Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47–9.20), p < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79–0.91, p < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.

BACKGROUND: Prognostic biomarkers are needed to identify patients at high-risk for severe COVID-19. Galectin-3 is known to drive neutrophil infiltration and release of pro-inflammatory cytokines contributing to airway inflammation. METHODS: In this prospective cohort, we assessed galectin-3 levels in 156 hospitalized patients with confirmed COVID-19. COVID-19 patients were diagnosed as either critical (>50% lung damage) or moderate (<50% of lung damage) based on computerized tomography. Patients who required invasive mechanical ventilation (IMV) and/or died during hospitalization were categorized as having a severe outcome, and non-severe outcome if they were discharged and none of the former occurred. RESULTS: Elevated serum galectin-3 was significantly higher in critical patients compared to moderate ones (35.91 ± 19.37 ng/mL vs. 25 ± 14.85 ng/mL, p<0.0001). Patients who progressed to a severe outcome including IMV and/or in-hospital death, presented higher galectin-3 levels (41.17 ng/mL [IQR 29.71 - 52.25] vs. 23.76 ng/mL [IQR 15.78 - 33.97] compared to those of a non-severe outcome, p<0.0001). Galectin-3 discriminated well between those with severe and non-severe outcome, with an AUC of 0.75 (95% CI 0.67 - 0.84, p<0.0001)and was found to be an independent predictor of severe outcome regardless of the percentage of lung involvement. Additionally, the combination of galectin-3, CRP and albumin, significantly improved its individual predicting ability with an AUC 0.84 (95% CI 0.77 - 0.91, p<0.0001). CONCLUSION: Circulating galectin-3 levels can be used to predict severe outcomes in COVID-19 patients, including the requirement of mechanical ventilation and/or death, regardless of the initial severity of the disease.

No abstract

Introduction Breast cancer (BC) is a heterogeneous disease composed of multiple histologic subtypes. Invasive ductal carcinoma is the most common subtype, accounting for 75% of all BC cases and is followed by lobular carcinoma which represents another 15%. Other rare histologic subtypes make up the remaining 10%. To date, limited evidence exists regarding about the frequency, clinicopathologic characteristics, and prognoses of these uncommon variants in Mexico. Methods A single center retrospective cohort including women diagnosed with invasive BC between January 1990 and December 2019 was conducted. Only patients with rare histologic subtypes, excluding not otherwise specified ductal and lobular carcinoma, were included. The main objective of this study was to describe the frequency, clinicopathological characteristics, and outcomes of these histologic subtypes. Descriptive statistics including means, medians, and standard deviations, were used to analyze clinicopathological characteristics. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test. A p value of &lt; 0.05 was considered statistically significant. Results Out of 1744 women diagnosed with invasive BC, 106 patients (6.1%) had a rare histologic subtype. Among the most frequent subtypes, 39 (36.8%) were mucinous, 12 (11.3%) metaplastic, 11 (10.4%) tubulolobular, 11 (10.4%) papillary, 10 (9.4%) tubular, and 8 (7.5%) medullary carcinomas. In the less common histologic subtypes (referred as “others”), 7 (6.6%) were apocrine, 4 (3.8%) neuroendocrine, 1 (0.9%) micropapillary, 1 (0.9%) signet cell, 1 (0.9%) acinic cell, and 1 (0.9%) histiocytoid carcinoma. In the overall population, the median age at diagnosis was 58 years, 76.4% were postmenopausal at diagnosis, 29.2% had a family history of BC, and 7.5% had personal history of BC. Seventy percent of the patients were overweight or obese at time of diagnosis and 82.1% had diabetes mellitus type 2 diagnosis. An important proportion of women were diagnosed by self-detected tumors (61.3%), as opposed to less than a quarter (24.5%) detected by screening mammography. The median time of diagnosis interval was 3 months, 71.7% were diagnosed with early (I – IIA), 22.6% with locally advanced (IIB – IIIC) and 5.7% with metastatic (IV) disease. Most tumors (58.3%) expressed hormone receptors (HR), 7.2% were HER2 enriched, 8.3% expressed both HR and HER2, whereas 26% were triple negative. Clinicopathological characteristics according to the most frequent histologic subtypes are listed in Table 1. With a median follow-up of 108 months, 12 recurrences were identified (5 mucinous, 3 metaplastic, 2 tubulolobular and 2 apocrine), 41% were local and 59% were distant recurrences. Globally, 15-year RFS and OS were 83% and 61%, respectively. Differences in RFS and OS were not statistically different according to histologic subtypes. The 15-year RFS and OS was 83% and 80% for mucinous, 100% and 78% for tubular, 100% and 58% for medullary, 65% and 52% for metaplastic, 77% and 86% for tubulolobular, and 100% and 49% for papillary carcinoma, respectively. Conclusions To our knowledge, this is the first study describing the frequency, clinicopathological characteristics, and outcomes of rare histologic BC subtypes in a large Mexican cohort. Our results show that these subtypes represent 6% of all invasive BC cases, that they are commonly diagnosed at an early stage, and present long RFS and OS. Table 1: Clinicopathological characteristics according to the most frequent histologic subtypes Citation Format: Paola Valdez-Sandoval, Bertha Alejandra Martinez-Cannon, Sandra Ileana Perez Alvarez, Eucario Leon-Rodriguez. Rare Breast Cancer Histologic Subtypes: 30-year experience in a Mexican Cancer Center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-38.

No abstract