Transforming a paediatric ICU to an adult ICU for severe Covid-19: lessons learned.

During the first Covid-19 wave, our paediatric intensive care unit (PICU), like many others across the globe, was transformed into an adult ICU for patients with severe Covid-19, due to a shortage of adult ICU beds. Here, we provide a comprehensive description of all the conditions that must be fulfilled to successfully accomplish this transformation. Strong support from all hospital departments was crucial, as their activity was modified by the change. Healthcare workers from various units, notably the paediatric anaesthesiology department, worked in the adult ICU to ensure sufficient staffing. The number of physiotherapists and psychologists was increased. A support system for both healthcare workers and patients' relatives was set up with the help of the mobile paediatric palliative care and support team. Supplies suitable for adults were ordered. Protocols for numerous procedures were written within a few days. Video tutorials, checklists, and simulation sessions were circulated to the entire staff. The head nurses guided and supported the new staff and usual PICU staff. The transformation was achieved within a week. The main difficulties were healthcare worker stress, changes in recommendations over time, absence of visits from relatives, and specific adult issues that paediatricians are unfamiliar with.Conclusion: For the staff, caring for adult patients was made easier by working in their familiar unit instead of being moved to an adult hospital with unfamiliar staff members and equipment. Strong support from the hospital and the assistance of consultants from adult hospital departments were crucial. What is Known: • The dramatic spread across the world of coronavirus disease 2019 generated critical care needs that drastically exceeded resources in many countries worldwide. • Paediatric ICU activity during this period decreased due to lockdown measures and the fact that children rarely required ICU for coronavirus disease 2019. What is New: • We describe how an 18-bed adult Covid-19 ICU was successfully set up in a paediatric hospital during the first wave of the Covid-19 pandemic. • Specific requirements regarding supply, human resources, and procedures, as well as difficulties encountered, are described.

Mowat Wilson syndrome and Hirschsprung disease: a retrospective study on functional outcomes.

AIM OF THE STUDY: Mowat Wilson syndrome (MWS) is a complex genetic disorder due to mutation or deletion of the ZEB2 gene (ZFHX1B), including multiple clinical features. Hirschsprung disease is associated with this syndrome with a prevalence between 43 and 57%. The aim of this study was to demonstrate the severe outcomes and the high complication rates in children with MWS, focusing on their complicated follow-up. METHODS: A retrospective comparative study was conducted on patients referred to Robert-Debré Children's Hospital for MWS from 2003 to 2018. Multidisciplinary follow-up was carried out by surgeons, geneticists, gastroenterologists, and neurologists. Data regarding patient characteristics, surgical management, postoperative complications, and functional outcomes were collected. RESULTS: Over this period of 15 years, 23 patients were diagnosed with MWS. Hirschsprung disease was associated with 10 of them (43%). Of these cases, two patients had recto-sigmoïd aganglionosis (20%), three had aganglionic segment extension to the left colic angle (30%), two to the right colic angle (20%), and three to the whole colon (30%). The median follow-up was 8.5 years (2 months-15 years). All patients had seizures and intellectual disability. Six children (60%) presented with cardiac defects. At the last follow-up, three patients still had a stoma diversion and 7 (70%) were fed orally. One patient died during the first months. Eight (80%) of these children required a second surgery due to complications. At the last follow-up, three patients reported episodes of abdominal bloating (42%), one recurrent treated constipation (14.3%), and one soiling (14.3%). Genetic analysis identified three patients with heterozygous deletions, three with codon mutations, and three with frameshift mutations. CONCLUSIONS: MWS associated with Hirschsprung disease has a high rate of immediate surgical complications but some patients may achieve bowel function comparable with non-syndromic HD patients. A multidisciplinary follow-up is required for these patients. LEVEL OF EVIDENCE: Retrospective observational single cohort study, Level 3.

Ventilator-Associated Pneumonia and Events in Pediatric Intensive Care: A Single Center Study.

OBJECTIVES: Ventilator-associated pneumonia is the second most common nosocomial infection in pediatric intensive care. The Centers for Disease Control and Prevention recently issued diagnosis criteria for pediatric ventilator-associated pneumonia and for ventilator-associated events in adults. The objectives of this pediatric study were to determine the prevalence of ventilator-associated pneumonia using these new Centers for Disease Control and Prevention criteria, to describe the risk factors and management of ventilator-associated pneumonia, and to assess a simpler method to detect ventilator-associated pneumonia with ventilator-associated event in critically ill children. DESIGN: Retrospective, observational, single-center. SETTING: PICU in a tertiary-care university hospital. PATIENTS: Consecutive critically ill children mechanically ventilated for greater than or equal to 48 hours between November 2013 and November 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 304 patients mechanically ventilated for greater than or equal to 48 hours, 284 were included. Among them, 30 (10.6%) met clinical and radiologic Centers for Disease Control and Prevention criteria for ventilator-associated pneumonia, yielding an prevalence of 7/1,000 mechanical ventilation days. Median time from mechanical ventilation onset to ventilator-associated pneumonia diagnosis was 4 days. Semiquantitative culture of tracheal aspirates was the most common microbiological technique. Gram-negative bacteria were found in 60% of patients, with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Antibiotic therapy complied with adult guidelines. Compared with patients without ventilator-associated pneumonia, those with ventilator-associated pneumonia had significantly longer median durations of mechanical ventilation (15 vs 6 d; p < 0.001) and PICU stay (19 vs 9 d; p < 0.001). By univariate analysis, risk factors for ventilator-associated pneumonia were younger age, reintubation, acute respiratory distress syndrome, and continuous enteral feeding. Among the 30 patients with ventilator-associated pneumonia, 17 met adult ventilator-associated event's criteria (sensitivity, 56%). CONCLUSIONS: Ventilator-associated pneumonia is associated with longer times on mechanical ventilation and in the PICU. Using the ventilator-associated event criteria is of interest to rapidly screen for ventilator-associated pneumonia in children. However, sensitivity must be improved by adapting these criteria to children.

CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study.

BACKGROUND: Combined immunodeficiencies (CIDs) form a heterogeneous group of inherited conditions that affect the development, function, or both of T cells. The treatment of CIDs with allogeneic hematopoietic stem cell transplantation (HSCT) is complicated by a high incidence of life-threatening infections and an increased risk of graft-versus-host disease (GVHD). OBJECTIVE: In view of the growing evidence that alloreactivity is mainly derived from human naive T cells, the selective depletion of naive T cells from allografts might constitute a way of reducing alloreactivity while maintaining memory T-cell responsiveness to pathogens. METHODS: Five consecutive patients with CIDs and chronic viral infections underwent an allogeneic, HLA-mismatched HSCT. Given the patients' infection status and the potential risk of severe GVHD in the mismatched setting, the CD34(-) fraction of the allograft was depleted of naive T cells by using magnetic CD45RA beads. RESULTS: Engraftment occurred in 4 of the 5 patients. No severe GVHD occurred. In the 4 engrafted patients viral infections were cleared within 2 months of the HSCT, and both cellular and humoral immunity were re-established within a year of the HSCT. An early T-cell response against viral pathogens was documented in 2 patients. CONCLUSION: The present pilot study shows that clinical-grade depletion of naive T cells from an allograft through the use of magnetic CD45RA beads seems to be a feasible and efficacious option for the treatment of patients with CIDs at high risk of GVHD, infection, or both in an HLA-mismatched setting.

Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection.

BACKGROUND: Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa. METHODS: We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy. RESULTS: We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele. CONCLUSIONS: These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections.