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Since its launch in 2011, 59 governments have used the World Bank's Systems Approach for Better Education Results (SABER) policy tool to design their national school-based health and nutrition programs. This tool guides governments to self-evaluate their education system policies against international benchmarks and identify actionable priorities to strengthen national programs. Thirty-two of the 49 countries in sub-Saharan Africa (65%) have undertaken a SABER review, and globally the approach has been adopted by 68% of the world's low-income countries and 54% of lower-middle-income countries. Analysis of 51 comparable SABER School Feeding surveys suggests that countries with longer established national school meals frameworks tend also to be more advanced in other policy areas, and vice versa. The SABER reviews consistently identify, perhaps predictably, that the weakest policy areas relate to program design, implementation and fiscal space. This analysis also found that the tool had an additional value in tracking the evolution of policies when implemented over several time points, and showed that policy areas become more advanced as national programs mature. These benefits of the tool are particularly relevant to the 98 countries that co-created the global School Meals Coalition in 2021. The Coalition member countries have the specific goal of enhancing coverage and support for the well-being of schoolchildren and adolescents affected by the school closures during the COVID-19 pandemic. The SABER tool has the demonstrated potential to implement, accelerate and track changes in school meals policy and, since it has been previously used by 74% (31/42) of low- and lower-middle-income countries in sub-Saharan Africa, is an already accepted element of the political economies of those countries and so has the potential to be deployed rapidly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor EP declared a past co-authorship with the author(s) DB, CB, and LS. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Schultz, Renaud, Bundy, Barry, Benveniste, Burbano de Lara, Lo, Neitzel, O’Grady and Drake.)

The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking. By the end of December 2022, 486 people were enrolled, of which 353 were still undergoing active follow-up. Of the 486 participants, 86% had an acute infection, and 14% a recent HIV-1 infection. Men who have sex with men accounted for 74% of the study population. The median time from the estimated date of infection to diagnosis was 32 days. The median time from diagnosis to the initiation of antiretroviral therapy was 11 days, and this has consistently decreased over the last two decades. During the seroconversion phase, 447 (92%) patients reported having symptoms, of which only 73% of the patients were classified as having typical acute retroviral syndrome. The ZPHI study is a well-characterized cohort belonging to the most extensively studied primary HIV infection cohort. Its findings contribute to advancing our understanding of the early stages of HIV infection and pathogenesis, and it is paving the way to further improve HIV translational research and HIV medicine.

Background: Results of IBCSG-23-01-trial which included breast cancer patients with involved sentinel nodes (SN) by isolated-tumor-cells or micro-metastases supported the non-inferiority of completion axillary-lymph-node-dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN-micro-metastases., Methods: To investigate the impact of cALND omission on disease-free-survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN-micro-metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan-Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission., Results: Weighted log-rank tests comparing adjusted Kaplan-Meier survival curves showed significant differences in OS (p-value = 0.002) and borderline significant differences in DFS (p-value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36-5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND., Conclusions: Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients., Methods: Our retrospective observational study included 5545 patients with pT1a-b ER-positive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression., Results: Most patients (80.3%: 4453) received ET and-when compared to those without ET-experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI[1.003-1.620]) but not OS or RFS in all patients, while in 2363 patients with pT1a-b ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI[1.001-2.252]), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC., Conclusion: Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique., Methods: In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, age &lt;65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records., Results: From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups., Conclusions: For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The similarities between sporadic basal-like breast cancer (BLBC) and BRCA1-mutated breast tumours raise the possibility that deregulation of the same pathway may underlie these tumour types. The aim of this study was to determine if PTEN aberrations are characteristic of both BRCA1 tumours and sporadic TN breast carcinomas with low BRCA1 expression, and can thus be used to identify sporadic tumours potentially sensitive to PARP inhibitors. Twelve BRCA1 tumours, 19 non-BRCA familial breast tumours and 71 unselected TN breast carcinomas were screened for PTEN mutations and assessed for PTEN expression and BRCA1 mRNA expression. Loss of PTEN expression was observed in 67% of BRCA1 tumours and more specifically in 89% of TN BRCA1 tumours highlighting the link between PTEN loss and BLBC in the context of germline BRCA1 mutations. Regarding unselected TN tumours, 56% showed PTEN expression loss and 35% displayed low BRCA1 mRNA expression. Unlike familial breast cancers with low BRCA1 mRNA expression, no significant correlation was observed between the loss of PTEN expression and low BRCA1 mRNA expression in this unselected TN tumours panel. Our data suggest that, unlike the germinal context, PTEN and BRCA1 alterations in sporadic TN breast tumours are independent events., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors., Patients and Methods: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan-Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients., Results: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors., Conclusion: The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers., Methods: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts., Results: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%)., Discussion: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient's and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p < 0.0001) and >2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient's eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient's and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND., (© 2021. The Author(s).)

Background and Objective: Recent research has reported methods that reconstruct cardiac MR images acquired with acceleration factors as high as 15 in Cartesian coordinates. However, the computational cost of these techniques is quite high, taking about 40 min of CPU time in a typical current machine. This delay between acquisition and final result can completely rule out the use of MRI in clinical environments in favor of other techniques, such as CT. In spite of this, reconstruction methods reported elsewhere can be parallelized to a high degree, a fact that makes them suitable for GPU-type computing devices. This paper contributes a vendor-independent, device-agnostic implementation of such a method to reconstruct 2D motion-compensated, compressed-sensing MRI sequences in clinically viable times., Methods: By leveraging our OpenCLIPER framework, the proposed system works in any computing device (CPU, GPU, DSP, FPGA, etc.), as long as an OpenCL implementation is available, and development is significantly simplified versus a pure OpenCL implementation. In OpenCLIPER, the problem is partitioned in independent black boxes which may be connected as needed, while device initialization and maintenance is handled automatically. Parallel implementations of both a groupwise FFD-based registration method, as well as a multicoil extension of the NESTA algorithm have been carried out as processes of OpenCLIPER. Our platform also includes significant development and debugging aids. HIP code and precompiled libraries can be integrated seamlessly as well since OpenCLIPER makes data objects shareable between OpenCL and HIP. This also opens an opportunity to include CUDA source code (via HIP) in prospective developments., Results: The proposed solution can reconstruct a whole 12-14 slice CINE volume acquired in 19-32 coils and 20 phases, with an acceleration factor of ranging 4-8, in a few seconds, with results comparable to another popular platform (BART). If motion compensation is included, reconstruction time is in the order of one minute., Conclusions: We have obtained clinically-viable times in GPUs from different vendors, with delays in some platforms that do not have correspondence with its price in the market. We also contribute a parallel groupwise registration subsystem for motion estimation/compensation and a parallel multicoil NESTA subsystem for l1-l2-norm problem solving., Competing Interests: Declaration of Competing Interest The entire research has been funded by the Government of Spain; the authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm., Patients and Methods: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status., Results: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS., Conclusion: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing The data sets generated and/or analyzed during the current study are not publicly available, as the study has used clinical databases of 13 different comprehensive cancer centers in France (ClinicalTrials.govNCT02869607)., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.

Objective: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol., Methods: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI)., Results: Successful technical treatments were achieved in 80 % of the patients. All patients underwent the treatment with no sedation and 60 % of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 ±1.8 mm while 6.2 ±1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 % and 70 % of patients, respectively., Conclusion: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts.

Background and Aims: Induction of functional helper CD4 + T cells is the hallmark of a protective immune response against hepatitis C virus (HCV), associated with spontaneous viral clearance. Heterologous prime/boost viral vectored vaccination has demonstrated induction of broad and polyfunctional HCV-specific CD8 + T cells in healthy volunteers; however, much less is known about CD4 + T-cell subsets following vaccination., Approach and Results: We analyzed HCV-specific CD4 + T-cell populations using major histocompatibility complex class II tetramers in volunteers undergoing HCV vaccination with recombinant HCV adenoviral/modified vaccinia Ankara viral vectors. Peptide-specific T-cell responses were tracked over time, and functional (proliferation and cytokine secretion) and phenotypic (cell surface and intranuclear) markers were assessed using flow cytometry. These were compared to CD4 + responses in 10 human leukocyte antigen-matched persons with HCV spontaneous resolution and 21 chronically infected patients treated with directly acting antiviral (DAA) therapy. Vaccination induced tetramer-positive CD4 + T cells that were highest 1-4 weeks after boosting (mean, 0.06%). Similar frequencies were obtained for those tracked following spontaneous resolution of disease (mean, 0.04%). In addition, the cell-surface phenotype (CD28, CD127) memory subset markers and intranuclear transcription factors, as well as functional capacity of peptide-specific CD4 + T-cell responses characterized after vaccination, are comparable to those following spontaneous viral resolution. In contrast, helper responses in chronic infection were infrequently detected and poorly functional and did not consistently recover following HCV cure., Conclusions: Helper CD4 + T-cell phenotype and function following HCV viral vectored vaccination resembles "protective memory" that is observed following spontaneous clearance of HCV. DAA cure does not promote resurrection of exhausted CD4 + T-cell memory in chronic infection., (© 2020 by the American Association for the Study of Liver Diseases.)

Many trials confirmed the safety of omitting axillary dissection in the selected patients treated for early breast cancer. The external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the French population representativity in the SERC trial and the differences between these two populations as well as comparing the French and the Swedish populations (the SENOMIC trial population and the Swedish National Breast Cancer Registry (NKBC) cohort) of patients with sentinel node (SN) micro-metastasis. A higher rate of smaller tumors and grade 1 tumors was observed in the French cohort when compared to the SERC population. Our findings conclude that both French populations show similar characteristics. Positive non-sentinel node (NSN) rates at completion axillary lymph node dissection (ALND) were 10.28 % and 11.3 % in the SERC trial and French cohort, respectively ( p = 0.5). The rate of grade 1 tumors was lower in the SENOMIC trial (16.2%) and in the NKBC cohort (17.4%) compared to the SERC trial population (27.3%) and the French cohort (34.4%). Our findings in addition to the previously demonstrated concordance between the SENOMIC trial and the NKBC populations imply that the results of both the SERC and the SENOMIC trials can be applied to both French and Swedish real populations.

Background: Hospital workers have been the most frequently and severely affected professional group during the COVID-19 pandemic, and have a big impact on transmission. In this context, innovative tools are required to measure the symptoms compatible with COVID-19, the spread of infection, and testing capabilities within hospitals in real time., Objective: We aimed to develop and test an effective and user-friendly tool to identify and track symptoms compatible with COVID-19 in hospital workers., Methods: We developed and pilot tested Hospital Epidemics Tracker (HEpiTracker), a newly designed app to track the spread of COVID-19 among hospital workers. Hospital staff in 9 hospital centers across 5 Spanish regions (Andalusia, Balearics, Catalonia, Galicia, and Madrid) were invited to download the app on their phones and to register their daily body temperature, COVID-19-compatible symptoms, and general health score, as well as any polymerase chain reaction and serological test results., Results: A total of 477 hospital staff participated in the study between April 8 and June 2, 2020. Of note, both health-related (n=329) and non-health-related (n=148) professionals participated in the study; over two-thirds of participants (68.8%) were health workers (43.4% physicians and 25.4% nurses), while the proportion of non-health-related workers by center ranged from 40% to 85%. Most participants were female (n=323, 67.5%), with a mean age of 45.4 years (SD 10.6). Regarding smoking habits, 13.0% and 34.2% of participants were current or former smokers, respectively. The daily reporting of symptoms was highly variable across participating hospitals; although we observed a decline in adherence after an initial participation peak in some hospitals, other sites were characterized by low participation rates throughout the study period., Conclusions: HEpiTracker is an already available tool to monitor COVID-19 and other infectious diseases in hospital workers. This tool has already been tested in real conditions. HEpiTracker is available in Spanish, Portuguese, and English. It has the potential to become a customized asset to be used in future COVID-19 pandemic waves and other environments., Trial Registration: ClinicalTrials.gov NCT04326400; https://clinicaltrials.gov/ct2/show/NCT04326400., (©Joan B Soriano, Esteve Fernández, Álvaro de Astorza, Luis A Pérez de Llano, Alberto Fernández-Villar, Dolors Carnicer-Pont, Bernardino Alcázar-Navarrete, Arturo García, Aurelio Morales, María Lobo, Marcos Maroto, Eloy Ferreras, Cecilia Soriano, Carlos Del Rio-Bermudez, Lorena Vega-Piris, Xavier Basagaña, Josep Muncunill, Borja G Cosio, Sara Lumbreras, Carlos Catalina, José María Alzaga, David Gómez Quilón, Carlos Alberto Valdivia, Celia de Lara, Julio Ancochea. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 21.09.2020.)

Background: Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This Phase I, randomized, observer-blind, placebo- and active-controlled study evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid, and transcription antitermination proteins., Methods: Healthy 18-45-year-old adults received ChAd155-RSV, a placebo, or an active control (Bexsero) at Days (D) 0 and 30. An escalation from a low dose (5 × 109 viral particles) to a high dose (5 × 1010 viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by enzyme-linked immunospot, functional neutralizing antibodies, anti RSV-F immunoglobin (Ig) G, and ChAd155 neutralizing antibodies., Results: There were 7 participants who received the ChAd155-RSV low dose, 31 who received the ChAd155-RSV high dose, 19 who received the placebo, and 15 who received the active control. No dose-related toxicity or attributable SAEs at the 1-year follow-up were observed. The RSV-A neutralizing antibodies geometric mean titer ratios (post/pre-immunization) following a high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over the fold-rise in RSV-A-neutralizing antibodies was 1.01. At D7 after the high dose of the study vaccine, the median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/106 (IgG) and 16.7/106 (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F-specific interferon γ-secreting T-cells after a ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose., Conclusions: In adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns., Clinical Trials Registration: NCT02491463., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination., Materials and Methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests., Results: The prevalence rates of HBsAg, anti-HBc total, anti- HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001)., Conclusions: These findings show the elimination of HBVmcarriers in children <11 years, eight years following introduction of the vaccination against HBV., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Purpose: There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC., Methods: In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI)., Results: In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3 years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34-6.17), P = 0.007 and HR 12.04 (95%CI 2.78-52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively)., Conclusions: These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.

Introduction: Ductal carcinoma in situ (DCIS) accounts for 15% of all breast cancers and generally, the prognosis is good if treated optimally. The standard treatment includes breast conservative surgery along with adjuvant radiotherapy. Skin-sparing mastectomy (SSM) preserves the breast skin envelope but its oncological safety poses a few concerns. Moreover, no DCIS-specific studies have compared the local recurrence (LR) rate following total mastectomy (TM) or SSM. We evaluated the LR rate in DCIS patients who underwent either TM or SSM., Methods: This is a retrospective study on women who underwent mastectomy with or without immediate breast reconstruction or secondary reconstruction for pure DCIS of the breast. All patients treated at Institut Bergonié by mastectomy for DCIS from January 1990 to December 2010 were included. LR and overall survival (OS) rates were estimated., Results: The study population included 399 patients who were categorized into two groups, 207 in the TM group and 192 in the SSM group. At 10 years of follow-up, the LR rate was 0.97% in the TM group and 1.04% in the SSM group (p = NS). The OS of the entire population was 94.7% [95% CI; 91.6-96.7], 92.8% [95% CI, 87.9-95.8] for the TM group and 96.8% [95% CI, 91.6-98.8] for the SSM group., Conclusions: In our study, the LR rate following mastectomy is low, regardless of the surgical technique used, with an excellent OS at 10 years., (Copyright © 2019. Published by Elsevier Ltd.)

Background : Persistent viruses such as murine cytomegalovirus (MCMV) and adenovirus-based vaccines induce strong, sustained CD8 + T-cell responses, described as memory "inflation". These retain functionality, home to peripheral organs and are associated with a distinct transcriptional program. Methods : To further define the nature of the transcriptional mechanisms underpinning memory inflation at different sites we used single-cell RNA sequencing of tetramer-sorted cells from MCMV-infected mice, analyzing transcriptional networks in virus-specific populations in the spleen and gut intra-epithelial lymphocytes (IEL). Results : We provide a transcriptional map of T-cell memory and define a module of gene expression, which distinguishes memory inflation in spleen from resident memory T-cells (T RM ) in the gut. Conclusions : These data indicate that CD8 + T-cell memory in the gut epithelium induced by persistent viruses and vaccines has a distinct quality from both conventional memory and "inflationary" memory which may be relevant to protection against mucosal infections., Competing Interests: No competing interests were disclosed.

Advancing interventions to tackle the huge global burden of hepatitis B virus (HBV) infection depends on improved insights into virus epidemiology, transmission, within-host diversity, drug resistance and pathogenesis, all of which can be advanced through the large-scale generation of full-length virus genome data. Here we describe advances to a protocol that exploits the circular HBV genome structure, using isothermal rolling-circle amplification to enrich HBV DNA, generating concatemeric amplicons containing multiple successive copies of the same genome. We show that this product is suitable for Nanopore sequencing as single reads, as well as for generating short-read Illumina sequences. Nanopore reads can be used to implement a straightforward method for error correction that reduces the per-read error rate, by comparing multiple genome copies combined into a single concatemer and by analysing reads generated from plus and minus strands. With this approach, we can achieve an improved consensus sequencing accuracy of 99.7% and resolve intra-sample sequence variants to form whole-genome haplotypes. Thus while Illumina sequencing may still be the most accurate way to capture within-sample diversity, Nanopore data can contribute to an understanding of linkage between polymorphisms within individual virions. The combination of isothermal amplification and Nanopore sequencing also offers appealing potential to develop point-of-care tests for HBV, and for other viruses.

Objectives: The aim of this study is to describe the current trends of breast reconstruction (BR) and breast oncoplasty (BO) for breast cancer patients in Reunion Island., Methods: This is a multicenter retrospective descriptive study of all BR and BO surgeries in 2016. We studied the first stage of BR that corresponds to the choice of surgical technique. Patient's age, care center, technique and duration of surgery, complications and their risk factors were reviewed. Patient satisfaction was assessed using the modified BREAST-Q © ., Results: In 2016, BR rate over total mastectomy was 47.6% and BO rate was 6.3% over partial mastectomy. Among the 92 patients included, 25 immediate BR were performed (84% in private institution) and 44 delayed BR (67% in public hospital). Although prosthetic techniques were the most used, satisfaction seems to be better with autologous techniques., Conclusions: The ratio of BR is high in Reunion Island with a wide range of techniques but uneven practice. Conversely, BO's ratio is low and improvement is needed., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: A strong correlation between breast cancer (BC) molecular subtypes and axillary status has been shown. It would be useful to predict the probability of lymph node (LN) positivity., Objective: To develop the performance of multivariable models to predict LN metastases, including nomograms derived from logistic regression with clinical, pathologic variables provided by tumor surgical results or only by biopsy., Methods: A retrospective cohort was randomly divided into two separate patient sets: a training set and a validation set. In the training set, we used multivariable logistic regression techniques to build different predictive nomograms for the risk of developing LN metastases. The discrimination ability and calibration accuracy of the resulting nomograms were evaluated on the training and validation set., Results: Consecutive sample of 12,572 early BC patients with sentinel node biopsies and no neoadjuvant therapy. In our predictive macro metastases LN model, the areas under curve (AUC) values were 0.780 and 0.717 respectively for pathologic and pre-operative model, with a good calibration, and results with validation data set were similar: AUC respectively of 0.796 and 0.725. Among the list of candidate's regression variables, on the training set we identified age, tumor size, LVI, and molecular subtype as statistically significant factors for predicting the risk of LN metastases., Conclusions: Several nomograms were reported to predict risk of SLN involvement and NSN involvement. We propose a new calculation model to assess this risk of positive LN with similar performance which could be useful to choose management strategies, to avoid axillary LN staging or to propose ALND for patients with high level probability of major axillary LN involvement but also to propose immediate breast reconstruction when post mastectomy radiotherapy is not required for patients without LN macro metastasis.

Purpose: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients., Methods: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone., Results: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed., Conclusion: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

Background: Respiratory syncytial virus (RSV) causes respiratory disease throughout life. Here we report differences in naturally acquired immunity with age and presumed exposure., Methods: A longitudinal, non-interventional, observational study was performed in healthy adults (20 paediatric healthcare workers and 10 non-healthcare workers), children (10 aged 3-6 years) and infants (5 aged 2-4 months and 20 aged 6-12 months). Blood samples were analysed for RSV-neutralising antibody titre, F/Ga/Gb-specific antibody titres, F-specific IgG/IgA memory B-cell frequencies and T-cell production of IFNγ, IL-4, IL-13 and IL-17., Results: Serum G-specific antibody titres were significantly lower in infants and children than adults. However, serum titres of F-specific and RSV-neutralising antibody and IFNγ-producing T-cell frequencies were low or absent in the infants, but comparable between children and adults. Interestingly, F-specific memory IgA B-cells could not be detected in paediatric samples and in samples from non-healthcare workers, but recordable IgA memory B-cells were found in 9/18 paediatric healthcare workers and 2/8 non-healthcare workers at the end of the RSV season. These responses waned 4-6 months later. By contrast, F-specific IgG memory B-cells were detectable in samples from all adults without significant variation across time points. T-cells producing IL-4, IL-13 and IL-17 responses were not detectable in peripheral blood from a subset of volunteers., Conclusions: Repeated RSV exposure in early life generates immune responses that are inversely related to frequency of severe disease. Induction of F-specific antibody and cellular immune responses through infant vaccination might help to accelerate the development of protective immune responses at an early age. Clinicaltrials.gov reference NCT01563692 and NCT01640652., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The efficacies of many new T cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory CD8 T cells. However, it is now increasingly recognized that prior infection history impacts on the host immune response. Additionally, the order in which these infections are acquired could have a major effect. Exploiting the ability to generate large sustained effector memory (i.e. inflationary) T cell populations from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, the impact of new infections on pre-existing memory and the capacity of the host's memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model. Simultaneous and sequential infections, first with MCMV followed by Ad-lacZ, generated inflationary populations towards both viruses with similar kinetics and magnitude to mono-infected groups. However, in Ad-lacZ immune mice, subsequent acute MCMV infection led to a rapid decline of the pre-existing Ad-LacZ-specific inflating population, associated with bystander activation of Fas-dependent apoptotic pathways. However, responses were maintained long-term and boosting with Ad-lacZ led to rapid re-expansion of the inflating population. These data indicate firstly that multiple specificities of inflating memory cells can be acquired at different times and stably co-exist. Some acute infections may also deplete pre-existing memory populations, thus revealing the importance of the order of infection acquisition. Importantly, immunization with an AdHu5 vector did not alter the size of the pre-existing memory. These phenomena are relevant to the development of adenoviral vectors as novel vaccination strategies for diverse infections and cancers. (241 words).

Background: Sentinel lymph node biopsy (SLNB) remains under discussion for large size tumors. The aim of this work has been to study the false negative rate (FNR) of SLNB for large tumors and predictive factors of false negative (FN)., Materials and Methods: A study of a multicentric cohort, involved patients presenting N0 breast cancer with a SLNB eventually completed by complementary axillary lymph node dissection (cALND). The main criteria were the FNR and the predictive factors of FN., Results: 12.415 patients were included: 748 with tumors ≥30 mm, 1101 with tumors >20 and < 30 mm and 10.566 with tumors ≤20 mm, with a cALND respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were respectively: 3.05% (IC95%: 1.3-4.8) for tumors ≥30 mm*, 3.5% (1.8-5.2) for tumors >20 and < 30 mm*, 1.8% (1-2.4) for tumors ≤20 mm (p < 0.05) (*Not significant). At multivariate analysis, SN number harvested ≤2 (OR:2.0, p = 0.023) and tumor size >20 and < 30 mm (OR:2.07, p = 0.017) were significant predictive factors of FN, without significant value for tumor size ≥30 mm (OR:1.83, p = 0.073)., Conclusion: The FNR of SLNB was not higher amongst large size tumors compared to tumors of a smaller size. These results support the validation of SNLB for tumors up to 50 mm., (Copyright © 2017. Published by Elsevier Ltd.)

Introduction: The aim of this study was to examine changes in therapeutic practices for early breast cancer T0-2 N0 managed by upfront surgery and SLNB., Population: Between 1999 and 2012, 15.508 patients were treated. Four periods were determined: 1999-2003, 2004-2006, 2007-2009 and > 2009. Five tumor subtypes were defined according to hormonal receptors (HR) and Her2: Luminal A (HR + Her2- Grade 1-2), Her2 (Her2+ HR-), Triple-negative (HR- Her2-), Luminal B Her2- (HR + Her2- Grade 3), Luminal B Her2+ (HR + HER2+)., Methods: Rates of axillary lymph node dissection (ALND), adjuvant chemotherapy ± trastuzumab, endocrine treatment, mastectomy and post mastectomy radiotherapy (PMRT) were analyzed according to treatment periods with univariate and multivariate analysis. Overall and disease-free survivals were analyzed according to treatment periods adjusted for HR and then for tumor subtypes., Results: Rates of ALND, adjuvant chemotherapy and endocrine treatment varied significantly according to treatment periods, for HR positive and negative tumors. ALND rate decreased for all tumor subtypes with a decrease of adjuvant chemotherapy rate for Luminal A tumors and an increase for Luminal B Her2+ and Her2-tumors. Endocrine treatment rate decreased for Luminal A and increased for Luminal B Her2+ tumors. In multivariate analysis, these modifications with time remained significant. Mastectomy and PMRT rates increased. In multivariate analysis, overall and disease-free survivals increased during successive periods., Conclusion: A global therapeutic de-escalation in ALND and adjuvant systemic treatment, combined with an actual escalation in some specific subsets was demonstrated, but without negative impact on survival., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: The objective of our study is to describe the practices of breast reconstruction in patients aged 70 years and over undergoing a radical mastectomy at institut Bergonié., Material and Methods: We performed a detailed single-site retrospective study from January 2005 to December 2015. Through a computerized review, we have identified and analyzed all patients aged 70 years and over who underwent a breast reconstruction., Results: Five hundred and ninety patients underwent a radical mastectomy during the period. Twenty-eight patients (4.7%) benefited from a breast reconstruction. Nineteen patients (67.9%) had an immediate breast reconstruction and 9 patients (32.1%) had a delayed breast reconstruction, within an average time of 2 years. Sixteen patients (57.1%) benefited from the insertion of an expander replaced by a permanent implant. Five patients (17.9%) benefited from the immediate placement of an implant. Six patients (21.4%) had a reconstruction by autologous latissimus dorsi flap and 1 patient (3.6%) by exclusive lipofilling. Four patients (14.3%) presented postoperative complications without the need for removal of an implant or flap loss. Twenty patients (71.4%) were satisfied with their final reconstruction., Conclusions: Breast reconstruction in elderly patients is possible. Further studies are needed to better describe French practices., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Omission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion., Methods: A retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts., Findings: Among 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36-4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74-2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46-5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90-2.73)., Interpretation: A separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications., Methods: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected., Results: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01)., Conclusion: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: Sentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context., Patients and Methods: From 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy., Results: The detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%., Conclusion: Previous conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement., Clinical Trial Registration Number: NCT00293865., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.

Objective: Since the last guidelines published by the French National Cancer Institute (INCa) and the learning society "Société française de sénologie et de pathologie mammaire (SFSPM)" in 2009 about diagnosis and management of ductal carcinoma in situ, new data raised issues about overdiagnosis and its consequences, overtreatment. Therefore, an update was necessary, to provide healthcare professionals up-to-date guidelines and study therapeutic desescalation in particular., Methods: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary experts workgroup. The recommendations are thus based on the best available evidence and experts agreement. Prior to publication, the guidelines are also reviewed by more than 100 independent practitioners in cancer care delivery., Results: This article presents French guidelines about MRI and vacuum assisted breast biopsy indications for DCIS diagnosis and the management of low-grade DCIS., (Copyright © 2016. Published by Elsevier Masson SAS.)

Background: The rate of axillary recurrence (AR) after sentinel lymph node biopsy is usually low but few studies investigated its impact on survival. Our aim was to determine the rate and predictive factors of AR in a large cohort of breast cancer patients and its impact on survival., Patients and Methods: From 1999 to 2013, 14,095 patients who underwent surgery for clinically N0 previously untreated breast cancer and had sentinel lymph node biopsy were analysed. A simplified score predictive of AR was established., Results: Median follow-up was 55.2 months. AR was observed in 0.51% of cases, with a median time to onset of 43.4 months. In multivariate analysis, the occurrence of AR was significantly correlated with grade 2 or 3 disease, absence of radiotherapy and tumour subtype (hormonal receptor [HR]- / human estrogen receptor [HER]+). AR rates were 1% for triple-negative tumours, 2.8% for HER2-positive tumours, 0.4% for luminal A tumours, 0.9% for HER2-negative luminal B tumours, and 0.5% for HER2-positive luminal B tumours. A simplified score predictive of the occurrence of AR was established. Patients could be divided into three different score groups (p < 0.0001). In multivariate analysis, overall survival was significantly lower in cases of AR (p < 0.0001), age >50, lymphovascular invasion, grade 3 disease, sentinel node (SN) macrometastases, tumour size >20 mm, absence of chemotherapy and triple-negative phenotype. Survival in patients with AR was significantly lower in case of early-onset (2 years) AR (p = 0.017)., Conclusions: Isolated AR is more common in Her2-positive/HR-negative triple-negative tumours with a more severe prognosis in triple-negative and Her2-positive/HR-negative tumours, and represents an independent adverse factor justifying an indication for systemic treatment for AR treatment. However, the benefit of any systemic treatment remains to be proven., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Following exposure to vaccines, antigen-specific CD8(+) T cell responses develop as long-term memory pools. Vaccine strategies based on adenoviral vectors, e.g., those developed for HCV, are able to induce and sustain substantial CD8(+) T cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8(+) T cell memory pools induced by an adenovector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include upregulation of homing receptors and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet. In humans, an adenovirus vaccine induced similar CMV-like phenotypes and transcription factor regulation. These data clarify the core features of CD8(+) T cell memory following vaccination with adenovectors and indicate a conserved pathway for memory development shared with persistent herpesviruses., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion., Methods: The SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed., Results: From May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56-77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion., Conclusions: Underestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy.

Objectives: To assess the prognostic factors of T1 and T2 infiltrating lobular breast cancers, and to investigate predictive factors of axillary lymph node involvement., Methods: This is a retrospective multicentric study, conducted from 1999 to 2008, among 13 french centers. All data concerning patients with breast cancer who underwent a primary surgical treatment including a sentinel lymph node procedure have been collected (tumors was stage T1 or T2). Patients underwent partial or radical mastectomy. Axillary lymph node dissection was done systematically (at the time of sentinel procedure evaluation), or in case of sentinel lymph node involvement. Among all the 8100 patients, 940 cases of lobular infiltrating tumors were extracted. Univariate analysis was done to identify significant prognosis factors, and then a Cox regression was applied. Analysis interested factors that improved disease free survival, overall survival and factors that influenced the chemotherapy indication. Different factors that may be related with lymph node involvement have been tested with univariate than multivariate analysis, to highlight predictive factors of axillary involvement., Results: Median age was 60 years (27-89). Most of patients had tumours with a size superior to 10mm (n=676, 72%), with a minority of high SBR grade (n=38, 4%), and a majority of positive hormonal status (n = 880, 93, 6%). The median duration of follow-up was 59 months (1-131). Factors significantly associated with decreased disease free survival was histological grade 3 (hazard ratio [HR]: 3,85, IC 1,21-12,21), tumour size superior to 2cm (HR: 2,85, IC: 1,43-5,68) and macrometastatic lymph node status (HR: 3,11, IC: 1,47-6,58). Concerning overall survival, multivariate analysis demonstrated a significant impact of age less than 50 years (HR: 5,2, IC: 1,39-19,49), histological grade 3 (HR: 5,03, IC: 1,19-21,25), tumour size superior to 2cm (HR: 2,53, IC: 1,13-5,69). Analysis concerning macrometastatic lymph node status nearly reached significance (HR: 2,43, IC: 0,99-5,93). There was no detectable effect of chemotherapy regarding disease free survival (odds ratio [OR] 0,8, IC: 0,35-1,80) and overall survival (OR: 0,72, IC: 0,28-1,82). Disease free survival was similar between no axillary invasion (pN0) and isolated tumor cells (pNi+), or micrometastatic lymph nodes (pNmic). There were no difference neither between one or more than one macromatastatic lymph node. But disease free survival was statistically worse for pN1 compared to other lymph node status (pN0, pNi+ or pNmic). Factors associated with lymph node involvement after logistic regression was: age from 51 to 65 years (OR: 2,1, IC 1,45-3,04), age inferior to 50 years (OR 3,2, IC: 2,05-5,03), Tumour size superior to 2cm (OR 4,4, IC: 3,2-6,14), SBR grading 2 (OR 1,9, IC: 1,30-2,90) and SBR grade 3 (OR 3,5, IC: 1,61-7,75)., Conclusion: The analysis of this series of 940 T1 and T2 lobular invasive breast carcinomas offers several information: factors associated with axillary lymph node involvement are age under 65 years, tumor size greater than 20mm, and a SBR grade 2 or 3. The same factors were significantly associated with the OS and DFS. The macrometastatic lymph node involvement has a significant impact on DFS and OS, which is not true for isolated cells and micrometastases, which seem to have the same prognosis as pN0., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults., Methods and Analysis: Heterologous and homologous 'prime'/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18-50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60-75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK., Ethics and Dissemination: RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere to International Conference on Harmonisation (ICH) Good Clinical Practice guidelines. The results of the trial are to be published in peer-reviewed journals, conferences and academic forums., Trial Registration Number: NCT01805921., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Focusing on the current context of national and international recommendations, techniques development to evaluate and preserve fertility and patients' claims, this study aims to make a survey about the management of patients' breast cancer regarding oncofertility., Methods: Retrospective and analytic study of medical practices at Bergonié Institute of health professionals (medical oncologists, surgical oncologists, nurses) dedicated to the care of non-disseminated breast cancer patients younger than 37, needing medical treatment., Results: The number of participants was 230. The most interested practitioners in fertility theme are those of multidisciplinary consultation and surgeons (P<0.001), with an increasing interest during last years (P<0.05). The information about hypofertilizing risks of treatments are delivered most of the time by oncologists (57.7%). The motherhood project is expressed by 11 patients (4.9%) before treatment, only 4 of them receive information on the risks and 49 patients (21.7%) during follow-up. Only 24 patients (48% of the 49) are encouraged for motherhood., Conclusion: To satisfy patients' requests, several improvements have to be made regarding the patients' information, the health professionals' awareness and care coordination., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: While the addition of targeted therapy to neoadjuvant chemotherapy (NACT) dramatically increases the rate of pathological complete response in HER2-positive breast cancer, no reduction in the rate of mastectomy has been observed in randomised studies., Methods: A retrospective single centre analysis of all patients treated with anti HER2-based NACT for T2-4 breast cancer, focusing on patients treated with mastectomy., Results: Among 165 patients treated between June 2005 and July 2012, surgery was performed immediately post-NACT in 152 cases (92%). Breast-conserving surgery could be performed for 108 of the patients (71%), with a 4-year local relapse-free survival of 97%. A mastectomy was performed in two cases following patients' wishes and in 37 cases based on pre-NACT findings (n = 18) or post-NACT outcomes (n = 19). For 21 out of the 37 cases, a good pathological response was observed, and multidisciplinary reanalysis suggests that breast-conserving surgery outright may have been sufficient for 12 patients. Finally, a salvage mastectomy based on post-lumpectomy pathological results was decided in five cases (11%). The 4-year metastasis-free survival was 84% for all patients operated on after NACT (n = 152)., Conclusions: Given the good efficacy of anti HER2-based NACT, breast-conserving surgery should be standard practice for most patients. Total mastectomy on the other hand should be restricted to a few patients, mainly those with positive margins on the lumpectomy specimen., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: We wished to estimate the proportion of patients with breast cancer eligible for an exclusive targeted intraoperative radiotherapy (TARGIT) and to evaluate their survival without local recurrence., Methods: We undertook a retrospective study examining two cohorts. The first cohort was multicentric (G3S) and contained 7580 patients. The second cohort was monocentric (cohort 2) comprising 4445 patients. All patients underwent conservative surgery followed by external radiotherapy for invasive breast cancer (T0-T3, N0-N1) between 1980 and 2005. Within each cohort, two groups were isolated according to the inclusion criteria of the TARGIT A study (T group) and RIOP trial (R group).In the multicentric cohort (G3S) eligible patients for TARGIT A and RIOP trials were T1E and R1E subgroups, respectively. In cohort number 2, the corresponding subgroups were T2E and R2E. Similarly, non-eligible patients were T1nE, R1nE and T2nE, and R2nE.The eligible groups in the TARGIT A study that were not eligible in the RIOP trial (TE-RE) were also studied. The proportion of patients eligible for TARGIT was calculated according to the criteria of each study. A comparison was made of the 5-year survival without local or locoregional recurrence between the TE versus TnE, RE versus RnE, and RE versus (TE-RE) groups., Results: In G3S and cohort 2, the proportion of patients eligible for TARGIT was, respectively, 53.2% and 33.9% according the criteria of the TARGIT A study, and 21% and 8% according the criteria of the RIOP trial. Survival without five-year locoregional recurrence was significantly different between T1E and T1nE groups (97.6% versus 97% [log rank=0.009]), R1E and R1nE groups (98% versus 97.1% [log rank=0.011]), T2E and T2nE groups (96.6% versus 93.1% [log rank<0. 0001]) and R2E and R2nE groups (98.6% versus 94% [log rank=0.001]). In both cohorts, no significant difference was found between RE and (TE-RE) groups., Conclusions: Almost 50% of T0-2 N0 patients could be eligible for TARGIT.

To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST)., Patients and Methods: Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized., Results: Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors., Conclusion: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.

CD161(++) CD8(+) T cells represent a novel subset that is dominated in adult peripheral blood by mucosal-associated invariant T (MAIT) cells, as defined by the expression of a variable-α chain 7.2 (Vα7.2)-Jα33 TCR, and IL-18Rα. Stimulation with IL-18+IL-12 is known to induce IFN-γ by both NK cells and, to a more limited extent, T cells. Here, we show the CD161(++) CD8(+) T-cell population is the primary T-cell population triggered by this mechanism. Both CD161(++) Vα7.2(+) and CD161(++) Vα7.2(-) T-cell subsets responded to IL-12+IL-18 stimulation, demonstrating this response was not restricted to the MAIT cells, but to the CD161(++) phenotype. Bacteria and TLR agonists also indirectly triggered IFN-γ expression via IL-12 and IL-18. These data show that CD161(++) T cells are the predominant T-cell population that responds directly to IL-12+IL-18 stimulation. Furthermore, our findings broaden the potential role of MAIT cells beyond bacterial responsiveness to potentially include viral infections and other inflammatory stimuli., (© 2013 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.)

Objectives: Abnormalities of signal transduction are considered among the susceptibility factors for bipolar disorder (BD). These include changes in G-protein-mediated signaling and subsequent modification of gene expression via transcription factors such as cAMP response element-binding protein (CREB)., Methods: We investigated levels of CREB in lymphoblasts from patients with BD, all responders to lithium prophylaxis (n = 13), and healthy control subjects (n = 15). Phosphorylated CREB (pCREB) was measured by immunoblotting in subjects with BD (n = 15) as well as in their affected (n = 17) and unaffected (n = 18) relatives, and healthy controls (n = 16)., Results: Basal CREB levels were comparable in patients and control subjects and were not changed by lithium treatment. pCREB levels were increased in both patients and their relatives compared to controls (p = 0.003). Forskolin stimulation led to a 24% increase in pCREB levels in cells from healthy subjects (p = 0.002) but not in the other three groups. When using basal and stimulated pCREB levels as a biochemical phenotype in a preliminary linkage study, we found the strongest support for linkage in regions largely overlapping with those showing linkage with the clinical phenotype (3p, 6p, 16p, 17q, 19q, and 21q)., Conclusions: Abnormal pCREB signaling could be considered a biochemical phenotype for lithium-responsive BD., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)