Prepandemic personal concentrations of per- and polyfluoroalkyl substances (PFAS) and other pollutants: Specific and combined effects on the incidence of COVID-19 disease and SARS-CoV-2 infection.

OBJECTIVE: To investigate the specific and combined effects of personal concentrations of some per- and polyfluoroalkyl substances (PFAS), other persistent organic pollutants (POPs), and chemical elements -measured in individuals' blood several years before the pandemic- on the development of SARS-CoV-2 infection and COVID-19 disease in the general population. METHODS: We conducted a prospective cohort study in 240 individuals from the general population of Barcelona. PFAS, other POPs, and chemical elements were measured in plasma, serum, and whole blood samples, respectively, collected in 2016-2017. PFAS were analyzed by liquid chromatography-triple quadrupole mass spectrometry. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or antibody serology in blood samples collected in 2020-2021. RESULTS: No individual PFAS nor their mixtures were significantly associated with SARS-CoV-2 seropositivity or COVID-19 disease. Previously identified mixtures of POPs and elements (Porta et al., 2023) remained significantly associated with seropositivity and COVID-19 when adjusted for PFAS (all OR > 4 or p < 0.05). Nine chemicals comprised mixtures associated with COVID-19: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, other DDT-related compounds, manganese, tantalum, and aluminium. And nine chemicals comprised the mixtures more consistently associated with SARS-CoV-2 seropositivity: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, gold, and (protectively) selenium, indium, and iron. CONCLUSIONS: The PFAS studied were not associated with SARS-CoV-2 seropositivity or COVID-19. The results confirm the associations between personal blood concentrations of some POPs and chemical elements and the risk of COVID-19 and SARS-CoV-2 infection in what remains the only prospective and population-based cohort study on the topic. Mixtures of POPs and chemical elements may contribute to explain the heterogeneity in the risks of SARS-CoV-2 infection and COVID-19 in the general population.

Automated quantification of stromal tumour infiltrating lymphocytes is associated with prognosis in breast cancer.

Stromal tumour infiltrating lymphocytes (sTIL) in haematoxylin and eosin (H&E) stained sections has been linked to better outcomes and better responses to neoadjuvant therapy in triple-negative and HER2-positive breast cancer (TNBC and HER2 +). However, the infiltrate includes different cell populations that have specific roles in the tumour immune microenvironment. Various studies have found high concordance between sTIL visual quantification and computational assessment, but specific data on the individual prognostic impact of plasma cells or lymphocytes within sTIL on patient prognosis is still unknown. In this study, we validated a deep-learning breast cancer sTIL scoring model (smsTIL) based on the segmentation of tumour cells, benign ductal cells, lymphocytes, plasma cells, necrosis, and 'other' cells in whole slide images (WSI). Focusing on HER2 + and TNBC patient samples, we assessed the concordance between sTIL visual scoring and the smsTIL in 130 WSI. Furthermore, we analysed 175 WSI to correlate smsTIL with clinical data and patient outcomes. We found a high correlation between sTIL values scored visually and semi-automatically (R = 0.76; P = 2.2e-16). Patients with higher smsTIL had better overall survival (OS) in TNBC (P = 0.0021). In the TNBC cohort, smsTIL was as an independent prognostic factor for OS. As part of this work, we introduce a new segmentation dataset of H&E-stained WSI.

Characterization and spatial distribution of the immune cell infiltrate in triple-negative breast cancer: a novel classification based on plasma cells and CD8+ T cells.

Stromal tumor-infiltrating lymphocytes (sTILs) are a robust prognostic and predictive biomarker in triple-negative breast carcinoma. However, the sTIL compartment comprises different cell populations. The aim of the study is to characterize the distribution of T cells (CD3+ and CD8+), B cells, and plasma cells and explore their association with outcome in the surgical specimen of 62 patients. Furthermore, programmed death ligand 1 expression and the presence of tertiary lymphoid structures (TLSs) are explored. Patients with higher sTILs achieve better progression-free survival (PFS) (P = .0013), and tumors have more plasma cells in the infiltrate. Specifically, higher counts of T cells (both CD3+ and CD8+) have better PFS (P = .002 and P = .0086, respectively) as it is observed in tumors with higher infiltration of CD8+ T cells in the tumor core (P = .035). Higher infiltration by B cells and plasma cells shows a positive tendency toward increased PFS (P = .06 and P = .058). Programmed death ligand 1 (SP142) is positive in 56% of tumors. Tumors with at least 1 TLS (42%) show higher CD8+ T cell infiltration in the tumor core and the sTIL value doubles compared to tumors devoid of TLSs [sTIL mean: 36 ± 11% and 18 ± 5% (CI [Confidence Interval]: 95%), respectively]. Our study demonstrates that the characterization of the immune cell infiltration is as relevant as its distribution. Moreover, the importance of considering different immune cell types for classification is emphasized. Therefore, a new classification of triple-negative breast carcinoma immune infiltration with CD8+ T cell and plasma cell densities in the tumor core and infiltrative margin is proposed.

Fecal pulmonary embolism: a case report and literature review.

Pulmonary embolism (PE) is a common cause of death in hospitalized patients. These emboli are usually related to deep venous thrombosis, but other etiologic factors may be the cause. A 60-year-old male was diagnosed with rectal adenocarcinoma and treated by surgical rectal resection. After surgery, he presented with a decreased level of consciousness and hypoxia with no signs of bleeding. PE was ruled out by pulmonary angiography. Given the hemodynamic instability, contrast-enhanced CT was performed, showing a discrete leak related to the rectal anastomosis, which required urgent surgery. The patient suffered cardiorespiratory arrest prior to surgery, and once resolved, the surgical procedure was limited to disconnecting the intestinal anastomosis, leaving the colon and rectal stumps free in the abdomen and keeping the abdominal cavity open with negative-pressure therapy. The patient suffered from another cardiorespiratory arrest after surgery, with abdominal distension and serous-hemorrhagic material discharge through the negative-pressure device. On a new surgical revision, no bleeding was identified, so the symptoms were attributed to coagulopathy. The patient died and autopsy was performed. The autopsy revealed no surgery-related complications. The lungs were increased in weight and showed a normal macroscopic appearance; in contrast, the histological study revealed multiple and bilateral thrombo-embolisms affecting small distal arteries. Those thrombi were composed of intestinal contents, including vegetal particles, mucinous and biliary material, fibrin, and bacterial structures. Fecal PE is an extremely infrequent event. Isolated cases have been described in association with communications between the digestive tract lumen and the systemic circulation, with a generally fatal prognosis.

Atypical double colorectal metastasis: spleen and uterus.

Oligometastatic disease is a relatively new concept that refers to an intermediate stage between disseminated and localized cancer. Most frequent locations for colorectal metastasis are lung and liver. We present an a typical case of an 85-year-old woman who was diagnosed with a low-grade adenocarcinoma in left colon; she underwent a left laparoscopic hemicolectomy which resulted in a stage IIIb. After 24 months of follow-up, an increase of carcinoembryonic antigen (CEA) leads to the diagnosis of two metastatic lesions in two uncommon locations: spleen and myometrium. Stepwise surgical resection of both lesions was performed without complications. Spleen and uterus are organs that are rarely affected in colorectal cancer, the affection of both organs being even more infrequent. Despite the atypicality, surgical treatment is a valid strategy in this case of oligometastatic disease, which enables the disease-free survival of the patients.

T2 Biomarkers as Predictors of Exacerbations of Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Type 2 (T2) biomarkers such as blood eosinophil count (BEC) and FeNO have been related to a higher risk of exacerbations in COPD. It is unknown whether combining these biomarkers could be useful in forecasting COPD exacerbations. METHODS: COPD patients were enrolled in this prospective, multicenter, observational study and followed up for 1 year, during which BEC were analysed at baseline (V0) while FeNO analyses were performed at baseline (V0), 6 months (V1) and 12 months (V2). The risk of moderate or severe exacerbation during follow up was assessed by Cox regression analysis, and the predictive capacity of both measurements was assessed by ROC curves and the DeLong test. Statistical significance was assumed at P<.05. RESULTS: Of the 322 COPD patients initially recruited, 287 were followed up. At baseline, 28.0% were active smokers, and experienced moderate airflow limitation (mean FEV1 56.4%±17.0% predicted). Patients with at least one elevated T2 biomarker (n=125, 42.5%) were at increased risk of COPD exacerbation (HR 1.75, 95% CI 1.25-2.45, P=.001) and of shorter time to first COPD exacerbation. There was no difference between BEC and FeNO regarding the predictive capacity for moderate to severe exacerbation (AUC 0.584 vs 0.576, P=.183) but FeNO predicted severe episodes more accurately than BEC (AUC 0.607 vs 0.539, P<.05). Combining the two biomarkers enhanced the detection of moderate and severe COPD exacerbations. CONCLUSIONS: Both eosinophil count and FeNO have limited utility for predicting COPD exacerbations. Combining these T2 biomarkers could enhance the detection of future COPD exacerbations.

Alveolar and Bronchial Nitric Oxide in Chronic Obstructive Pulmonary Disease and Asthma-COPD Overlap. / Óxido nítrico alveolar y bronquial en la enfermedad pulmonar obstructiva crónica y el solapamiento de asma y EPOC (ACO).

INTRODUCTION: Exhaled nitric oxide (FENO) measurements differentiate COPD phenotypes from asthma-COPD overlap (ACO). To date, no study has been conducted to determine whether alveolar and bronchial components differ in this group of patients. METHODS: This was an observational cross-sectional study recruiting ambulatory COPD patients. FENO was measured, differentiating alveolar (CANO) from bronchial (JawNO) components using a multiple-flow technique. CANO and JawNO values were compared between eosinophilic COPD patients (defined as ≥ 300 eosinophils/µL in peripheral blood test, or ≥ 2% eosinophils or ≥ 3% eosinophils), and a linear regression analysis was performed to determine clinical and biological variables related to these measurements. RESULTS: 73 COPD patients were included in the study. Eosinophil counts were associated with increased values of CANO and JawNO (for the latter only the association with ≥ 300 or ≥ 3% eosinophils was significant). CANO was also associated with CRP, and JawNO with smoking. CONCLUSIONS: Patients with COPD and ACO characteristics show increased inflammation in the large and small airways. CANO and JawNO are associated with clinical and biological variables.