A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals.

The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the second 69 atypical meningiomas (grade 2). Immunohistochemical Ki-67 and MCM6 labeling indices (LI) were evaluated independently by two observers. Among the atypical meningiomas, 33 cases were also studied by genome-wide DNA methylation. In grade 2 meningiomas, but not grade 1, both Ki-67 and MCM6 LIs were correlated with PFS (p = 0.004 and p = 0.005, respectively; Cox univariate analyses). Additionally, MCM6 was correlated with overall survival only in univariate analysis. In a multivariate model, including mitotic index, Ki-67, MCM6, age, sex, and the quality of surgical resection, only MCM6 was correlated with PFS (p = 0.046). Additionally, we found a significant correlation between PTEN loss and high MCM6 or Ki-67 LIs. Although no correlation was found with the methylation classes and subtypes returned by the meningioma algorithm MNGv2.4., MCM6 LI was significantly correlated with the methylation of 2 MCM6 gene body loci. In conclusion, MCM6 is a relevant prognostic marker in atypical meningiomas. This reproducible and easy-to-use marker allows the identification of a highly aggressive subtype of proliferative meningiomas, characterized notably by frequent PTEN losses, which was previously reported to be sensitive to histone deacetylase inhibitors.

Time-Controlled Adaptive Ventilation Does Not Induce Hemodynamic Impairment in a Swine ARDS Model.

Background: The current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model. Methods: In 10 pigs (63-73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH2O; (2) TCAV group with P-high set between 27 and 29 cmH2O, P-low at 0 cmH2O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3-4 s, with I:E > 6:1. Results: Both lung elastance and PaO2:FiO2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group (p < 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group (p < 0.05). Conclusion: No hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system.

Methylene Blue Reduces Fluid Loading and Norepinephrine Requirements for Post-Resuscitation Syndrome in a Pig Model of Refractory Cardiac Arrest Resuscitated with Veno-Arterial ECMO.

BACKGROUND: Refractory cardiac arrest management relies on extracorporeal cardiopulmonary resuscitation (ECPR), requiring the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Circulatory flow recovery can be associated with an ischemia-reperfusion injury, leading to vasoplegia and vasopressor requirement. The aim of this work was to evaluate the impact on hemodynamics of a methylene blue bolus infusion in a porcine model of ischemic refractory cardiac arrest. METHODS: Ischemic refractory cardiac arrest was induced in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and the pigs were randomly assigned to the standard care group (norepinephrine + crystalloids) or methylene blue group (IV 2 mg·kg-1 bolus of methylene blue over 30 min + norepinephrine and crystalloids). Macrocirculatory parameters and lactate clearance were measured. Sublingual microcirculation was evaluated with sidestream dark field (SDF) imaging. The severity of the ischemic digestive lesions was assessed according to the histologic Chiu/Park scale. RESULTS: Eighteen pigs were included. The total crystalloid load (5000 (6000-8000) mL vs. 17,000 (10,000-19,000) mL, p = 0.007, methylene blue vs. standard care group) and catecholamine requirements (0.31 (0.14-0.44) µg·kg-1·min-1 vs. 2.32 (1.17-5.55) µg·kg-1·min-1, methylene blue vs. standard care group, p = 0.004) were significantly reduced in the methylene blue group. There were no significant between-group differences in lactate clearance, sublingual capillary microvascular parameters assessed by SDF or histologic Chiu/Park scale. CONCLUSIONS: In our refractory cardiac arrest porcine model treated with ECPR, methylene blue markedly reduced fluid loading and norepinephrine requirements in comparison to standard care during the first 6 h of VA-ECMO.

Intraoperative prediction of non-sentinel lymph node metastases in breast cancer using cytokeratin 19 mRNA copy number: A retrospective analysis.

One-step nucleic acid amplification (OSNA) is a molecular procedure used intraoperatively for the detection of sentinel lymph node (SLN) metastases. The aim of the present study was to define a cut-off of cytokeratin (CK)19 mRNA copy number predictive of positive completion axillary lymph node dissection (ALND). The OSNA procedure was employed for SLN analysis in 812 patients with T1-T2 N0 breast cancer. A total of 197 patients with SLN metastases were retrospectively analyzed. A total of 40 patients (20%) had non-SLN metastases. Receiver operating characteristics curve analysis established a cut-off of 5,000 CK19 mRNA copy number with 75% sensitivity and 72% specificity. The positive and negative predictive values were 40.5 and 92%, respectively. Multivariate analysis showed that this cut-off and tumor localization in the outer or lower-outer quadrant of the breast were significantly associated with non-SNL involvement (P<0.001 and P=0.025, respectively). The findings of the present study support the conventional cut-off of 5,000 copies for intraoperative decision to perform ALND, whereas ALND can safely be avoided in patients with tumor located outside the outer or lower-outer quadrant of the breast if the CK19 mRNA copy number is <5,000.

Fatal massive pulmonary thromboembolism and concomitant pulmonary trophoblastic embolism associated with exaggerated placental site reaction: a case study.

Pulmonary embolism is a major cause of maternal morbidity during pregnancy. Beside the frequently encountered thromboembolism, trophoblastic cell embolism has also been reported in a few case reports. This phenomenon may be symptomless in physiological gestational process but is more pronounced in contexts of preeclampsia or gestational trophoblastic disease. It was exceptionally reported to be associated with death. Here, we report the case of a 15-year-old girl, who experienced dyspnea followed by cardiac arrests and disseminated intravascular coagulation. Echocardiography showed a massive proximal pulmonary embolism. Abdominal sonography revealed that she was 11 weeks pregnant. Autopsy confirmed the presence of multiple clot emboli in the proximal pulmonary arteries. Additionally, the histopathological examination showed a massive syncytiotrophoblastic embolism in the lung microcirculation. Microscopic examination of the uterus revealed an exaggerated placental site reaction. In conclusion, this exhaustive post-mortem study describes a previously unreported association between exaggerated placental site reaction and pulmonary trophoblastic embolism, with fatal issue. Forensic pathologists should be aware that a large sampling of the lungs and uterus and examination of both placenta and fetus are needed to achieve this diagnosis. This case study emphasizes the need for further work elucidating pathways of trophoblast deportation.