A national study of infective endocarditis models of care in Australia.

BACKGROUND: Multidisciplinary endocarditis team (MDET) management is supported by current evidence and recommended in international society guidelines. The extent to which this recommendation has been implemented in Australian centres and the attitudes, barriers and facilitators of this model are unclear. AIM: To describe current infective endocarditis (IE) models of care in Australian specialist referral centres and evaluate facilitators, barriers and attitudes towards MDET implementation. METHODS: Aims were addressed using two online surveys. Survey 1 audited IE models of care and was distributed to infectious disease physicians at specialist referral centres. Survey 2 assessed barriers, facilitators and attitudes towards MDETs and was distributed via societal email listings. RESULTS: From 56 identified cardiac surgery centres, survey 1 received 47 responses (84%). A total of 28% (13/47) of participating institutions had an existing MDET. A total of 85% (11/13) of MDETs were in public hospitals and 85% (11/13) were in high IE volume centres. Survey 2 had 109 respondents from seven specialties. Attitudes towards MDET implementation were generally favourable. Identified barriers to MDET implementation included a lack of funding, resources, expertise, time and collaboration. Facilitators included strong leadership, engagement from key stakeholders and tangible benefits. CONCLUSIONS: Even though it is recommended in international guidelines, the MDET model is used by less than one-third of Australian specialist referral centres. Stakeholders in IE care have generally favourable attitudes towards MDET implementation but cite a lack of resources, funding, collaboration and time as barriers to this. Dedication of financial and administrative support and leadership from key stakeholders are required to increase MDET utilisation.

Systemic Effects and Absorption of Subepithelial Dexamethasone Vocal Fold Injections.

OBJECTIVE/HYPOTHESIS: To compare the systemic changes following two office-based procedures-subepithelial vocal fold steroid injections (VFSI) and vocal fold augmentation (VFA), and to characterize the magnitude and chronicity of the effects observed. STUDY DESIGN: Prospective, controlled before-after comparative study. METHODS: Patients prospectively underwent VFSI with 0.8-2 mg of dexamethasone or VFA. Serum cortisol, white cell count (WCC), and C-reactive protein (CRP) were measured at day 0 (pre-procedure), 1 and 7. Salivary cortisol was measured at baseline and daily for 7 days post-procedure. RESULTS: Fourteen patients underwent VFSI and 36 VFA. At baseline serum cortisol measured 304.6 ± 116.6 nmol/L and fell significantly to 48.1 ± 41.8 nmol/L 1 day following dexamethasone injection (p = 0.001) and recovered by day 7 to 303.7 ± 78.7 nmol/L. Salivary cortisol demonstrated a similar pattern with significant recovery demonstrated by day 3 (p = 0.001). White cell counts were affected by the systemic absorption of exogenous steroid and normalized by day 7. Patients who underwent VFA demonstrated no significant change in their serum or salivary cortisol and no significant change in their WCC. No significant changes in CRP or patient's physiological parameters were observed in either procedure. CONCLUSION: Our findings demonstrate systemic absorption of dexamethasone following VFSI, with acute hypothalamic-pituitary-adrenal (HPA) axis suppression which normalizes day 3 post-procedurally. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

National outcomes of cardiac surgery in patients receiving kidney replacement therapy.

BACKGROUND: Studies estimating risks following cardiac surgery for patients receiving kidney replacement therapy have been limited by the size and generalizability of those cohorts. This study used data linked between registries to estimate short-term postoperative outcomes for large patient cohorts receiving kidney replacement therapy at the time of surgery. METHODS: This population-based observational cohort study included adult patients who had undergone cardiac surgery in Australia between 2010 and 2019. Patient data were linked with a kidney replacement therapy registry to accurately identify cohorts and extract relevant data. Multivariable logistic regression estimated risk of operative (30-day) mortality and other postoperative outcomes for long-term dialysis and functioning kidney transplant cohorts compared with each other and the general cardiac surgical population. RESULTS: Of 114,496 surgeries, 1,241 were for patients receiving long-term dialysis and 298 for those with a kidney transplant. The mortality rate was highest for valve-with-coronary artery bypass grafting for dialysis (18.78 per 100 surgeries (95% CI 13.37,25.25) and transplant patients (14.00 [5.82,26.74]). Dialysis patients had higher adjusted odds of mortality (odds ratio [OR] 4.17 [95% CI 3.31,5.25]) and all other measured outcomes than the general population. Kidney transplant recipients had similarly elevated odds of mortality (OR 3.52 [95% CI 2.16,5.72]). CONCLUSIONS: Despite the younger age of dialysis and transplant cohorts at surgery, operative mortality rates were higher, and for valve-with-coronary artery bypass grafting were 3.7- to 5-fold those of the general population. Dialysis patients were a high risk for cardiac surgery, and the prognosis for kidney transplant recipients was similarly poor.

Dexamethasone for Cardiac Surgery: A Practice Preference-Randomized Consent Comparative Effectiveness Trial.

BACKGROUND: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. The primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. The secondary aim was to evaluate efficiency, value, and impact of the novel trial design. METHODS: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across seven hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone 1 mg/kg or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (more than 48 h), sepsis, renal failure, myocardial infarction, stroke, and death. RESULTS: Of 2,562 patients assessed for eligibility, 1,951 were randomized (median age, 63 yr; 80% male). The median number of home days was 23.0 (interquartile range, 20.1 to 24.1) in the no dexamethasone group and 23.1 (interquartile range, 20.1 to 24.6) in the dexamethasone group (median difference, 0.1; 95% CI, -0.3 to 0.5; P = 0.66). The rates of prolonged mechanical ventilation (risk ratio, 0.72; 95% CI, 0.48 to 1.08), sepsis (risk ratio, 1.02; 95% CI, 0.57 to 1.82), renal failure (risk ratio, 0.94; 95% CI, 0.80 to 1.12), myocardial infarction (risk ratio, 1.20; 95% CI, 0.30 to 4.82), stroke (risk ratio, 1.06; 95% CI, 0.54 to 2.08), and death (risk ratio, 0.72; 95% CI, 0.22 to 2.35) were comparable between groups (all P > 0.10). Dexamethasone reduced intensive care unit stay (median, 29 h; interquartile range, 22 to 50 h vs. median, 43 h; interquartile range, 24 to 72 h; P = 0.004). The authors' novel trial design was highly efficient (89.3% enrollment). CONCLUSIONS: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.

Cytosolic DNA sensor AIM2 promotes KRAS-driven lung cancer independent of inflammasomes.

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co-operators of oncogenic KRAS in the lung remains ill-defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent-in-melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS-addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine-derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome-associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK-induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D-driven LAC in both hematopoietic (immune) and non-hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2-deficient mice is associated with unaltered protein levels of mature Caspase-1 and IL-1ß inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D-driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase-1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor-promoting role, independent of inflammasomes, in mutant KRAS-addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer.

Exploring Age-Related Variations in Carpal Bone Volume: Implications for Clinical Practice and Anatomical Understanding.

BACKGROUND: Clinically recognizing the changes in carpal bone volumes and understanding their implications in predicting osteoarthritis (OA) is crucial in clinical practice This study aimed to explore age-related differences in carpal bone volumes across genders, leveraging computed tomography (CT) wrist scans to create 3D surface models of these bones. METHODS: Carpal bone volumes were calculated using the 3D Slicer software from CT scans obtained from Frankston Hospital and additional datasets from Brown and Auckland Universities. The data were statistically processed using Stata V13. Double-sided P-values < .05 were considered statistically significant. The study was conducted in accordance with the ethical standards laid out in the Declaration of Helsinki. RESULTS: A total of 181 patients were analyzed, and 48% of whom were female. A statistically significant positive Spearman correlation (rho = 0.37-0.611, P <.05) was observed between increasing age and the volume of all surveyed carpal bones (scaphoid, lunate, triquetrum, pisiform, hamate, capitate, and trapezium) across genders. Intrauser and interuser reliabilities for 3D Slicer-generated volumes of trapezium and pisiform bones were statistically significant, with Interclass Correlation Coefficient (ICC) values of 0.86 and 0.95, respectively. CONCLUSION: Trapezial volumes increase with age, potentially due to the presence of OA and consequent osteophyte formation. This pattern is more prevalent among older individuals and women. However, the positive correlation between carpal bone volume and age was consistent across all carpal bones and both genders, regardless of OA presence. These findings suggest that carpal bone volume may naturally increase with age, independent of OA-related changes. LEVEL OF EVIDENCE: III, cohort study.

Association of perioperative transfusion of fresh frozen plasma and outcomes after cardiac surgery.

BACKGROUND: Fresh frozen plasma (FFP) transfusion is used to manage coagulopathy and bleeding in cardiac surgery patients despite uncertainty about its safety and effectiveness. METHODS: We performed a propensity score matched analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database including patients from 39 centres from 2005 to 2018. We investigated the association of perioperative FFP transfusion with mortality and other clinical outcomes. RESULTS: Of 119,138 eligible patients, we successfully matched 13,131 FFP recipients with 13,131 controls. FFP transfusion was associated with 30-day mortality (odds ratio (OR), 1.41; 99% CI, 1.17-1.71; p < .0001), but not with long-term mortality (hazard ratio (HR), 0.92; 99% CI, 0.85-1.00; p = .007, Holm-Bonferroni α = 0.0004). FFP was also associated with return to theatre for bleeding (OR, 1.97; 99% CI, 1.66-2.34; p < .0001), prolonged intubation (OR, 1.15; 99% CI, 1.05-1.26; p < .0001) and increased chest tube drainage (Mean difference (MD) in mL, 131; 99% CI, 120-141; p < .0001). It was also associated with reduced postoperative creatinine levels (MD in g/L, -6.33; 99% CI, -10.28 to -2.38; p < .0001). CONCLUSION: In a multicentre, propensity score matched analysis, perioperative FFP transfusion was associated with increased 30-day mortality and had variable associations with secondary clinical outcomes.

Prolonged Non-Steroidal Anti-Inflammatory Drug Exposure After Pleurodesis Increases Pneumothorax Recurrence: A Retrospective Cohort Study.

INTRODUCTION: The use of non-steroidal anti-inflammatory drugs (NSAID) in patients undergoing pleurodesis remains controversial. Although many surgeons are comfortable prescribing NSAIDs post-operatively, some oppose this practice due to concerns of suppressing the inflammatory response and quality of pleurodesis. Only a small body of inconsistent publications exists with respect to guiding therapy in this common clinical scenario. METHODS: A retrospective cohort study was undertaken assessing effect of NSAID exposure on pleurodesis outcomes. An institutional thoracic surgery database was reviewed yielding 147 patients who underwent pleurodesis for pneumothorax between 2010 and 2018. Medical records and imaging were reviewed for patient characteristics, NSAID exposure, recurrent pneumothorax and other adverse events. RESULTS: There was no overall difference between rates of recurrence and procedural failure of pleurodesis (Relative Risk [RR] 1.67 [95% CI 0.74-3.77]). However, NSAID exposure of >48 hours was associated with increased risk of recurrent pneumothorax (RR 2.16 [95% CI 1.05-4.45]). There was no increased rate of other adverse events related to NSAID usage. CONCLUSIONS: NSAID exposure does not increase failure rates or other adverse events following pleurodesis for pneumothorax. However, prolonged NSAID exposure post-pleurodesis may increase procedural failure rates. Further large volume randomised control trials are required.

Sex Differences in Opioid Administration After Cardiac Surgery.

OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.

Platelet versus fresh frozen plasma transfusion for coagulopathy in cardiac surgery patients.

BACKGROUND: Platelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown. METHODS: We conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005-2021 across 58 sites were included. The primary outcome was operative mortality. RESULTS: Of 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P<0.001) and 1-year (RR, 1.50; 95% CI, 1.32 to 1.71; P<0.001) mortality. FFP was associated with increased rates of 4-hour chest drain tube output (Adjusted mean difference in ml, 28.37; 95% CI, 19.35 to 37.38; P<0.001), AKI (RR, 1.13; 95% CI, 1.01 to 1.27; P = 0.033) and readmission to ICU (RR, 1.24; 95% CI, 1.09 to 1.42; P = 0.001). CONCLUSION: In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.