Publications by authors named "Gustavo Cernera"

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-COVID condition due to a delayed hyperimmune response to SARS-CoV-2. High-density lipoproteins (HDL) are pivotal players in inflammatory and immune modulation through the remodeling of their subfractions.

Methods: This study aimed to evaluate serum levels of cholesterol, HDL, and HDL subfractions (HDL-SUB) to define their role in the pathogenesis of MIS-C and their potential use as biomarkers of this condition.

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The triple combination therapy for cystic fibrosis (CF), including elexacaftor, tezacaftor and ivacaftor (ETI or Trikafta), has been shown to improve lung function and reduce pulmonary exacerbations, thereby enhancing the quality of life for most CF patients. Recent findings suggest that both the individual components and ETI may have potential off-target effects, highlighting the need to understand how these modulators impact cellular physiology, particularly in cells that do not express CF transmembrane conductance regulator (CFTR). We used HEK293 cells, as a cell model not expressing the CFTR protein, to evaluate the effect of ETI and each of its components on autophagic machinery and on the Rab5/7 components of the Rab pathway.

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  • The study analyzed saliva from 63 hospitalized COVID-19 patients and 30 healthy controls using advanced techniques to identify biochemical changes and potential noninvasive diagnostic biomarkers.
  • It found significant differences in the levels of 77 proteins, with unique and varied expressions among COVID-19 patients, highlighting a complex interplay between pro-inflammatory and anti-inflammatory responses.
  • The research also noted alterations in peptides and amino acids, establishing a diagnostic algorithm with high efficiency to differentiate between COVID-19 patients and healthy individuals.
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Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) improved cystic fibrosis (CF) patients' outcome. The elexacaftor/tezacaftor/ivacaftor (ETI) combination was safe and effective improving lung function in patients with different CFTR genotypes, including at least one F508del mutation. However, cases with liver damage were reported.

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  • Thymic epithelial tumors (TETs) are rare tumors often linked to immune issues, like Good's syndrome (GS), which increases mortality risk from infections.
  • The study reviewed COVID-19 incidence and severity among TET patients from March 2020 to April 2023, noting that about 66% of participants contracted COVID-19, regardless of GS presence.
  • Results showed a significant correlation between GS and increased COVID-19 severity, with 45% of GS patients experiencing higher severity scores compared to just 7.7% in patients without GS.
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  • Cystic fibrosis (CF) is a serious genetic disorder caused by mutations in the CFTR gene that affect chloride ion transport, and early detection improves patient outcomes.
  • Researchers discovered an overlooked Alu element insertion in the CFTR gene that was identified using traditional molecular techniques, which corrected the diagnosis missed by standard sequencing methods.
  • Their findings show that this insertion negatively impacts CFTR gene expression and protein structure, highlighting the need for combining human expertise with modern technologies in genomic medicine for better healthcare solutions.
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  • Thymic epithelial tumor (TET) patients are at risk for autoimmune issues, prompting a study on the effects of the SARS-Cov-2 vaccine on inflammatory reactions in these individuals compared to healthy controls.
  • The study evaluated serum biomarkers related to inflammation and vascular damage in 44 TET patients and 30 healthy individuals, finding that about 50% showed increased markers after vaccination, with TET patients experiencing changes primarily after the second dose.
  • The vaccine was deemed safe for TET patients as no serious complications occurred, but the researchers call for more studies to understand the implications of the biomarker increases observed.
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  • The study aimed to evaluate the presence of nine prothrombotic gene variants in women with a history of pregnancy loss and recurrent pregnancy loss (RPL), including those who underwent assisted reproductive technology (ART).
  • The research involved comparing different groups: women with one or two pregnancy losses, those with RPL, women with ongoing pregnancies post-ART, and those with recurrent implantation failures (RIF) to a control group from the general population.
  • Results indicated that certain genetic variants, particularly factor V Leiden and others, were linked to a higher risk of RPL and RIF, suggesting these variants contribute to issues with embryo implantation and development.
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  • Thymic epithelial tumors (TETs) are rare cancers often linked to autoimmune disorders and severe immunodeficiency, which complicates responses to COVID-19 vaccines.
  • A study was conducted to assess immune responses to the SARS-Cov-2 mRNA vaccine in TET patients, focusing on humoral and cellular responses and vaccination safety over a full cycle including a booster.
  • The results showed significant immune responses post-vaccination, with a correlation between baseline lymphocyte levels and vaccine effectiveness, and most patients did not experience severe COVID-19 even when infected during the study period.
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  • Thymic epithelial tumors (TETs) are rare cancers that affect the immune system, and this study investigates how patients with TET respond to the SARS-CoV-2 mRNA vaccine after two doses.
  • The study involved 39 patients, analyzing their antibody levels before and after vaccination, revealing that all had negative antibody levels before vaccination, with differences in seroconversion based on their disease status.
  • Results indicated that patients with evidence of disease (ED) had a significantly lower chance of generating an immune response compared to those with no evidence of disease, highlighting the impact of their existing health conditions on vaccine effectiveness.
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  • Sars-CoV-2 infections vary widely in severity, influenced by factors like age, preexisting health issues, and genetic susceptibility, particularly relating to the mannose-binding lectin (MBL) protein.
  • A study of 419 COVID-19 patients revealed that those with specific MBL2 haplotypes, especially null alleles, tend to experience more severe symptoms and inflammation.
  • The findings suggest that testing for MBL2 genotypes and serum MBL levels could guide treatment strategies, with early MBL therapy potentially benefiting patients with defective genotypes.
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  • The Italian Ministry of Health implemented a COVID vaccination plan for frail patients and healthcare workers starting in January 2021, using a three-dose regimen.
  • A study involving 53 family pediatricians was conducted to assess immune responses post-vaccination through various laboratory techniques, revealing that while antibody levels rose significantly after the third dose, they did not predict infection risk.
  • The research found that after the booster, activated T cell responses, particularly CD8 IFN-γ levels, were significantly associated with a lower risk of infection in the following six months, highlighting potential implications for other vaccine strategies.
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  • - Clinical outcomes between the first and second waves of COVID-19 in Europe showed that patients in the second wave had significantly lower levels of iNOS, IL-6, and IL-10 compared to those in the first wave, indicating a less severe illness.
  • - Serum levels of iNOS and inflammatory markers (IL-6 and IL-10) correlated with the severity of COVID-19 in the first wave but did not do so in the second wave, suggesting a shift in the disease's impact over time.
  • - In severe cases during the second wave, patients who were treated with steroids or azithromycin before hospitalization had decreased iNOS levels, leading to concerns about their immune response, and highlighting the potential need for
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The molecular basis of the wide clinical heterogeneity of Coronavirus disease 2019 (COVID-19) is still unknown. Matrix metalloproteinases (MMPs) may have a role in the lung damage and regeneration that occur in severe patients. We studied serum MMP3 and MMP9 as potential biomarkers of COVID-19 severity, in 108 hospitalized patients with different World Health Organization (WHO) severity stage and in 48 controls.

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A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects.

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Systemic vascular damage with micro/macro-thrombosis is a typical feature of severe COVID-19. However, the pathogenesis of this damage and its predictive biomarkers remain poorly defined. For this reason, in this study, serum monocyte chemotactic protein (MCP)-2 and P- and E-selectin levels were analyzed in 204 patients with COVID-19.

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Clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seem to differ in children compared to that in adults. It has been hypothesized that the lower clinical severity in children could be influenced by differential expression of the main host functional receptor to SARS-CoV-2, the angiotensin-converting enzyme 2 (ACE2), but data are still conflicting. To explore the origin of age-dependent clinical features of coronavirus disease 2019 (COVID-19), we comparatively evaluated the expression in children and adult subjects of the most relevant mediators of the SARS-CoV-2 infection: ACE2, angiotensin-converting enzyme 1 (ACE1), transmembrane serine protease-2 (TMPRSS2), and neuropilin-1 (NRP1), at upper respiratory tract and small intestine level.

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: ischemic stroke (IS) is among the most frequent causes of death worldwide; thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk subjects. :we tested nine variants in genes involved in thrombotic pathway in 282 patients that experienced IS and 87 that had transient ischemic attacks (TIA) in comparison to 430 subjects from the general population (GP) of the same geographic area (southern Italy). We included cases of young and child IS to evaluate the eventual differences in the role of the analyzed variants.

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COVID-19 may appear with a widely heterogeneous clinical expression. Thus, predictive markers of the outcome/progression are of paramount relevance. The neutrophil/lymphocyte ratio (NLR) has been suggested as a good predictive marker of disease severity and mortality.

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Cystic fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge.

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Congenital diarrheal disorders (CDDs) are early-onset enteropathies generally inherited as autosomal recessive traits. Most patients with CDDs require rapid diagnosis as they need immediate and specific therapy to avoid a poor prognosis, but their clinical picture is often overlapping with a myriad of nongenetic diarrheal diseases. We developed a next-generation sequencing (NGS) panel for the analysis of 92 CDD-related genes, by which we analyzed patients suspect for CDD, among which were (i) three patients with sucrose-isomaltase deficiency; (ii) four patients with microvillous inclusion disease; (iii) five patients with congenital tufting enteropathy; (iv) eight patients with glucose-galactose malabsorption; (v) five patients with congenital chloride diarrhea.

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