BACKGROUND:There is a growing body of evidence supporting neoadjuvant systemic therapy to improve outcomes for people with early-stage non-small cell lung cancer (NSCLC). However, not all patients will respond, necessitating the need to explore novel combinations and predictors of response to neoadjuvant therapies. PATIENTS AND METHODS:In this open-label Phase 1B/2 signal-seeking trial, we recruited people with resectable Stage IB-IIIA NSCLC. Participants received two cycles of nivolumab with denosumab or nivolumab alone prior to surgical resection. Key clinical outcomes included the degree of pathological response, radiological overall response rate, recurrence-free survival, and overall survival. Tumor-immune correlates with pathological response were also investigated. RESULTS:Ten participants were recruited between August 2019 and September 2021, with five participants allocated to each treatment arm using minimization for tumor stage and histopathology. Two participants (20%) achieved a pathological complete response, with a further one patient achieving a major pathological response. Density of infiltrating CD8+ T cells correlated with the degree of pathological response to neoadjuvant therapy. With a median follow-up of 38.1 months, all patients remained alive at data cutoff. The 36-month recurrence-free survival was 80%. Treatment-related adverse events were reported in three patients (30%), all of which were Grade 1-2. CONCLUSION:Our results support the feasibility of neoadjuvant systemic therapy in resectable NSCLC and explore the novel combination of nivolumab with denosumab. CD8 T-cell infiltration correlates with pathological response, warranting ongoing translational research to better understand patient selection for such novel combinations.

Leucocytes regulate the immune response through multiple pathways including cytokine release, which is critical for mediating host defences. Coronary artery bypass grafting (CABG) initiates a systemic inflammatory response that may contribute to adverse patient outcomes. Full blood counts (FBC) provide insight into patient’s haematological status, however FBC don’t provide comprehensive analysis of leucocyte subsets. We investigated the impact of CABG on circulating leucocyte subsets and plasma cytokine levels. Whole blood was collected from CABG patients (n=75) at five time-points (admission, intra-operative, ICU, day three (D3), day five (D5)). The absolute count of monocytes, natural killer (NK) cells, B-cells, T-cell subsets, and dendritic cell (DC) subsets were assessed using Trucount tubes. A full blood count was performed on each patient sample and used to calculate the lymphocyte monocyte ratio and neutrophil lymphocyte ratio. Cytokine levels in patient plasma were measured via cytometric bead array. The relationship between CABG-associated immunomodulation and patient outcomes (atrial fibrillation (AF) and ICU length of stay (LOS)) was also explored. Compared to admission, patient monocyte numbers increased, and T-cell numbers decreased from the ICU period. B-cell numbers initially decreased during CABG surgery before increasing from D3. During the CABG procedure, classical DC numbers decreased, while plasmacytoid DC numbers increased. CABG also increased plasma levels of IL-6, MCP-10 and IP-10. Modulation of DC subsets, DC subset activation markers and T-cell subsets were associated with AF and ICU LOS. This study demonstrates the utility of comprehensive leucocyte subset and ratio analyses in CABG patients and provides further insight into cardiac immunobiology. Detailed assessment of the patient haematological status could be used as a clinical tool to guide post-operative management.

[This corrects the article DOI: 10.1371/journal.pone.0322592.].

OBJECTIVE:Statistical Process Control methods have proven effective in enhancing outcomes monitoring and improvement within various clinical domains. This study investigates their application in supporting thoracic surgical quality assurance processes across public hospitals in Queensland, Australia. METHODS:Retrospective evaluation of clinical data from thoracic surgeries performed at five public hospitals between January 1, 2019, and June 30, 2023, was conducted. Performance benchmarks were developed and assessed. Exponentially Weighted Moving Average charts and Funnel Plots were utilised for analysis and reporting. To account for common cause variation, Risk Adjustment models were developed and incorporated into the monitoring process. RESULTS:Outcome indicators of service quality throughout patient care were examined. Clinical outcome indicators identified as being suitable quality markers included: Death within 90 days, Major Acute Morbidity, Return to Theatre, Length of Stay, Readmission within 30 days and Tumour/Node/Metastasis (TNM) Up/Down Staging. SPC tools revealed patterns of variation over time and between sites, prompting investigation into contributing factors and opportunities for quality improvement projects. While the primary goal is to efficiently and effectively identify instances of underperformance, a structured approach to signal investigation can be used to initiate quality improvement projects when sustained performance is identified that is better than expected. CONCLUSIONS:SPC tools effectively facilitate clinical performance monitoring, aiding in timely detection and intervention in instances of altered performance. Careful interpretation of performance charts assists in identifying both declines and positive experiences, fostering continuous learning and improvement.

Surgical aortic valve replacement (AVR) is the standard of care for severe aortic valve disease; however, post-operative complications continue to pose challenges. Inflammation caused by increased release of cell-free mitochondrial DNA (cf-mtDNA) during surgery may be a contributing factor. The aim of this pilot study was to investigate the relationship between cf-mtDNA release and the risk of inflammatory-mediated post-operative complications in adult AVR patients. Plasma was collected from patients undergoing an AVR with cardiopulmonary bypass (CPB) at baseline, intra-operatively and post ICU admission at 6, 12 and 18 h. Cf-mtDNA was quantified and inflammatory biomarker expression in leukocytes and plasma was assessed. Cf-mtDNA levels increased 16-fold at the end of CPB with a corresponding increase in average fragment size. Cf-mtDNA levels may be associated with post-operative bleeding, infection, hepatic failure and hospital length of stay. Gene expression and plasma analysis revealed altered levels of markers associated with inflammation and innate immune responses. Several markers were associated with post-operative complications and outcomes. Our results indicate that cf-mtDNA levels, including average fragment sizes, are increased following initiation of CPB in AVR patients, and may be associated with post-operative complications and outcomes. However, larger studies are needed to validate these findings.

Background Inadequate time for preoperative optimization can lead to adverse outcomes after urgent cardiac surgical procedures. In this audit, we compared the incidence of postoperative pulmonary complications (PPCs) and other adverse outcomes after elective and urgent cardiac surgical procedures. Methods Adult patients who underwent nonemergency open heart surgical procedures were included. PPCs were defined as a composite of atelectasis, pneumonia, acute respiratory distress syndrome, respiratory failure, and pulmonary aspiration. Logistic regression analysis identified factors associated with PPCs. Other pulmonary and systemic complications were examined. Results In a sample of 6138 patients, PPCs were observed in 1996 (32.5%) participants. The urgent group had higher rates of pneumonia, respiratory failure, pleural effusion, and pulmonary embolism compared with elective patients (P < .001). Mild and moderate-severe respiratory diseases were associated with PPCs (adjusted odds ratio [OR], 1.34; 95% CI, 1.14-1.58; P < .001 and OR, 1.66; 95% CI, 1.32-2.09; P < .001, respectively). Other associated factors included age (P = .006), coronary artery bypass surgery, obesity, reduced left ventricular ejection fraction, preoperative creatinine level, and perfusion time (P < .001). Conclusions Pulmonary complications increased after urgent compared with elective cardiac surgical procedures, with a higher incidence of pneumonia, respiratory failure, pleural effusion, and pulmonary embolism.

OBJECTIVES There is limited consensus on the optimal strategy for surgical treatment of severe tricuspid valve pathology. At our institution, we have implemented a unique technique of using a tricuspid homograft with its supporting apparatus for partial replacement of the native tricuspid valve. We now present the long-term outcomes of these patients.METHODS We analysed a cohort of patients who underwent partial tricuspid valve replacement using tricuspid homograft. Yearly clinical and echocardiographic follow-up was performed. Fine-Gray methods were used to estimate freedom from death and reoperation and reverse Kaplan-Meier methods were used to calculate follow-up.RESULTS Fourteen patients were included (age range 15 days to 73 years). Indications included congenital anomalies (n = 9, 64%) and infective endocarditis (n = 5, 36%). The median follow-up was 17 years (95% confidence interval (CI) 10-21 years). Two patients (14%) died due to causes unrelated to the primary tricuspid valve surgery, and three (21%) underwent redo tricuspid valve operations. In the remaining cohort, seven (50%) were asymptomatic and two (14%) reported class II dyspnoea, while none had severe tricuspid regurgitation on echocardiogram. Estimated freedom from death was 93% at 10 years and 83% at 15 and 20 years, while estimated freedom from reoperation was 77% at 10, 15 and 20 years.CONCLUSIONS Partial replacement of the tricuspid valve using tricuspid homograft tissue effectively restores the anatomical conformity of the native tricuspid valve and has durable long-term survival and freedom from severe tricuspid regurgitation in patients with congenital anomalies and infective endocarditis. Tricuspid valve replacement has several limitations.

BACKGROUND:Psychological comorbidities are common in cardiac surgery patients, however much research on their prevalence, correlates and effects remains subject to methodological inconsistencies, with screening and interventions to address the problem not being systematically applied. More information about patient preferences for support and formative contextual knowledge is needed to improve screening program design, uptake, and benefits. AIMS:This study aims to estimate the prevalence and relationship of psychosocial comorbidity with cardiac surgery post-operative health outcomes and explore patients' support interests and preferences in the public hospital acute surgical setting. These findings will generate contextualised knowledge for subsequent development and implementation of a psychosocial screening and support program. METHODS:A sample of 260 patients will be screened using a pragmatic informatics platform of pre-operatively self-reported psychometric instruments including for depression, anxiety, PTSD, perceived stress, and personality traits. Post-operative outcomes and medical covariates will be linked from routinely collected clinical data as well as post-operative psychometric surveys. Prevalence of exposures of interest will be ascertained, and multivariable regression will assess associations with the primary outcome of Days Alive and Out of Hospital to 30 days (DAOH), controlling for patient-level covariates. Secondary outcomes will include measures of post-operative morbidity, Quality of Life and resource utilisation to 1 year of follow-up. Simultaneously, mixed methods will be used to elucidate patient interests and preferences for available support options including online eMental Health resources in blended care, via a post-operative preferences survey and a nested subsample of semi-structured interviews. CONCLUSION:Inconsistent evidence on screening program implementation and patient benefit necessitates a re-evaluation of locally contextualised evidence. This formative research study design will provide a contextual evidence-base including patient perspectives. This can be used to underpin the collaborative co-design of a multidisciplinary, blended model of care leveraging efficient and cost-effective care services suited to patient preferences.

Cardiac herniation is a rare potentially life-threatening complication that can occur after pneumonectomy, involving displacement of the heart through a pericardial defect, which can lead to hemodynamic instability, impaired cardiac function, and in severe cases, death. We describe a case of delayed cardiac herniation 1-month post left pneumonectomy for pulmonary leiomyosarcoma.

BACKGROUND:It is unclear if immunomodulation via cytokine adsorption (CA) to reduce perioperative inflammatory cascade in cardiothoracic transplants is associated with better outcomes. OBJECTIVE:This pilot study aims to assess the clinical outcomes of intraoperative CA in heart/lung transplantation. METHODS:From July to October 2020, intraoperative CA was instituted in 11 patients who underwent heart/lung transplantation. One-to-one propensity score matching without replacement was conducted with historical patients who did not receive CA at the time of surgery. Primary end-points evaluated were vasopressor/ inotropic demands, blood loss and mortality. Secondary end-points measured were operative morbidities. RESULTS:After matching, there were 2 (18.2%) ventricular assist device explant with heart transplantation, 2 (18.2%) heart transplantation and 7 (63.6%) lung transplantation in each group. Mean age in both groups were 53.3 years and 54.9 years respectively. The duration of noradrenaline requirement in the CA group was shorter (median, 1627 versus 3144 min, P = 0.5) and postoperative dopamine demand was significantly higher (median peak dose, 5.0 versus 0 μg/kg/min, P = 1.0; median duration of use, 7729 versus 0 min, P = 0.01). Non-red blood cell transfusion rate was two times higher in CA patients (90.9% versus 45.4%, P = 0.06). Early mortality was higher in the control group (18.2% versus 9.1%, P = 1.0). No differences were observed in the incidences of operative morbidities. CONCLUSION:Intraoperative CA in heart and lung transplantation in our institution was not associated with significant improvement in clinical outcomes, including vasopressor/inotropic demand. Larger studies are required to evaluate the transfusion requirements and mortality risks with CA use in this patient population.

A pragmatic informatics approach was developed to create knowledge tools for co-design of a new model of mental healthcare in cardiac surgery The real-world evidence generation leverages existing technological platforms and routine data collections plus tailored brief tools, surveys and qualitative data.

Primary pleuropulmonary tumours presenting as recurrent pneumothoraces are rare findings but are being increasingly reported in literature.1,2 A case report of a 73 year old male with recurrent pneumothoraces secondary to epithelioid diffuse mesothelioma is presented. A CT-scan of his chest showed a large left pneumothorax with multiple calcified plaques at lung bases suggesting prior asbestos exposure and multiple ground glass opacities in addition to nodules in both the right and left lung. Thoracoscopy found apical scarring with adhesion formation on left upper lobe parenchyma in keeping with the appearance of resolved bullae.

Introduction: Indigenous Australians (Aboriginal and Torres Strait Islander) have lower overall survival from lung cancer compared with nonindigenous Australians. Indigenous Australians receive higher rates of chemo-therapy and/or radiotherapy. The equity of peri-operative care and thoracic surgical outcomes in Australian indigenous populations have not been contemporarily evaluated. Methods: We performed a retrospective registry analysis of the Queensland Cardiac Outcomes Registry Thoracic Data-base evaluating all adult lung cancer resections across Queensland from January 1, 2016 to April 20, 2022. Evaluating the time from diagnosis to surgery, operative data, and postoperative morbidity and mortality comparing Aboriginal and/or Torres Strait Islander people with nonindigenous Australians. Results: There were 31 patients (2.56%) of 1208 who identified as indigenous. The mean age at surgery was 68.2years versus 66 years in the indigenous and nonindigenous, respectively (p 1/40.23). There was female predominance among indigenous patients (n 1/4 28, 90.32%,p<0.01) and the average body mass index was lower (22.52 versus27.09,p<0.01). There was no variation in the surgical parameters or histopathologic distribution of cancer type between groups. Multivariable logistic regression analysis suggested that indigenous patients were at elevated risk of blood transfusion (relative risk 3.9,p 1/40.014, OR 1/49.01,95% confidence interval [CI]: 2.25-36.33,p<0.01) and had greater transfusion requirements (risk ratio 4.08,p<1/4>0.0116 and OR 1/4 12.67, 95% CI: 2.25-71.49,p<0.01); however, the influence of low absolute number of trans-fusions must be acknowledged here. Indigenous status was not associated with increased intensive care unit admission(OR<1/4>1.79, 95% CI: 0.17-18.80,p 1/40.62), return to operating theater (OR 1/42.1, 95% CI: 0.24-18.15,p 1/40.50),new atrial fibrillation (OR 1/40.52, 95% CI: 0.07-4.01,p 1/40.55), prolonged air leak (OR 1/40.29, 95% CI: 0.04-2.16,p 1/40.228), or pneumonia postoperatively (OR 1/44.77, 95%CI: 0.55-41.71,p 1/40.16). With only three deaths, no meaningful trends were observed. Time from diagnosis to surgery was comparable in the indigenous and nonindigenous groups (88.6 d, 95% CI: 54.26-123.24 versus 86.2 d,81.40-91.02,p 1/40.87). Postoperative length of stay was not numerically or statistically different between groups.(indigenous 7.54 d versus nonindigenous 7.13 d,p 1/40.90). Conclusions: Indigenous patients are more likely to receive a blood transfusion than nonindigenous patients during lung resection. Reassuringly, the perioperative care pro-vided to indigenous Australians undergoing lung resection in Queensland seems to be comparable to that of the nonindigenous population.& Oacute;2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license.

Background: Anaemic cardiac surgery patients are at greater risk of intraoperative red blood cell transfusion. This study questions the application of the World Health Organization population-based anaemia thresholds (haemoglobin <120 g L-1 in non-pregnant females and <130 g L-1 in males) as appropriate preoperative optimisation targets for cardiac surgery. Methods: A retrospective cohort study was conducted on adults >= 18 yr old undergoing cardiopulmonary bypass surgery. Logistic regression was applied to define sex-specific preoperative haemoglobin concentrations with reduced probability of intraoperative red blood cell transfusion for cardiac surgery patients. Results: Data on 4384 male and 1676 female patients were analysed. Binarily stratified multivariable logistic regression odds of receiving intraoperative red blood cell transfusion increased in cardiac surgery patients 45 yr old (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.33-2.55), surgery urgency <30 days (OR 2.03; 95% CI 1.66-2.48), combined coronary artery bypass grafting and valve surgery, or other surgery types (OR 2.24; 95% CI 1.87-2.67), and female sex (OR 1.92; 95% CI 1.62-2.28). The odds decreased by 8.4% with each 1 g L-1 increase in preoperative haemoglobin (OR 0.92; 95% CI 0.91-0.92). Logistic regression predicted females required a preoperative haemoglobin concentration of 133 g L-1 and males 127 g L-1 to have a 15% probability of intraoperative transfusion. Conclusions: The World Health Organization female anaemia threshold of haemoglobin <120 g L-1 disproportionately disadvantages female cardiac surgery patients. A preoperative haemoglobin concentration >= 130 g L-1 in adult cardiac surgery patients would minimise their overall probability of intraoperative red blood cell transfusion to <15%.

BACKGROUND:The coronavirus disease-19 (COVID-19) pandemic poses unprecedented challenges to global healthcare. The contemporary influence of COVID-19 on the delivery of lung cancer surgery has not been examined in Queensland.METHODS:We performed a retrospective registry analysis of the Queensland Cardiac Outcomes Registry (QCOR), thoracic database examining all adult lung cancer resections across Queensland from 1/1/2016 to 30/4/2022. We compared the data prior to, and after, the introduction of COVID-restrictions.RESULTS:There were 1207 patients. Mean age at surgery was 66 years and 1115 (92%) lobectomies were performed. We demonstrated a significant delay from time of diagnosis to surgery from 80 to 96 days (P < 0.0005), after introducing COVID-restrictions. The number of surgeries performed per month decreased after the pandemic and has not recovered (P = 0.012). 2022 saw a sharp reduction in cases with 49 surgeries, compared to 71 in 2019 for the same period.CONCLUSION:Restrictions were associated with a significant increase in pathological upstaging, greatest immediately after the introduction of COVID-restrictions (IRR 1.71, CI 0.93-2.94, P = 0.05). COVID-19 delayed the access to surgery, reduced surgical capacity and consequently resulted in pathological upstaging throughout Queensland.

PURPOSE:Non-small cell lung cancer is the most common malignancy of the elderly, with 5-year survival estimates of 16.8%. The prognostic benefit of surgical resection for early lung cancer is irrefutable and maintained irrespective of age, even in patients over 75 years. Concerningly, despite the prognostic benefit of surgery there are deviations from standard treatment protocols with increasing age due to concerns of increased morbidity and mortality with surgery, without evidence to support this. METHOD:A state-wide retrospective registry study of Queensland's Cardiac Outcomes Registry's (QCOR) Thoracic Database examining the influence of age on the safety of Lung Resection (1 January 2016-20 April 2022). RESULTS:This included 1,232 patients, mean age at surgery was 66 years (range 14-91 years), with 918 thoracotomies performed. Three deaths occurred within 30-days (0.24%). Octogenarians (n=60) had lower rates of smoking (26% vs 6%), respiratory, cardiovascular, and cerebrovascular disease suggesting this subset of patients is carefully selected. Octogenarian status was not associated with an increased all-cause morbidity (p=0.09) or 30-day mortality (p=0.06). Further to this it was not associated with re-operation (4.4% vs 8.3%, p=0.1), increased postoperative stay (6.66 vs 6.65 days, p=0.99) or myocardial infarction. An independent predictor of morbidity was male sex (OR 1.58, CI 1.2-2.1 p=0.001). CONCLUSION:Age ≥80 years did not increase surgical morbidity or mortality in the appropriately selected patient and should not be a barrier to referral for consideration of surgical resection.

Marfan syndrome patients with a dilated aortic root carry a risk of aortic dissection during pregnancy.

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.

Context and Aims: To describe current fluid and vasopressor practices after cardiac surgery in Australia and New Zealand cardiothoracic intensive care units (ICU). Design and Setting: This web-based survey was conducted in cardiothoracic ICUs in Australia and New Zealand. Methods: Intensivists, cardiac surgeons, and anesthetists were contacted to complete the online survey that asked questions regarding first and second choice fluids and vasopressors and the tools and factors that influenced these choices. Results: There were 96 respondents including 51 intensivists, 27 anesthetists, and 18 cardiac surgeons. Balanced crystalloids were the most preferred fluids (70%) followed by 4% albumin (18%) overall and among intensivists and anesthetists; however, cardiac surgeons (41%) preferred 4% albumin as their first choice. The most preferred second choice was 4% albumin (74%). Among vasopressors, noradrenaline was the preferred first choice (93%) and vasopressin the preferred second choice (80%). 53% initiated blood transfusion at a hemoglobin threshold of 70 g/L. Clinical acumen and mean arterial pressure were the most commonly used modalities in determining the need for fluids. Conclusions: There is practice variation in preference for fluids used in cardiac surgical patients in Australia and New Zealand; however, balanced crystalloids and 4% albumin were the most popular choices. In contrast, there is broad agreement with the use of noradrenaline and vasopressin as first and second-line vasopressors. These data will inform the design of future studies that aim to investigate hemodynamic management post cardiac surgery.