Regenerative medicine: postnatal approaches.

Paper 2 of the paediatric regenerative medicine Series focuses on recent advances in postnatal approaches. New gene, cell, and niche-based technologies and their combinations allow structural and functional reconstitution and simulation of complex postnatal cell, tissue, and organ hierarchies. Organoid and tissue engineering advances provide human disease models and novel treatments for both rare paediatric diseases and common diseases affecting all ages, such as COVID-19. Preclinical studies for gastrointestinal disorders are directed towards oesophageal replacement, short bowel syndrome, enteric neuropathy, biliary atresia, and chronic end-stage liver failure. For respiratory diseases, beside the first human tracheal replacement, more complex tissue engineering represents a promising solution to generate transplantable lungs. Genitourinary tissue replacement and expansion usually involve application of biocompatible scaffolds seeded with patient-derived cells. Gene and cell therapy approaches seem appropriate for rare paediatric diseases of the musculoskeletal system such as spinal muscular dystrophy, whereas congenital diseases of complex organs, such as the heart, continue to challenge new frontiers of regenerative medicine.

Maintaining a minimally invasive surgical service during a pandemic.

PURPOSE: The safety of minimally invasive surgery (MIS) was questioned in the COVID-19 pandemic due to concern regarding disease spread. We continued MIS during the pandemic with appropriate protective measures. This study aims to assess the safety of MIS compared to Open Surgery (OS) in this setting. METHODS: Operations performed during 2020 lockdown were compared with operations from the same time-period in 2019 and 2021. Outcomes reviewed included all complications, respiratory complications, length of stay (LOS) and operating surgeon COVID-19 infections (OSI). RESULTS: In 2020, MIS comprised 52% of procedures. 29% of MIS 2020 had complications (2019: 24%, 2021: 15%; p = 0.08) vs 47% in OS 2020 (p = 0.04 vs MIS). 8.5% of MIS 2020 had respiratory complications (2019: 7.7%, 2021: 6.9%; p = 0.9) vs 10.5% in OS 2020 (p = 0.8 vs MIS). Median LOS[IQR] for MIS 2020 was 2.5[6] days vs 5[23] days in OS 2020 (p = 0.06). In 2020, 2 patients (1.2%) were COVID-19 positive (MIS: 1, OS: 1) and there were no OSI. CONCLUSION: Despite extensive use of MIS during the pandemic, there was no associated increase in respiratory or other complications, and no OSI. Our study suggests that, with appropriate protective measures, MIS can be performed safely despite high levels of COVID-19 in the population.

Intussusception and COVID-19 in Infants: Evidence for an Etiopathologic Correlation.

Nonrespiratory conditions related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been largely described. Ileocolic intussusception has been reported in association with SARS-CoV-2 infection in 10 children, raising the possibility of an etiopathologic role for the virus, but none of these cases documented tissue pathology that would have supported SARS-CoV-2 intestinal inflammation. We report 2 cases of intussusception in patients with SARS-CoV-2 infection who were treated at different pediatric tertiary centers in Europe and provide evidence of the presence of the virus in mesenteric and intestinal tissues of the patients.

Local and systemic responses to SARS-CoV-2 infection in children and adults.

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Junior doctor burnout following the first wave of the COVID-19 pandemic

ObjectiveThe aim of the present study was to assess the burden of burnout in junior medical staff working across all surgical specialities at Great Ormond Street Hospital following the first wave of the COVID-19 pandemic.MethodsWe conducted a cross-sectional study in surgical junior doctors at Great Ormond Street Hospital following relaxation of the COVID-19-related restrictions at the end of June 2020. Burnout was evaluated using the Maslach Burnout Inventory (MBI). This is a widely-used, validated questionnaire, which evaluates burnout across three domains: emotional exhaustion, depersonalisation, and personal accomplishment. All responses were anonymised, points (0–6) were awarded for each response, and composite scores were generated using an online tool. The degree of burnout was classified as low, medium or high for each of the three domains using standardised score ranges.ResultsA total of 25 surgical junior doctors were included in our study. The response rate was 48%, and scores from 12 fully completed MBI-HSS were included in subsequent analysis. 10 of the responders (83%) reported high burnout levels in at least one domain, and 6 (50%) across at least two domains. The main contributor to burnout was the lack of feeling of personal accomplishment that was found to be high in 67%, medium in 25%, and low in 8% of the responders. We also found significant levels of emotional exhaustion (high: 42%;medium 42%;low 17%) as well as depersonalisation (high: 42%;medium 42%;low 17%).ConclusionsOur study confirms the significant burden of burnout among junior doctors working in surgical specialities at Great Ormond Street Hospital for Children during the first wave of the COVID-19 pandemic. This could have detrimental effects on both doctor health and patient outcomes. Future work needs to focus on strategies to improve junior doctor wellbeing and prevent burnout.

Foreign body ingestion: a real hazard during the covid pandemic

IntroductionChildren curiosity for exploring their surrounding environment make them prone to foreign body (FB) ingestion which may lead to injuries and surgical intervention. COVID pandemic and national lockdown has impacted children’s normal environment in addition to the changes in the health care system provision. The aim was to determine if the pandemic had a direct impact on the number and management of FB ingestion cases.MethodAll patients who were referred to our institution with diagnosis of FB from March 2020 to December 2020 were included. They were compared with FB referral during the period March-Dec 2019 as a control. Data included patients’ demographics, time to presentation, type of FB ingested and management approach.ResultsThere was a total of 30 patients with diagnosis of gastrointestinal FB during the study period as compared to 12 patients during the control periods. Thus, during the COVID pandemic there was 2.5 times rise in number of cases. The mean age at presentation was 6.4 years during the study period as compared to 4.6 years in the control group. Timing of presentation varied from 0 to 57 days during the COVID pandemic as compared to control group who presented within 24hr except one who presented after 48hr.The most common foreign bodies encountered during the pandemic were button batteries (12), magnets (7), coins (5), other sharp and metallic objects (6). Two third (67%) of patients in the study period required surgical intervention as compared to one third (33%) during the control period. Most common site of impaction was stomach (40%) followed by oesophagus (36.6%).ConclusionThe total number of children diagnosed with FB ingestion had significantly increased during the COVID pandemic. Public campaigns should be focused on raising awareness about the danger and medical emergency as a result of FB ingestion.

SARS-CoV-2 infection and replication in human gastric organoids.

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission.

Foreign body ingestion during the COVID-19 pandemic: a retrospective single centre review.

Introduction: During the COVID-19 pandemic in 2020, there were many changes in the provision of healthcare as well as home and educational environments for children. We noted an apparent increase in the number of children presenting with ingested foreign bodies and due to the potential impact of injury from this, further investigated this phenomenon. Method: Using a prospective electronic record, data were retrospectively collected for patients referred to our institution with foreign body ingestion from March 2020 to September 2020 and compared with the same period the year prior as a control. Results: During the 6-month pandemic period of review, it was observed that 2.5 times more children were referred with foreign body ingestion (n=25) in comparison to the control period (n=10). There was also a significant increase in the proportion of button battery and magnet ingestions during the COVID-19 pandemic (p 0.04). Conclusion: These findings raise concerns of both increased frequency of foreign body ingestion during the COVID-19 pandemic and the nature of ingested foreign bodies linked with significant morbidity. This may relate to the disruption of home and work environments and carries implications for ongoing restrictions. Further awareness of the danger of foreign body ingestion, especially batteries and magnets, is necessary (project ID: 2956).

COVID-19 pandemic experiences of parents caring for children with oesophageal atresia/tracheo-oesophageal fistula.

Purpose: The COVID-19 pandemic has resulted in a global health crisis of unparalleled magnitude. The direct risk to the health of children is low. However, disease-containment measures have society-wide impacts. This study explored the pandemic experiences of parents of children with oesophageal atresia/tracheo-oesophageal fistula (OA/TOF) in the UK. Design: A phenomenological approach underpinned use of an asynchronous online forum method, in collaboration with a patient support group. Data were evaluated using thematic analysis. Results: The online forum ran between 7 November and 18 December 2020 with 109 participants.Pandemic experiences were divided into themes relating to healthcare and disease containment. Participants described positive experiences with remote healthcare but identified limitations. Delays and cancellations led to escalation of care to an emergency level, slower developmental progress and feelings of being abandoned by services. Inpatient care was perceived as safe but caring alone was emotionally and practically challenging. Disease containment themes revealed anxiety regarding health risks, 'collateral' damage to well-being because of isolation, and an impact on finances and employment. Parents described a transition from worry about direct health risks to concern about the impact of isolation on socialisation and development. A process of risk-benefit analysis led some to transition to a more 'normal life', while others continued to isolate. Benefits to their child's health from isolation were reported. Conclusions: Parents' experiences of caring for a child with OA/TOF during the pandemic were varied. Rapid adoption of telehealth has demonstrated the enormous potential of remote healthcare delivery but requires refinement to meet the needs of the individual. Future pandemic planning should aim to retain community healthcare services to avoid escalation of care to an emergency, manage chronic and developmental concerns, and support parental well-being. Accurate and consistent disease-specific information is highly valued by parents. Third sector organisations are ideally positioned to support this.