Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study.

BACKGROUND: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS: A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS: In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION: In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.

Multi-centennial mass balance of perennial ice deposits in Alpine caves mirrors the evolution of glaciers during the Late Holocene.

Mid-latitude alpine caves preserve a record of past solid precipitation during winter, locally spanning several centuries to millennia. Dating organic macro-remains trapped in ice layers allows the determination of timing and duration of past periods of positive and negative ice mass balance. We present here the largest comparative study of ice cave sites yet published, using Bayesian age-modelling on a database comprising 107 radiocarbon dates, spread over eight caves in the Austrian Alps. We show that periods of positive mass balance coincide with past glacier advances. We find organic and macro-remain rich layers dated to the Medieval Climate Anomaly (between 850 and 1200 CE) marking widespread ice retreat. We demonstrate positive ice mass balance at all studied sites for the Little Ice Age, coinciding with the largest glacier advances in the Holocene between 1400 and 1850 CE. At the sites with records spanning over 2000 years, positive mass balance is also observed during the periods from 300 BCE to 100 CE and 600-800 CE. These subterranean ice deposits show widespread evidence of accelerated negative mass balances in recent years and their record is under imminent threat of disappearing.

Management of an Acinetobacter baumannii outbreak in an intensive care unit.

INTRODUCTION: Acinetobacter baumannii is a ubiquitous pathogen resistant to desiccation and responsible for healthcare-associated infections (HAI), especially in intensive care units (ICU) where it is responsible for 5-10% of HAIs. An A. baumannii outbreak occurred in the ICU of the University Hospital of Angers, France. OBJECTIVES: To describe the A. baumannii outbreak and to evaluate the control measures taken. The secondary objective was to evaluate the impact of the electronic alert system on the incidence of multidrug resistance to antibiotics. METHODS: We performed a descriptive study of A. baumannii carriers during the outbreak. Case contacts and carriers were described using the epidemic curve and a case synopsis table. RESULTS: From August 2011 to September 2013, 49 patients presenting with an extended-spectrum beta-lactamase-producing A. baumannii infection were identified: thirty-four were colonized and 15 were infected. No death was due to the outbreak. Measures taken were: geographical and technical isolation of patients, dedicated team implementation, contact precaution implementation including hand hygiene measures, appropriate use of gloves, and reinforcement of bio-cleaning procedures. CONCLUSION: Some patients were re-admitted to hospital while still being carriers; this could explain epidemic peaks. The immersion mission of the hygiene nurse contributed to answering healthcare workers' queries and led to a better cooperation between the ICU and the hygiene team.

[Practical issues in the management of tuberculosis disease]. / Description des pratiques en matière de prise en charge de la tuberculose maladie.

INTRODUCTION: Tuberculosis disease warrants standard therapeutic management as detailed in a guide published by the High Authority for Health (HAS) following the publication of the Public Health Law in 2004. METHODS: The medical services of the régime social des indépendants (RSI) carried out a national survey by targeting patients who, in 2011, were reimbursed for tuberculosis treatment or were admitted for long-term tuberculosis disease. Their physicians were contacted to detail the care pathway and treatment they had received. RESULTS: A total of 148 tuberculosis disease patients were enrolled, of whom 71.6% had respiratory localization of their disease. The diagnosis was made in healthcare institutions in 84.5% of cases. Standard treatment (phases 1 and 2) was used in 30.1% of cases. The recommended quadruple therapy was given in 55.2% of treatments in phase 1 and in accordance with the time recommended in 62.9% of cases. Phase 2 was the recommended two drugs combination therapy 80.4% of the time with the treatment duration respected in 51.0% of treatments. The difference from standard treatment was explained by the detection of health or social events in only 39.0% of cases. CONCLUSION: This survey allows us to highlight a relative lack of knowledge of standard treatment as recommended by the HAS.

[Course and progression of children admitted before 4 years of age in a French child welfare center]. / Parcours et devenir de 128 enfants admis avant l'âge de quatre ans en pouponnière sociale.

AIM: The purpose of this study was to determine the institutional trajectory and future of young children in child welfare. MATERIALS AND METHODS: A catamnestic study - based on data from the child welfare office in Maine and Loire, France, from 1994 to 2001 - was conducted by a child psychiatrist and a psychologist. Medical, judicial, and educational data (development, health, pathways in child protection services) were collected and analyzed regarding the status of these children 15 years later, adding information gathered by interviewing the child welfare and foster family consultant. RESULTS: We included 128 children admitted to the child welfare office before 4 years of age. Admission to the child welfare system suffers from care delays (a mean of 13.1 months between the first child protection referral and placement) with an average entry age of 17 months and frequent cases of child abuse (e.g., seven Silverman syndrome cases). The physical and mental health status of these children was poor (poorly monitored pregnancies, prematurity, low birth weight). More than one third of the children had growth failure at admission, with catch-up in half of the cases. The average length of stay in the child welfare system was 13.2±4.6 years. At the end of the follow-up, there were specific measures to safeguard vulnerable adults: "young adult" (24 cases), "major protection" (eight cases) and "disabled living allowance" (nine cases). One hundred and sixteen children suffered from psychiatric disorders at entry and 98 at the end. The general functioning of children as assessed by the Children's Global Assessment Scale (CGAS) showed a statistically significant improvement. One out of two young adults showed problems integrating socially with chaotic pathways: many foster placements, unsuccessful return to the family, and academic failures. CONCLUSION: The clinical situations of children in the child welfare office and their long-term progression confirm the importance of this public health problem. Although the measures can greatly improve their physical and psychological recovery, with evidence of thriving, this remains limited: only a few of these children are well integrated socially and academically.

[National survey on short-term circulatory and/or respiratory support in 2009]. / Enquête nationale sur l'assistance circulatoire et respiratoire de courte durée en 2009.

OBJECTIVE: Indications for short-term circulatory and/or respiratory support (STCRS) increased during the last years. The goal of this survey was to characterize this activity in France in 2009. STUDY DESIGN: Observational retrospective pluricentral. MATERIAL AND METHODS: Each center of cardiothoracic surgery received a questionnaire validated by the Société française de perfusion about the activity, materials and organization used for STCRS. Data were expressed as percentages or median (25-75 percentiles). RESULTS: Forty-one centers on 61 (67%) answered. STCRS was performed respectively by 33 (80.5 %), 36 (87.8 %) and 39 (95.1 %) of centers in 2007, 2008 and 2009 including 10 [4-26], 18 [6-29] and 18 [5-33] cases/center per year. In 2009, types of STCRS installed were veno-arterial in 39 centres (95.1 %), veno-venous in 27 (65.9 %) and Novalung(®) in four (9.8 %), including 18 [5-32], five [2-7] and 15 [1-17] cases respectively. Twenty-nine centers (70.7%) installed STCRS outside the operating theater, and 24 (58.5%) in non-cardiothoracic surgery. A mobile circulatory support unit was created in eight centers (19.5%), however 21 (51.2%) have installed STCRS externally, at distances between 10 [5-55] to 100 [15-200] km, using emergency vehicles in most of the cases (90.5%), but helicopter seldom (19%). CONCLUSION: STCRS has increased over the last few years in France. Externalized activity outside the operating theater was important, time-consuming and used hospital resources therefore modifying the professional activity of perfusionists.

[Prenatal breastfeeding information: survey in Pays de Loire, France]. / Information prénatale sur l'allaitement maternel : enquête en Pays de Loire.

OBJECTIVES: The main aim of this study was to evaluate how well expectant mothers were informed on breastfeeding by healthcare professionals. The secondary objective was to determine the factors associated with the initiation of breastfeeding. POPULATION AND METHODS: The survey was conducted in a group of 500 women who had delivered at the Angers Hospital (France), based on a questionnaire filled out by the postpartum women during their hospital stay. RESULTS: The rate of breastfeeding was 61.2%. More than a quarter (26.9%) of the women did not receive any prenatal breastfeeding information. The survey showed that 77.8% of the women had been informed of breastfeeding advantages for infants and 51.5% of breastfeeding advantages for themselves. Only 27.5% had received the advice of exclusive breastfeeding for 6months. Only 5.2% had been informed of the uselessness of breast preparation during pregnancy and a minority had been informed of correct and incorrect breastfeeding contraindications. Only 15.4% of fathers had been involved in a discussion on infant feeding practices during prenatal consultations. Only 4.8% of the women had come to prenatal classes on breastfeeding with a relative. The maternal factors positively associated with breastfeeding initiation were age between 25 and 34 years, non-French origin, a high socioeconomic status, being married, having been breastfed, and having previous experience with breastfeeding. Breastfeeding initiation was negatively associated with maternal smoking. All the factors concerning prenatal breastfeeding information in women were associated with the choice of breastfeeding. CONCLUSION: This study pointed out the populations at risk of not breastfeeding. Breastfeeding information given to pregnant women by healthcare professionals may influence them on whether or not they choose to breastfeed their newborn. However, this survey showed that women are insufficiently informed on prenatal breastfeeding. Therefore, prenatal breastfeeding information should be improved.

[Aborting women social characteristics: a study in Maine-et-Loire region (France) in 2007]. / Caractéristiques sociodémographiques des femmes recourant à l'interruption volontaire de grossesse, et de sa prise en charge dans le Maine-et-Loire en 2007.

The number of voluntary termination of pregnancies (VTOP) in the district of Maine-et-Loire (France) has been slightly increasing in the last ten years but the rate of childbearing age seems to be stable as it is on a national or regional data. The aborting women in this district seem to be representative of French women terminating pregnancy regarding sociodemographical, gynaecological and contraception criteria. When they come to abort, the terms of the pregnant women are also representative. But if we compare the three family planning clinics of this department, we realise that the psycho-social interview is not equally carried out. In these three centres, there is the same proportion of medication abortion (as on a national and regional scale) but much less surgical abortion under general anaesthetic in Cholet (3.9%) than in Angers (27.7%) or Saumur (64.2%). The regional rate was of 30% and the national one of 65%. The explanation is the lack of time slot for general anaesthetics in Cholet and Angers. The majority of these women used a contraception method to avoid unwanted pregnancies but we observe a lot of failures due to natural methods and condoms (especially with young people). School prevention as well as prevention on a larger population of women and couples must be comprehensive and carried out seriously. It is essential to train doctors sufficiently and regularly on the questions of contraception in general (methods, instructions…).

[Tolerance of the contraceptive implant by prescription context (postabortion or not): Prospective study on 127 consultants]. / Évaluation de la tolérance de l'implant contraceptif selon le contexte de prescription (post-IVG ou non) : étude prospective chez 127 patientes.

AIM: While contraceptive methods increased in number, the number of abortions has remained stable. The aim of this study was to estimate the satisfaction of women toward a contraceptive implant (Implanon(®)) available in France in order to clarify prescription. METHOD: The survey concerned 127 women who visited Angers and Nantes family planning centres between January2009 and January2010 in two implant prescription contexts (postabortion or not). They agreed to answer a first questionnaire describing the reasons for their choice. A second questionnaire was sent six months after to assess its tolerance. RESULTS: In our study, 82% of patients were using a contraceptive method prior to implant (68% in postabortion and 88% in the other group). The first reason for choosing the implant was the fear of forgetting - it was more important in the postabortion group (88% vs. 61%). The main side effects were amenorrhea (50%), weight gain (30%) and mood disorders (19%). More than one in two women (54%) was very satisfied by the implant. It should be noted that in one quarter of cases, women seek early withdrawal of the contraceptive implant (23% in postabortion and 21% in the other group), a rate that is 39% in patients under 25years and 47% in patients who reported a mood disorder. CONCLUSION: There is a tendency to better tolerance of the implant out of a context of abortion. Furthermore, mood disorders appear to be poorly tolerated. These elements encourage greater caution in prescribing the contraceptive implant in postabortion, situation in which patients have already psychological disorders, and even more among younger patients.

[Comparison of the automated oscillometric method with Doppler ultrasound method to access the Ankle-Brachial Pressure Index (ABPI)]. / Etude comparative tensiomètre automatique versus doppler à ultrasons dans la mesure de l'index de pression systolique à la cheville (Ipsc).

OBJECTIVE: The Ankle-Brachial Pressure Index (ABPI) is the easiest non-invasive method for the assessment of peripheral arterial diseases (PAD) but remains uncommon in general practice, because of the need for training and specific devices. The purpose of this survey was to assess the reliability of the automated oscillometric measurement of the ABPI, compared with the gold-standard Doppler ultrasound measurement. METHODS: A study was conducted on patients aged 65 years and over without diagnosed PAD hospitalized in the Teaching Hospital of Angers (France) from July 2008 to March 2009. In compressive ankle arteries and atrial fibrillation were exclusion criteria. ABPI measurements were performed by the same examiner with oscillometric and Doppler devices. Reproducibility was assessed by the intra-class correlation coefficient of agreement (ICC) and the Bland-Altman method. RESULTS: Out of the 287 eligible hospitalized patients, 221 patients were included in the study and 56 (25%) had an ABPI below 0.90. The inter-method reliability is poor (ICC = 0.35+/-0.08) and the mean difference between the methods was 0.08+/-0.26 according to the Bland-Altman method. CONCLUSION: Automatic oscillometric devices cannot be recommended as a reliable alternative to access the ABPI.

[Renal leiomyosarcoma, rheumatoid arthritis and methotrexate]. / Léiomyosarcome de la veine rénale gauche dans un contexte de polyarthrite rhumatoïde sous méthotrexate.

Leiomyosarcoma of the renal vein is a rare and malignant tumor difficult to diagnose. No standard treatment has been defined and prognosis is poor. We described the case of a 68-year-old woman with rheumatoid arthritis treated by methotrexate who developed a leiomyosarcoma of the left renal vein with a fatal outcome in less than 1 year. Association of a leiomyosarcoma and rheumatoid arthritis raises the question of a casual association or of a predisposing factor since studies have shown increased risk of cancer with this rheumatism.

[General practitioners' (GPs) practice regarding the line to take in case of missed pill]. / Le médecin généraliste et l'oubli de pilule.

OBJECTIVE: To explore general practitioners' (GPs) practice face of missed pill and prevention of such missings. MATERIAL AND METHOD: Twenty-five GPs from Sarthe Department (Western France) took part in semistructured interview during which they expressed themselves on the prevention of missed pill and its consequences. RESULTS: Twelve out of 20 physicians stated positively that their female patients often forget their pill. However, they noted that missed pill was seldom a reason for phone call or consultation. During the initial pill prescription, GPs insisted on how to take the pill (14/25) as well as advice in case of a missed pill (22/25), their availability (12/25) and the instruction leaflet (16/25). But only five quoted the importance of involving women in the choice of contraception. On prescription renewal, only nine out of 25 ask their patients about observance defect and eight out of 25 repeated the information. If patients asked for further explanation, only two doctors out of 25 had practices in line with the French National Authority for Health's (HAS) recommandation guidelines. CONCLUSION: GPs' attitudes are partly due to a lack of practice's knowledge in primary and emergency contraception methods. It seems essential to promote GPs' training and to take into account their expectations and needs. Furthermore, female patient must be actor of the choice of her contraceptive method in order to improve compliance and, therefore, effectiveness.

Controlling the release of peptide antimicrobial agents from surfaces.

Medical conditions are often exacerbated by the onset of infection caused by hospital dwelling bacteria such as Staphylococcus aureus. Antibiotics taken orally or intravenously can require large and frequent doses, further contributing to the sharp rise in resistant bacteria observed over the past several decades. These existing antibiotics are also often ineffective in preventing biofilm formation, a common cause of medical device failure. Local delivery of new therapeutic agents that do not allow bacterial resistance to occur, such as antimicrobial peptides, could alleviate many of the problems associated with current antibacterial treatments. By taking advantage of the versatility of layer-by-layer assembly of polymer thin films, ponericin G1, an antimicrobial peptide known to be highly active against S. aureus, was incorporated into a hydrolytically degradable polyelectrolyte multilayer film. Several film architectures were examined to obtain various drug loadings that ranged from 20 to 150 microg/cm2. Release was observed over approximately ten days, with varying release profiles, including burst as well as linear release. Results indicated that film-released peptide did not suffer any loss in activity against S. aureus and was able to inhibit bacteria attachment, a necessary step in preventing biofilm formation. Additionally, all films were found to be biocompatible with the relevant wound healing cells, NIH 3T3 fibroblasts and human umbilical vein endothelial cells. These films provide the level of control over drug loading and release kinetics required in medically relevant applications including coatings for implant materials and bandages, while eliminating susceptibility to bacterial resistance.

[Bilateral traumatic dissection of the renal arteries]. / Dissection bilatérale traumatique des artères rénales.

The bilateral dissection of the renal arteries is uncommon after blunt trauma. The clinical symptoms are scarce and inconstant. The diagnosis is based on contrast-enhanced computed tomography with intravenous contrast and angiographic examination is required only if an endovascular revascularization is envisaged. We reported here, an exceptional case of bilateral traumatic dissection of the renal arteries associated with acute renal failure. The delayed revascularization does not allow the recuperation of a renal function.

Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer.

Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)). Patients with objective response (N=179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem cell support (N=88), or no further treatment (N=91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P=0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.

Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis.

OBJECTIVE: Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. METHODS AND RESULTS: Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (P<0.05). Fibrin of young CAD patients was stiffer (P=0.002), made of numerous (P=0.002) and shorter fibers (P=0.04), and lysed at a slower rate than that of controls (P=0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. CONCLUSIONS: This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. The determinants of this particular phenotype warrant further investigation.

AGS3, an alpha(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experimentally infected mice.

The cell wall of human fungal pathogen Aspergillus fumigatus protects the fungus against threats from environment and interacts with the host immune system. Alpha(1-3)glucan is the major polysaccharide of Aspergillus fumigatus cell wall, and it has been shown to contribute to the virulence of diverse fungal pathogens. In A. fumigatus, three putative alpha(1-3)glucan synthase genes AGS1, AGS2 and AGS3 have been identified. AGS1 is responsible for cell wall alpha(1-3)glucan biosynthesis, but strains with deletions of either AGS1 or AGS2 are not defective in virulence [Beauvais, A., Maubon, D., Park, S., Morelle, W., Tanguy, M., Huerre, M., Perlin, D.S., Latgé, J. P., 2005. Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus. Appl. Environ. Microbiol. 71, 1531-1538]. In contrast, we present evidence that AGS3 is also responsible for cell wall alpha(1-3)glucan biosynthesis and can modulate the virulence of A. fumigatus. An AGS3 deletion strain was found to produce faster and more robust disease than the parental strain in an experimental mouse model of aspergillosis. The apparent hyper-virulence in the AGS3-deleted mutant was correlated with an increased melanin content of the conidial cell wall, a better resistance to reactive oxygen species and a quicker germination rate. These results suggest an indirect role for AGS3 in virulence through an adaptive mechanism.