Universita' degli Studi "Magna Græcia" di Catanzaro
Recent publications
Viruses have been recognized as the etiological agents responsible for many pathological conditions ranging from asymptomatic infections to serious diseases, even leading to death. For this reason, many efforts have been made to identify selective viral targets with the aim of developing efficient therapeutic strategies, devoid of drug-resistance issues. Considering their crucial role in the viral life cycle, polymerases are very attractive targets. Among the classes of compounds explored as viral polymerases inhibitors, here we present an overview of non-nucleoside triazole-based compounds identified in the last fifteen years. Furthermore, the structure-activity relationships (SAR) of the different chemical entities are described in order to highlight the key chemical features required for the development of effective antiviral agents.
Purpose: To present a case of hematocornea occurring in a post-penetrating keratoplasty (PK) eye and to report the outcomes of deep anterior lamellar keratoplasty (DALK) performed by simple stromal peeling. Observations: A 45-year-old female presented with hematocornea in the left eye that previously underwent PK 26 months prior for keratoconus. Clinical examination revealed a dense reddish-brown opacity within the PK graft which was associated with deep corneal neovascularization. Over 6 months, intracorneal hemorrhage developed a rust-colored appearance with minimal clearing. DALK was performed using the stromal peeling technique for post-PK eyes. Briefly, a dense partially organized hemorrhage was identified at the natural plane of separation, as confirmed by ex vivo histologic examination; after peeling of the deep corneal stroma and evacuation of the intracorneal hemorrhage, the residual bed appeared akin to pre-Descemet's layer-Descemet membrane-endothelium complex. One year after DALK, the graft remained clear with ECD of 1034 cells/mm2. Conclusions and importance: Intracorneal hemorrhage is a rare but potentially sight-threatening complication following PK. Using the stromal peeling technique, DALK can be attempted to preserve functional endothelium in post-PK eyes. In the presence of a dense intracorneal hemorrhage, the spread of erythrocytic debris within the stroma can guide deep lamellar cleavage.
Background and aims: Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. Methods: All data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. Results: 798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. Conclusions: PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.
This article proposes a series of insights that are drawn from the most up-to-date scientific literature and functional for an optimal implementation of Audit & Feedback (A&F). The focus is on the "feedback" component of the methodology. Some key issues of the feedback are the capability to address changes perceived as priorities for the recipients, recommend actions that bring real improvements, and allow the people to whom recommendations are addressed to manage them. Other suggestions concern how to share the data: it is important to provide feedback as soon as possible, multiple times, starting from individual rather than general data, and including comparisons able to promote the desired change. Other operational indications concern the most effective way to display the feedback, such as tightly linking the graphical representation and the summary message, presenting the feedback in multiple ways, and simplifying the message to minimize cognitive overload. Finally, some suggestions are about how to transmit feedback: tailor interventions according to the specific barriers of a given clinical-organizational context, provide short and easily understandable messages followed by more details, emphasize the credibility of information, increase motivation to change practice, and encourage participatory feedback construction rather than passive delivery. It also proposes an analysis of some of the challenges related to the design of A&F interventions translatable into improvements in practice starting from the context of the Easy-Net network program.
In this review we discuss the role of intraocular surgery preoperative prophylaxis. The correct choice of antimicrobial drug is variable in each surgical setting, according to the available strengths of evidence, the anatomical district involved, and the type of procedure. In the ophthalmic surgical field, there has been a progressive shift from antibiotic formulations, which are known to cause antibiotic resistance, to a new class of antiseptic compounds, which proved to be effective not only against bacteria, but also against fungi, protozoa, and viruses. Among these, povidone-iodine (PVI) is a water-soluble polymer that can form a complex with iodine, and the perioperative application of PVI 5-10% eye drop for 3 min is the gold standard for infection prophylaxis. A new formulation of 0.6% PVI eye drop is a new option for infection prophylaxis in the days before surgery. Chlorhexidine is a biguanide compound, which is a valid alternative with a good safety and efficacy profile and is the antiseptic of choice in patients with iodine allergy. New compounds that are currently being studied include polyhexamethylene biguanide (PHMB), picloxydine, ozone, hypochlorous acid (HOCl), and Biosecur. PHMB is a biguanide polymer that was found to be more effective than PVI in in vitro studies for reducing microorganisms and extending the duration of antisepsis, but to date, there are no formulations available on the market for preoperative ocular surgery in which it is present as main ingredient. Ozone is a molecule with oxidizing effect, which showed interesting preliminary results but is not effective against virus, Staphylococcus aureus and Candida albicans. HOCl has a natural bactericidal propriety but its applicability to prophylaxis of ocular infection in the setting of ocular surgery is not established. Biosecur is a non-toxic organic alcohol-free compound that exhibited bactericidal and fungicidal effect versus all common microorganisms and is currently available as an ocular spray.
Encephalitis lethargica developed in epidemic from 1919 to 1926 in Europe and throughout the world. From the clinical point of view, the disturbances of consciousness and alertness and the possible outcomes of a postencephalitic Parkinsonism has attracted much attention. For a long time, it was thought that such a disease may still occur sporadically. In this review, the authors examined historical and current pictures of epidemics that may be related to Encephalitis lethargica. The previous Nona and Russian Influenza exhibited frequent neurological symptoms. The Spanish flu, formerly related to Encephalitis lethargica, would appear an epidemic that had its development in a partially overlapping period. The current pandemic linked to COVID-19 sometimes has aspects that can resemble Encephalitis lethargica. Based on historical analysis and the more recent immunological data, it could be suggested that Encephalitis lethargica was an autoimmune encephalitis that arose in a secondary form to the action of a viral agent. It cannot be ruled out that this agent was a coronavirus. From the nosological point of view, the term Encephalitis lethargica should be abolished in designating autoimmune encephalitis pictures that run sporadically.
Background As patients with immune conditions were excluded from COVID-19 vaccine clinical trials, it is important to accumulate real-world data in this setting, particularly to identify those who would benefit from repeated doses. Methods Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE) is a prospective, multicentre, observational study assessing effectiveness and safety of COVID-19 vaccines in patients with IBD (ClinicalTrials.gov ID: NCT04769258). Here we present data on the rate of breakthrough SARS-CoV-2 infections in the timeframe between 14 days after the second dose and the third dose of COVID-19 vaccine (or a maximum of 9 months from the second dose). The risk factors for SARS-CoV-2 infection, including lack of seroconversion (cut-off for IgG anti-SARS-CoV-2: OD 0.28) and IgG anti-SARS-CoV-2 levels after 8 weeks from the second dose, and treatment for IBD, were assessed. Results Out of the 1076 patients with IBD enrolled in the ESCAPE study, data on breakthrough SARS-CoV-2 infection were available in 953 cases. Most of the patients received homologous, double-dose mRNA-based vaccines (BNT162b2 or mRNA-1273: 99.2%). Seroconversion was reported in 92.7% of cases (median OD 1.60 [IQR 0.8-3.6]), while SARS-CoV-2 infection was documented in 95 patients (10.0%), of whom 9 died. At multivariable regression analyses, age (OR 0.97, 95% CI 0.96-0.99; p<0.001) being former smoker (OR 2.23, 95% CI 1.26-3.88; p=0.005), and lack of seroconversion (OR 0.42, 95% CI 0.20-0.99; p=0.034) were independent predictors of SARS-CoV-2 infection. Conversely, none of the treatments for IBD was associated with breakthrough SARS-CoV-2 infection. Notably, all 9 patients who died had reported seroconversion after the second dose. Conclusion IBD patients without seroconversion after COVID-19 vaccines are at increased risk for SARS-CoV-2 infection, while medications for IBD had no impac
Background Prevention of postoperative recurrence (POR) in Crohn’s disease (CD) after ileo-colonic (IC) resection is still a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in presence of at least one clinical risk factor (RF). Due to drug-related adverse events and the relative high cost of biologics, we aimed to determine whether prevention of POR can be postponed and guided by endoscopy in CD patients with only one RF. Methods A multicentre retrospective study was conducted in 12 IG-IBD Italian centres. CD patients with only one RF for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, or active smoking were considered. Patients who performed a colonoscopy between 6 to 12 months after curative IC resection were included. Two groups were formed based on whether immunosuppressive therapy was started immediately after surgery (prophylaxis group) or guided by endoscopy (observation group). Primary endpoints were the rates of any endoscopic recurrence (Rutgeerts ≥i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence (HBI≥5) rates at 6, 12 and 24 months after surgery. Results A total of 195 patients were enrolled. Out of all, 61 (31.3%) received immunoprophylaxis at a median time of 32 days [IQR 26-55] after surgery (n=14 infliximab, n=37 adalimumab, n=7 azathioprine, n=3 ustekinumab). Baseline patient characteristics are detailed in Table 1. Particularly, risk factors for POR were homogeneously distributed between the 2 groups. Colonoscopy was performed after a median time of 8 months [IQR 6-11]. No differences between immunoprophylaxis and endoscopy-driven approach was found regarding any endoscopic recurrence (36.1% in prophylaxis group vs 45.5% in observation group, p=0.10) and severe endoscopic recurrence (9.8% in prophylaxis group vs 15.7% in observation group, p=0.15). In 32 patients with a second colonoscopy at a median time of 30.5 months [IQR 22-43.75] after surgery, any recurrence and severe recurrence rates were also similar (p=0.55 and p=0.43, respectively). Early clinical recurrence at 6 months was reported in 23.4% of patients on immunoprophylaxis vs 31.5% who were not (p=0.43). Clinical recurrence rates between prophylaxis and observation group were also similar at 12 months (17.9% vs 34.8%, respectively, p=0.09) and at 24 months (17.9% vs 24.1%, respectively, p=0.63). Conclusion In CD patients with only one RF for POR, immediate immunoprophylaxis after curative IC resection does not decrease the rate of early clinical and endoscopic recurrence. Prospective and larger studies are needed to confirm our results.
Background Current data about long-term use of vedolizumab (VDZ) in ulcerative colitis (UC) versus Crohn’s disease (CD) patients are limited. We aimed to assess whether there are differences in term of long-term efficacy and safety of VDZ in UC vs. CD patients. Methods Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission within 6 month of treatment, maintenance of clinical remission during a long follow-up, and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), steroid discontinuation, and treatment optimization during the follow-up. Results The study group consisted of 729 patients (475 patients with UC and 254 CD patients with CD) with a median follow-up of 18 (interquartile range 6-36) months. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients, higher in CD patients (74.4 vs. 62.9, p<0.000) while, at the maximal follow-up, it was achieved and maintained in 81.5% of patients (UC vs. CD, p=0.667). At uni- and multivariate analysis, reaching clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics were significantly associated with longer clinical remission (p<0.0001). Long-term follow up clinical response was significantly higher in UC vs. CD (p=0.023) and surgery occurred more frequently in CD (p=0.04), while no difference were found between UC and CD about the other secondary endpoints Conclusion Overall, no significant differences were found about the long-term use of VDZ in UC vs. CD. However, we identified some parameters the can help the physician to predict the long-term efficacy of this drug.
Background Minimally invasive surgery (MIS), including laparoscopic and robotic approaches, is widely adopted in elective digestive surgery, but selectively used for surgical emergencies. The present position paper summarizes the available evidence concerning the learning curve to achieve proficiency in emergency MIS and provides five expert opinion statements, which may form the basis for developing standardized curricula and training programs in emergency MIS. Methods This position paper was conducted according to the World Society of Emergency Surgery methodology. A steering committee and an international expert panel were involved in the critical appraisal of the literature and the development of the consensus statements. Results Thirteen studies regarding the learning curve in emergency MIS were selected. All but one study considered laparoscopic appendectomy. Only one study reported on emergency robotic surgery. In most of the studies, proficiency was achieved after an average of 30 procedures (range: 20–107) depending on the initial surgeon’s experience. High heterogeneity was noted in the way the learning curve was assessed. The experts claim that further studies investigating learning curve processes in emergency MIS are needed. The emergency surgeon curriculum should include a progressive and adequate training based on simulation, supervised clinical practice (proctoring), and surgical fellowships. The results should be evaluated by adopting a credentialing system to ensure quality standards. Surgical proficiency should be maintained with a minimum caseload and constantly evaluated. Moreover, the training process should involve the entire surgical team to facilitate the surgeon’s proficiency. Conclusions Limited evidence exists concerning the learning process in laparoscopic and robotic emergency surgery. The proposed statements should be seen as a preliminary guide for the surgical community while stressing the need for further research.
Sommario Il diabete mellito gestazionale (DMG), è il disordine endocrino-metabolico a maggiore prevalenza nelle donne in gravidanza e si associa a un alto rischio di complicanze materno-fetali. L’eziologia di tale condizione è complessa e multifattoriale, con fattori di rischio e meccanismi patogenetici in gran parte comuni a quelli del diabete mellito di tipo 2 (DMT2), il quale spesso compare nelle donne che hanno una storia di DMG anche a soli pochi anni di distanza dal parto. Tuttavia, mentre per la prevenzione del DMT2 gli interventi multimodali di modifica dello stile di vita, comprendenti programmi di attività fisica o esercizio fisico, uniti a cambiamenti nutrizionali e comportamentali, sono associati a benefici certi, lo stesso non vale per il DMG, per cui esistono evidenze scientifiche di natura osservazionale e sperimentale a volte contrastanti. Dall’analisi della letteratura più recente, riassunta in questa rassegna, emerge la necessità di spostare l’attenzione della ricerca sugli effetti di una prevenzione di precisione, che adatti il timing di inizio, la tipologia e l’intensità del programma di esercizio fisico per la prevenzione del DMG alle caratteristiche fisiologiche delle singole gestanti. Si ravvisa, inoltre, il bisogno di estendere la “finestra d’intervento” al periodo preconcezionale per massimizzare le possibilità di successo, soprattutto nelle donne ad alto rischio.
Background This single-center preliminary prospective observational study used bedside ultrasound to assess the lung aeration modifications induced by recruitment maneuver and pronation in intubated patients with acute respiratory disease syndrome (ARDS) related to coronavirus 2019 disease (COVID-19). All adult intubated COVID-19 patients suitable for pronation were screened. After enrollment, patients underwent 1 h in a volume-controlled mode in supine position (baseline) followed by a 35-cmH2O-recruitment maneuver of 2 min (recruitment). Final step involved volume-controlled mode in prone position set as at baseline (pronation). At the end of the first two steps and 1 h after pronation, a lung ultrasound was performed, and global and regional lung ultrasound score (LUS) were analyzed. Data sets are presented as a median and 25th–75th percentile. Results From January to May 2022, 20 patients were included and analyzed. Global LUS reduced from 26.5 (23.5–30.0) at baseline to 21.5 (18.0–23.3) and 23.0 (21.0–26.3) at recruitment (p < 0.001) and pronation (p = 0.004). In the anterior lung regions, the regional LUS were 1.8 (1.1–2.0) following recruitment and 2.0 (1.6–2.2) in the supine (p = 0.008) and 2.0 (1.8–2.3) in prone position (p = 0.023). Regional LUS diminished from 2.3 (2.0–2.5) in supine to 2.0 (1.8–2.0) with recruitment in the lateral lung zones (p = 0.036). Finally, in the posterior lung units, regional LUS improved from 2.5 (2.3–2.8) in supine to 2.3 (1.8–2.5) through recruitment (p = 0.003) and 1.8 (1.3–2.2) with pronation (p < 0.0001). Conclusions In our investigation, recruitment maneuver and prone positioning demonstrated an enhancement in lung aeration when compared to supine position, as assessed by bedside lung ultrasound. Trial registration: www. clini caltr ials. gov, Number NCT05209477, prospectively registered and released on 01/26/2022. Keywords Acute respiratory distress syndrome, COVID-19, Lung ultrasound
Atopic dermatitis (AD) may be more common than previously thought in adults aged ≥60 years, a population underrepresented in clinical trials. Rigorous demonstration of efficacy and safety in older adults is clinically important due to distinct disease presentations in this group, age-related immune shifts, changes in drug metabolism and risks associated with a heightened burden of medical comorbidities and polypharmacy. Treatment options providing efficacy with acceptable safety profiles are of particular importance. Here, we report the efficacy and safety of dupilumab for the treatment of moderate-to-severe AD in patients aged ≥60 years. Data were pooled from four randomized, placebo-controlled dupilumab trials in patients with moderate-to-severe AD (LIBERTY AD SOLO 1 & 2 [NCT02277743, NCT02277769], LIBERTY AD CAFÉ [NCT02755649] and LIBERTY AD CHRONOS [NCT02260986]). Patients aged ≥60 years (N = 183) received dupilumab 300 mg weekly (qw), every 2 weeks (q2w) or a placebo. Topical corticosteroids (TCSs) were permitted in LIBERTY AD CAFÉ and LIBERTY AD CHRONOS. Reported efficacy measures include the percentage of patients achieving a 75% reduction in Eczema Area and Severity Index (EASI-75), mean change in Peak Pruritus Numerical Rating Scale (PP-NRS) scores, and mean change in Dermatology Life Quality Index (DLQI). Safety data are also presented. Among patients aged ≥60 years, significant increases in EASI-75 responses were observed in patients treated with dupilumab 300 mg qw (61.6%) and 300 mg q2w (63.0%) vs. placebo (14.3%; P < 0.0001 for both) at week 16. Least squares (LS) mean change (± standard error [SE]) in PP-NRS scores was significantly greater in patients treated with dupilumab 300 mg qw (−1.6 [0.2]) and 300 mg q2w (−1.7 [0.3]) vs. placebo (−0.9 [0.3]; P < 0.05 for both) at week 2. Improvements continued to week 16 in patients treated with dupilumab 300 mg qw (−4.0 [0.3]) and 300 mg q2w (−3.8 [0.3]) vs. placebo (−1.7 [0.3]; P < 0.0001 for both). Similarly, significant improvement (LS mean change [±SE]) in DLQI was seen in patients treated with dupilumab 300 mg qw (−5.0 [0.6]) and 300 mg q2w (−6.0 [0.7]) vs. placebo (−2.8 [0.6]; P < 0.01 vs. qw and P < 0.001 vs. q2w) at week 2; improvements continued to week 16 in patients treated with dupilumab 300 mg qw (−8.0 [0.6]) and 300 mg q2w (−9.65 [0.7]) vs. placebo (−3.3 [0.7]; P < 0.0001 for both). 52 (72.2%) patients in the 300 mg qw treatment group, 32 (58.2%) patients in the 300 mg q2w treatment group, and 40 (71.4%) patients in the placebo group experienced ≥1 TEAE. The two most common treatment-emergent adverse events (TEAEs) were injection-site reactions (13.9%) and nasopharyngitis (9.7%) during 300 mg qw dupilumab treatment; dermatitis atopic (20.0%) and nasopharyngitis (5.5%) during 300 mg q2w dupilumab treatment; and dermatitis atopic (30.4%) and upper respiratory tract infection (7.1%) during placebo treatment. 3 (4.2%) patients during 300 mg qw dupilumab treatment and 2 (3.6%) patients during 300 mg q2w dupilumab treatment discontinued treatment permanently as a result of TEAEs. Dupilumab efficacy and safety profiles in patients aged ≥60 years were generally consistent with that seen in patients aged <60 years with atopic dermatitis, and have been previously reported. Dupilumab, with or without TCS, improves AD signs, symptoms and quality of life with a consistent and acceptable safety profile in patients aged ≥60 years with moderate-to-severe AD.
Background Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, posing them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodelling and worse CV outcomes, scarce evidence exist on their role in this setting. Methods We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectly followed (median 22 mo.). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results Circulating levels of all miRNAs were lower in HD patients as compared to healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (p<0.001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox-regression analyses (HR ranging from 0.943 to 0.995; p = 0.05 to 0.02) while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal ROC-derived cut-off value (p ranging from 0.001 to <0.0001; crude HRs 7.95 to 8.61). Conclusions Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short-mid term. Future studies on larger HD populations are needed to generalize these findings.
Background Sepsis is a leading cause of death and it is characterized not only by profound vasoplegia but also by myocardial dysfunction. Critical care Echocardiography is the preferred modality for the initial assessment of the cause of shock. Moreover, it can be extremely helpful in the identification of progressing myocardial dysfunction during the course of sepsis, also known as septic cardiomyopathy. Main body One of the issues in the identification of septic cardiomyopathy is that it can be manifest with different clinical phenotypes, from overt biventricular dysfunction to isolated left ventricular (LV) systolic and/or diastolic dysfunction, from right ventricular (RV) systolic dysfunction to RV failure and dilatation. However, the commonly used echocardiography parameters for the assessment of LV and/or RV function are not always entirely reliable. Indeed, these are influenced by variable preload and afterload conditions imposed by critical illness such as fluid shifts, sedation level and mechanical ventilation with positive pressure. Conclusions Strain echocardiography is a promising tool for the early identification of myocardial dysfunction in the context of sepsis. Studies reporting data on strain echocardiography should be particularly detailed in order to increase the reproducibility of results and to favor comparison with future studies.
Background: Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. Objectives: To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. Methods: The data of 16022 patients considered having OCD after patch testing within the ESSCA network between January 2011 and December 2020 were evaluated. Patients (n=46652) in whom an occupational causation was refuted served as comparison group. Results: The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. Conclusions: Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives. This article is protected by copyright. All rights reserved.
Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1–7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized.
Networks are present in different aspects of our life: communication networks, World Wide Web, Social Networks, and can be used to conveniently describe biological and clinical data, such as the interactions of proteins in an organism or the connections of neurons in the brain. Therefore, network science, focusing on the network representations of physical, biological and social phenomena and leading to predictive models of these phenomena, currently represents a vast field of application and research for many scientific and social disciplines. The mathematical background for the study and analysis of networks has its roots in the theory of graphs that allows studying real phenomena in a quantitative way. According to the formalism coming from graph theory, nodes of the graph represent entities, whereas edges represent the associations among them. Currently, in bioinformatics and systems biology, there is a growing interest in analyzing associations among biological molecules at a network level. Since the study of associations in a system-level scale has shown great potential, the use of networks has become the de facto standard for representing such associations, and its application fields span from molecular biology to brain connectome analysis [1]. Molecules of different types, e.g. genes, proteins, ribonucleic acids and metabolites, have fundamental roles in the mechanisms of the cellular processes. The study of their structure and interactions is crucial for different reasons, comprising the development of new drugs and the discovery of disease pathways. Thus, the modeling of the complete set of interactions and associations among biological molecules as a graph is convenient for a variety of reasons. Networks provide a simple and intuitive representation of heterogeneous and complex biological processes. Moreover, they facilitate modeling and understanding of complicated molecular mechanisms combining graph theory, machine learning and deep learning techniques. While proteomics and genomics data, represented as data streams or data tables, are mainly used to screen large populations in case–control studies (e.g. for early detection of diseases), interactomics data are represented as graphs and they add a new dimension of analysis, allowing, for instance, the graph-based comparison of organism’s properties. In general, complex biological systems represented as networks provide an integrated way to look into the dynamic behavior of the cellular system through the interactions of components. For instance, biological networks also referred to as Protein–Protein Interaction Networks, model biochemical interactions among proteins. Nodes represent the proteins from a given organism, and the edges represent the protein–protein interactions [2]. Also, gene regulatory network (GRN) is a collection of genes in a cell, which interact each other and with other substances in the cell, such as proteins or metabolites, thereby governing the rates at which genes in the network are transcribed into mRNA. Similarly, the graph-based modeling of the whole system of the brain elements and their relations, so-called brain connectome, is based on the representation of the regions of interest as nodes, and the representation of functional or anatomical connections as edges [3]. Furthermore, recent discoveries in biology have elucidated that the interplay of molecules of different types (e.g. genes, proteins and ribonucleic acids) is a constitutive block of mechanisms inside cells. Consequently, models describing the interplay should be able to consider the presence of multiple different agents and associations, i.e. multiple different types of nodes and edges, that yield to the so-called heterogeneous networks [4].
Patient – ventilator asynchrony is a major issue during non-invasive ventilation and may lead to discomfort and treatment failure. Therefore, the identification and prompt management of asynchronies are of paramount importance during non-invasive ventilation (NIV), in both pediatric and adult populations. In this review, we first define the different forms of asynchronies, their classification, and the method of quantification. We, therefore, describe the technique to properly detect patient – ventilator asynchronies during NIV in pediatric and adult patients with acute respiratory failure, separately. Then, we describe the actions that can be implemented in an attempt to reduce the occurrence of asynchronies, including the use of non-conventional modes of ventilation. In the end, we analyzed what the literature reports on the impact of asynchronies on the clinical outcomes of infants, children, and adults.
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1,380 members
Carlo Torti
  • Department of Medical and Surgical Sciences
Antonio Gambardella
  • Department of Medical and Surgical Sciences
Gaia Chiara Mannino
  • Department of Medical and Surgical Sciences
Salvatore De Rosa
  • Department of Medical and Surgical Sciences
Francesca Cuzzocrea
  • Department of Health Sciences
Viale Europa, Localita' Germaneto 88100 , Catanzaro, Italy, Italy
Head of institution
Prof. Giovambattista De Sarro