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Background: Macrophage migration inhibitory factor (MIF) is a constitutively expressed pro-inflammatory cytokine and a regulator of immune responses. D-dopachrome tautomerase (DDT) shares sequence homology and biological activities with MIF. We recently reported that circulating levels of MIF and DDT are strikingly elevated in early-life, and that MIF sustains neonatal innate immune responses. Yet, during sepsis, MIF may favor uncontrolled inflammation, leading to adverse outcomes. Our goal was to determine circulating levels of MIF and DDT in septic children.

Methods: MIF and DDT concentrations were quantified in serum of children with blood culture-proven sepsis and healthy subjects by ELISA. Patients were stratified according to age and sepsis with presence of organ dysfunctions (ODs) or death.

Results: MIF and DDT serum levels were measured in 433 infants <1 year and 357 children ≥1 year, including 162 and 73 non-infected subjects, 211 and 221 patients with sepsis and 0-1 OD, 48 and 56 patients with sepsis and ≥2 OD, and 12 and 7 patients who died following sepsis. MIF levels correlated with DDT levels (R=0.71, P <0.0001).

Box and whisker plots represent median (IQR) with 5th and 95th percentile.*, P <0.05 vs healthy subjects; **, P <0.05 vs healthy subjects and 0-1 OD; † , P <0.05 vs healthy subjects, 0-1 OD and ≥2 ODs.

Discussion: Circulating levels of MIF and DDT are markedly elevated in septic infants and children with multiple OD and/or death. Thus, MIF and DDT are attractive candidate biomarkers and potential targets for immunomodulating therapy during sepsis.

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Background and aims: Optimization of the management of community-onset severe bacterial infections (COSBI) in children could reduce its morbidity and mortality. We analysed the factors associated with suboptimal initial management of COSBI in a population-based study.

Methods: We prospectively included all children aged between 4 weeks and 16 years admitted for a COSBI or deceased prior to admission between 2009 and 2014 in the West of France (13% of the French paediatric population). The quality of the management prior to admission to an intensive care unit was evaluated by two independent experts according to current guidelines and blinded to the child’s outcome. We studied the associations between suboptimal management and potential determinants by multivariate analyses using a logistic regression model.

Results: Of the 259 children included (median age 24 months), 27 (10.4%) died, 25 (9.7%) had severe immediate sequelae, and 189 (73%) had suboptimal initial management. Only three factors were independently associated with suboptimal management: an age <5 years old (adjusted odds ratio –aOR- 2.24, 95%CI: 1.13-4.49 vs older children), living in an area with low medical density (aOR 2.53, 95%CI: 1.10-6.01 vs high density) and being initially cared for the COSBI in private practice (aOR 2.75, 95%CI: 1.24-6.66 vs paediatric hospital ward).

Conclusions: We identified 3 targets to improve the very frequent suboptimality observed in the initial management of children with COSBI: territorial inequalities in access to care, training of primary care physicians and management of sepsis in the youngest children.

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Background

The PICU in Queens Medical Centre is a tertiary referral centre for the East Midlands region of the UK. We examined the patterns of adenovirus disease encountered over a 9 year period in our unit and the associated morbidity and mortality. Disseminated adenovirus is a rare complication of adenovirus infection with a high mortality rate. It often affects immunocompromised patients but has also been seen in patients who are thought to be immunocompetent.

Methods

The PICU database holds records for admissions dating from September 2011 to Mar 2020. These were reviewed and cross-referenced with the hospital’s digital blood results system. This identified 125 children who had a positive PCR test for Adenovirus. The medical records were then reviewed for clinical course and outcome. Data was interrogated for evidence of disseminated Infection for each patient.

Results

Of 125 patients with adenovirus, 93% had positive respiratory secretions, 10% stool, 1% urine, and 7% blood. 11 patients (9%) had evidence of disseminated infection (positive PCR in more than one body fluid). . 19 (15%) had a bacterial co-infection. 8 patients needed HFOV, 11 had ARDS, 3 patients were referred for ECMO. 5 patients (4%) died. 4 patients were treated with cidofovir.

Conclusion

Patients with atypical sepsis should be screened for disseminated adenovirus infection. Disseminated adenovirus infection can cause considerable morbidity and mortality. For the sickest, treatment with cidofovir and IVIG may be indicated.

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Background: Hyperferritinemia is increasingly associated with mortality in sepsis. Studies estimating the prevalence of hyperferritinemia in pediatric scrub typhus is limited.

Methods: We conducted a prospective observational study from a tertiary care teaching hospital in North India where 72 children with confirmed scrub typhus;17(24%)-PCR positive, 68(94%)-IgM ELISA positive and 13(18%)-both PCR and ELISA positive. Serum ferritin was measured in 62 children to identify the prevalence of hyperferritinemia and determine its association with mortality.

Results: Hyperferritinemia (>500µg/L) was seen in 72.6% [n=45] children; 26(42%) were mild (500-2000µg/L), 13(21%) were moderate (2000-10000µg/L) and 6(9.7%) were severe (>10000µg/L). A biphasic pattern of hyperferritinemia was seen with two peaks when plotted against duration since symptoms onset; one between 2 and 3 days (early onset hyperferritinemia) and second peak between 12 and14 days (late onset hyperferritinemia). Early onset hyperferritinemia more survivors than late onset hyperferritinemia. Non survivors had significantly higher PRISM III, PELOD-2, hyperlactatemia, hypoalbuminemia, organ dysfunction, need for mechanical ventilation and need of RRT. Ferritin had poor sensitivity and specificity in predicting survival with AUC of 0.56. Organ dysfunction and risk scores as PRISM III, PELOD 2 and VIS at admission were better predictors with AUC(95%CI) of 0.72(0.56,0.89), 0.77(0.63,0.92) and 0.90(0.78,1.0) respectively.

Conclusions: Hyperferritinemia is common in scrub typhus. A distinct biphasic response was observed with worse outcome in late onset hyperferritinemia. Organ dysfunction and risk scores were better predictors of mortality than ferritin.