Fertility Counseling Pattern over Time in Young Patients with Breast Cancer: A Retrospective Analysis at a Large Comprehensive Cancer Center

Background: One main issue to be considered in young patients diagnosed with early breast cancer (BC) is the impact of oncological treatments on fertility and future chances of conception. Current guidelines recommend a comprehensive addressing of oncofertility as part of the management of premenopausal BC patients, including counselling on available assisted reproduction technologies and fertility preservation (FP) strategies. The COVID-19 pandemic represented a potential hurdle to the integration of these procedures into clinical practice. This study aims to describe the time-related evolution in addressing oncofertility issues. Methods: This retrospective mono-institutional observational study considered 206 patients who received neoadjuvant chemotherapy, adjuvant chemotherapy (CT) or adjuvant endocrine therapy (ET), diagnosed with breast cancer at the age of 40 or younger in the years 2014-2015 and 2020-2021. Timerelated evolution in addressing oncofertility during oncological consultations and adoption of a fertility or ovarian function preservation (OFP) method were analyzed comparing the two different timeframes. Results: Comparing the two cohorts 2014-2015 and 2020-2021, we found a significant difference in the presence of fertility discussion records (37.4% vs 57.9%, p < 0.01), and in the application of OFP/FP techniques (54.5 vs 78.5%, p < 0.01). In the two cohorts there was a significant difference in OFP (57.6% vs 70%, p = 0.03) and FP techniques application rates (5.1% vs 19.6%, p < 0.01). In the study population, age at diagnosis resulted to influence clinicians' approach towards counseling and/or OFP/FP strategies (87.3% in patients <35 years old (yo) vs 56.7% in older patients, p < 0.01). In the 2020-2021 cohort, age resulted less influential in the choice of using an OFP/FP strategy (87% vs 72.1%, p = 0.18). A higher rate of documented fertility discussion and/or OFP/FP techniques application was recorder in patients who had not had children before BC diagnosis (80.6% vs 64.5%, p = 0.02). When considering only the 2020-2021 timeframe, parity no longer significantly affected the prescription of an OFP/FP strategy (80.4% vs 78.3%, p = 0.93). Conclusions: This study on real world data demonstrates the progressive evolution in the way clinicians approach oncofertility issues, showing a greater attention across years, with more BC patients receiving a dedicated counseling, despite the COVID-19 pandemic

Immune characterization of breast cancer metastases: prognostic implications.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available. METHODS: Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry. RESULTS: TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p\u2009=\u20090.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p\u2009=\u20090.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p =\u20090.002) and lower CD8/FOXP3 ratio (p\u2009=\u20090.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p\u2009=\u20090.005, HER2+: p\u2009=\u20090.011, TN: p\u2009=\u20090.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p\u2009=\u20090.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p\u2009=\u20090.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant). CONCLUSIONS: Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

NEMO: A Project for a km3^3 Underwater Detector for Astrophysical Neutrinos in the Mediterranean Sea

The status of the project is described: the activity on long term characterization of water optical and oceanographic parameters at the Capo Passero site candidate for the Mediterranean km$^3$ neutrino telescope; the feasibility study; the physics performances and underwater technology for the km$^3$; the activity on NEMO Phase 1, a technological demonstrator that has been deployed at 2000 m depth 25 km offshore Catania; the realization of an underwater infrastructure at 3500 m depth at the candidate site (NEMO Phase 2).Comment: Proceeding of ISCRA 2006, Erice 20-27 June 200

Estimation of Pap-test coverage in an area with an organised screening program: challenges for survey methods

BACKGROUND: The cytological screening programme of Viterbo has completed the second round of invitations to the entire target population (age 25–64). From a public health perspective, it is important to know the Pap-test coverage rate and the use of opportunistic screening. The most commonly used study design is the survey, but the validity of self-reports and the assumptions made about non respondents are often questioned. METHODS: From the target population, 940 women were sampled, and responded to a telephone interview about Pap-test utilisation. The answers were compared with the screening program registry; comparing the dates of Pap-tests reported by both sources. Sensitivity analyses were performed for coverage over a 36-month period, according to various assumptions regarding non respondents. RESULTS: The response rate was 68%. The coverage over 36 months was 86.4% if we assume that non respondents had the same coverage as respondents, 66% if we assume they were not covered at all, and 74.6% if we adjust for screening compliance in the non respondents. The sensitivity and specificity of the question, "have you ever had a Pap test with the screening programme" were 84.5% and 82.2% respectively. The test dates reported in the interview tended to be more recent than those reported in the registry, but 68% were within 12 months of each other. CONCLUSION: Surveys are useful tools to understand the effectiveness of a screening programme and women's self-report was sufficiently reliable in our setting, but the coverage estimates were strongly influenced by the assumptions we made regarding non respondents

Uniform electron gases

We show that the traditional concept of the uniform electron gas (UEG) --- a homogeneous system of finite density, consisting of an infinite number of electrons in an infinite volume --- is inadequate to model the UEGs that arise in finite systems. We argue that, in general, a UEG is characterized by at least two parameters, \textit{viz.} the usual one-electron density parameter $\rho$ and a new two-electron parameter $\eta$. We outline a systematic strategy to determine a new density functional $E(\rho,\eta)$ across the spectrum of possible $\rho$ and $\eta$ values.Comment: 8 pages, 2 figures, 5 table

Magnetic resonance imaging of abnormal ventricular septal motion in heart diseases: a pictorial review

The purpose of this article is to illustrate the usefulness of MR imaging in the clinical evaluation of congenital and acquired cardiac diseases characterised by ventricular septal wall motion abnormality. Recognition of the features of abnormal ventricular septal motion in MR images is important to evaluate the haemodynamic status in patients with congenital and acquired heart diseases in routine clinical practice

Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial

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Caregivers' active role in palliative home care – to encourage or to dissuade? A qualitative descriptive study

<p>Abstract</p> <p>Background</p> <p>Spouses' involvement in palliative care is often a prerequisite for home death, but it is unclear whether active involvement of the spouse, e.g. administering and being in charge of oral or subcutaneous medication or taking care of the patient's personal hygiene, could be harmful or have negative effects on the spouse's experience of the palliative course of disease. The aim of this study was to explore the impact of bereaved spouses' active involvement in medical and physical care on their experience of the palliative course of disease.</p> <p>Methods</p> <p>The study was a qualitative, descriptive study based on semi-structured individual interviews with seven bereaved spouses.</p> <p>Results</p> <p>Four main categories were found: Degree of involvement, Positive and Negative impact and Prerequisites. The prerequisites found for a positive outcome were Safety (24-hour back-up), Confidence (Professionals' confidence in the spouses' abilities) and Dialog (Spouses' influence on decision-making and being asked).</p> <p>Conclusion</p> <p>The results from this study identified important issues whenever spouses take an active part in medical treatment and physical care of critically ill patients in palliative care. The results question the previous research that active involvement of family care givers could be harmful and add preconditions to a positive outcome. More research into these preconditions is needed.</p