Marco Denina - Academia.edu (original) (raw)

Papers by Marco Denina

JAMA Network Open

IMPORTANCE Severe gastrointestinal (GI) manifestations have been sporadically reported in childre... more IMPORTANCE Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. OBJECTIVE To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome.

International Journal of Molecular Sciences

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better progn... more Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. RIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin...

Multisystem inflammatory syndrome related to SARS-CoV-2 infection (MIS-C) is a rare severe illnes... more Multisystem inflammatory syndrome related to SARS-CoV-2 infection (MIS-C) is a rare severe illness affecting paediatric patients. No data are available in literature about the presence of SARS-CoV-2 RNA in faces in patients with MIS-C. The SARS-CoV-2 positivity was evaluated in fecal samples obtained in a prospective cohort of paediatric patients admitted to our tertiary Hospital and diagnosed with MIS-C or COVID-19 between April 15, 2020, and February 29, 2021. The real-time RT-PCR was performed using a validated kit. The assay measures 3 target genes: SARS-CoV-2 gene E, gene N, gene ORF1ab. Overall, 16/63 (25%) fecal samples revealed the presence of SARS -CoV-2 RNA. No differences were detected about time from presumptive viral exposure and the time of stool collection (14 vs 8 days, p> 0,05) as well as about the presence of gastrointestinal symptoms (p>0.05) between patients with positive (+) stools for SARS-CoV-2 RNA and patients tested negative (-). Among children with MI...

Pediatric Allergy and Immunology, 2020

Since April 2020, an increasing number of authors have reported a new clinical syndrome related t... more Since April 2020, an increasing number of authors have reported a new clinical syndrome related to SARS-COV2 infection in children, characterized by rapidly progressive systemic inflammation with multiorgan dysfunction. This syndrome has been addressed with many names since its description such as Multisystem Inflammatory Syndrome in children (MIS-C), Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-ST), and SARS-CoV-2-Induced Kawasaki-Like Hyperinflammatory Syndrome (SCiKH).1-3 The pathogenesis of MIS-C is still unknown, even if the positivity of a nasopharyngeal RT-PCR assay for the SARS-COV2 and/or of specific antibody testing in most patients suggests that this syndrome develops while the immune system is activated against the SARS-COV2 virus.

Cornea

PURPOSE This study aimed to present the efficacy and safety of cenegermin eye drop (Oxervate; Dom... more PURPOSE This study aimed to present the efficacy and safety of cenegermin eye drop (Oxervate; Dompè Farmaceutici, Milan, Italy) treatment in a pediatric patient affected by neurotrophic keratopathy (NK) with Goldenhar syndrome. METHODS This case reports an infant presenting ulceration and a small central opacity in the cornea of the right and left eyes, respectively. The NK bilaterally worsened despite the use of therapeutic contact lenses and temporary partial tarsorrhaphy. Magnetic resonance imaging showed absence and hypoplasia of the right and left trigeminal nerves, respectively. Cenegermin eye drops were administered 1 drop/each eye, 6 times daily for 8 weeks to promote corneal healing. RESULTS Complete healing was achieved in both eyes after treatment. During the 16-month follow-up period, no epithelial defect, recurrence, or complications were noticed, whereas corneal opacities progressively became clearer, although insignificant improvements in corneal sensitivity or in the reflex tearing were observed. CONCLUSIONS Cenegermin was effective in treating NK in an infant with Goldenhar syndrome.

SSRN Electronic Journal

Background: Severe gastrointestinal (GI) involvement has been occasionally reported in children w... more Background: Severe gastrointestinal (GI) involvement has been occasionally reported in children with SARS-CoV-2 infection or among those with multisystem inflammatory syndrome (MIS-C). We aimed to investigate the clinical, radiological and histopathological GI characteristics in order to identify factors associated with severe outcome. Methods: In this multicenter retrospective nationwide cohort study, symptomatic children with laboratory confirmed SARS-CoV-2 infection or MIS-C were enrolled. Children who received a diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, diffuse adeno-mesenteritis or abdominal fluid collections requiring surgical consultation and temporally correlated with SARS-CoV-2 infection were classified as having a severe GI involvement. Logistic regression models were used to estimate odds ratios (OR [95% confidence intervals]) between potential explanatory factors and severe outcome. Findings: 685 children were enrolled between February 2020 and January 2021. The presence of GI symptoms was associated with a higher chance of hospital admission (OR 2·64 [1·89–3·69]) and of intensive care support (OR 3·90 [1·98–7·68]).Overall, 65 children (9.5%) showed a severe GI involvement featuring atypical presentations including disseminated adeno-mesenteritis (39·6%), appendicitis (33·5%), abdominal fluid collections (21·3%), pancreatitis (6·9%) or ileal intussusception (4·6%). Twenty-seven (42%) of these children underwent surgery, and remarkably only half of clinically suspected appendicitis were histologically confirmed. Children aged 5-10 years (OR 8·33 [2·62–26·5]) or > 10 years of age (OR 6·37 [2·12-19·1]) had a higher chance of severe outcome, compared to preschool-age children. Severe GI outcomes were more frequent in patients with abdominal pain (aOR 34·5 [10·1–118]), lymphopenia (aOR 8·93 [3·03-26·3]) or MIS-C (aOR 6·28 [1·92–20·5]). Diarrhea was associated with a higher chance of adeno-mesenteritis (aOR 3·13 [1·08–9·12]) and abdominal fluid collections (aOR 3·22 [1·03-10]). Interpretation: About 10% of symptomatic children with COVID-19 may have severe GI involvement, frequently associated with MIS-C. Early identification of at-risk patients can improve the management of serious complications. Funding Statement: None. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Ethical Committee of the coordinating center (protocol number 0031296) as well as by independent ethics committees and/or institutional review boards of any single enrolling center.

European Journal of Clinical Microbiology & Infectious Diseases

Antimicrobial resistance is one of the most relevant threats in public health worldwide. Strategi... more Antimicrobial resistance is one of the most relevant threats in public health worldwide. Strategies as antimicrobial stewardship programs, aiming to preserve our antibiotic armamentarium, have been implemented since 2007 in adult and paediatric patients. We aim to describe the first experience of a paediatric antimicrobial stewardship program. We conducted a retrospective observational study in a tertiary care children's hospital. A team composed of a microbiologist, an infectious diseases physician, and a paediatrician led the project. All positive blood and cerebrospinal fluid cultures and other biological samples yielding multi-drug-resistant bacteria were collected and reviewed through a prospective-audit-with-feedback strategy. We recorded patient characteristics and worth monitoring prescribed antibiotics. The antimicrobial stewardship audit could end in intervention (step-up/step-down and broadening/narrowing) or recommendation(s). We then checked out wards staff compliance. The team performed 192 interventions out of 584 reviews, mostly suggesting discontinuation of antibiotics (in 76.0% of cases and 39.7% of running molecules). The antibiotic spectrum was more likely tapered than expanded (p < 0.0001), and we ordered more narrow-spectrum antibiotic molecules than local medical staff straightaway did (p = 0.0113). Interventions were most likely needed in case of documented infections (p < 0.0001) and in surgical patients (p = 0.0002). In 85.9% of interventions, ward teams fully agreed with our argument. This study demonstrated an antimicrobial stewardship program to be a suitable method for improving the appropriateness of antimicrobial use in hospitalized children.

Child and Adolescent Obesity

Journal of the American Academy of Dermatology

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Archives of Disease in Childhood

Irish Journal of Medical Science (1971 -)

Background Rapid identification of Covid-19 in the paediatric emergency department is critical; A... more Background Rapid identification of Covid-19 in the paediatric emergency department is critical; Antigen tests are fast but poorly investigated in children. Aims To investigate Sars-CoV-2 antigen rapid test in children. Methods We compare the performance of LumiraDx with molecular tests in a paediatric emergency department. Results A retrospective cohort of 191 patients with AT and PCR tests performed in the same episode was analysed; 16% resulted positive for Sars-CoV-2. Using the PCR test as the gold standard, we calculated antigen testing overall sensitivity of 94.1%, specificity of 91.9%, and NPV of 99.4%. Only one false-negative test was found. Conclusions AT may be helpful in the initial screening of patients at PED.

Pediatric Infectious Disease Journal

BACKGROUND Despite efforts made to prevent the spread of multi-drug-resistant bacteria, carbapene... more BACKGROUND Despite efforts made to prevent the spread of multi-drug-resistant bacteria, carbapenemase-producing Enterobacteriaceae (CPE) has become one of the most dangerous threat worldwide. However, data on the epidemiology of CPE and on the correlation between CPE colonization and infection are scanty. The objectives of this study were first to describe the epidemiological characteristics of colonizations and invasive CPE infections in the pediatric population, and second, to apply the Giannella Risk Score (GRS) to the pediatric population for the assessment of the risk of invasive CPE infection in patients with already known colonization. METHODS Pediatric patients with evidence of colonization by CPE were retrospectively enrolled. For each colonized patient, the subsequent development of an infection by CPE was then assessed for a 90-day period after the first CPE isolation; GRSs were compared between patients who had developed any type of CPE infection and those without infection. RESULTS A total of 215 patients (113 males and 102 females) with at least 1 isolation of CPE during hospitalization were analyzed. Median age was 5.6 years [interquartile range (IQR), 1.89-12.2 years]. Overall, 28 CPE infections (13%) were documented: 23 blood stream infections and 5 complicated urinary tract infections. The 30-day mortality of invasive CPE infections was 34.8%. The GRS values in patients with any CPE infection were statistically higher than in noninfected patients: median GRS 9 (IQR, 4-12.5) versus 4 (IQR, 2-4), respectively; P < 0.0001. The analysis of the receiver operating characteristic curves identified a GRS cut-off value ≥8 as the best predictor of CPE infection. The likelihood ratio of the results was <2 and the informedness of the test had a value <0.50. CONCLUSIONS Our study confirms that the spread of CPE is an impelling problem also in the pediatric population, with a high mortality rate of invasive infections. However, the application of the GRS appears to be poorly informative in the pediatric setting; it might sometimes help to identify patients at very low risk of CPE infection, in whom it is reasonable to spare targeted antimicrobial treatments.

Pediatrics

We describe 2 children with persistent fever and profuse diarrhea who developed signs of mucocuta... more We describe 2 children with persistent fever and profuse diarrhea who developed signs of mucocutaneous involvement (conjunctivitis, fissured lips, skin rash, erythema, and edema of the hands and feet). Blood tests revealed elevated markers of inflammation, lymphopenia, thrombocytopenia, and complement consumption. Afterward, diffuse edema with hypoalbuminemia appeared in the context of a capillary leak syndrome. In both patients, repeated nasal swabs were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but each patient had high titers of immunoglobulin G and immunoglobulin M against the SARS-CoV-2 virus. The negative PCR results in the presence of immunoglobulin M and immunoglobulin G suggested that the inflammatory response developed in the late phase of viral infection, when SARS-CoV-2 was not detectable in the upper airway. In this report, we describe patients with what we propose to name as SARS-CoV-2–induced Kawasaki-like hyperinflammatory syndrome. S...

Journal of Thrombosis and Haemostasis

Multiple investigators have described an increased incidence of thromboembolic events in SARS‐CoV... more Multiple investigators have described an increased incidence of thromboembolic events in SARS‐CoV‐2–infected individuals. Data concerning hemostatic complications in children hospitalized for COVID‐19/multisystem inflammatory syndrome in children (MIS‐C) are scant.

Pediatric Infectious Disease Journal

Eurosurveillance

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and ... more Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.