MMP-11 expression in early luminal breast cancer: associations with clinical, MRI, pathological characteristics, and disease-free survival.

BACKGROUND: Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers. METHODS: In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed. RESULTS: Among the patients (aged 31-89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11. CONCLUSION: MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

The Safety of Early Discharge Following Transcatheter Aortic Valve Implantation Among Patients in Northern Ontario and Rural Areas Utilizing the Vancouver 3M TAVI Study Clinical Pathway.

Background: Early hospital ( < 48 hours) discharge following transcatheter aortic valve implantation (TAVI) is an increasingly adopted practice; however, data on the safety of such an approach among patients residing in North Ontario, including remote and medically underserved areas, are lacking. Methods: This retrospective study included patients who underwent TAVI in Sudbury, Ontario. The safety of early discharge after implementation of the Vancouver 3M (multidisciplinary, multimodality, but minimalist) clinical pathway was assessed. The primary endpoint was 30-day mortality. Resource utilization before vs after 3M clinical pathway implementation was also compared. Results: A total of 291 patients who underwent TAVI between 2012 and 2021 were included in the study. One in-hospital death (0.6%) occurred after the 3M clinical pathway implementation, with no mortality observed beyond hospital discharge. Eleven patients (6.7%) required rehospitalization within 30 days. The need for mechanical ventilation and surgical vascular cut-down declined from 100% and 97%, respectively, at baseline, to 6% and 2%. The number of patients receiving TAVI on a given procedural day increased from 2 to 3 patients. The median post-TAVI hospital length of stay decreased from 5 days (2-6 days) to 1 day (1-3 days) after 3M clinical pathway implementation. Conclusions: Following TAVI, early discharge of selected patients residing in Northern Ontario, including rural areas, using the Vancouver 3M clinical pathway was associated with favourable outcomes, short length of stay, and more-efficient resource utilization. These data can help improve healthcare efficiency and bridge variations in TAVI funding and accessibility in underserved locations.

Contexte: Il est de plus en plus admis d'accorder un congé rapide de l'hôpital (< 48 heures) après une implantation valvulaire aortique par cathéter (IVAC); toutefois, on ne dispose pas de données sur l'innocuité de cette pratique pour les patients du nord de l'Ontario, y compris ceux qui résident en régions éloignées moins bien desservies par les services médicaux. Méthodologie: Cette étude rétrospective a porté sur des patients ayant subi une IVAC à Sudbury (Ontario). L'innocuité d'un congé rapide après l'implantation selon le parcours de soins Vancouver 3M (multidisciplinaire, multimodal, mais minimaliste) a été évaluée. Le principal paramètre d'évaluation était la mortalité à 30 jours. Une comparaison de l'utilisation des ressources avant et après la mise en œuvre du parcours de soins 3M a également été effectuée. Résultats: Au total, 291 patients ayant subi une IVAC entre 2012 et 2021 ont été inclus dans l'étude. Un décès à l'hôpital (0,6 %) est survenu après la mise en œuvre du parcours de soins 3M, et aucune mortalité n'a été relevée après le congé de l'hôpital. Onze patients (6,7 %) ont dû être réhospitalisés dans les 30 jours suivants. Le recours à la ventilation mécanique et à la dénudation vasculaire a chuté, passant de 100 % et 97 % au départ, respectivement, à 6 % et 2 %. Le nombre de patients par jour d'intervention subissant une IVAC est passé de deux à trois patients. À la suite de la mise en œuvre du parcours de soins 3M, la durée médiane du séjour à l'hôpital après une IVAC est passée de cinq jours (deux à six jours) à un jour (un à trois jours). Conclusions: Après une IVAC, le congé rapide de patients sélectionnés habitant dans le nord de l'Ontario, y compris ceux habitant en région rurale, selon le parcours de soins Vancouver 3M a été associé à des résultats de santé favorables, à une durée courte d'hospitalisation et à une utilisation plus efficace des ressources. Ces données peuvent contribuer à améliorer l'efficacité des soins de santé et à combler des écarts liés aux variations du financement et de l'accessibilité des IVAC dans les régions moins bien desservies.

Preclinical Modeling of DCD Class III Donation: Paving the Way for the Increased Use of This Challenging Donor Type.

Deceased after circulatory death (DCD) donors offer a viable solution to the current organ shortage, particularly the Maastricht Class III (arrest subsequent to cessation of life support in the hospital). Although current results from these donors are very satisfactory, the number of included donors is too low and future expansion of inclusion criteria will likely decrease organ quality, with negative consequences on the complication rate. This donor type thus represents a priority in terms of scientific exploration, so as to study it in controlled settings and prepare for future challenges. Hence, we mimicked the DCD Class III clinical conditions a Large White pig model. Herein, we detail the different strategies attempted to attain our objectives, including technical approaches such as animal positioning and ventilator settings, as well as pharmacological intervention to modulate blood pressure and heart rate. We highlight the best combination of factors to successfully reproduce DCD Class III conditions, with perfusion pressures and functional warm ischemia (hypoperfusion) closely resembling clinical situations. Finally, we detail the functional and histological impacts of these conditions. Such a model could be of critical value to explore novel management alternative for these donors, presenting a uniquely adapted platform for such therapeutics as normothermic regional circulation and/or pharmacological intervention.

A novel machine learning-derived decision tree including uPA/PAI-1 for breast cancer care.

Background uPA and PAI-1 are breast cancer biomarkers that evaluate the benefit of chemotherapy (CT) for HER2-negative, estrogen receptor-positive, low or intermediate grade patients. Our objectives were to observe clinical routine use of uPA/PAI-1 and to build a new therapeutic decision tree integrating uPA/PAI-1. Methods We observed the concordance between CT indications proposed by a canonical decision tree representative of French practices (not including uPA/PAI-1) and actual CT prescriptions decided by a medical board which included uPA/PAI-1. We used a method of machine learning for the analysis of concordant and non-concordant CT prescriptions to generate a novel scheme for CT indications. Results We observed a concordance rate of 71% between indications proposed by the canonical decision tree and actual prescriptions. Discrepancies were due to CT contraindications, high tumor grade and uPA/PAI-1 level. Altogether, uPA/PAI-1 were a decisive factor for the final decision in 17% of cases by avoiding CT prescription in two-thirds of cases and inducing CT in other cases. Remarkably, we noted that in routine practice, elevated uPA/PAI-1 levels seem not to be considered as a sufficient indication for CT for N≤3, Ki 67≤30% tumors, but are considered in association with at least one additional marker such as Ki 67>14%, vascular invasion and ER-H score <150. Conclusions This study highlights that in the routine clinical practice uPA/PAI-1 are never used as the sole indication for CT. Combined with other routinely used biomarkers, uPA/PAI-1 present an added value to orientate the therapeutic choice.