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Abstract Background A rebound in antibiotic consumption has been observed in the European community at the end of the COVID-19 pandemic. Here we evaluate the extent of this increase, when it exactly occurred, and how the seasonality in antibiotic use changed during the late-pandemic period. Methods Data on community antibiotic consumption were available from the European Surveillance of Antimicrobial Consumption Network for 28 European countries between 2015 and 2022. Antibiotic consumption was expressed as defined daily doses per 1000 inhabitants per day (DID). The evolution in antibiotic use was investigated using non-linear changepoint mixed models for quarterly and yearly data. Results An increase in overall antibiotic consumption was found in Europe between 2021 and 2022, mainly due to an increase in the consumption of penicillins, macrolides, lincosamides and streptogramins, and other β-lactam antibacterials. The analysis of quarterly data estimated a gradual increase in overall antibiotic consumption of 0.55 DID per quarter, as of the second quarter of 2020 and a decrease in seasonal variation of 1.64 DID between the first and second quarter of 2020. The changepoint analysis of yearly data estimated an increase of 3.33 DID in overall antibiotic consumption between 2021 and 2022. Conclusions A gradual but significant rebound in the use of antibiotics was found in Europe, along with a decrease in its seasonal variation. The rapid rise in antibiotic consumption above pre-pandemic levels in several countries underlines the importance of continued antimicrobial stewardship.

Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

Background: Antimicrobial resistance (AMR) is a global public health concern, necessitating close and timely monitoring of antibiotic consumption (AMC). In Belgium, AMC surveillance traditionally relies on reimbursement data, excluding over-the-counter non-reimbursed or imported products and involving a time lag. This study investigates disparities in AMC between reimbursement data and retail data, providing insights into AMC variations. Additionally this study seeks to critically evaluate the validity and representativeness of the reimbursed data in accurately reflecting the true extent of AMC in the country. Method: Utilizing reimbursement data from the National Institute for Health and Disability Insurance (NIHDI) and retail data (IQVIA Sales data; www.iqvia.com) for systemic antibacterials (ATC Group J01), outpatient consumption was estimated for the period 2013-2022. Volume of antimicrobials was measured in Defined Daily Doses (DDDs - WHO ATC/DDD Index 2023), while population data were extracted from Eurostat. Relative differences (RDs) in DDDs per 1000 inhabitants per day (DID) were computed, and validated through correlation analysis (Pearson’s r) and Bland–Altman plots. Result: J01 antibacterial sales declined from 23.10 DID (2013) to 20.85 (2022). Non-linear decreases, notably during the Covid-19 pandemic (21.54 DID in 2019 to 16.69 in 2020), followed by a rebound to pre-pandemic quantities in 2022 were observed (Figure 1). Reimbursement NIHDI data slightly underestimated IQVIA sales, with RDs ranging from 2% (2013) to 9% (2022). Notable differences, especially in recent years were attributed to quinolone reimbursement criteria changes implemented by law in Belgium in 2018, reducing the reimbursed proportion from 99% (2017) to 35% (2022). ATC-3 level analysis revealed disparities in low-DID groups (J01B, J01E and J01G). Notably, a small proportion of amphenicols (J01B) were reimbursed ( < 1 0%), with a congestion relieving combination product of tiamphenicol (+ N-acetylcysteine; Fluimucil®) frequently bought and remaining unreimbursed. Overall and across ATC3 groups, the correlation between NIDHI and IQVIA estimates was almost perfect across years and the Bland–Altman plots showed high agreement. Conclusion: Reimbursement data are reliable for outpatient AMC monitoring with slightly lower estimates than retail data across most categories. The 2018 quinolone reimbursement criteria change highlights the necessity of incorporating retail data for accurate assessments in this specific category. The synergistic use of reimbursement and retail datasets is crucial for a comprehensive understanding of consumption patterns, supporting effective AMR mitigation strategies in Belgium.

Background: Point prevalence surveys (PPS) organized by the European Centre for Disease Prevention and Control (ECDC) play a crucial role in assessing healthcare-associated infections (HAIs) and antimicrobial use (AU) in European acute care hospitals. In 2017, a crude prevalence of 28.1% (95% CI 27.3-29.0%) of inpatients receiving at least one antimicrobial was recorded in Belgium (patients ≥65 years: 29.6% (95% CI 28.5-30.7%), < 6 5 years : 26.5% (95%CI 25.3-27.6%)) . Following the challenges posed by the COVID-19 pandemic, the 2022 ECDC-PPS aimed to reassess AU levels. Method: A cross-sectional study was conducted between September and November 2022 in 57 representative acute care Belgian hospital sites (35 mergers), following the ECDC-PPS protocol version 6.0. All patients present in surveyed wards at 8 a.m. on the PPS day and not discharged at that time were included. Infection prevention and control teams collected comprehensive data on hospitals, wards, and AU, including agents and indications. Results: Among the 10,142 included inpatients, 29.3% (95%CI 28.4-30.2) were receiving at least one antimicrobial (patients ≥65 years: 31.1% (95% CI 29.7-32.4%), < 6 5 years : 27.1% (95%CI 25.6-28.6%)). Intensive care units (56.3%), surgical (38.7%), and medical wards (33.1%) demonstrated the highest AU prevalence, while psychiatric wards exhibited the lowest (3.0%). A total of 3,549 antimicrobials were recorded, commonly prescribed for treating community-acquired infections (48.6%) and HAIs (30.3%, including 4.2% of long-term care facility acquired infections), as well as for surgical and medical prophylaxis (12.4 and 6.6%, respectively). Notably, only 22.7% of surgical prophylaxis courses (n=100/440) lasted more than one day. The top three most used antimicrobial agents consisted of amoxicillin in combination with a beta-lactamase inhibitor (J01CR02, 20.0%), cefazolin (J01DB04, 9.8%) and piperacillin in combination with a beta-lactamase inhibitor (J01CR05, 9.6%). The most frequently reported diagnoses for medical antimicrobial treatment were pneumonia (25.7%) and urinary tract infections (17.1%). The reason for AU was available in 80.0% of the medical notes. Conclusion: The 2022 PPS reveals an increased AU prevalence (+1.2%) in Belgian acute care hospitals, especially in patients over 65 years of age (+1.5%). This increase was less pronounced in younger patients (< 6 5y) (+0.6%). Future investigations are crucial to delve into prescription attitudes and modifiable practices, emphasizing the urgent need for robust antimicrobial stewardship programs in these healthcare settings.

This study aimed to evaluate the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in Belgian hospitals from 2017 to 2021, using data from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and the Belgian Hospitals Surveillance of Antimicrobial Consumption (BeH-SAC). Antimicrobial volume was quantified in Defined Daily Doses (DDDs), and AMC was expressed in DDDs/1000 inhabitants/day (DIDs), DDDs/1000 patient days and DDDs/1000 admissions. Linear regressions were employed to analyze 5-year trends for the ATC J01 group, at the ATC-3 level and for broad-spectrum antimicrobials. Broad-spectrum antibiotics included combinations of penicillins, incl. beta-lactamase inhibitors (J01CR), second-generation cephalosporins (J01DC), third-generation cephalosporins (J01DD), macrolides, lincosamides and streptogramins (J01F, excluding erythromycin J01FA01), and fluoroquinolones (J01MA). The compound annual growth rate (CAGR) calculated for the years preceding the pandemic was used to forecast 2020 and 2021 AMC, enabling a comparison with the actual use. Hospital AMC measured as DIDs decreased by 12% from 2019 to 2020. In contrast, when expressed as DDDs/1000 patient days and DDDs/1000 admissions, a 5% and 7% increase was observed, respectively. Antibacterials for systemic use (J01) showed a significant decrease over the 5 years only when expressed in DIDs. Notable trends included a negative trend for quinolone antibacterials (J01M) when expressed in the three incidence units, as for amphenicols (J01B) when using hospital denominators only. Positive trends were observed for sulfonamides and trimethoprim (J01E) using hospital denominators and for other beta-lactam antibacterials (J01D) with the ‘patient days’ denominator. While the consumption of all J01 antimicrobial subclasses deviated negatively from predicted use both in 2020 and 2021 when expressed in DIDs, positive deviations were recorded using hospital denominators, except for macrolides (J01F). The use of broad-spectrum antimicrobials showed a notable decrease between 2017 and 2021 when expressed in DIDs. However, when using hospital denominators, the observed use of broad-spectrum antimicrobials exceeded the forecasted values in 2020, to regress below the forecasted levels in 2021 (Figure 1). Contrary to results obtained using the widely applied country’s population as the denominator, a notable surge in AMC, particularly for broad-spectrum antimicrobials, was observed in 2020 when using hospital-specific denominators. This increase coincided with the onset of the COVID-19 crisis. These findings emphasize the need for a national hospital surveillance system that uses denominators that accurately represent the specific population being monitored. Implementing robust hospital-specific surveillance mechanisms would improve the precision of evaluations and facilitate targeted interventions aimed at optimizing antimicrobial utilization.

Vaccination has played a major role in overcoming the COVID-19 pandemic. However, vaccination status can be influenced by demographic and socio-economic factors at individual and area level.In the context of the LINK-VACC project, the Belgian vaccine register for the COVID-19 vaccination campaign was linked at individual level with other registers, notably the COVID-19 laboratory test results and demographic and socio-economic variables from the DEMOBEL database. The present article aims at investigating to which extent COVID-19 vaccination status is associated with area level and/or individual level demographic and socio-economic factors. From a sample of all individuals tested for SARS-CoV-2 (LINK-VACC sample) demographic and socio-economic indicators are derived and their impact on vaccination coverages at an aggregated geographical level (municipality) is quantified. The same indicators are calculated for the full Belgian population, allowing to assess the representativeness of the LINK-VACC sample with respect to the impact of demographic and socio-economic disparities on vaccination uptake.In a second step, hierarchical models are fitted to the individual level LINK-VACC data to disentangle the individual and municipality effects allowing to evaluate the added value of the availability of individual level data in this context.The most important effects observed at the individual level are reflected in the aggregated data at the municipality level. Multilevel analyses show that most of the demographic and socio-economic impacts on vaccination are captured at the individual level, although accounting for area level in individual level analyses improve the overall description.

Abstract Objective This study aimed to investigate factors influencing the uptake of first and second COVID-19 booster vaccines among adults in Belgium, particularly age, sex, region of residence and laboratory confirmed COVID-19 infection history. Results A binomial regression model was used with having received the first or second booster as outcome and age, sex, region of residence and infection history as fixed variables. Among adults, there was generally a higher uptake to receive the first booster among older age groups compared to younger ones. Females, individuals residing in Flanders and those with no previous COVID-19 infection were more likely to receive the first booster. For the second booster, the same age trend was seen as for the first booster. Males, individuals residing in Flanders and those who tested positive for COVID-19 once after first booster were more likely to receive the second booster. Individuals with multiple positive COVID-19 tests before and after primary course or first booster were less likely to receive the subsequent booster dose compared to COVID-naïve individuals. This information could be used to guide future vaccination campaigns during a pandemic and can provide valuable insights into booster uptake patterns.

Abstract Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.

La multiplication des indicateurs quantitatifs dans les politiques publiques liées à l’environnement engendre le recours croissant aux systèmes d’information géographique et aux données environnementales géoréférencées. L’enjeu est de traduire spatialement les changements globaux pour la planification et le suivi des dynamiques naturelles et anthropiques. L’article questionne le rapport à la temporalité de ces données : leur trajectoire d’évolution, rythmée par les progrès technologiques, et leur difficile adéquation avec les temporalités de l’objet qu’elles cherchent à représenter et celles de leurs utilisations. Il décortique l’incidence des croisements de données aux temporalités multiples. À partir de deux cas d’étude, l’article affirme l’importance de prendre le temps de la discussion durant le traitement des données afin d’en améliorer la compréhension et la comptabilité avec les objectifs attendus.

Abstract Background The diagnosis and management of eruptions after hematopoietic cell transplantation (HCT) is a challenge due to their atypical clinical presentation and the biology biased by immunosuppression and graft. The diagnosis is therefore based on multiple grounds. Few studies have focused on the occurrence of a skin rash during the first year of transplantation. Objectives To assess the frequency of rashes in this period, as well as their differential diagnosis and multidisciplinary management. Methods We performed a retrospective monocentric descriptive study in the Department of Blood Diseases of Lille University Hospital. All patients who received allogeneic HCT between January 1, 2018, and December 31, 2019, were included. Results We included 196 patients with allogeneic HCT. Of these, 89 (45.4%) presented a skin rash during the first year after transplantation. Among them, 78.7% were diagnosed with acute graft versus host disease (GVHD), 6.7% chemotherapy toxicity, 4.5% chronic GVH, 2.2% of infectious origin and 1.1% drug hypersensitivity. The outcome was mainly favourable (74.2% experienced resolution). A skin biopsy was performed in 9% of cases. Viral polymerase chain reactions (PCRs) were positive in 7.1% of tested patients. Conclusions Our study revealed a high frequency of skin rashes in stem cell transplant patients, thus justifying the multidisciplinary management of these high‐risk patients, which require both dermatological and haematological early expert assessment.

ABSTRACTThis study aimed to validate the prognostic value of Immunoscore (IS) in stage II colorectal cancer (CRC), and explore the roles of IS and circulating tumor DNA (ctDNA) in the adjuvant treatment for early-stage CRC. Resected tumor samples from stage II CRC patients were collected from the Sun Yat-sen University Cancer Center. The densities of CD3+ and CD8+ lymphocytes were quantified and converted to IS and classified into Low, Intermediate (Int), and High groups according to predefined cutoffs. A total of 113 patients were included in the study. Patients with IS-High, Int, and Low were 43 (38%), 62 (55%), and 8 (7%), respectively. Patients with IS-High had an excellent clinical outcome, with none recurring during a median follow-up of 3 years, including 15 (35%) clinical high-risk patients. The 3-year disease-free survival (DFS) was 100% for IS-High, 76% for IS-Int, and 47% for IS-Low (P

Summary: Background: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. Methods: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. Findings: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. Interpretation: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. Funding: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR).

We extend the autocorrelation-based approaches currently used in standards to full correlation-matrix-based approaches in order to identify correlation between both spatially adjacent and non-adjacent samples in reverberation-chamber measurements. We employ a scalar metric that allows users to identify the number of effectively uncorrelated samples in new types of stirring sequences. To make these approaches practical and enhance their accuracy, we implement a thresholding technique that retains correlation related to important aspects of chamber configuration such as loading conditions. We develop a method to propagate uncertainty in the complex correlation coefficients through to the number of effective samples for a given reverberation-chamber set-up by use of a bootstrap technique that is accurate even for highly skewed distributions of correlation coefficients. We further apply this method in a sensitivity study regarding the choice of threshold value. Agreement with existing approaches in determining the number of effectively uncorrelated samples is presented for a measurement example where spatially adjacent samples are utilized. Examples are then illustrated for non-spatially-adjacent correlated samples at microwave and millimeter-wave frequencies.

Abstract Background Differences in the genetic material of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in altered virulence characteristics. Assessing the disease severity caused by newly emerging variants is essential to estimate their impact on public health. However, causally inferring the intrinsic severity of infection with variants using observational data is a challenging process on which guidance is still limited. We describe potential limitations and biases that researchers are confronted with and evaluate different methodological approaches to study the severity of infection with SARS-CoV-2 variants. Methods We reviewed the literature to identify limitations and potential biases in methods used to study the severity of infection with a particular variant. The impact of different methodological choices is illustrated by using real-world data of Belgian hospitalized COVID-19 patients. Results We observed different ways of defining coronavirus disease 2019 (COVID-19) disease severity (e.g., admission to the hospital or intensive care unit versus the occurrence of severe complications or death) and exposure to a variant (e.g., linkage of the sequencing or genotyping result with the patient data through a unique identifier versus categorization of patients based on time periods). Different potential selection biases (e.g., overcontrol bias, endogenous selection bias, sample truncation bias) and factors fluctuating over time (e.g., medical expertise and therapeutic strategies, vaccination coverage and natural immunity, pressure on the healthcare system, affected population groups) according to the successive waves of COVID-19, dominated by different variants, were identified. Using data of Belgian hospitalized COVID-19 patients, we were able to document (i) the robustness of the analyses when using different variant exposure ascertainment methods, (ii) indications of the presence of selection bias and (iii) how important confounding variables are fluctuating over time. Conclusions When estimating the unbiased marginal effect of SARS-CoV-2 variants on the severity of infection, different strategies can be used and different assumptions can be made, potentially leading to different conclusions. We propose four best practices to identify and reduce potential bias introduced by the study design, the data analysis approach, and the features of the underlying surveillance strategies and data infrastructure.

Background In the era of “precision medicine,” the availability of high-quality tumor biomarker tests is critical and tumor proliferation evaluated by Ki-67 antibody is one of the most important prognostic factors in breast cancer. But the evaluation of Ki-67 index has been shown to suffer from some interobserver variability. The goal of the study is to develop an easy, automated, and reliable Ki-67 assessment approach for invasive breast carcinoma in routine practice. Patients and Methods A total of 151 biopsies of invasive breast carcinoma were analyzed. The Ki-67 index was evaluated by 2 pathologists with MIB-1 antibody as a global tumor index and also in a hotspot. These 2 areas were also analyzed by digital image analysis (DIA). Results For Ki-67 index assessment, in the global and hotspot tumor area, the concordances were very good between DIA and pathologists when DIA focused on the annotations made by pathologist (0.73 and 0.83, respectively). However, this was definitely not the case when DIA was not constrained within the pathologist's annotations and automatically established its global or hotspot area in the whole tissue sample (concordance correlation coefficients between 0.28 and 0.58). Conclusions The DIA technique demonstrated a meaningful concordance with the indices evaluated by pathologists when the tumor area is previously identified by a pathologist. In contrast, basing Ki-67 assessment on automatic tissue detection was not satisfactory and provided bad concordance results. A representative tumoral zone must therefore be manually selected prior to the measurement made by the DIA.

Background: A ductal adenoma is a rare benign epithelial tumour of the breast. Its origin is unclear, but some authors consider that they arise from intraductal papilloma that undergoes sclerosis and lose their papillary architecture. Case presentation: A 43-year-old woman presented a palpable mass in the right breast. Mammography revealed a well-demarcated nodule of 9 mm. Histological examination showed a nodular proliferation of glands without papillary structures circumscribed by a dense fibrous wall. Glandular tubules were round or ovoid. The epithelial cells showed no atypia and mitosis were absent. Gene mutation testing has been performed. Conclusion: To the best of our knowledge, we reported the first case of a ductal adenoma with AKT1 and EGFR mutations. We also reviewed the literature concerning the molecular profile of ductal adenoma and papillary lesions.

Summary: Background: Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non-small cell lung cancer (NSCLC) patients. Only a minority of patients responds to these treatments and biomarkers predicting response are currently lacking. Methods: Immunoscore-Immune-Checkpoint (Immunoscore-IC), an in vitro diagnostic test, was used on 471 routine single FFPE-slides, and the duplex-immunohistochemistry CD8 and PD-L1 staining was quantified using digital-pathology. Analytical validation was performed on two independent cohorts of 206 NSCLC patients. Quantitative parameters related to cell location, number, proximity and clustering were analysed. The Immunoscore-IC was applied on a first cohort of metastatic NSCLC patients (n = 133), treated with anti-PD1 or anti-PD-L1 mAbs. Another independent cohort (n = 132) served as validation. Findings: Anti-PDL1 clone (HDX3) has similar characteristics as anti-PD-L1 clones (22C3, SP263). Densities of PD-L1+ cells, CD8+ cells and distances between CD8+ and PD-L1+ cells were quantified and the Immunoscore-IC classification was computed. Using univariate Cox model, 5 histological dichotomised variables (CD8 free of PD-L1+ cells, CD8 clusters, CD8 cells in proximity of PD-L1 cells, CD8 density and PD-L1 cells in proximity of CD8 cells) were significantly associated with Progression-Free Survival (PFS) (all P

This paper aims to document the mapping of environmental objects, such as wetlands functions and landscape, with digital geography tools. Even though these maps are used to support public policies on water management and climate change anticipation, their political dimension is not explicitly discussed. We focus on the methodological issues involved in the processes of describing, recognizing and locating these environmental objects. We undid the illusion of a quick and automatic digital mapping, allowing addressing of any issue in an objective way: methodological choices must be discussed according to the purpose of the map. In an interdisciplinary context, it is necessary to get the measure of the polysemy of terms to reach an agreement on a common definition of objects to be represented. Digital tools challenge expertise: scientists standing between practice and research must consider the political underpinnings of maps produced with data and algorithms with issues that are not made explicit. This is why we question the purpose of the maps based on observations and interviews with their sponsors and end users. This provides key elements to renew the mapping process by examining a plurality of technical solutions, in particular the choice of relevant databases and spatial resolution.

Background Tumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC).Methods We characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features.Results Out of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen

Summary: Background: Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities is, however, not well understood. Methods: We studied brain structure and function in women with and without PCOS using proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging combined with fiber tractography. Then, using a mouse model of PCOS, we investigated by electron microscopy whether AMH played a role on the regulation of hypothalamic structural plasticity. Findings: Increased AMH serum levels are associated with increased hypothalamic activity/axonal-glial signalling in PCOS patients. Furthermore, we demonstrate that AMH promotes profound micro-structural changes in the murine hypothalamic median eminence (ME), creating a permissive environment for GnRH secretion. These include the retraction of the processes of specialized AMH-sensitive ependymo-glial cells called tanycytes, allowing more GnRH neuron terminals to approach ME blood capillaries both during the run-up to ovulation and in a mouse model of PCOS. Interpretation: We uncovered a central function for AMH in the regulation of fertility by remodeling GnRH terminals and their tanycytic sheaths, and provided insights into the pivotal role of the brain in the establishment and maintenance of neuroendocrine dysfunction in PCOS. Funding: INSERM (U1172), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n° 725149), CHU de Lille, France (Bonus H).

Objectives Women of low socioeconomic status have been described as having suboptimal prenatal care, which in turn has been associated with poor pregnancy outcomes. Many types of conditional cash transfer (CCT) programmes have been developed, including programmes to improve prenatal care or smoking cessation during pregnancy, and their effects demonstrated. However, ethical critiques have included paternalism and lack of informed choice. Our objective was to determine if women and healthcare professionals (HPs) shared these concerns.Design Prospective qualitative research.Setting We included economically disadvantaged women, as defined by health insurance data, who participated in the French NAITRE randomised trial assessing a CCT programme during prenatal follow-up to improve pregnancy outcomes. The HP worked in some maternities participating in this trial.Participants 26 women, 14 who received CCT and 12 who did not, mostly unemployed (20/26), and - 7 HPs.Interventions We conducted a multicentre cross-sectional qualitative study among women and HPs who participated in the NAITRE Study to assess their views on CCT. The women were interviewed after childbirth.Results Women did not perceive CCT negatively. They did not mention feeling stigmatised. They described CCT as a significant source of aid for women with limited financial resources. HP described the CCT in less positive terms, for example, expressing concern about discussing cash transfer at their first medical consultation with women. Though they emphasised ethical concerns about the basis of the trial, they recognised the importance of evaluating CCT.Conclusions In France, a high-income country where prenatal follow-up is free, HPs were concerned that the CCT programme would change their relationship with patients and wondered if it was the best use of funding. However, women who received a cash incentive said they did not feel stigmatised and indicated that these payments helped them prepare for their baby’s birth.Trial registration number NCT02402855