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1.
Frontiers in pediatrics ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1877195

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) time exacerbated some of the conditions already considered critical in pediatric health assistance before the pandemic. A new form of pediatric social abandonment has arisen leading to diagnostic delays in surgical disorders and a lack of support for the chronic ones. Health services were interrupted and ministerial appointments for pediatric surgical healthcare reprogramming were postponed. As a result, any determination to regulate the term “pediatric” specificity was lost. The aim is, while facing the critical issues exacerbated by the COVID-19 pandemic, to rebuild future perspectives of pediatric surgical care in Italy. Methods Each Pediatric Society, including the Italian Society of Pediatric Surgery (SICP), was asked by the Italian Federation of Pediatric Associations and Scientific Societies to fill a questionnaire, including the following the main issues: evaluation of pre-pandemic criticalities, pediatric care during the pandemic and recovery, and current criticalities. The future care model of our specialty was analyzed in the second part of the questionnaire. Results Children are seriously penalized both for surgical treatment as well as for the diagnostic component. In most centers, the pediatric surgical teams have been integrated with the adult ones and the specificity of training the pediatric operating nursing is in danger of survival. “Emotional” management of the child is not considered by the general management and the child has become again an adults patient of reduced size. Conclusion A new functional pediatric surgical model needs to be established in general hospitals, including activities for day surgery and outpatient surgery. To support the care of the fragile child, a national health plan for the pediatric surgery is required.

2.
Int J Mol Sci ; 22(21)2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1488618

ABSTRACT

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.


Subject(s)
Mesenchymal Stem Cells/metabolism , Respiratory System Abnormalities , SARS-CoV-2/physiology , Transcriptome , COVID-19/genetics , COVID-19/metabolism , COVID-19/pathology , Case-Control Studies , Cells, Cultured , Gene Expression Profiling , Host-Pathogen Interactions/genetics , Humans , Infant , Lung/abnormalities , Lung/metabolism , Lung/pathology , Male , Mesenchymal Stem Cells/pathology , Mesenchymal Stem Cells/virology , RNA-Seq , Respiratory System Abnormalities/genetics , Respiratory System Abnormalities/pathology , Respiratory System Abnormalities/virology
3.
Cells ; 10(9)2021 08 25.
Article in English | MEDLINE | ID: covidwho-1374305

ABSTRACT

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.


Subject(s)
COVID-19/genetics , COVID-19/virology , Cellular Senescence/genetics , Gene Expression Profiling , Neurons/pathology , Oxidative Stress/genetics , SARS-CoV-2/physiology , Caspase 3/metabolism , Cell Death , Cell Line , Cyclooxygenase 2/metabolism , Humans , Superoxide Dismutase/metabolism , Virus Replication/physiology
4.
Int J Mol Sci ; 22(15)2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1335097

ABSTRACT

Different mechanisms were proposed as responsible for COVID-19 neurological symptoms but a clear one has not been established yet. In this work we aimed to study SARS-CoV-2 capacity to infect pediatric human cortical neuronal HCN-2 cells, studying the changes in the transcriptomic profile by next generation sequencing. SARS-CoV-2 was able to replicate in HCN-2 cells, that did not express ACE2, confirmed also with Western blot, and TMPRSS2. Looking for pattern recognition receptor expression, we found the deregulation of scavenger receptors, such as SR-B1, and the downregulation of genes encoding for Nod-like receptors. On the other hand, TLR1, TLR4 and TLR6 encoding for Toll-like receptors (TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-κB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptors for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKε and IRF3 were downregulated. We also found the upregulation of genes encoding for chemokines and accordingly we found an increase in cytokine/chemokine levels in the medium. According to our results, it is possible to speculate that additionally to ACE2 and TMPRSS2, also other receptors may interact with SARS-CoV-2 proteins and mediate its entry or pathogenesis in pediatric cortical neurons infected with SARS-CoV-2. In particular, TLRs signaling could be crucial for the neurological involvement related to SARS-CoV-2 infection.


Subject(s)
COVID-19/metabolism , Cerebral Cortex/metabolism , Neurons/virology , SARS-CoV-2/pathogenicity , Toll-Like Receptors/metabolism , COVID-19/genetics , COVID-19/immunology , Child , Cytokines/metabolism , Gene Expression Profiling , Gene Expression Regulation , Humans , Neurons/immunology , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Signal Transduction/genetics , Toll-Like Receptors/genetics , Virus Replication
5.
Children (Basel) ; 8(5)2021 May 13.
Article in English | MEDLINE | ID: covidwho-1227003

ABSTRACT

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride-glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70-180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141-180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.

6.
Healthcare (Basel) ; 9(5)2021 May 08.
Article in English | MEDLINE | ID: covidwho-1223985

ABSTRACT

Considerable reorganization of the regional network for pediatric burn treatment during the pandemic was required to cope with severe burn injuries in small children. In support of the emergency network for burns during the COVID-19 pandemic, we referred to regional indications for centralization in our hospital for all children aged less than 5 years who presented with severe burns, >15% of total body surface area (TBSA), or who necessitated admittance to the pediatric intensive care unit (PICU). A new service with a dedicated management protocol was set up to treat pediatric burns in our SARS-CoV-2 pediatric hospital during the lockdown period. A multidisciplinary burn treatment team was set up to offer compassionate and comprehensive burn care. Patient's clinical data, burn features, treatment and follow up were recorded. A higher number of admissions was recorded from February to December 2020 compared with the same period in 2019 (52 vs. 32 admissions). Eighteen patients were admitted to the COVID-19 Service (10 M/8 F; 3.10 ± 2.6 yrs); ten children (55.5%) were hospitalized in the ward and eight in the ICU (44.5%). Fifty percent of the cases presented with lesions extending over >15% TBSA; in one case, TBSA was 35%. All patients suffered 2nd-degree burns; while five patients also had 3rd degree lesions covering more than 15% TBSA. All of the injuries occurred at home. No major secondary infections were recorded. Successful treatment was achieved in 94.4% of cases. The average length of stay was 15.2 ± 12.6 days. A proactive, carefully planned service, involving a multidisciplinary team, was created to ensure appropriate care in a pediatric hospital during the COVID-19 period, despite the effective pandemic associated challenges. Better health promotion in pediatric burn cases should also include dedicated TBSA assessment and a database of children's burn characteristics.

7.
Acta Anaesthesiol Scand ; 65(6): 755-760, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1096648

ABSTRACT

BACKGROUND: The initial wave of the Covid-19 pandemic has hit Italy, and Lombardy in particular, with violence, forcing to reshape all hospitals' activities; this happened even in pediatric hospitals, although the young population seemed initially spared from the disease. "Vittore Buzzi" Children's Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), had to stop elective procedures-with the exception of urgent/emergent ones-between February and May 2020 to leave space and resources to adults' care. We describe the challenges of reshaping the hospital's identity and structure, and restarting pediatric surgery and anesthesia, from May on, in the most hit area of the world, with the purpose to avoid and contain infections. Both patients and caregivers admitted to hospital have been tested for Sars-CoV-2 in every case. METHODS: Observational cohort study via review of clinical charts of patients undergoing surgery between 16th May and 30th September 2020, together with SARS-CoV -2 RT-PCR testing outcomes, and comparison to same period surgeries in 2019. RESULTS: An increase of approximately 70% in pediatric surgeries (OR 1.68 [1.33-2.13], P < .001) and a higher increase in the number of surgeries were reported (OR 1.75 (1.43-2.15), P < .001). Considering only urgent procedures, a significant difference in the distribution of the type of surgery was observed (Chi-squared P-value < .001). Sars-CoV-2-positive patients have been 0.8% of total number; 14% of these was discovered through caregiver's positivity. CONCLUSION: We describe our pathway for safe pediatric surgery and anesthesia and the importance of testing both patient and caregiver.


Subject(s)
Anesthesia Department, Hospital/organization & administration , Appointments and Schedules , COVID-19 Nucleic Acid Testing , COVID-19/epidemiology , Hospitals, Pediatric/organization & administration , Hospitals, University/organization & administration , Pandemics , SARS-CoV-2 , Surgery Department, Hospital/organization & administration , Surgical Procedures, Operative/statistics & numerical data , Tertiary Care Centers/organization & administration , Adolescent , COVID-19 Nucleic Acid Testing/statistics & numerical data , Caregivers , Child , Child, Preschool , Cohort Studies , Diagnosis-Related Groups , Elective Surgical Procedures/statistics & numerical data , Emergencies/epidemiology , Female , Hospital Bed Capacity/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Hospitals, University/statistics & numerical data , Hospitals, Urban/organization & administration , Hospitals, Urban/statistics & numerical data , Humans , Infant , Infant, Newborn , Infection Control/methods , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Italy/epidemiology , Male , Nasopharynx/virology , Patients , SARS-CoV-2/isolation & purification , Symptom Assessment , Tertiary Care Centers/statistics & numerical data , Young Adult
8.
Pediatr Rep ; 12(3): 114-123, 2020 Nov 12.
Article in English | MEDLINE | ID: covidwho-1024622

ABSTRACT

During the coronavirus disease of 2019 (COVID-19) emergency, in the pediatric surgical setting, it has been essential to avoid and contain infections as well as to protect both the patients and the surgical team. During this emergency, procedures and workflow were adapted to provide the safest possible environment for both the surgical team and the patients. Pediatric surgical activities were reorganized during the COVID-19 pandemic at the "Vittore Buzzi" Children's Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), Italy. Resources were optimized in order to maintain high levels of care and quality of assistance. During the COVID-19 emergency, the pediatric surgical department at the "Vittore Buzzi" Children's Hospital became an acute care surgical service. For the reorganization of surgical activities, institutional protocols were adapted in order to preserve the pediatric-specific characteristics of our service; five crucial points were specifically addressed. The pediatric surgical procedures carried out during the initial two months of the Italian lockdown are also reported. Continuity of care was maintained for children affected by severe diseases, such as tumors and neurosurgical conditions, whose treatment could not be deferred. Telemedicine and telecommunication were adopted as quick-support modalities for pre- and post-operative care. This reorganization allowed us to preserve the "pediatric specificity" and all care-related procedures offered at this high-quality/high-volume surgical care referral center.

9.
Front Pediatr ; 8: 600320, 2020.
Article in English | MEDLINE | ID: covidwho-1000117

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the routine activities of pediatric surgical centers, and it determined the reduction of admissions in the pediatric emergency departments (PED). We reviewed the records of patients affected by acute appendicitis (AA) during the COVID-19 pandemic period in a large Italian COVID-19 pandemic area. Methods: Data regarding demographics, age, macroscopic and microscopic findings, and time between symptom onset and PED admission of patients affected by confirmed AA in the period between March and April 2020 were considered. The data were compared with those obtained during the same period of 2019, 2018, and 2017 in the included centers. Data were quoted as median (range) or absolute number. Non-parametric statistical tests were used to compare groups. A p ≤ 0.05 was regarded as significant. Since only anonymous data have been used and the data storage meets current data protection regulations, ethical committee approval was not required for this study. Results: Eighty-six patients underwent surgical appendectomy for AA between February 20th, 2020 and April 20th, 2020; 32.5% were complicated appendicitis and 67.5% were uncomplicated. Fifty-three patients were males and 33 were females. Patients' age ranged from 3 to 17 years and the median age was 10 years. The median time between the onset of symptoms and the admission in PED was 1.85 days. The average time between the symptom onset and PED admission was 1.8 days. Conclusions: Although fear from the COVID-19 pandemic determined a delayed diagnosis of serious pediatric diseases, the increasing prevalence and severity of AA were not demonstrated in the most COVID-19-affected areas of Italy.

10.
Pediatric Reports ; 12(3), 2020.
Article in English | MDPI | ID: covidwho-918928

ABSTRACT

During the coronavirus disease of 2019 (COVID-19) emergency, in the pediatric surgical setting, it has been essential to avoid and contain infections as well as to protect both the patients and the surgical team. During this emergency, procedures and workflow were adapted to provide the safest possible environment for both the surgical team and the patients. Pediatric surgical activities were reorganized during the COVID-19 pandemic at the “Vittore Buzzi”Children’s Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), Italy. Resources were optimized in order to maintain high levels of care and quality of assistance. During the COVID-19 emergency, the pediatric surgical department at the “Vittore Buzzi”Children’s Hospital became an acute care surgical service. For the reorganization of surgical activities, institutional protocols were adapted in order to preserve the pediatric-specific characteristics of our service;five crucial points were specifically addressed. The pediatric surgical procedures carried out during the initial two months of the Italian lockdown are also reported. Continuity of care was maintained for children affected by severe diseases, such as tumors and neurosurgical conditions, whose treatment could not be deferred. Telemedicine and telecommunication were adopted as quick-support modalities for pre- and post-operative care. This reorganization allowed us to preserve the “pediatric specificity”and all care-related procedures offered at this high-quality/high-volume surgical care referral center.

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