devices may shift treatment recommendations toward endovascular options. This protocol study aims to collect evidence supporting the latest hypothesis.
The devices under investigation are the Penumbra/Indigo Systems (Penumbra Inc). The objective of this clinical investigation is to evaluate, in a controlled setting, the early safety and effectiveness of the devices and to define the optimal technique for the use of these systems in patients with confirmed peripheral acute occlusions.
This study will be an interventional prospective trial of patients with a diagnosis of ALLI treated with Penumbra/Indigo devices. This project is intended to be a national platform where every physician invited to participate could register his or her own data procedure. The primary outcome is the technical success of thromboaspiration with the Indigo System. Assessment of vessel patency will be recorded using the Thrombolysis in Myocardial Infarction (TIMI) score classifications before and after use of the device. Clinical success at follow-up is defined as an improvement of Rutherford classification at 1-month follow-up of one class or more as compared to the preprocedure Rutherford classification. Secondary endpoints include the following: (1) safety rate at discharge, defined as the absence of any serious adverse events; (2) primary patency at 1 month, defined as a target lesion without a hemodynamically significant stenosis or reocclusion on duplex ultrasound (>50%) and without target lesion reintervention within 1 month; and (3) limb salvage at 1 month.
The study is currently in the recruitment phase and the final patient is expected to be treated by the end of March 2019. A total of 150 patients will be recruited. Analyses will focus on primary and secondary endpoints.
These new endovascular thrombectomy devices that are specifically designed for peripheral intervention in this difficult set of patients, as those under investigation in the proposed registry, may offer improved clinical outcomes with lower rates of major systemic and local complications. Following completion of this study, it is expected that the value of the Indigo Thrombectomy System in the treatment of ALLI will be better defined. As a result, a shift of treatment recommendations toward endovascular options may be observed in the near future.
DERR1-10.2196/9972.
Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific interest. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in ...patients hospitalized in a tertiary care center.
This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student’s t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data.
A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years.
In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture.
Abstract Background In patients with idiopathic dilated cardiomyopathy (DCM) a more depressed left atrial (LA) booster pump function has been observed compared to ischemic patients although under ...similar loading conditions, and attributed both to altered LA overload and to LA larger involvement in the myopathic process. Aim of the study To detect by speckle-tracking two-dimensional strain (2DSE) LA systolic dysfunction in patients with either idiopathic or ischemic DCM, and to assess in these patients possible correlation between LA myocardial function and exercise capacity during cardiopulmonary test. Methods Three-hundred-fourteen patients (52.4 ± 11.2 years) with either idiopathic (160 patients) or ischemic (154 patients) DCM underwent cardiopulmonary stress test, standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof. Results The two groups were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. Also LA diameter and maximal volume were similar between the two groups. Conversely, LA active empting volume and fraction were both lower in patients with idiopathic DCM (< 0.001). Peak systolic myocardial atrial strain was significantly reduced in patients with idiopathic DCM compared with ischemic DCM at the level of all the analyzed atrial segments ( p < 0.0001). By multivariable analysis, in the overall population, ischemic aetiology of DCM ( p < 0.0001) and LA volume ( p < 0.001) were the only independent determinants of LA lateral wall systolic strain. On the other hand, LA lateral wall systolic strain ( p < 0.0001) and LA volume ( p < 0.001) were powerful independent predictors of peak oxygen consumption during cardiopulmonary exercise testing. Conclusions Two-dimensional strain represents a promising non-invasive technique to assess LA atrial myocardial function in patients with DCM. LA systolic deformation is more depressed in idiopathic compared with ischemic DCM, and is closely associated with functional capacity during effort. Future longitudinal studies are warranted to further our understanding of the natural history of LA myocardial function, the extent of reversibility of LA dysfunction with therapy, and the possible prognostic impact of such indexes in patients with congestive heart failure.
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