Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression.

Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets' impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML-niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.

On-table Extubation After Minimally Invasive Cardiac Surgery: A Retrospective Observational Pilot Study.

OBJECTIVE: To assess the safety of "on-table" extubation after minimally-invasive heart valve surgery. DESIGN: A single-center retrospective observational study. SETTING: At a tertiary referral academic hospital. PARTICIPANTS: Patients who underwent nonemergent isolated heart valve surgery through a minithoracotomy approach between January 2016 and August 2021. INTERVENTION: All patients were treated by 1 of the 6 cardiac anesthesiologists of the hospital. Only some of them practiced "on-table" extubation, and the outcome of patients extubated "on-table" was compared to those extubated in the intensive care unit (ICU). MEASUREMENT AND MAIN RESULTS: The primary outcome was the occurrence of any postoperative respiratory complication during the entire hospital stay. Secondary outcomes included the use of inotropes and vasopressors, de novo atrial fibrillation, and lengths of stay in the ICU and the hospital. A total of 294 patients met inclusion criteria, of whom 186 (63%) were extubated "on-table." Cardiopulmonary bypass duration was significantly longer, and moderate intraoperative hypothermia was significantly more frequent in patients extubated in the ICU. After adjustment for these confounders and for the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II using a multivariate logistic model, no association was found between the extubation strategy and postoperative pulmonary complications (adjusted odds ratio = 0.84; 95% CI = 0.40-1.77; p = 0.64). "On-table" extubation was associated with a lower risk of postoperative pneumonia and fewer vasopressors requirements. CONCLUSION: "On-table" extubation was not associated with an increased incidence of respiratory complications. A randomized controlled trial is warranted to confirm these results and determine whether "on-table" extubation offers additional benefits.

Development and Validation of a Prediction Score for Low-Cardiac-Output Syndrome After Adult Cardiac Surgery.

OBJECTIVES: The authors aimed to develop a simple prediction score to help identify patients at high risk of low-cardiac-output syndrome after adult cardiac surgery. DESIGN: A single-center, retrospective, observational study. SETTING: At a tertiary hospital. PARTICIPANTS: Adult patients who underwent on-pump cardiac surgery between April 2016 and March 2021. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among the 2,806 patients retained for final analyses, 355 (12.7%) developed low-cardiac-output syndrome. Using a stepwise backward variable selection procedure applied to a multivariate logistic regression, a prediction model, including 8 risk factors, could be identified-preoperative left ventricular ejection fraction, glomerular filtration rate <60 mL/min according to the Cockcroft formula or preoperative dialysis, combined surgery, nonelective surgery, mitral valve surgery for mitral valve regurgitation, history of extracardiac arteriopathy, preoperative hemoglobin <13 g/dL, and New York Heart Association functional class III or IV. A clinical prediction score was derived from the regression coefficients. The model had a good discriminative ability, with an area under the receiver operating characteristics curve of 0.8 (95% CI: 077-0.84). Using a threshold value of 5, the score had a 68% sensitivity, 79% specificity, a positive-predictive value of 33%, and a negative-predictive value of 94%. These results were validated on a validation sample using the bootstrap resampling technique. CONCLUSIONS: The authors developed a clinical score to facilitate the prediction of low- cardiac-output syndrome after adult cardiac surgery. This could help tailor patient management by contributing to the early identification of those at high risk of postoperative low cardiac output.