Diagnosis and stabilisation of familial chylomicronemia syndrome in two infants presenting with hypertriglyceridemia-induced acute pancreatitis.

Familial chylomicronemia syndrome (FCS) is a rare disorder of triglyceride (TG) metabolism caused by loss of function variants in one of five known canonical genes involved in chylomicron lipolysis and clearance-LPL, APOC2, APOA5, LMF1, and GPIHBP1. Pathogenic variants in LPL, which encodes the hydrolytic enzyme lipoprotein lipase, account for over 80%-90% of cases. FCS may present in infancy with hypertriglyceridemia-induced acute pancreatitis and is challenging to manage both acutely and in the long-term. Here, we report our experience managing two unrelated infants consecutively diagnosed with hypertriglyceridemia-induced acute pancreatitis caused by LPL deficiency. Both had elevated TGs at presentation (205 and 30 mmol/L, respectively) and molecular genetic testing confirmed each infant carried a different homozygous pathogenic variant in the LPL gene, specifically, c.987C>A (p.Tyr329Ter) and c.632C>A (p.Thr211Lys). The more severely affected infant had cutaneous xanthomata, lipemia retinalis and lipemic plasma at presentation, and required management in an intensive care setting. Acute stabilisation was achieved using insulin and heparin infusions together with the iterative implementation of a fat-restricted diet, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT). In both cases, provision of adequate caloric intake (~110-120 kcal/kg/day) was also found to be important for a sustained TG reduction during the acute phase of management. In summary, a high index of suspicion is required to diagnose FCS in infants with hypertriglyceridemia-induced acute pancreatitis, management of which can be challenging, highlighting the need for more evidence-based recommendations.

Evaluation of a multiplex-qPCR for paediatric pleural empyema-An observational study in hospitalised children.

Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.

Characteristics, management and changing incidence of children with empyema in a paediatric intensive care unit.

AIM: Paediatric intensive care unit (PICU) admissions for empyema increased following the 13-valent pneumococcal conjugate vaccine (PCV13). We describe the clinical characteristics, management and outcomes for children with empyema and compare incidence before and after PCV13. METHODS: Retrospective study of patients <18 years admitted to The Royal Children's Hospital Melbourne PICU with empyema between January 2016 and July 2019. We investigated the incidence of empyema during two time periods: 2007-2010 (pre-PCV13) and 2016-2019 (post-PCV13). RESULTS: Seventy-one children (1.9% of all PICU admissions) were admitted to PICU with empyema between 2016 and 2019. Sixty-one (86%) had unilateral disease, 11 (16%) presented with shock and 44 (62%) were ventilated. Streptococcus pneumoniae and group A Streptococcus were the most commonly identified pathogens. Forty-five (63%) were managed with video-assisted thoracoscopic surgery (VATS). There was a 31% reduction in empyema hospitalisations as a proportion of all hospitalisations (IRR 0.69, 95% CI 0.59-0.8), but a 2.8-fold increase in empyema PICU admissions as a proportion of all PICU admissions (95% CI 2.2-3.5, P < 0.001). For the PICU cohort, this was accompanied by reduction in PIM2 probability of death (median 1% vs. 1.9%, P = 0.02) and duration of intubation (median 69 h vs. 126.5 h, P = 0.045). CONCLUSIONS: In children with empyema in PICU 62% required ventilation, 16% had features of shock and 63% received VATS. Empyema admissions, as a proportion of all PICU admissions, increased in the era post-PCV13 compared to pre-PCV13 despite no increase in illness severity at admission.

Extracorporeal Life Support Organization (ELSO): Guidelines for Pediatric Cardiac Failure.

These guidelines are applicable to neonates and children with cardiac failure as indication for extracorporeal life support. These guidelines address patient selection, management during extracorporeal membrane oxygenation, and pathways for weaning support or bridging to other therapies. Equally important issues, such as personnel, training, credentialing, resources, follow-up, reporting, and quality assurance, are addressed in other Extracorporeal Life Support Organization documents or are center-specific.

Modified pediatric lung ultrasound score compared with computed tomography for assessment of lung aeration in children.

BACKGROUND: Lung ultrasound can be used to assess lung density and aeration at the bedside. Few authors have investigated scores based on the ultrasonographic interstitial syndrome for this purpose, but none have compared them with the gold standard computed tomography in children. METHODS: Children <10 kilograms undergoing a chest computed tomography for clinical purposes at a tertiary hospital Pediatric Intensive Care Unit were enrolled in the study. An ultrasound scan was performed shortly after computed tomography. Each hemithorax was divided in six zones, and each zone was scored: 1, no B lines; 2, <3 B lines; 3, >3 well separated B lines; 4, crowded, coalescent B lines; 5, white lung; 6, consolidation. The pediatric lung ultrasound score was obtained by adding all zones. Interobserver variation for two separate operators was calculated. RESULTS: Ten children, median age 95 days (range 23-721) were enrolled. Mean pediatric lung ultrasound score had a significant correlation with lung density (r=0.68) and percentage of hypoaerated lung (r=0.51). Median density and percentage of hypoaerated lung increased along the ultrasound patterns values (P<0.05) although not all patterns were significantly different from adjacent ones in the pairwise comparison. Interobserver variability in scoring of ultrasonographic patterns was moderate. CONCLUSIONS: The pediatric lung ultrasound score correlates with lung density and percentage of hypoaerated lung measured with computed tomography.

Successful Treatment of a Severe Vision-Threatening Paradoxical Tuberculous Reaction with Infliximab: First Pediatric Use.

A 7-year-old girl with tuberculous (TB) meningitis developed optochiasmatic arachnoiditis, a vision-threatening paradoxical reaction, after starting TB treatment including adjunctive steroid therapy. She was treated with infliximab with complete recovery. This is the first report of the use of a tissue necrosis factor α inhibitor for the treatment of a severe paradoxical TB reaction in a child.

Antecedents to cardiac arrests in a teaching hospital intensive care unit.

BACKGROUND: In hospital cardiac arrests (CA) treated with cardio-pulmonary resuscitation (CPR) outside of the intensive care unit (ICU) have poor outcomes. Most are preceded by deranged vital signs. There are, however, limited studies assessing antecedents to CAs inside the ICU. OBJECTIVES: To study the antecedents to, and characteristics of CAs in ICU. STUDY POPULATION: We prospectively identified CA cases that occurred inside our ICU between January 2010 and July 2012. Controls were obtained by sequentially matching ICU patients based on APACHE III diagnosis, APACHE III score, age, gender and length of stay in ICU. RESULTS: Thirty-six patients had a CA during the study period (6.28/1000 admissions). In the 12h prior to CA, index patients had higher maximum (22 breaths/min vs. 18 breaths/min, p=0.001) and minimum respiratory rates (16 breaths/min vs. 12 breaths/min, p=0.031), a lower median mean arterial pressure (65 mmHg vs. 70 mmHg, p=0.029) and systolic blood pressure (97 mmHg vs. 106 mmHg, p=0.033), a higher central venous pressure (14 cm H2O vs. 11 cm H2O, p=0.008) and a lower bicarbonate level (20.5 mmol vs. 26 mmol, p=0.018) compared to controls. CA patients also had a higher maximum dose of noradrenaline (norepinephrine) (17.5 mcg/min vs. 8.0 mcg/min, p=0.052) but there was no difference in any other levels of intensive care support. Two-thirds of CA's occurred within the first 48 h of ICU admission. The initial monitored rhythm was non-shock responsive (pulseless electrical activity, bradycardia or asystole) in 26/36 (72%). Return of spontaneous circulation was achieved in 29/36 (80.6%) patients, with 16/36 (44.4%) surviving to hospital discharge. CONCLUSIONS: In the period leading up to the CA inside ICU, there were signs of physiological instability and the need for higher doses of noradrenaline. Return of spontaneous circulation was achieved in 80%. However, in-hospital mortality was greater than 50%.