A Need for a Novel Survival Risk Scoring System for Intensive Care Admissions Due to Sepsis in Pediatric Hematology/Oncology Patients.

Background: Children with hemato-oncological diseases or following stem cell transplantation (SCT) are at high risk for life-threatening infections; sepsis in this population constitutes a substantial proportion of pediatric intensive care unit (PICU) admissions. The current pediatric prognostic scoring tools to evaluate illness severity and mortality risk are designed for the general pediatric population and may not be adequate for this vulnerable subpopulation. Methods: Retrospective analysis was performed on all PICU admissions for sepsis in children with hemato-oncological diseases or post-SCT, in a single tertiary pediatric hospital between 2008 and 2021 (n = 233). We collected and analyzed demographic, clinical, and laboratory data and outcomes for all patients, and evaluated the accuracy of two major prognostic scoring tools, the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) and the Pediatric Risk of Mortality III (PRISM III). Furthermore, we created a new risk-assessment model that contains additional parameters uniquely relevant to this population. Results: The survival rate for the cohort was 83%. The predictive accuracies of PELOD-2 and PRISM III, as determined by the area under the curve (AUC), were 83% and 78%, respectively. Nine new parameters were identified as clinically significant: age, SCT, viral infection, fungal infection, central venous line removal, vasoactive inotropic score, bilirubin level, C-reactive protein level, and prolonged neutropenia. Unique scoring systems were established by the integration of these new parameters into the algorithm; the new systems significantly improved their predictive accuracy to 91% (p = 0.01) and 89% (p < 0.001), respectively. Conclusions: The predictive accuracies (AUC) of the PELOD-2 and PRISM III scores are limited in children with hemato-oncological diseases admitted to PICU with sepsis. These results highlight the need to develop a risk-assessment tool adjusted to this special population. Such new scoring should represent their unique characteristics including their degree of immunosuppression and be validated in a large multi-center prospective study.

Mucosal IL-10 and IL-10 receptor expression patterns in paediatric patients with ulcerative colitis.

Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. We aimed to assess IL-10 and IL-10 receptor (IL-10R) expression in the gut, and determine whether these patterns are altered in patients with ulcerative colitis (UC). Formalin-fixed paraffin-embedded rectal and transverse colon sections were collected from three groups of patients: (a) control subjects with normal colonoscopy and without history of inflammatory bowel disease; (b) UC patients with extensive colitis or pancolitis (E3/E4 phenotype); and (c) UC patients with limited distal disease (E1/E2 phenotype; n = 8-10 subjects per group). Immunohistochemistry (IHC) was performed to assess expression patterns of IL-10, IL-10R1 and IL-10R2, and was correlated with clinical, endoscopic and histologic severity indices among patients. A trend towards increased IL-10 expression was noted in rectal biopsies of patients with active UC, compared with controls. Moreover, IL-10 levels were significantly increased in transverse colon biopsies of patients with extensive/pancolitis, compared with control subjects and patients with limited distal disease. Rectal IL-10R1 and IL-10R2 levels were comparable between control subject and patients with active UC. However, transverse colon IL-10R1 levels were significantly higher in patients with E3/E4 colitis, compared with controls. Finally, we found no correlation between clinical, endoscopic and histologic severity of inflammation among UC patients and IL-10, IL-10R1 or IL-10R2 expression in rectal sections. Mucosal expression patterns of IL-10 and IL-10R, evaluated by IHC, were overall similar between control subjects and patients with active UC. Given IL-10's anti-inflammatory properties, additional studies are required to determine whether signalling through the IL-10R is altered among these patients.

Characteristics and risk factors of infections following CD28-based CD19 CAR-T cells.

CAR T-cells are approved for the treatment of relapsed and refractory leukemia and lymphoma. Here, we studied the infectious complications in 88 patients treated with CD28-based CD19 CAR T-cells. Overall, 36 infections were documented in 24 patients within the first month after CAR T-cell infusion: Six events of bacteremia, sixteen focal bacterial infections, and fourteen systemic or localized viral infections. Seven patients had nine infectious episodes beyond the first 30 days of follow-up, including three events of bacteremia, three focal bacterial, two viral and one fungal infection. The presence of neutropenia, neutropenic fever and lack of response to treatment were associated with a higher rate of infections. Children had less severe infections than adults. In a multivariate analysis lack of response to treatment was the only significant risk factor. Overall, the incidence of bacterial infections following CAR T-cells is modest especially in children and in patients responding to therapy.