Secular trends in the utility of SGLT-2 inhibitors in heart failure patients with type 2 diabetes mellitus across Metro South Health hospitals in South-East Queensland.

BACKGROUND: The 2018 Australian Heart Failure (HF) guidelines strongly recommended commencing sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in HF patients with type 2 diabetes mellitus (T2DM). The uptake of SGLT-2is for HF patients with T2DM in our health service is unknown. AIMS: To determine the adoption of the 2018 HF guidelines by assessing the temporal trends of SGLT-2is' usage in HF patients with T2DM at Metro South Health (MSH) hospitals, in South-East Queensland. METHODS: Retrospective analysis of all HF patients (ejection fraction (EF) < 50%) with T2DM who were managed within MSH hospitals between June 2018 and June 2021. RESULTS: A total of 666 patients met the inclusion criteria with 918 HF encounters. Mean age was 72 years and 71% were male (473/666). Mean EF was 30% (SD ± 11%), and mean estimated glomerular filtration rate was 48 mL/min/1.73 m2 (SD ± 25). Fifty-four per cent (362/666) had contraindications to SGLT-2is. Among those without contraindications, there was a five-fold increase in the utility of SGLT-2is, 7% (2/29) before versus 38% (103/275) after implementation of the HF guidelines (P < 0.001). Patients on SGLT-2is were younger (64 years vs 69 years, P = 0.002) and had a lower number of HF hospitalisations (1.1 vs 2.1, P = 0.01). CONCLUSIONS: During the study period, 54% of our HF patients with T2DM were not on SGLT-2is due to prescribing guidelines/limitations in the Australian context. We observed a five-fold significant increase in the uptake of SGLT-2is before and after implementation of HF guidelines among patients without contraindications to SGLT-2is. There were significantly fewer HF hospitalisations among patients on SGLT-2is compared to those without.

Long Term Survival After Surgery for Ischaemic Mitral Regurgitation: A Single Centre Australian Experience.

BACKGROUND: Ischaemic mitral regurgitation (IMR) is associated with an increase in both mortality and congestive heart failure in patients undergoing coronary artery bypass grafting (CABG). Intervention for moderate to severe IMR involves either valve repair or replacement. The ideal option is yet to be fully defined with relatively poor long-term survival being noted in the literature. METHOD: A retrospective observational study was conducted to review the outcomes of patients undergoing CABG in combination with either mitral valve repair (MVr) or mitral valve replacement (MVR) for concurrent coronary artery disease with moderate to severe IMR at The Prince Charles Hospital in Brisbane between the years 2002 to 2015. RESULTS: One hundred and five (105) patients were included, 81 patients (77%) undergoing CABG and MVr and 24 patients (23%) undergoing CABG and MVR. There was no difference in 30-day mortality between the two groups (1% in MVr and 0% in MVR, p=0.589), however patients in the MVr group were significantly more likely, in univariate and multivariate analysis, to develop at least moderate MR (40% v. 8%, p=0.006). The 5-year survival was 87% and 55% at 10 years. CONCLUSIONS: In patients undergoing CABG and mitral valve intervention for IMR, long-term mortality remains high. There was no difference in short- or long-term mortality between repair and replacement although recurrence of at least moderate mitral regurgitation was significantly higher with mitral valve repair.

Proteomic analysis of human fetal atria and ventricle.

In this study we carried out a mass spectrometry-based proteome analysis of human fetal atria and ventricles. Heart protein lysates were analyzed on the Q-Exactive mass spectrometer in biological triplicates. Protein identification using MaxQuant yielded a total of 2754 atrial protein groups (91%) and 2825 ventricular protein groups (83%) in at least 2 of the 3 runs with ≥ 2 unique peptides. Statistical analyses using fold-enrichment (>2) and p-values (≤ 0.05) selected chamber-enriched atrial (134) and ventricular (81) protein groups. Several previously characterized cardiac chamber-enriched proteins were identified in this study including atrial isoform of myosin light chain 2 (MYL7), atrial natriuretic peptide (NPPA), connexin 40 (GJA5), and peptidylglycine alpha-amidating monooxygenase (PAM) for atria, and ventricular isoforms of myosin light chains (MYL2 and MYL3), myosin heavy chain 7 (MYH7), and connexin 43 (GJA1) for ventricle. Our data was compared to in-house generated and publicly available human microarrays, several human cardiac proteomes, and phenotype ontology databases.

Correlation between cancer-related cognitive impairment and resting cerebral glucose metabolism in patients with ovarian cancer.

Background: An increasing number of research have applied neuroimaging techniques to explore the potential neurobiological mechanism of Cancer-related cognitive impairment (CRCI). Purpose: To explore the correlation between resting brain glucose metabolism and CRCI using 18F-FDG PET/CT in ovarian cancer (OC) patients. Methods: From December 2021 to March 2022, 38 patients with OC were selected as the study group, and 38 healthy women of the same age (±1 year) who underwent routine physical examination using PET/CT were selected as the control group. Patients received further assessment with the Montreal Cognitive Assessment Scale (MoCA) and Perceived Deficit Questionnaire (PDQ). Independent sample t-test and Spearman correlation were conducted for data analysis. Results: The resting brain glucose metabolism in the OC group was significantly lower than in the healthy controls. 60.52 % patients had neuropsychological impairment and retrospective memory were the most serious perceived cognitive impairments. The resting brain glucose metabolism in OC patients did not significantly correlate with neuropsychological performance but had significant positive correlation with subjective cognitive evaluation. Discussion: Resting glucose metabolism was low in OC patients and associated with subjective cognitive impairment but not objective neuropsychological test results. 18F-FDG PET/CT can be used to evaluate brain function in OC patients and provide reliable imaging indicators for early recognition of and intervention for changes in cognitive function.

The Role of Albumin in the Diagnosis of Neonatal Sepsis Over the Last 11 Years: A Retrospective Study.

Background: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together. Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy. Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P<0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB. Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.

Characteristics and treatment outcomes of children and adolescents accessing treatment in Child and Youth Mental Health Services.

AIM: To provide insight into the characteristics and treatment outcomes of children and adolescents accessing outpatient Child and Youth Mental Health Services (CYMHS), and to explore whether outcomes differ by age, sex, and ancestry background. This information can guide how to optimize the treatment delivered at these services. METHODS: An observational retrospective study was performed based on data from 3098 children and adolescents between age 5 and 18 who received treatment at Brisbane, Australia, community CYMHS between 2013-2018. Patient characteristics, service use, and clinician and parent rated Routine Outcome Measures (ROM) were extracted from electronic health records. RESULTS: Anxiety and mood disorders were the most common mental disorders (37% and 19%). In 1315 children and adolescents (42%), two or more disorders were diagnosed, and the far majority (88%) had experienced at least one psychosocial stressor. The ROM scores improved between start and end of treatment with Cohen's d effect sizes of around 0.9. However, ~50% of the children still scored in the clinical range at the end of treatment. Outcomes did not differ over gender and Indigenous status. CONCLUSIONS: Children and adolescents accessing CYMHS have severe and complex mental disorders as reflected by high rates of comorbidity, exposure to adverse circumstances and high symptom scores at the start of treatment. Despite the clinically relevant and substantial improvement, end ROM scores indicated the presence of residual symptoms. As this increases the risk for relapse, services should explore ways to improve treatment to further reduce mental health symptoms.

Comparing Treatment Outcomes in Children and Adolescents With ADHD to Other Disorders Within an Australian and Dutch Outpatient Cohort.

OBJECTIVE: Previous studies at child and youth mental health services (CYMHS) suggest that children with ADHD have poorer outcomes compared to those with other diagnoses. This study investigates this in more detail. METHODS: Children with ADHD were compared to those with ASD and those with emotional disorders, on routinely collected outcomes at CYMHS in Australia (N = 2,513) and the Netherlands (N = 844). RESULTS: Where the emotional disorders group reached a similar level of emotional symptoms at the end-of-treatment as the ADHD and ASD groups, the latter two groups still had higher scores on ADHD and ASD symptoms (attention and peer problems). The poorer outcomes were mainly explained by higher severity at baseline. In Australia, an ADHD and/or ASD diagnosis also independently contributed to worse outcomes. CONCLUSION: Those with neurodevelopmental disorders within both countries had poorer outcomes than those with emotional disorders. Services should aim to optimize treatment to ensure best possible outcomes.

Attenuation of doxorubicin-induced cardiotoxicity in a human in vitro cardiac model by the induction of the NRF-2 pathway.

Dose-dependent cardiotoxicity is the leading adverse reaction seen in cancer patients treated with doxorubicin. Currently, dexrazoxane is the only approved drug that can partially protect against this toxicity in patients, however, its administration is restricted to those patients receiving a high cumulative dose of anthracyclines. Investigations into the mechanisms of cardiotoxicity and efforts to improve cardioprotective strategies have been hindered by the limited availability of a phenotypically relevant in vitro adult human cardiac model system. Here, we adapted a readily reproducible, functional 3D human multi-cell type cardiac system to emulate patient responses seen with doxorubicin and dexrazoxane. We show that administration of two NRF2 gene inducers namely the semi-synthetic triterpenoid Bardoxolone methyl, and the isothiocyanate sulfurophane, result in cardioprotection against doxorubicin toxicity comparable to dexrazoxane as evidenced by an increase in cell viability and a decrease in the production of reactive oxygen species. We further show a synergistic attenuation of cardiotoxicity when the NRF2 inducers and dexrazoxane are used in tandem. Taken together, our data indicate that the 3D spheroid is a suitable model to investigate drug induced cardiotoxicity and we reveal an essential role of the NRF2 pathway in cardioprotection providing a novel pharmacological mechanism and intervention route towards the alleviation of doxorubicin-induced toxicity.