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.

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.

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.

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.

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.

Platelet Transfusion in Cardiac Surgery: An Entropy-Balanced, Weighted, Multicenter Analysis.

BACKGROUND: Platelet transfusion is common in cardiac surgery, but some studies have suggested an association with harm. Accordingly, we investigated the association of perioperative platelet transfusion with morbidity and mortality. METHODS: We conducted a retrospective analysis of prospectively collected data from the Australian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. We included consecutive adults from 2005 to 2018 across 40 centers. We used inverse probability of treatment weighting via entropy balancing to investigate the association of perioperative platelet transfusion with our 2 primary outcomes, operative mortality (composite of both 30-day and in-hospital mortality) and 90-day mortality, as well as multiple other clinically relevant secondary outcomes. RESULTS: Among 119,132 eligible patients, 25,373 received perioperative platelets and 93,759 were considered controls. After entropy balancing, platelet transfusion was associated with reduced operative mortality (odds ratio [OR], 0.63; 99% confidence interval [CI], 0.47-0.84; P < .0001) and 90-day mortality (OR, 0.66; 99% CI, 0.51-0.85; P < .0001). Moreover, it was associated with reduced odds of deep sternal wound infection (OR, 0.57; 99% CI, 0.36-0.89; P = .0012), acute kidney injury (OR, 0.84; 99% CI, 0.71-0.99; P = .0055), and postoperative renal replacement therapy (OR, 0.71; 99% CI, 0.54-0.93; P = .0013). These positive associations were observed despite an association with increased odds of return to theatre for bleeding (OR, 1.55; 99% CI, 1.16-2.09; P < .0001), pneumonia (OR, 1.26; 99% CI, 1.11-1.44; P < .0001), intubation for longer than 24 hours postoperatively (OR, 1.13; 99% CI, 1.03-1.24; P = .0012), inotrope use for >4 hours postoperatively (OR, 1.14; 99% CI, 1.11-1.17; P < .0001), readmission to hospital within 30 days of surgery (OR, 1.22; 99% CI, 1.11-1.34; P < .0001), as well as increased drain tube output (adjusted mean difference, 89.2 mL; 99% CI, 77.0 mL-101.4 mL; P < .0001). CONCLUSIONS: In cardiac surgery patients, perioperative platelet transfusion was associated with reduced operative and 90-day mortality. Until randomized controlled trials either confirm or refute these findings, platelet transfusion should not be deliberately avoided when considering odds of death.

Fresh frozen plasma transfusion after cardiac surgery.

INTRODUCTION: Fresh frozen plasma (FFP) transfusion in the intensive care unit (ICU) is commonly used to treat coagulopathy and bleeding in cardiac surgery, despite suggestion that it may increase the risk of morbidity and mortality through mechanisms such as fluid overload and infection. METHODS: We retrospectively studied consecutive adults undergoing cardiac surgery from the Medical Information Mart for Intensive Care III and IV databases. We applied propensity score matching to investigate the independent association of within-ICU FFP transfusion with mortality and other key clinical outcomes. RESULTS: Of our 12,043 adults who met inclusion criteria, 1585 (13.2%) received perioperative FFP with a median of 2.48 units per recipient (interquartile range [IQR]: 2.04, 4.33) at a median time of 1.83 h (IQR: 0.75, 3.75) after ICU admission. After propensity matching of 952 FFP recipients to 952 controls, we found no significant association between FFP use and hospital mortality (odds ratio (OR): 1.58; 99% confidence interval (CI): 0.57, 3.71), suspected infection (OR: 0.72; 99% CI: 0.49, 1.08), or acute kidney injury (OR: 1.23; 99% CI: 0.91, 1.67). However, FFP was associated with increased days in hospital (adjusted mean difference (AMD): 1.28; 99% CI: 0.27, 2.41; p = .0050), days in intensive care (AMD: 1.28; 99% CI: 0.27, 2.28; p = .0011), and chest tube output in millilitres up to 8 h after transfusion (AMD: 92.98; 99% CI: 52.22, 133.74; p < .0001). CONCLUSIONS: After propensity matching, FFP transfusion was not associated with increased hospital mortality, but was associated with increased length of stay and no decrease in bleeding in the early post-transfusion period.

The pathophysiology and management of depression in cardiac surgery patients.

Background: Depression is common in the cardiac surgery population. This contemporary narrative review aims to explore the main pathophysiological disturbances underpinning depression specifically within the cardiac surgery population. The common non-pharmacological and pharmacological management strategies used to manage depression within the cardiac surgery patient population are also explored. Methods: A total of 1291 articles were identified through Ovid Medline and Embase. The findings from 39 studies were included for qualitative analysis in this narrative review. Results: Depression is associated with several pathophysiological and behavioral factors which increase the likelihood of developing coronary heart disease which may ultimately require surgical intervention. The main pathophysiological factors contributing to depression are well characterized and include autonomic nervous system dysregulation, excessive inflammation and disruption of the hypothalamic-pituitary-adrenal axis. There are also several behavioral factors in depressed patients associated with the development of coronary heart disease including poor diet, insufficient exercise, poor compliance with medications and reduced adherence to cardiac rehabilitation. The common preventative and management modalities used for depression following cardiac surgery include preoperative and peri-operative education, cardiac rehabilitation, cognitive behavioral therapy, religion/prayer/spirituality, biobehavioral feedback, anti-depressant medications, and statins. Conclusion: This contemporary review explores the pathophysiological mechanisms leading to depression following cardiac surgery and the current management modalities. Further studies on the preventative and management strategies for postoperative depression in the cardiac surgery patient population are warranted.

Survival Benefit of Multiple Arterial Revascularization With and Without Supplementary Saphenous Vein Graft.

Background It is unknown if the presence of saphenous vein grafting (SVG) adversely affects late survival following coronary surgery with multiple arterial grafting (MAG) versus single arterial grafting. Methods and Results A retrospective, observational, multicenter cohort study from 2001 to 2020 was conducted using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Database linked to the National Death Index. Patients undergoing primary isolated coronary artery bypass grafting with ≥2 grafts were included, and exclusions were patients aged <18 years, reoperations, concomitant or previous cardiac surgery, and the absence of arterial grafting. Demographics, comorbidities, medication, and operative configurations were propensity score matched between cohorts. The primary outcome was all-cause late death. Of 59 689 eligible patients, 35 113 were MAG (58.8%), and 24 576 were single arterial grafting (41.2%). Of the MAG cohort, 17 055 (48.6%) patients did not receive supplementary SVG (total arterial revascularization). Matching separately generated 22 764 patient pairs for MAG versus single arterial grafting, and 11 137 patient pairs for MAG with total arterial revascularization versus MAG with ≥1 supplementary vein grafts. At a median follow-up duration of 5.0 years postoperatively, the mortality rate was significantly lower for MAG than single arterial grafting (hazard ratio [HR], 0.79 [95% CI, 0.76-0.83]; P<0.001). The stratified MAG analysis found that MAG with total arterial revascularization had a lower risk of late death (HR, 0.85 [95% CI, 0.80-0.91]; P<0.001) compared with MAG with ≥1 supplementary vein grafts. Sensitivity analyses produced consistent outcomes as the primary analysis. Following adjustment for the presence of SVG in the Cox model, the survival advantage of incremental number of arteries was lost. Conclusions Multiple arterial grafting has significantly improved long-term survival compared with single arterial grafting. A further incremental survival benefit exists when no SVG is used.

Paying attention to cardiac surgical risk: An interpretable machine learning approach using an uncertainty-aware attentive neural network.

Machine learning (ML) is increasingly applied to predict adverse postoperative outcomes in cardiac surgery. Commonly used ML models fail to translate to clinical practice due to absent model explainability, limited uncertainty quantification, and no flexibility to missing data. We aimed to develop and benchmark a novel ML approach, the uncertainty-aware attention network (UAN), to overcome these common limitations. Two Bayesian uncertainty quantification methods were tested, generalized variational inference (GVI) or a posterior network (PN). The UAN models were compared with an ensemble of XGBoost models and a Bayesian logistic regression model (LR) with imputation. The derivation datasets consisted of 153,932 surgery events from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Cardiac Surgery Database. An external validation consisted of 7343 surgery events which were extracted from the Medical Information Mart for Intensive Care (MIMIC) III critical care dataset. The highest performing model on the external validation dataset was a UAN-GVI with an area under the receiver operating characteristic curve (AUC) of 0.78 (0.01). Model performance improved on high confidence samples with an AUC of 0.81 (0.01). Confidence calibration for aleatoric uncertainty was excellent for all models. Calibration for epistemic uncertainty was more variable, with an ensemble of XGBoost models performing the best with an AUC of 0.84 (0.08). Epistemic uncertainty was improved using the PN approach, compared to GVI. UAN is able to use an interpretable and flexible deep learning approach to provide estimates of model uncertainty alongside state-of-the-art predictions. The model has been made freely available as an easy-to-use web application demonstrating that by designing uncertainty-aware models with innately explainable predictions deep learning may become more suitable for routine clinical use.