Paediatric obesity diagnosis and intervention practices in Australian hospitals - Australia-wide survey.

AIM: Previous studies suggest a lack of a unified approach in identifying and addressing children with obesity while being inpatients in individual Australian hospitals. Our study aimed to describe current clinical practice across Australia and identify discrepancies that can aid in developing a more unified response to children identified with obesity as hospital inpatients. METHODS: A cross-sectional exploratory online survey was distributed to major paediatric in-patient departments in Australia, with a response rate of 68%. Questions focused on education, identification, interventions and attitudes towards a national protocol. RESULTS: Twenty percent of respondents indicated that staff in their department regularly record body mass index, 66% address weight issues and only 8% consistently refer to appropriate outpatient services. Although 88% of respondents believe that a national protocol for addressing paediatric obesity would be beneficial, respondents emphasised concerns regarding their local resources. CONCLUSION: Our study can inform the development of a guideline for a unified response to opportunistically identify children with overweight and obesity as inpatients.

Maternal and neonatal health outcomes for First Nations Australian women and children: A retrospective cohort study in a Western Sydney metropolitan tertiary referral centre.

AIM: To analyse key pregnancy and birth outcomes for First Nations women and children at a Western Sydney metropolitan tertiary referral centre. METHODS: The birth and health-determining characteristics of 470 First Nations infants born at Nepean Hospital in 2018 and their mothers were included in a retrospective audit and compared with a contemporaneous control group of 470 infants and their mothers. RESULTS: Mothers of First Nations infants had significantly higher rates of socioeconomic disadvantage (P < 0.001), psychosocial vulnerability (P < 0.007), mental illness (P < 0.001), teenage pregnancy (P < 0.001), smoking (45.6% vs. 19.4%, P < 0.001) and drug and alcohol use than control mothers (P < 0.001, P < 0.048). First Nations peoples did not have increased rates of maternal morbidity, nor any difference in rates of Caesarean section, resuscitation at birth, NICU admission, preterm birth or low birth weight in multivariable analysis. However, multivariable analysis demonstrated significant associations between low birth weight and maternal smoking (P < 0.001), hypertension (P < 0.01) and drug use (P < 0.01). CONCLUSIONS: Despite challenges facing First Nations mothers and infants, our study found no significant difference in maternal morbidity nor adverse birth outcomes for First Nations infants. The study occurred in the context of culturally specific, First Nations-led antenatal and infant services. Future studies should further investigate relationships between participation in these services and health outcomes. This could identify strengths and areas for improvement in current services, with the goal of further improving outcomes for First Nations peoples through targeted health services that address their psychosocial vulnerabilities and support women to make healthy choices during pregnancy.

Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder initiated by antibodies to complexes between platelet factor 4 (PF4) and heparin. The risk of recurrent thromboembolism persists after heparin is cleared and platelet activation leading to release of PF4 has dissipated. We asked whether antigenic complexes between polyphosphates and PF4 released from activated platelets might intensify or sustain the prothrombotic phenotype of HIT. PF4 forms stable, ultralarge complexes with polyphosphates of various sizes, including those released from platelets, which are recognized by the HIT-like monoclonal KKO, an immunoglobulin G2bκ monoclonal heparin/PF4 binding antibody, and by human HIT antibodies. KKO helps to protect PF4/polyphosphate complexes from degradation by phosphatases. Complement is activated when HIT antibodies bind to PF4/polyphosphate complexes and PF4 reverses the inhibition of complement by polyphosphates. Polyphosphates and PF4 are stored primarily in separate granules in resting platelets, but they colocalize when the cells are activated. Platelets activated by subaggregating doses of thrombin receptor activating peptide release polyphosphates and PF4, which form antigenic complexes that allow KKO to further activate platelets in the absence of heparin and exogenous PF4. These studies suggest that thrombin- or immune complex-mediated release of endogenous antigenic PF4/polyphosphate complexes from platelets may augment the prothrombotic risk of HIT and perpetuate the risk of thrombosis after heparin has been discontinued.

Polyphosphate suppresses complement via the terminal pathway.

Polyphosphate, synthesized by all cells, is a linear polymer of inorganic phosphate. When released into the circulation, it exerts prothrombotic and proinflammatory activities by modulating steps in the coagulation cascade. We examined the role of polyphosphate in regulating the evolutionarily related proteolytic cascade complement. In erythrocyte lysis assays, polyphosphate comprising more than 1000 phosphate units suppressed total hemolytic activity with a concentration to reduce maximal lysis to 50% that was 10-fold lower than with monophosphate. In the ion- and enzyme-independent terminal pathway complement assay, polyphosphate suppressed complement in a concentration- and size-dependent manner. Phosphatase-treated polyphosphate lost its ability to suppress complement, confirming that polymer integrity is required. Sequential addition of polyphosphate to the terminal pathway assay showed that polyphosphate interferes with complement only when added before formation of the C5b-7 complex. Physicochemical analyses using native gels, gel filtration, and differential scanning fluorimetry revealed that polyphosphate binds to and destabilizes C5b,6, thereby reducing the capacity of the membrane attack complex to bind to and lyse the target cell. In summary, we have added another function to polyphosphate in blood, demonstrating that it dampens the innate immune response by suppressing complement. These findings further establish the complex relationship between coagulation and innate immunity.