Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU.

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0-17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

Rhinovirus Detection in the Nasopharynx of Children Undergoing Cardiac Surgery Is Not Associated With Longer PICU Length of Stay: Results of the Impact of Rhinovirus Infection After Cardiac Surgery in Kids (RISK) Study.

OBJECTIVES: To determine whether children with asymptomatic carriage of rhinovirus in the nasopharynx before elective cardiac surgery have an increased risk of prolonged PICU length of stay. STUDY DESIGN: Prospective, single-center, blinded observational cohort study. SETTING: PICU in a tertiary hospital in The Netherlands. PATIENTS: Children under 12 years old undergoing elective cardiac surgery were enrolled in the study after informed consent of the parents/guardians. INTERVENTIONS: The parents/guardians filled out a questionnaire regarding respiratory symptoms. On the day of the operation, a nasopharyngeal swab was obtained. Clinical data were collected during PICU admission, and PICU/hospital length of stay were reported. If a patient was still intubated 3 days after operation, an additional nasopharyngeal swab was collected. Nasopharyngeal swabs were tested for rhinovirus and other respiratory viruses with polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Of the 163 included children, 74 (45%) tested rhinovirus positive. Rhinovirus-positive patients did not have a prolonged PICU length of stay (median 2 d each; p = 0.257). Rhinovirus-positive patients had a significantly shorter median hospital length of stay compared with rhinovirus-negative patients (8 vs 9 d, respectively; p = 0.006). Overall, 97 of the patients (60%) tested positive for one or more respiratory virus. Virus-positive patients had significantly shorter PICU and hospital length of stay, ventilatory support, and nonmechanical ventilation. Virus-negative patients had respiratory symptoms suspected for a respiratory infection more often. In 31% of the children, the parents reported mild upper respiratory complaints a day prior to the cardiac surgery, this was associated with postextubation stridor, but no other clinical outcome measures. CONCLUSIONS: Preoperative rhinovirus polymerase chain reaction positivity is not associated with prolonged PICU length of stay. Our findings do not support the use of routine polymerase chain reaction testing for respiratory viruses in asymptomatic children admitted for elective cardiac surgery.

Automatic quantification of lymphocyte vacuolization in peripheral blood smears of patients with Batten's disease (CLN3 disease).

Quantifying lymphocyte vacuolization in peripheral blood smears (PBSs) serves as a measure for disease severity in CLN3 disease-a lysosomal storage disorder of childhood-onset. However, thus far quantification methods are based on labor-intensive manual assessment of PBSs. As machine learning techniques like convolutional neural networks (CNNs) have been deployed quite successfully in detecting pathological features in PBSs, we explored whether these techniques could be utilized to automate quantification of lymphocyte vacuolization. Here, we present and validate a deep learning pipeline that automates quantification of lymphocyte vacuolization. By using two CNNs in succession, trained for cytoplasm-segmentation and vacuolization-detection, respectively, we obtained an excellent correlation with manual quantification of lymphocyte vacuolization (r = 0.98, n = 40). These results show that CNNs can be utilized to automate the otherwise cumbersome task of manually quantifying lymphocyte vacuolization, thereby aiding prompt clinical decisions in relation to CLN3 disease, and potentially beyond.

Effect of dexamethasone on postoperative cardiac troponin T production in pediatric cardiac surgery.

OBJECTIVE: Pediatric cardiac surgery is associated with a temporary rise in cardiac troponin T (cTnT) during the postoperative period. We examined whether dexamethasone given before cardiopulmonary bypass has myocardial protective effects as assessed by the postoperative production of cTnT. DESIGN AND SETTING: Prospective randomized interventional study in the pediatric intensive care unit in a university hospital. INTERVENTIONS: Patients were randomly allocated to act as controls or receive a single dose of dexamethasone (1 mg/kg) during induction of anesthesia. MEASUREMENTS AND RESULTS: cTnT was measured four times postoperatively: immediately after admission to the pediatric intensive care unit (PICU) and 8, 15, and 24 h thereafter. The two groups had similar mean cTnT concentrations on PICU admission: those receiving dexamethasone 1.85 ng/ml (1.55-2.15) and those not receiving it 2 ng/ml (95% confidence interval 1.56-2.51). Concentrations of cTnT 8 h after admission to the PICU differed significantly after 8 h: 1.99 ng/ml (1.53-2.45) in those receiving dexamethasone and 3.08 ng/ml (2.46-3.69) in those not receiving it. After subgroup statistical analysis differences between the two groups remained significant only at 8 h, not those after 15 or 24 h. CONCLUSIONS: The use of dexamethasone (1 mg/kg) before cardiopulmonary bypass is associated with a brief but significant reduction in postoperative cTnT production. The clinical significance of this effect is unclear.

Evaluation of a bedside device to assess the activated partial thromboplastin time for heparin monitoring in infants.

To determine the relationship between the activated partial thromboplastin time (aPTT) measured with a standard laboratory assay and the aPTT measured with a bedside device in infants on heparin therapy after cardiothoracic surgery. Twenty infants aged below 1 year who were on heparin therapy were included. Exclusion criteria were prematurity, dysmaturity and the use of anticoagulants other than heparin. Nineteen samples were obtained from four adults in intensive care who were on heparin. The aPTT values were analyzed with the Coaguchek Pro/DM bedside device (aPTTbed) and compared with the aPTT values obtained from the laboratory Electra 1800C coagulation analyzer (aPTTlab). Correlation analysis was performed by linear regression. The agreement was calculated using Bland-Altman analysis. The correlation coefficient of samples obtained from infants was lower (r = 0.48) compared with samples from adults (r = 0.85). A substantial positive bias (27 s) and scatter [95% confidence interval (CI) -11; +65 s) was found. The bias showed a genuine trend to increase at higher aPTT values (r = 0.90; P < 0.001). The bedside device overestimates the aPTT in infants treated with heparin. The disagreement between the bedside device and laboratory increases at higher aPTTs. Bedside devices should not be used to monitor heparin therapy in infants in intensive care.

Mortality prediction models for pediatric intensive care: comparison of overall and subgroup specific performance.

AIM: To validate paediatric index of mortality (PIM) and pediatric risk of mortality (PRISM) models within the overall population as well as in specific subgroups in pediatric intensive care units (PICUs). METHODS: Variants of PIM and PRISM prediction models were compared with respect to calibration (agreement between predicted risks and observed mortality) and discrimination (area under the receiver operating characteristic curve, AUC). We considered performance in the overall study population and in subgroups, defined by diagnoses, age and urgency at admission, and length of stay (LoS) at the PICU. We analyzed data from consecutive patients younger than 16 years admitted to the eight PICUs in the Netherlands between February 2006 and October 2009. Patients referred to another ICU or deceased within 2 h after admission were excluded. RESULTS: A total of 12,040 admissions were included, with 412 deaths. Variants of PIM2 were best calibrated. All models discriminated well, also in patients <28 days of age (neonates), with overall higher AUC for PRISM variants (PIM = 0.83, PIM2 = 0.85, PIM2-ANZ06 = 0.86, PIM2-ANZ08 = 0.85, PRISM = 0.88, PRISM3-24 = 0.90). Best discrimination for PRISM3-24 was confirmed in 13 out of 14 subgroup categories. After recalibration PRISM3-24 predicted accurately in most (12 out of 14) categories. Discrimination was poorer for all models (AUC < 0.73) after LoS of >6 days at the PICU. CONCLUSION: All models discriminated well, also in most subgroups including neonates, but had difficulties predicting mortality for patients >6 days at the PICU. In a western European setting both the PIM2(-ANZ06) or a recalibrated version of PRISM3-24 are suited for overall individualized risk prediction.

Serum cortisol concentration with exploratory cut-off values do not predict the effects of hydrocortisone administration in children with low cardiac output after cardiac surgery.

OBJECTIVES: Low cardiac output syndrome is common after paediatric cardiac surgery. Previous studies suggested that hydrocortisone administration may improve haemodynamic stability in case of resistant low cardiac output syndrome in critically ill children. This study was set up to test the hypothesis that the effects of hydrocortisone on haemodynamics in children with low cardiac output syndrome depend on the presence of (relative) adrenal insufficiency. METHODS: A retrospective study was done on paediatric patients who received hydrocortisone when diagnosed with resistant low cardiac output syndrome after paediatric cardiac surgery in the period from 1 November 2005 to 31 December 2008. We studied the difference in effects of treatment with hydrocortisone administration between patients with adrenal insufficiency defined as an exploratory cut-off value of total cortisol of <100 nmol/l and patients with a serum total cortisol of ≥ 100 nmol/l. RESULTS: A total of 62 of patients were enrolled, meeting the inclusion criteria for low cardiac output syndrome. Thirty-two patients were assigned to Group 1 (<100 nmol/l) and 30 were assigned to Group 2 (≥ 100 nmol/l). Haemodynamics improved after hydrocortisone administration, with an increase in blood pressure, a decrease in administered vasopressors and inotropic drugs, an increase in urine production and a decrease in plasma lactate concentrations. CONCLUSIONS: The effects of treatment with hydrocortisone in children with low cardiac output after cardiac surgery was similar in patients with a low baseline serum cortisol concentration and those with normal baseline cortisol levels. A cortisol value using an exploratory cut-off value of 100 nmol/l for adrenal insufficiency should not be used as a criterion to treat these patients with hydrocortisone.