RESUMEN
The early diagnosis of acute ischemic stroke (AIS) can be challenging in cases presenting with a scarcity of clinical signs, normal cerebral imaging in early stages and a lack of specific serum markers. Thrombomodulin has been shown to be associated with cerebrovascular ischemic events and can be considered an important biomarker for the acute onset of ischemic stroke. In our study, we compared the serum levels of thrombomodulin (sTM) between a relevant patient group of 70 AIS patients and a control group of patients without AIS admitted into the neurology department between June 2022 and May 2023. sTM levels were measured at 24 h and 48 h after patients' admissions into the hospital. There was a significant difference between the two groups (AIS: 23.2 ± 9.17 ng/mL vs. controls: 3.64 ± 1.72 ng/mL; p-value < 0.001). sTM values were correlated with the score of neurological deficits, with gender and dyslipidemia. The association of sTM values with the acute onset of AIS as an end point was significant, which allows rapid therapeutic interventions, even in the absence of a well-defined clinical syndrome (AUC = 0.99). Reanalysis of the patients after propensity score matching increased the power of sTM as a biomarker (AUC = 1). sTM represents a potentially useful biomarker to diagnose the onset of an AIS, even in scarce clinical presentations, which makes thrombomodulin a valuable indicator for early treatment initiation.
RESUMEN
Compartmentation of the immune response into three main spatial cancer-immune phenotypes (SCIs) - inflamed, excluded, and desert - has been proposed as the main predictor of response to immune checkpoint inhibitors in solid tumors. The objective of the study is to define and characterize the SCI in a consecutive series of 213 endometrial carcinomas (ECs) by correlating it with molecular subtypes, clinicopathologic features, and prognosis. Immunohistochemistry (IHC) and Next-Generation Sequencing (NGS) were used to assign surrogate molecular EC subtypes: POLE mutant (POLE), mismatch repair deficient (MMRd), TP53 mutant (p53abn), and no specific molecular profile (NSMP). Immune cell markers (CD20, CD3, CD8, CD68, PD-L1) were assessed by IHC on whole sections and quantified by digital image analysis to define the three SCIs. ECs were stratified into four molecular subtypes: 17 (8.0%) POLE, 68 (31.9%) MMRd, 42 (19.7%) p53abn, and 86 (40.4%) NSMP. SCI determination showed 105 (49.3%) inflamed, 62 (29.1%) desert, and 46 (25.6%) excluded tumors. The inflamed phenotype was more prevalent in MMRd (64.7%) and POLE (76.5%) subtypes compared to NSMP (45.3%) and p53abn (21.4%). SCI revealed a strong correlation with DFS in NSMP tumors: inflamed 96.2%, desert 83.2% and excluded 40.5%. The SCI prognostic impact was also maintained in NSMP cases treated with adjuvant therapy resulting in a significant difference in recurrence between the inflamed and excluded phenotypes. To simplify SCI determination, a subset of immune cell markers was selected as appropriate to define the three SCI patterns: high intraepithelial CD8 for the inflamed phenotype; CD68, CD20, and PD-L1 to discriminate between desert and excluded tumors. The integration of SCI into molecular classification could be a promising opportunity to improve the prognostic risk stratification of patients and may guide the therapeutic approach, particularly in the NSMP subtype. Thus, the different patterns of immune response are a new prognostic parameter in the NSMP subtype.