Prognostic Value of Lymph Node Ratio in Patients with Uterine Carcinosarcoma.

Uterine carcinosarcoma is a rare high-grade endometrial cancer. Controversy has surrounded a number of aspects in the diagnosis and management of this unique clinicopathological entity, including the efficacy of adjuvant therapy, which has been questioned. An unusual surgico-pathological parameter with prognostic significance in a number of tumour sites is the lymph node ratio (LNR). The availability of data in this respect has been scarce in the literature. The primary aim of this collaborative study was to evaluate the prognostic value of LNR in patients with uterine carcinosarcoma. LNR is a recognized lymph node metric used to stratify prognosis in a variety of malignancies. In this European multinational retrospective study, 93 women with uterine carcinosarcoma were included in the final analysis. We used t-tests and ANOVA for comparison between quantitative variables between the groups, and chi-square tests for qualitative variables. A multivariate analysis using Cox regression analysis was performed to determine potential prognostic factors, including the LNR. Patients were grouped with respect to LNR in terms of 0%, 20% > 0% and >20%. The analysis revealed LNR to be a significant predictor of progression-free survival (HR 1.69, CI (1.12-2.55), p = 0.012) and overall survival (HR 1.71, CI (1.07-2.7), p = 0.024). However, LNR did not remain a significant prognostic factor on multivariate analysis. Due to limitations of the retrospective study, a prospective large multinational study, which takes into effect the most recent changes to clinical practice, is warranted to elucidate the value of the pathophysiological metrics of the lymphatic system associated with prognosis.

Prognostic factors in patients with uterine sarcoma: the SARCUT study.

OBJECTIVE: Uterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the impact of the different prognostic factors on overall survival and disease-free survival of patients with uterine sarcoma. METHODS: This international multicenter retrospective study included 683 patients diagnosed with uterine sarcoma at 46 different institutions between January 2001 and December 2007. RESULTS: The 5-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma, and adenosarcoma was 65.3%, 78.3%, 52.4%, and 89.5%, respectively, and the 5-year disease-free survival was 54.3%, 68.1%, 40.3%, and 85.3%, respectively. The 10-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma and adenosarcoma was 52.6%, 64.8%, 52.4%, and 79.5%, respectively, and the 10-year disease-free survival was 44.7%, 53.3%, 40.3%, and 77.5%, respectively. The most significant factor associated with overall survival in all types of sarcoma except for adenosarcoma was the presence of residual disease after primary treatment. In adenosarcoma, disease stage at diagnosis was the most important factor (hazard ratio 17.7; 95% CI 2.86 to 109.93). CONCLUSION: Incomplete cytoreduction, tumor persistence, advanced stage, extra-uterine and tumor margin involvement, and the presence of necrosis were relevant prognostic factors significantly affecting overall survival in uterine sarcoma. The presence of lymph vascular space involvement and administration of adjuvant chemotherapy were significantly associated with a higher risk of relapse.

Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. DATA SOURCES: A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). METHODS: Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, ß, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. RESULTS: The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). CONCLUSION: Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.

Seasonal Evaluation of Phlorotannin-Enriched Extracts from Brown Macroalgae Fucus spiralis.

Fucus spiralis that was collected in the four seasons was submitted to an extraction with ethanol:water (crude extracts Et80), followed by a liquid-liquid fractionation with organic solvents (fraction He from n-hexane; aqueous fractions AQ1, AQ2, AQ3 and AQ4; ethyl acetate fraction EA), with the aim of obtaining phlorotannin-enriched extracts. All the extracts (Et80, He, AQ1, AQ2, AQ3, AQ4 and EA) that were obtained for the F. spiralis of the four seasons were evaluated for their antioxidant capacity and total phenolic compounds. The summer extracts presented the highest contents in polyphenols (TPC), as well as the highest ferric reducing antioxidant power (FRAP), when compared to the samples from the other seasons. The reductive percentage of the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) compound was similar between the seasons. For all the seasons, the EA extract showed the highest polyphenol content (TPC), and the highest antioxidant capacity (highest ferric reducing power (FRAP) and lowest concentration needed to reduce 50% of the DPPH compound), which is in agreement with a phlorotannin-enriched fraction. This study revealed that the polyphenol content and antioxidant power of the F. spiralis extracts are influenced by the time of harvest, as well as by the solvents used for their extraction.

Bioaccessibility of Antioxidants and Fatty Acids from Fucus Spiralis.

Fucus spiralis is an edible brown seaweed (SW) found in the Portuguese Coast. It has been reported to have high antioxidant activity, which may elicit a potential use for the food industry. However, little information is available on how the SW behaves during the digestive process and how the freeze-drying process might affect the bioaccessibility of the different compounds. Therefore, antioxidant activity, total polyphenols, lipid, and fatty acid contents were measured before and after in vitro simulation of the human digestive process, both in fresh and freeze-dry SW. F. spiralis had a lipid content of 3.49 ± 0.3% of dry weight (DW), which is a usual amount described for this SW genus. The total lipid bioaccessibility was 12.1 ± 0.1%. The major omega-3 fatty acid detected was eicosapentaenoic acid, 7.5 ± 0.1%, with a bioaccessibility percentage of 13.0 ± 1.0%. Four different methods-total phenolic content (TPC), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH)-were used to assess the antioxidant activity of F. spiralis. The bioaccessibility of the antioxidants studied, ranged between 42.7% and 59.5%, except the bioaccessibility of polyphenols in freeze-dried SW (23.0% ± 1.0%), suggesting that the freeze-drying process reduces the bioaccessibility of these compounds.

Risk assessment of trihalomethanes exposure by consumption of IV gamma products: Evidences from a Portuguese regional survey.

Due to the current demand for healthier food, the IV gamma products industry has grown over the years. Additionally, it is well known that chlorine is a disinfectant largely used in this industry. However, the risk assessment associated with the formation of carcinogenic by-products from this halogenated disinfection has not been widely studied. The aim of this study was to assess the trihalomethanes (THMs) exposure through the consumption of IV gamma products, more specifically, salad mixes, and potential health risk in Portuguese population using a deterministic method. The quantification of THMs in salad mixes from the most representative Portuguese brands was performed by gas chromatography coupled to mass spectrometry (GC-MS). The THMs exposures were estimated by combining the THMs concentration data with a ready-to-eat salad mix consumption survey (case study applied in the Lisboa e Vale do Tejo area; n = 271). The concentration of THMs in all samples was below the limit of quantification of the equipment (1 µg/L), and this limit was used for the evaluation of the exposure. It was found that it is very small for the consumption pattern of these products in the studied population categories, suggesting that there is no risk for consumers due to the halogenated disinfection process. The highest estimated daily exposure was 7,65X10-5 mg/ kg bw/ week, which corresponds to a person who consumes such products daily.

Characterization of Nutritional, Physicochemical, and Phytochemical Composition and Antioxidant Capacity of Three Strawberry "Fragaria × ananassa Duch." Cultivars ("Primoris", "Endurance", and "Portola") from Western Region of Portugal.

In this study, nutritional composition (protein, lipids, carbohydrates, ash, and moisture), physicochemical properties (soluble solid content, titratable acidity, texture and instrumental colour on surface, and internal section), phytochemicals (total phenolic content and anthocyanin content), and antioxidant capacity (DPPH-2,2'-diphenyl-1-picrylhydrazyl radical scavenging capacity and ferric-reducing antioxidant power) of three strawberry (Fragaria × ananassa Duch.) cultivars (cv. "Primoris", cv. "Endurance", and cv. "Portola") produced in the western region of Portugal (Caldas da Rainha) were evaluated. From the obtained, results no significant differences (P > 0.05) in nutritional composition were detected in all of the cultivars; with the exception of lower protein content observed in cv. "Portola" (0.57 g/100 g ± 0.04; P < 0.05). Regarding the a* value of whole strawberry fruits, no significant differences (P > 0.05) were found in any of the cultivars, which revealed a similar redness. The cv. "Endurance" revealed the highest bioactivity content compared to the other cultivars. Overall, these results provide important information about the high quality of strawberry produced in the western region of Portugal and may be used as a tool for adding value to a functional food in the Mediterranean diet due to the phytochemical composition and nutritional value of strawberry fruits.

Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/MAC25).

IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) has been shown to bind both IGFs and insulin, albeit with low affinity, and to inhibit insulin signaling. We hypothesized that IGFBP-rP1 is associated with insulin resistance and components of the IGF system in humans. To this aim, a cross-sectional study was conducted in 113 nondiabetic and 43 type 2 diabetic men. Insulin sensitivity (insulin sensitivity index [S(i)] from intravenous glucose tolerance tests in nondiabetic subjects, or the rate constant for disappearance of glucose [K(ITT)] from insulin tolerance tests in type 2 diabetic subjects), circulating IGFBP-rP1 (from enzyme-linked immunosorbent assay), adiponectin (from radioimmunoassay), C-reactive protein (CRP; from immunoturbidimetry), soluble tumor necrosis factor receptor 2 (sTNFR2; from enzyme-amplified sensitivity immunoassay), and IGF system parameters (IGF-I, free IGF-I, and IGFBP-1 from immunoradiometric assay) were assessed in all subjects. Among nondiabetic men, those in the highest quartile for circulating IGFBP-rP1 exhibited decreased S(i) and adiponectin (both P < 0.01) as well as increased CRP and sTNFR2 (both P < 0.05). Circulating IGFBP-rP1 was also found to be increased in previously undiagnosed type 2 diabetic patients (P = 0.01) but not in known type 2 diabetic patients receiving pharmacological therapy. Although no changes in IGF system components were evident by IGFBP-rP1 quartiles in nondiabetic subjects, independent positive associations of IGFBP-rP1 with circulating fasting IGFBP-1 were evident after adjustment for insulin resistance parameters in both nondiabetic and type 2 diabetic subjects, with IGFBP-rP1 explaining 2 and 11% of IGFBP-1 variance, respectively. In additional multivariate analyses, S(i), sTNFR2, and age stood as independent predictive variables of IGFBP-rP1 (together explaining 18% of its variance) in nondiabetic subjects, and BMI became the only independent predictive variable of IGFBP-rP1 (explaining 26% of its variance) in type 2 diabetic men. These findings show for the first time that circulating IGFBP-rP1 is increased with insulin resistance, and they also suggest novel interactions between IGFBP-rP1 and the IGF system in humans.