The Effect of Sustainable Feeding Systems, Combining Total Mixed Rations and Pasture, on Milk Fatty Acid Composition and Antioxidant Capacity in Jersey Dairy Cows

This study was carried out to assess the effect of using pasture combined with total mixed ration (TMR) on milk production and composition, fatty acid (FA) profiles, fat-soluble antioxidant content, and total milk antioxidant capacity (TAC). In addition, the effect of milk pasteurization and storage at 2 °C for 4 days, lipophilic antioxidants and TAC were assessed. Two homogeneous groups of Jersey cows (n = 8) were constituted, which were randomly assigned to one of the two treatments: TMR (without access to pasture), or partial mixed diet (pTMR: grazing 8 h/day + TMR indoors). To establish FA profiles and lipophilic antioxidants’ changes in milk during the grazing period, in case of the pTMR group the experimental period was spilt in three grazing periods: P1 (May), P2 (June), and P3 (June/July). Milk yielded from cows having limited access on pasture (pTMR diet) showed an improved FA profile, with higher concentrations of FAs considered benefic for human health (vaccenic acid (VA), conjugated linoleic acid (CLA), omega-3 FA (n-3 FA)) (p < 0.01) and a lower concentration of FAs with hypercholesterolemiant potential (C12:0, C14:0, and C16:0) (p < 0.05), compared to that of the TMR diet. This change in FA profile was correlated with improved sanogenous lipid indices of milk fat (n-6/n-3 FA atherogenic index and thrombogenic index). Milk yielded during the P1 grazing period had higher concentrations of VA, CLA, and n-3 FA (p < 0.05) and lower concentrations of C14:0 and C16:0 (p < 0.01); it exhibited the best values for the main sanogenous fat lipid indices of fat. Moreover, pTMR milk showed a higher α-tocopherol, retinol, and β-carotene content (p < 0.05), positively correlated with TAC values in milk (P1 ˃ P2 ˃ P3). By comparison, cows fed using the TMR diet yielded a higher quantity of milk (p < 0.05), but a lower fat and protein content (p < 0.01), and also a higher saturated FAs and n-6 FA content (p < 0.05) together with a lower concentration of lipophilic antioxidants in milk. Thermal treatment showed no effect on α-tocopherol and retinol content in milk, but their concentrations decreased during the storage, at the same time a TAC decrease. The results of this study prove the positive effect of using pasture combined with TMR on FA profiles, milk antioxidant content, and antioxidant capacity, with beneficial effects on nutrition and health in humans

Morphological intratumor heterogeneity in ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease in terms of morphological characteristics, protein expression profiles, genetic abnormalities, and potential for progression. Molecular heterogeneity has been extensively studied in DCIS. Yet morphological heterogeneity remains relatively undefined. This study investigated morphological intratumor heterogeneity in a series of 51 large DCIS. Nuclear atypia, DCIS architecture, necrosis, calcifications, stromal architecture, and stromal inflammation were assessed in one biopsy slide and three representative slides from each corresponding resection. For each histopathological feature, a histo-score was determined per slide and compared between the biopsy and the resection, as well as within a single resection. Statistical analysis comprised of Friedman tests, post hoc Wilcoxon tests with Bonferroni corrections, Mann-Whitney U tests, and chi-square tests. Despite substantial morphological heterogeneity in around 50% of DCIS, the histopathological assessment of the biopsy did not statistically significantly differ from the resection. Morphological heterogeneity was not significantly associated with patient age, DCIS size, or type of surgery, except for a weak association between heterogeneous stromal inflammation and smaller DCIS size. At the group level, the degree of heterogeneity did not significantly affect the representativity of a biopsy. At the individual patient level, however, the presence of necrosis, intraductal calcifications, myxoid stromal changes, and high-grade nuclear atypia was underestimated in a minority of DCIS patients. This study confirms the presence of morphological heterogeneity in DCIS for all six evaluated histopathological features. This should be kept in mind when taking biopsy-based treatment decisions for DCIS patients

The Effect of Sustainable Feeding Systems, Combining Total Mixed Rations and Pasture, on Milk Fatty Acid Composition and Antioxidant Capacity in Jersey Dairy Cows

This study was carried out to assess the effect of using pasture combined with total mixed ration (TMR) on milk production and composition, fatty acid (FA) profiles, fat-soluble antioxidant content, and total milk antioxidant capacity (TAC). In addition, the effect of milk pasteurization and storage at 2 °C for 4 days, lipophilic antioxidants and TAC were assessed. Two homogeneous groups of Jersey cows (n = 8) were constituted, which were randomly assigned to one of the two treatments: TMR (without access to pasture), or partial mixed diet (pTMR: grazing 8 h/day + TMR indoors). To establish FA profiles and lipophilic antioxidants’ changes in milk during the grazing period, in case of the pTMR group the experimental period was spilt in three grazing periods: P1 (May), P2 (June), and P3 (June/July). Milk yielded from cows having limited access on pasture (pTMR diet) showed an improved FA profile, with higher concentrations of FAs considered benefic for human health (vaccenic acid (VA), conjugated linoleic acid (CLA), omega-3 FA (n-3 FA)) (p p 1 grazing period had higher concentrations of VA, CLA, and n-3 FA (p p p 1 ˃ P2 ˃ P3). By comparison, cows fed using the TMR diet yielded a higher quantity of milk (p p p < 0.05) together with a lower concentration of lipophilic antioxidants in milk. Thermal treatment showed no effect on α-tocopherol and retinol content in milk, but their concentrations decreased during the storage, at the same time a TAC decrease. The results of this study prove the positive effect of using pasture combined with TMR on FA profiles, milk antioxidant content, and antioxidant capacity, with beneficial effects on nutrition and health in humans

The Effect of Sustainable Feeding Systems, Combining Total Mixed Rations and Pasture, on Milk Fatty Acid Composition and Antioxidant Capacity in Jersey Dairy Cows

This study was carried out to assess the effect of using pasture combined with total mixed ration (TMR) on milk production and composition, fatty acid (FA) profiles, fat-soluble antioxidant content, and total milk antioxidant capacity (TAC). In addition, the effect of milk pasteurization and storage at 2 &deg;C for 4 days, lipophilic antioxidants and TAC were assessed. Two homogeneous groups of Jersey cows (n = 8) were constituted, which were randomly assigned to one of the two treatments: TMR (without access to pasture), or partial mixed diet (pTMR: grazing 8 h/day + TMR indoors). To establish FA profiles and lipophilic antioxidants&rsquo; changes in milk during the grazing period, in case of the pTMR group the experimental period was spilt in three grazing periods: P1 (May), P2 (June), and P3 (June/July). Milk yielded from cows having limited access on pasture (pTMR diet) showed an improved FA profile, with higher concentrations of FAs considered benefic for human health (vaccenic acid (VA), conjugated linoleic acid (CLA), omega-3 FA (n-3 FA)) (p &lt; 0.01) and a lower concentration of FAs with hypercholesterolemiant potential (C12:0, C14:0, and C16:0) (p &lt; 0.05), compared to that of the TMR diet. This change in FA profile was correlated with improved sanogenous lipid indices of milk fat (n-6/n-3 FA atherogenic index and thrombogenic index). Milk yielded during the P1 grazing period had higher concentrations of VA, CLA, and n-3 FA (p &lt; 0.05) and lower concentrations of C14:0 and C16:0 (p &lt; 0.01); it exhibited the best values for the main sanogenous fat lipid indices of fat. Moreover, pTMR milk showed a higher &alpha;-tocopherol, retinol, and &beta;-carotene content (p &lt; 0.05), positively correlated with TAC values in milk (P1 &#707; P2 &#707; P3). By comparison, cows fed using the TMR diet yielded a higher quantity of milk (p &lt; 0.05), but a lower fat and protein content (p &lt; 0.01), and also a higher saturated FAs and n-6 FA content (p &lt; 0.05) together with a lower concentration of lipophilic antioxidants in milk. Thermal treatment showed no effect on &alpha;-tocopherol and retinol content in milk, but their concentrations decreased during the storage, at the same time a TAC decrease. The results of this study prove the positive effect of using pasture combined with TMR on FA profiles, milk antioxidant content, and antioxidant capacity, with beneficial effects on nutrition and health in humans

Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA -rearranged lung adenocarcinoma who developed a A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers

Prognostic Significance of IgA+ B Cells in Non-Small Cell Lung Cancer [P72.10]

Introduction : Lung cancer is the most frequent and the deadliest cancer in the world. In non-small cell lung cancer (NSCLC), which represents 85% of all lung cancers, up to 55% patients relapse following surgery alone or in combination with chemotherapy or radiotherapy. Tumor-infiltrating lymphocytes play a key role in the control of the malignancy and display different phenotypes whilst interacting with cancer cells. Hence, immunoglobulin-A (IgA)-producing cells have been described to have an immunosuppressive function, promoting tumor development and growth in hepatocarcinoma and prostate cancer. Due to the important role of IgA in the lung, we aimed to study the prognostic significance of IgA+ cell infiltration in the epithelial and stromal compartments of resected NSCLCs. [...

Complete tumor response of a locally advanced lung large-cell neuroendocrine carcinoma after palliative thoracic radiotherapy and immunotherapy with nivolumab.

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff's alpha (KA), Cohen's kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.status: publishe

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff's alpha (KA), Cohen's kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge