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Purpose: The prevalence of type 2 diabetes mellitus (T2DM) in cancer patients is high. During the medication review process, clinical pharmacists could detect and manage drug-related problems (DRP) to optimize pharmacotherapy but there is a need to standardize pharmacists' interventions (PI) especially for T2DM-related DRP. The present study aims to describe DRP in cancer patients with T2DM undergoing anticancer treatment (AT) and to propose related preliminary guidelines to manage T2DM-related DRP., Methods: The study was conducted in one oncology outpatient hospital where a clinical pharmacy team performs medication reviews to detect and manage DRP by performing PI in cancer patients undergoing AT. All the data from November 23rd, 2015 to November 23rd, 2019 were extracted and demographic, clinical, oncological, and biological data were collected and analyzed. Based on these results and a literature review, a working group (2 pharmacists and one diabetologist) was constituted to propose a first set of preliminary guidelines clinical pharmacists that were then reviewed using the Delphi method by an expert panel of oncologists and pharmacists., Results: A total of 161 T2DM cancer patients were included in the study (19.7% of all cancer patients screened). Overall, 152 DRP (mean 1.67/patient) were detected (49.3% drug interaction) and 152 PI were performed by clinical pharmacists, mainly drug monitoring (48.0) and drug discontinuation (25.7%). Specifically, there was 24 T2DM-related DRP (including 29.2% drug interactions). Twenty-four DRPs were directly related to T2DM status. The five proposed guidelines reached a consensus after revisions and a sixth has been added., Conclusion: DRPs were frequent among cancer patients with T2DM and we hypothesize that the preliminary guidelines should improve the detection of DRPs directly related to T2DM. The implementation of the preliminary guidelines should now be assessed in clinical practice., Competing Interests: Declarations Ethics approval The study was conducted in accordance with the Helsinki declaration. Patients’ records were anonymized prior to analysis. A database from ONCOPTIMAL (F20220817142044) was created in accordance with the reference methodology MR004 of the National Commission of Liberties and Informatics (no. MR00414012022). As per French regulations about retrospective study, no informed consent and additional ethical committee review were required. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Knowledge about environmental pancreatic adenocarcinoma (PA) risk factors, including pesticide exposure, remains limited. Organochlorine (OC) accumulates in adipose tissue and can help reflect long-term exposure., Patients and Methods: Age and body mass index (BMI) of patients with PA were matched with those undergoing a surgery for a benign disease on age and BMI (1:1). Targeted analyses screened 345 pesticides and metabolites, including 29 OC, in adipose tissue and urine samples. The primary aim was to investigate the association between organochlorine concentrations in visceral fat or urine, and PA. Adjusted conditional logistic regressions were carried out accounting for multiple testing., Results: Trans-nonachlor (odds ratio [OR] = 1.325, 95% confidence interval [CI] [1.108-1.586]), cis-nonachlor (OR = 15.433, 95% CI [2.733-87.136]), Mirex (OR = 2.853, 95% CI [1.213-6.713]) and 4,4 DDE (OR = 1.019, 95% CI [1.005-1.034]) in fat and a greater number of positive samples (OR = 1.758 95% CI [1.11-2.997]) were significantly associated with higher odds of PA. In contrast, as awaited, urine samples did not yield any statistically significant associations for all tested pesticides., Conclusion: Some OCs were associated with higher odds of PA. The underlying mechanisms of pancreatic aggression need to be investigated to refine these findings., Trial Registration: Clinicaltrials.gov NCT04429490., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: Treatment of advanced HepatoCellular Carcinoma (HCC) is based on first-line (L1) combination of atezolizumab and high-dose (HD) bevacizumab while second-line (L2) refers one antiangiogenic protein kinase inhibitors (aaPKI). This prolonged antiangiogenic pressure let us to observe an increasing occurrence of Hand-Foot Syndromes (HFS) in patients receiving aaPKI after HD bevacizumab combination. This study reports observations and discussions about the evidence and hypothesis that could be made., Methods: Patients who received the L1 combination from September 1 st 2020 to December 31 st 2022 to identify L2 aaPKI. Demographic, biological, oncological data and occurrence of HFS were collected. In addition were collected the number of L1 combination cycles, type of aaPKI, and delay between last L1 cycle and L2 initiation. This study had a purely exploratory purpose, so no statistical analysis was planned., Results: 17 patients received an aaPKI after the L1 HD bevacizumab combination with a median time of 26 days from last L1 cycle to L2 start. Five patients experienced HFS including grade 3 ( n  = 2) with sorafenib and cabozantinib. The HFS occurred with a median delay of 23 days (IQR: 21-28) from aaPKI start. Three patients experienced aaPKI-related dose-limiting toxicity., Conclusions: Proportion of patients experienced HFS in our cohort did not differ from pivotal trials data and the sample size do not allow to conclude. Hypotheses include timing of aaPKI start in HCC treatment, vascular toxicity at aaPKI start after HD bevacizumab discontinuation instead combination, patient-related outcome for a better understanding of these aaPKI-related HFS post HD bevacizumab., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Profile similarity measures are used to quantify the similarity of two sets of ratings on multiple variables. Yet, it remains unclear how different measures are distinct or overlap and what type of information they precisely convey, making it unclear what measures are best applied under varying circumstances. With this study, we aim to provide clarity with respect to how existing measures interrelate and provide recommendations for their use by comparing a wide range of profile similarity measures. We have taken four steps. First, we reviewed 88 similarity measures by applying them to multiple cross-sectional and intensive longitudinal data sets on emotional experience and retained 43 useful profile similarity measures after eliminating duplicates, complements, or measures that were unsuitable for the intended purpose. Second, we have clustered these 43 measures into similarly behaving groups, and found three general clusters: one cluster with difference measures, one cluster with product measures that could be split into four more nuanced groups and one miscellaneous cluster that could be split into two more nuanced groups. Third, we have interpreted what unifies these groups and their subgroups and what information they convey based on theory and formulas. Last, based on our findings, we discuss recommendations with respect to the choice of measure, propose to avoid using the Pearson correlation, and suggest to center profile items when stereotypical patterns threaten to confound the computation of similarity., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Midurethral slings are the gold standard for treating stress urinary incontinence, but their complications may raise concerns. Complications may differ by the approach used to place them., Objective: This study aimed to compare serious complications and reoperations for recurrence after midurethral sling procedures when using the retropubic vs the transobturator route for female stress urinary incontinence., Study Design: This analysis was of patients included in the French, multicenter VIGI-MESH register since February 2017 who received a midurethral sling for female stress urinary incontinence either by the retropubic or the transobturator route and excluded patients with single-incision slings. Follow-up continued until October 2021. Serious complications (Clavien-Dindo classification ≥ grade III) attributable to the midurethral sling and reoperations for recurrence were compared using Cox proportional hazard models including any associated surgery (hysterectomy or prolapse) and a frailty term to consider the center effect. Baseline differences were balanced by propensity score weighting. Analyses using the propensity score and Cox models were adjusted for baseline differences, center effect, and associated surgery., Results: A total of 1830 participants received a retropubic sling and 852 received a transobturator sling in 27 French centers that were placed by 167 surgeons. The cumulative 2-year estimate of serious complications was 5.8% (95% confidence interval, 4.8-7.0) in the retropubic group and 2.9% (95% confidence interval, 1.9-4.3) in the transobturator group, that is, after adjustment, half of the retropubic group was affected (adjusted hazard ratio, 0.41; 95% confidence interval, 0.3-0.6). The cumulative 2-year estimate of reoperation for recurrence of stress urinary incontinence was 2.7% (95% confidence interval, 2.0-3.6) in the retropubic group and 2.8% (95% confidence interval, 1.7-4.2) in the transobturator group with risk for revision for recurrence being higher in the transobturator group after adjustment (adjusted hazard ratio, 1.9; 95% confidence interval, 1.2-2.9); this surplus risk disappeared after exclusion of the patients with a previous surgery for stress urinary incontinence., Conclusion: The transobturator route for midurethral sling placement is associated with a lower risk for serious complications but a higher risk for surgical reoperation for recurrence than the retropubic route. Despite the large number of surgeons involved, these risks were low. The data are therefore reassuring., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Epithelial ovarian cancer is associated with high mortality due to diagnosis at later stages associated with peritoneal involvement. Several trials have evaluated the effect of intraperitoneal treatment. In this preclinical study, we report the efficacy, pharmacokinetics and pharmacodynamics of intraperitoneal treatment with two approved nanomolecular formulations of paclitaxel (nab-PTX and mic-PTX) in a murine ovarian cancer xenograft model., Methods: IC50 was determined in vitro on three ovarian cancer cell lines (OVCAR-3, SK-OV-3 and SK-OV-3-Luc IP1). EOC xenografts were achieved using a modified subperitoneal implantation technique. Drug treatment was initiated 2 weeks after engraftment, and tumor volume and survival were assessed. Pharmacokinetics and drug distribution effects were assessed using UHPLC-MS/MS and MALDI imaging mass spectrometry, respectively. Pharmacodynamic effects were analyzed using immunohistochemistry and transmission electron microscopy using standard protocols., Results: We demonstrated sub-micromolar IC 50 concentrations for both formulations on three EOC cancer cell lines in vitro. Furthermore, IP administration of nab-PTX or mic-PTX lead to more than 2-fold longer survival compared to a control treatment of IP saline administration (30 days in controls, 66 days in nab-PTX treated animals, and 76 days in mic-PTX animals, respectively). We observed higher tissue uptake of drug following nab-PTX administration when compared to mic-PTX, with highest uptake after 4 hours post-treatment, and confirmed this lower uptake of mic-PTX using HPLC on digested tumor samples. Furthermore, apoptosis was not increased in tumor implants up to 24h post-treatment., Conclusion: Intraperitoneal administration of both nab-PTX and mic-PTX results in a significant anticancer efficacy and survival benefit in a mouse OC xenograft model., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Demuytere et al.)

Background/objectives: Genetic counselling (GC) is a key step in the identification of inherited germline mutations. However, the oncogenetic practices are poorly described for pancreatic adenocarcinoma (PA) in Europe. The CAPANCOGEN study aimed to describe the GC referral practices in France and assess the implementation of international guidelines in patients with PA., Methods: Information about GC referrals with PA was collected in 13 French centres from September 2019 to October 2021. In the 5 largest centres, personal and familial histories of cancers and diseases associated with a higher risk of germline mutations were collected in 460 patients, according to international, American, European and French GC referral guidelines. Univariate and multivariate logistic regression analysis were performed to identify the factors influencing GC referral., Results: Among 833 patients, a total of 100 patients (12%) had an indication of GC according to local multidisciplinary tumour board meetings (MTBM). Among these patients, 41% did not undergo GC. The median time between MTBM and GC was 55 days (IQR: 14.5-112). Among 460 patients with collected personal and familial history, 31.5% were not referred to a GC despite an existing indication. In multivariate logistic regression analysis, suspected CDKN2A (p = 0.032) or BRCA mutation (p < 0.001), familial pancreatic cancer history (p < 0.001) and controlled disease with first-line platinum-based chemotherapy (p < 0.001) increased the referral rate. Conversely, older age (p = 0.002) and a locally advanced PA (p = 0.045) decreased the risk of GC referral., Conclusions: GC referral is inadequate despite valuable information in patients' medical files., Competing Interests: Declaration of competing interest C.C. reports personal fees as a speaker from Bristol Myers Squibb, outside the submitted work. D.T. reports personal fees as a speaker and/or in an advisory role from Merck KGaA, Roche, Bayer, Astra-Zeneca, BMS, MSD, Amgen, Sanofi, Servier, Ipsen and Pierre Fabre, outside the submitted work. G.P. reports personal fees as a speaker and/or in an advisory role from BMS, MSD, Stryker and Medtronic, outside the submitted work. A.T. reports personal fees as a speaker and/or in an advisory role from Merck KGaA, BMS, MSD, Servier, Mylan and Pierre Fabre and travel accommodations expenses from AstraZeneca, outside the submitted work. D.B. reports personal fees as a speaker and/or in an advisory role from Accord Healthcare, Amgen, Sanofi, Servier, and Pierre Fabre, outside the submitted work. O.B. reports personal fees as a speaker and/or in an advisory role from Apmomia Therapeutics, Merck KGaA, Bayer, Grunenthal, MSD, Amgen, Servier, and Pierre Fabre, outside the submitted work. All other authors declared no conflicts of interest for this study., (Copyright © 2023. Published by Elsevier B.V.)

Background: Cannabis is the main illicit psychoactive substance used in French childbearing women and very few data are available about adverse events (AEs) related to its use during pregnancy. The aim of this study was to evaluate the association between recreational cannabis use during pregnancy and adverse outcomes from a real-world clinical data warehouse., Methods: Data from the Poitiers University Hospital warehouse were analyzed between 1 January 2010 and 31 December 2019. Logistic regression models were used to evaluate associations between outcomes in three prenatal user groups: cannabis alone ± tobacco (C ± T) ( n = 123), tobacco alone (T) ( n = 191) and controls (CTRL) ( n = 355)., Results: Pregnant women in the C ± T group were younger (mean age: 25.5 ± 5.7 years), had lower pre-pregnancy body mass index (22.8 ± 5.5 kg/m 2 ), more psychiatric history (17.5%) and were more likely to benefit from universal free health-care coverage (18.2%) than those in the T and CTRL groups. Cannabis use increases the occurrence of voluntary interruption of pregnancy, at least one AE during pregnancy, at least one neonatal AE, the composite adverse pregnancy outcome over 28, prematurity and small for gestational age., Conclusion: Given the trivialization of recreational cannabis use during pregnancy, there is an urgent need to communicate on AEs of cannabis use during pregnancy.

Introduction: The growing interest of cannabidiol (CBD) in medical care prompted French health authorities to explore the potential of CBD in cancer-related severe symptoms. This study aimed to assess the prevalence of CBD use among cancer patients with potential associated factors and to measure the cancer patient's health literacy (HL) on CBD consumption., Methods: In a prospective study in oncology day-care hospital including patients from 29 October to 20 December 2021, we collected demographic, biological, and oncological characteristics. Patient CBD HL was measured by the hetero-questionnaire 8-item-CBD HL scale (HLS-8-CBD) whose conception has been validated by a psychometric analysis., Results: Among 363 participants, 20 patients (5.5%) reported CBD use. Factors associated with CBD use were: age <60 years (odd ratio = 7.80[1.36-13.32], p  < 10 -4 versus ≥60 years), smoking history (OR = 5.53[1.81-16.88], p  < 0.01), and no smoking cessation (OR = 5.07[1.66-15.46], p  < 0.01). CBD use was also associated with a better CBD total HL score than non-users ( p -value = 0.02)., Conclusion: Identification of factors associated with CBD use and a relatively high patient CBD HL in CBD users showed that CBD use in cancer patients care represented a new concern and should enhance health professionals to consider CBD with its associated drug-related problems.

Cannabidiol (CBD) consumption in cancer patients is growing and there is a need to investigate how to detect cannabidiol-drug interactions (CDIs). However, CDIs and the clinical relevance between CBD, anticancer treatment, supportive care and conventional drugs is poorly studied especially in real-life settings. In 1 oncology day-hospital, a cross-sectional study in 363 cancer patients treated with chemotherapy revealed 20 patients (5.5%) who consumed CBD. In this study we aimed to explore the prevalence and clinical relevance of CDIs among these 20 patients. CDI detection used the Food and Drug Administration Drugs.com database and clinical relevance was assessed accordingly. Ninety CDIs with 34 medicines were detected (4.6 CDI/patient). The main clinical risks were central nervous system depression and hepatoxicity. The main CDIs were assessed as moderate and anticancer treatment do not seem to add to the risk. CBD discontinuation appears to be the most consistent management. Future studies should explore the clinical relevance of drug interactions with CBD in cancer patients., (© 2023 British Pharmacological Society.)

Background: Palliative care (PC) is integrated into standard oncology care. However, its clinical impact at the end of life remains unclear in pancreatic adenocarcinoma (PA). We aimed to describe the end-of-life care pathway and to assess whether PC referral influences survival after chemotherapy discontinuation (CD) among advanced PA patients., Methods: This retrospective single-centre observational study was conducted among deceased patients with advanced PA who had received chemotherapy between January 1, 2016, and December 31, 2021. Baseline characteristics, the timing of PC referral and events after CD were collected. The primary outcome was time from CD to death., Results: Among the 148 included patients, 53.4% (n = 79) received PC, mostly late after the CD (n = 133, 89.9%), 16.9% (n = 25) received chemotherapy in the last 14 days of life and 75.6% died at the hospital. None received PC in the 8 weeks following the diagnosis. PC referral significantly increased PC department admissions (p < 0.001) and decreased medical unit admissions (p < 0.001). The median survival after the CD was 35 days (IQR: 19-64.5). PC referral was associated with increased survival after CD (HR: 0.65 [0.47-0.90], p = 0.010, Cox) and after adjusting (HR: 0.65 [0.42-0.99], p = 0.045, Cox)., Conclusion: The study suggests that PC may be associated with longer survival after CD in advanced PA patients. However, PC is underused, and patients are referred late in their care pathway., Competing Interests: Declaration of Competing Interest C.C. reports personal fees as a speaker from Bristol Myers Squibb, outside the submitted work. D.B. reports personal fees as a speaker and/or in an advisory role from Accord Healthcare, Amgen, Sanofi, Servier, and Pierre Fabre, outside the submitted work. O.B. reports personal fees as a speaker and/or in an advisory role from Apmomia Therapeutics, Merck KGaA, Bayer, Grunenthal, MSD, Amgen, Servier, and Pierre Fabre, outside the submitted work. All other authors declared no conflicts of interest for this study., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Preclinical studies have demonstrated the possible role of beta-adrenergic receptors in pancreatic ductal adenocarcinoma (PDAC) tumor invasion and migration. The current study aimed to explore the possible association between survival outcomes and beta-blocker (BB) exposure in patients with advanced PDAC. Methods: This retrospective single-center study included 182 patients with advanced PDAC. Clinical [age, sex, BMI, cardiovascular condition, presence (SBB) or absence (NSBB) of beta-1 selectivity of BB, exposure duration, and multimorbidity], oncological (stage and anticancer treatment regimen), and biological (renal and liver function) data were collected. The endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for survival outcomes associated with BB exposure were estimated using Cox regression model and propensity score (PS) methods. Results: Forty-one patients (22.5%) were exposed to BB. A total of 104 patients progressed (57.1%) to PDAC and 139 (76.4%) patients died at the end of follow-up (median, 320 days; IQR, 438.75 days). When compared to the non-exposed group, there was no increase in survival outcomes associated with BB use (OS: HR = 1.38, 95% CI = 0.80-2.39, p = 0.25; PFS: adjusted HR = 0.95, 95% CI = 0.48-1.88, p = 0.88). Similar results were obtained using the PS method. Compared to no BB usage, SBB use was associated with a significant decrease in OS (HR = 1.80, 95% CI = 1.16-2.80, p < 10 -2 ). Conclusion: BB exposure was not associated with improved PDAC survival outcomes. Beta-1-selectivity was not independently associated with any differences., 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., (Copyright © 2023 Le Bozec, Brugel, Djerada, Ayad, Perrier, Carlier, Botsen, Nazeyrollas, Bouché and Slimano.)

Background: Dihydropyrimidine dehydrogenase (DPD) deficiency screening is a pre-therapeutic standard to prevent severe fluoropyrimidine-related toxicity. Although several screening methods exist, the accuracy of their results remains debatable. In France, the uracilemia measurement is considered the standard in DPD deficiency screening. The objective of this study was to describe the hyperuracilemia (⩾16 ng/mL) rate and investigate the influence of hepatic and renal impairment in uracilemia measurements since the guidelines were implemented., Patients and Methods: Using a cohort of 1138 patients screened between 18 October 2018 and 18 October 2021, basic demographic characteristics, date of blood sampling, and potential biological confounders including liver function tests [aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin] and estimated glomerular filtration rate (eGFR) were collected. The second same-patient uracilemia analysis was also performed. Temporal change was graphically represented while potential confounders were stratified to show linearity when suspected., Results: Hyperuracilemia was diagnosed in 12.7% ( n  = 150) samples with 6.7%, 5.4%, 0.5%, and 0.08% between 16 and 20 ng/mL, 20 and 50 ng/mL, 50 and 150 ng/mL, and >150 ng/mL, respectively. The median uracilemia concentration was 9.4 ng/mL (range: 1.2 and 172.3 ng/mL) and the monthly hyperuracilemia rate decreased steadily from >30% to around 9%. Older age, normalized AST, γGT, ALP results, bilirubin levels, and decreased eGFR were linearly associated with higher plasma uracil concentrations (all p  < 0.001). In the adjusted multivariate linear model, AST, eGFR, and ALP remained associated with uracilemia ( p  < 0.05). When measured twice in 39 patients, the median uracilemia rate of change was -2.5%, which subsequently changed the diagnosis in nine patients (23.1%)., Conclusions: Better respect of pre-analytical conditions may explain the steady decrease in monthly hyperuracilemia rates over the 3 years. Elevated AST, ALP levels, and reduced eGFR could induce a false increase in uracilemia and second uracilemia measurements modified the first DPD deficiency diagnosis in almost 25% of the patients., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Objective: To evaluate the rates of serious complications and reoperation for recurrence following sacrospinous ligament fixation (SSLF) for apical pelvic organ prolapse. Methods: This was a national registry ancillary cohort comparative study. The VIGI-MESH registry includes data from 24 French health centers prospectively collected between May 2017 and September 2021. Time to occurrence of a serious complication or reoperation for genital prolapse recurrence was explored using the Kaplan-Meier curve and Log-rank test. The inverse probability of treatment weighting, based on propensity scores, was used to adjust for between-group differences. Results: A total of 1359 women were included and four surgical groups were analyzed: Anterior SSLF with mesh (n = 566), Anterior SSLF with native tissue (n = 331), Posterior SSLF with mesh (n = 57), and Posterior SSLF with native tissue (n = 405). Clavien-Dindo Grade III complications or higher were reported in 34 (2.5%) cases, with no statistically significant differences between the groups. Pelvic organ prolapse recurrence requiring re-operation was reported in 44 (3.2%) women, this was higher following posterior compared with anterior SSLF ( p = 0.0034). Conclusions: According to this large database ancillary study, sacrospinous ligament fixation is an effective and safe surgical treatment for apical prolapse. The different surgical approaches (anterior/posterior and with/without mesh) have comparable safety profiles. However, the anterior approach and the use of mesh were associated with a lower risk of reoperation for recurrence compared with the posterior approach and the use of native tissue, respectively.

Background: The COVID-19 pandemic led to a widely documented disruption in cancer care pathway. Since a resurgence of the pandemic was expected after the first lockdown in France, the global impact on the cancer care pathway over the year 2020 was investigated., Aims: This study aimed to describe the changes in the oncology care pathway for cancer screening, diagnosis, assessment, diagnosis annoucement procedure and treatment over a one-year period., Materials & Methods: The ONCOCARE-COV study was a comprehensive, retrospective, descriptive, and cross-sectional study comparing the years 2019 and 2020. All key indicators along the cancer care pathway assessing the oncological activity over four periods were described. This study was set in a high-volume, public, single tertiary care center divided in two complementary sites (Reims University Hospital and Godinot Cancer Institute, Reims, France) which was located in a high COVID-19 incidence area during both peaks of the outbreak., Results: A total of 26,566 patient's files were active during the year 2020. Breast screening (-19.5%), announcement dedicated consultations (-9.2%), Intravenous and Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPECs) (-25%), and oncogeriatric evaluations (-14.8%) were heavily disrupted in regard to 2020 activity. We identified a clear second outbreak wave impact on medical announcement procedures (October, -14.4%), radiotherapy sessions (October, -16%), number of new health record discussed in multidisciplinary tumor board meeting (November, -14.6%) and HIPECs (November, -100%). Moreover, 2020 cancer care activity stagnated compared to 2019., Discussion: The oncological care pathway was heavily disrupted during the first and second peaks of the COVID-19 outbreak. Between lockdowns, we observed a remarkable but non-compensatory recovery as well as a lesser impact from the pandemic resurgence. However, in absence of an increase in activity, a backlog persisted., Conclusion: Public health efforts are needed to deal with the consequences of the COVID-19 pandemic on the oncology care pathway., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Pancreatic adenocarcinoma (PA) incidence is rising worldwide, especially in France. The evolution of known risk factors such as tobacco smoking, obesity, type 2 diabetes, chronic pancreatitis, or constitutional mutations is not sufficient to explain this trend. Pesticides are known risk factors in other malignancies. Previous studies have outlined pesticides' influence in PA, such as dichlorodiphenyltrichloroethane as plausible risk factors. The general population is directly or indirectly exposed to pesticides through air, food or water. Some of these chemicals may accumulate in the body all along lifetime and may harm carriers. The toxic mixing effects of these chemicals are not well documented. Several hypotheses have been put forward to explain how pesticides can induce indirect (fatty pancreas, induced diabetes) or direct (oxidative stress, cell damage) carcinogenesis in pancreatic cells through inflammation. A strong corpus exists acknowledging pesticides as a PA risk factor. However, published studies do not provide a sufficient level of evidence to prove causality and current prospective case-control studies are still ongoing., Competing Interests: Declaration of Competing Interest C.C. reports personal fees as a speaker from Bristol Myers Squibb, outside the submitted work. O.B. reports personal fees as a speaker and/or in an advisory role from Merck KGA, Roche, Bayer, Astra-Zeneca, Grunenthal, MSD, Amgen, Sanofi, Servier, and Pierre Fabre, outside the submitted work. All other authors have no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Previous studies have observed an increased incidence of Cetuximab-induced hypersensitivity infusion reactions (CI-IRs) in the southeastern states of the USA. Tick's bites were suspected of generating cross-reactions between cetuximab and alpha-gal. This study aims was to describe the incidence and associated risk factors of CI-IRs, in the French areas chosen according to their Lyme disease incidence., Patients and Methods: A retrospective chart review was conducted on patients that received cetuximab infusion from January 2010 to June 2019 in 4 French areas with different Lyme disease incidence rates., Results: Of 1392 patients, 117 (8.4%) experienced a CI-IR, including 68 severe (grade 3 or 4) reactions (4.9%). This CI-IR incidence was significantly higher in the Lyme disease high-risk area than in the other areas (13.2% versus 7.1%, 8.1% and 6.4%; P = 0.016). Sex (P = 0.53), premedication (P = 0.91), primary cancer location (P = 0.46) and chemotherapy regimen type (P = 0.78) had no impact on CI-IR incidence in the overall population. In the head and neck squamous cell carcinoma (HNSCC) patient subgroup, CI-IRs were significantly more frequent in the high-risk area (16.4% versus 6.7%, 7.1% and 7.0%; P = 0.0015)., Conclusion: This study suggests that patients treated in the French area with the highest incidence of Lyme disease are at a higher risk of CI-IRs., (© 2022. The Author(s).)

In the FIGHTDIGO study, digestive cancer patients with dynapenia experienced more chemotherapy-induced neurotoxicities. FIGHTDIGOTOX aimed to evaluate the relationship between pre-therapeutic handgrip strength (HGS) and chemotherapy-induced dose-limiting toxicity (DLT) or all-grade toxicity in digestive cancer patients. HGS measurement was performed with a Jamar dynamometer. Dynapenia was defined according to EWGSOP2 criteria (<27 kg (men); <16 kg (women)). DLT was defined as any toxicity leading to dose reduction, treatment delay, or permanent discontinuation. We also performed an exploratory analysis in patients below the included population’s median HGS. A total of 244 patients were included. According to EWGSOP2 criteria, 23 patients had pre-therapeutic dynapenia (9.4%). With our exploratory median-based threshold (34 kg for men; 22 kg for women), 107 patients were dynapenic (43.8%). For each threshold, dynapenia was not an independent predictive factor of overall DLT and neurotoxicity. Dynapenic patients according to EWGSOP2 definition experienced more hand-foot syndrome (p = 0.007). Low HGS according to our exploratory threshold was associated with more all-grade asthenia (p = 0.014), anemia (p = 0.006), and asthenia with DLT (p = 0.029). Pre-therapeutic dynapenia was not a predictive factor for overall DLT and neurotoxicity in digestive cancer patients but could be a predictive factor of chemotherapy-induced anemia and asthenia. There is a need to better define the threshold of dynapenia in cancer patients.

Dihydropyrimidine dehydrogenase (DPD) deficiency is associated with severe fluoropyrimidines-induced toxicity. As of September 2018, French recommendations call for screening for DPD deficiency by plasma uracil quantification prior to all fluoropyrimidine-based chemotherapy. A dose reduction of fluoropyrimidine is recommended when uracil concentration is equal to or greater than 16 ng/mL. This matched retrospective study assessed the impact of DPD screening on the reduction of severe side effects and on the management of DPD-deficient patients. Using a propensity score, we balanced the factors influencing 5-Fluorouracil (5-FU) toxicity. Then, the severity scores (G3 and G4 severity as well as their frequency) of patients who did not benefit from DPD screening were compared with those of patients who benefited from DPD screening for each treatment cycle (from 1 to 4). Among 349 screened patients, 198 treated patients were included. Among them, 31 (15.7%) had DPD deficiency (median uracilemia 19.8 ng/mL (range: 16.1−172.3)). The median toxicity severity score was higher in the unscreened group for each treatment cycle (0 vs. 1, p < 0.001 at each cycle from 1 to 4) as well as the cumulative score during all courses of treatment (p = 0.028). DPD-deficient patients received a significantly lower dose of 5-FU (p < 0.001). This study suggests that pretherapeutic plasmatic uracil assessment, along with 5-FU dosage adjustment, may be beneficial in reducing 5-FU toxicity in real-life patients.

The availability of water for agricultural use in the savannah plateau of Adamawa, Cameroon, is addressed in this paper. Specific field tests coupled with climatic data analysis have helped to characterize the hydrological and hydrogeological conditions of water resources in a small catchment. An agricultural suitability map, based on the water availability during the dry season, is produced. Measured saturated hydraulic conductivities indicated an acceptable disposition of the soils for agriculture. The transmissivity values indicated moderate groundwater potential with mean annual recharge of 96 mm. The agricultural suitability map shows that only 8.8% of the basin area is very favorable for agriculture and that 51% of the basin is not suitable for agriculture, due to water scarcity during the dry season. Due to the considerable depth to the water table, pumping for irrigation purposes is not affordable for the local low-income farmers. Therefore, there is a need to implement adapted solutions for irrigation to support farmers' endeavors, such as the development of water retention basins or the construction of boreholes equipped with electric pumps supplied by solar energy for irrigation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown., Methods: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown., Results: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%)., Conclusion: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up., Trial Registration: Clinicaltrials.gov NCT04406571., Competing Interests: Conflict of interest statement D.T. reports personal fees as a speaker and/or in an advisory role from Merck KGaA, Roche, Bayer, Astra-Zeneca, BMS, MSD, Amgen, Sanofi, Servier, Ipsen and Pierre Fabre, outside the submitted work. G.P. reports personal fees as a speaker and/or in an advisory role from BMS, MSD, Stryker and Medtronic, outside the submitted work. A.T. reports personal fees as a speaker and/or in an advisory role from Amgen, Merck KGaA, Servier, Mylan and Pierre Fabre and travel accommodations expenses from Pfizer and Sanofi, outside the submitted work. G.R. reports personal fees as a speaker and/or in an advisory role from Accord Healthcare, Abbvie, Amgen, Ipsen, Sanofi, Servier, and MSD, outside the submitted work. F.D.F. reports personal fees as a speaker and/or in an advisory role from Roche, Amgen, Merck KGaA, Sanofi, Ipsen, Pierre Fabre, Servier, Janssens, Mylan, Sandoz and Bayer, outside the submitted work. C.B. reports personal fees as a speaker and/or in an advisory role from MSD, Sanofi, Bayer and a research grant from Servier, Roche, outside the submitted work. V.M reports personal fees as a speaker and/or in an advisory role from Sanofi, outside the submitted work. A.L. reports personal fees as a speaker and/or in an advisory role from Amgen, Vifor-Pharma, Bayer, Merck KGaA, Sanofi, Ipsen, Servier, Pierre Fabre, a research grant from Roche, and travel accommodation expenses from Abbvie, Amgen, Bayer, MSD, Vifor-Pharma, Mundi Pharma, Ipsen, Novartis outside the submitted work. D.B. reports personal fees as a speaker and/or in an advisory role from Accord Healthcare, Amgen, Sanofi, Servier, and Pierre Fabre, outside the submitted work. C.C. reports personal fees as a speaker from Bristol Myers Squibb, outside the submitted work. O.B. reports personal fees as a speaker and/or in an advisory role from Merck KGaA, Roche, Bayer, Astra-Zeneca, Grunenthal, MSD, Amgen, Sanofi, Servier, and Pierre Fabre, outside the submitted work. All other authors declared no conflicts of interest for this study., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To assess the incidence of serious complications and reoperations for recurrence after surgery for pelvic organ prolapse (POP) and compare the three most common types of repair., Design: Prospective cohort study using a registry., Setting: Nineteen French surgical centres., Population: A total of 2309 women participated between 2017 and 2019., Methods: A multivariate analysis including an inverse probability of treatment weighting approach was used to obtain three comparable groups., Main Outcome Measures: Serious complications and subsequent reoperations for POP recurrence., Results: The median follow-up time was 17.6 months. Surgeries were native tissue vaginal repairs (n = 504), transvaginal mesh placements (n = 692) and laparoscopic sacropexies with mesh (n = 1113). Serious complications occurred among 52 women (2.3%), and reoperation for POP recurrence was required for 32 women (1.4%). At 1 year the cumulative weighted incidence of serious complications was 1.8% for native tissue vaginal repair, 3.9% for transvaginal mesh and 2.2% for sacropexy, and the rates for reoperation for recurrence of POP were 1.5, 0.7 and 1.1%, respectively. Compared with native tissue vaginal repair, the risk of serious complications was higher in the transvaginal mesh group (weighted hazard ratio, wHR 3.84, 95% CI 2.43-6.08) and the sacropexy group (wHR 2.48, 95% CI 1.45-4.23), whereas the risk of reoperation for prolapse recurrence was lower in both the transvaginal mesh (wHR 0.22, 95% CI 0.13-0.39) and sacropexy (wHR 0.29, 95% CI 0.18-0.47) groups., Conclusions: Our results suggest that native tissue vaginal repairs have the lowest risk of serious complications but the highest risk of reoperation for recurrence. These results are useful for informing women and for shared decision making., Tweetable Abstract: Laparoscopic sacropexy had fewer serious complications than transvaginal mesh and fewer reoperations for recurrence than vaginal repair., (© 2021 John Wiley & Sons Ltd.)

Background: Emotions and mood are important for overall well-being. Therefore, the search for continuous, effortless emotion prediction methods is an important field of study. Mobile sensing provides a promising tool and can capture one of the most telling signs of emotion: language., Objective: The aim of this study is to examine the separate and combined predictive value of mobile-sensed language data sources for detecting both momentary emotional experience as well as global individual differences in emotional traits and depression., Methods: In a 2-week experience sampling method study, we collected self-reported emotion ratings and voice recordings 10 times a day, continuous keyboard activity, and trait depression severity. We correlated state and trait emotions and depression and language, distinguishing between speech content (spoken words), speech form (voice acoustics), writing content (written words), and writing form (typing dynamics). We also investigated how well these features predicted state and trait emotions using cross-validation to select features and a hold-out set for validation., Results: Overall, the reported emotions and mobile-sensed language demonstrated weak correlations. The most significant correlations were found between speech content and state emotions and between speech form and state emotions, ranging up to 0.25. Speech content provided the best predictions for state emotions. None of the trait emotion-language correlations remained significant after correction. Among the emotions studied, valence and happiness displayed the most significant correlations and the highest predictive performance., Conclusions: Although using mobile-sensed language as an emotion marker shows some promise, correlations and predictive R 2 values are low., (©Chiara Carlier, Koen Niemeijer, Merijn Mestdagh, Michael Bauwens, Peter Vanbrabant, Luc Geurts, Toon van Waterschoot, Peter Kuppens. Originally published in JMIR Mental Health (https://mental.jmir.org), 11.02.2022.)

Obstetric anal sphincter injury (OASI) is strongly associated with a major negative impact on women's health. Due to the consequences of an undiagnosed and therefore unrepaired OASI, it is essential to prevent or at least diagnose OASI at childbirth. We need to promote training of professionals to improve OASI screening at childbirth. High-risk situations such as operative delivery must be identified and preventive strategies such as the choice of a less traumatic instrument (vacuum) and mediolateral episiotomy should be considered. For a woman with OASI and/or symptoms, postnatal consultation with a specialist on pelvic floor disorders is essential to correctly orient her toward an adequate care pathway and to eventually identify occult or underestimated OASI. More data are required on therapeutic approaches for symptomatic women, primarily including physical therapy, sacral neuromodulation, delayed sphincter repair and palliative devices., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to disclose., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Long bone pathological fractures very much reflect bone metastases morbidity in many types of cancer. Bearing in mind that they not only compromise patient function but also survival, identifying impending fractures before the actual event is one of the main concerns for tumor boards. Indeed, timely prophylactic surgery has been demonstrated to increase patient quality of life as well as survival. However, early surgery for long bone metastases remains controversial as the current fracture risk assessment tools lack accuracy. This review first focuses on the gold standard Mirels rating system. It then explores other unique imaging thresholds such as axial or circumferential cortical involvement and the merits of nuclear imaging tools. To overcome the lack of specificity, other fracture prediction strategies have focused on biomechanical models based on quantitative computed tomography (CT): computed tomography rigidity analysis (CT-RA) and finite element analysis (CT-FEA). Despite their higher specificities in impending fracture assessment, their limited availability, along with a need for standardization, have limited their use in everyday practice. Currently, the prediction of long bone pathologic fractures is a multifactorial process. In this regard, machine learning could potentially be of value by taking into account clinical survival prediction as well as clinical and improved CT-RA/FEA data.

Introduction and Hypothesis: The use of new lightweight meshes in pelvic organ prolapse (POP) surgery may reduce complications related to mesh retraction (chronic pain, dyspareunia, and mesh exposure). The aim of this study was to investigate changes in the area and position of Uphold Lite™ mesh 6 weeks and 12 months after anterior and/or apical prolapse repair., Methods: This observational prospective multicenter study included patients who had undergone transvaginal surgery for symptomatic POP-Q stage ≥ II anterior and/or apical compartment prolapse with placement of Uphold Lite mesh. The dimensions and position of the mesh were evaluated at 6 weeks and 12 months by ultrasonography. Correlations between ultrasonographic mesh characteristics and POP recurrence were analyzed., Results: Fifty evaluable women with an average age of 66.8 years were included. No statistically significant difference in mesh area was found between week 6 and month 12 postoperatively, either at rest (1746.92 vs. 1574.48 mm 2 ; p = 0.15) or on Valsalva (1568.81 vs. 1542.98 mm 2 ; p = 0.65). The ROC-AUC of the distance between the mesh and the bladder neck (M-BN) at 6 weeks for predicting cystocele recurrence at 12 months was 0.764 (95% CI 0.573-0.955) at rest and 0.724 (95% CI 0.533-0.916) on Valsalva. An M-BN distance > 12.5 mm could predict cystocele recurrence at month 12 with a sensitivity of 80% and a specificity of 69%., Conclusions: Ultrasonographic measurements of the Uphold Lite™ mesh appear to remain stable between 6 weeks and 12 months postoperatively. M-BN distance correlates with cystocele recurrence. These results appear to confirm the value of ultrasound in mesh evaluation.

The coronavirus disease 2019 (COVID-19) pandemic may have affected cancer management. We aimed to evaluate changes in every oncology care pathway essential step, from screening to treatment, during the pandemic. Monthly oncological activity differences between 2019 and 2020 (screening tests, histopathological analyzes, multidisciplinary tumor board meetings (MTBMs), diagnostic announcement procedures (DAPs), and treatments were calculated in two French areas experiencing different pandemic intensity (Reims and Colmar). COVID-19 has had a dramatic impact in terms of screening (-86% to -100%), diagnosis (-39%), and surgical treatment (-30%). This global decrease in all essential oncology care pathway steps contrasted with the relative stability of chemotherapy (-9%) and radiotherapy use (-16%). Outbreak occurred earlier and with more intensity in Colmar but had a comparable impact in both areas regarding MTMBs and DAPs. The current ONCOCARE-COV study is still in progress and with a longer follow-up to analyze postlockdown situation., (© 2020 AlphaMed Press.)

Introduction: Pathologic fracture is the most feared complication in long-bone metastasis. Various radiographic tools are available for identifying at-risk patients and guide preventive treatment. The Mirels score is the most frequently studied and widely used, but has been criticized, many patients not being operated on until the actual fracture stage. We therefore conducted a French national multicenter prospective study: (1) to determine the proportion of patients operated on at fracture stage versus preventively; (2) to compare Mirels score between the two; and (3) to identify factors for operation at fracture stage according to Mirels score and other epidemiological, clinical and biological criteria., Hypothesis: Simple discriminatory items can be identified to as to complete the Mirels score and enhance its predictive capacity., Material and Methods: A non-controlled multicenter prospective study included 245 patients operated on for non-revelatory long-bone metastasis, comparing patients operated on for fracture versus preventively according to body-mass index (BMI), ASA score, Katagiri score items and the 4 Mirels items., Results: One hundred and twenty-six patients (51.4%) were operated on at fracture stage: 106 (84.1%) showed high risk on Mirels score (score>8), and 15 (11.9%) moderate risk (score=8). On multivariate analysis, 4 independent factors emerged: in increasing order, advanced age (OR=1.03; 95%CI 1.01-1.06), VAS pain score>6 (OR=1.47; 95%CI 1.02-2.11), WHO grade>2 (OR=2.74; 95%CI 1.22-6.15), and upper-limb location (OR=5.26; 95%CI 2.13-12.84)., Discussion: The present study confirmed that more than half of patients with long-bone metastasis are operated on at actual fracture stage, in agreement with the literature. Several studies highlighted the weakness of the Mirels score as a predictive instrument. Comparison between preventive and fracture-stage surgery showed that upper-limb location, intense pain, advanced age and impaired functional status were associated with fracture-stage surgery, and should be taken into account alongside the original Mirels criteria. This improved scoring instrument remains to be validated in a prospective study., Level of Evidence: IV, prospective cohort study without control group., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: The occurrence of peri-acetabular metastasis (PAM) is a turning point in the progression of cancer because the disabling pain prevents the patient from walking or makes it difficult. Recent progress in controlling cancers that spread to the bone and controlling local bone destruction justify this national study. Since the data in France is incomplete or based on small studies, we analysed a multicentre retrospective cohort of patients with PAM who underwent total hip arthroplasty (THA) to evaluate 1) the clinical and radiological outcomes and 2) the factors impacting patient survival., Hypothesis: The clinical outcomes, complication rate and survivorship are comparable to that of recent published studies., Methods: Ninety-one patients (27 men, 64 women) with a mean age of 62.7±10.5 years (extremes 38 and 88) with PAM secondary to breast cancer [42 patients (46%)] or lung cancer [20 patients (22%)] underwent THA. The metastasis was the first sign of cancer in 33 cases (36%). Concurrent visceral metastases were present in 30 patients (33%), multiple peripheral bone metastasis in 48 patients (53%) and synchronous spine metastasis in 39 patients (43%). The most common construct was a cemented stem with metal reinforcement cage and cemented dual mobility cup [71 times (78%), while 85/91 had a dual mobility cup (93%)]., Results: Elimination or reduction of pain was reported in 81 patients (91%). Overall walking ability was deemed normal or acceptable in 74 patients (83%). Six patients died (7%) before the end of the 3rd month. There were seven general complications (8%) including five thromboembolic events. There were 22 complications related to the surgical procedure in 20 patients (22%) that required surgical revision, including 10 surgical site infections (11%) and 3 dislocations (3%) (one concerning a dual mobility cup and 2 after single mobility cup). The median survivorship all causes combined was 19.5 months; it was 23.7 months for patients with breast cancer and 8.9 months for those with lung cancer., Conclusion: Despite different endpoints being used, the clinical outcomes in our study are like those in other published studies, as were the incidence of surgery-related complications and the survivorship. The recommended surgical technique is the implantation of an acetabular reinforcement cage, curettage with cement filling of osteolytic areas, dual mobility cup and cemented stem followed by radiation therapy. The role of THA versus interventional radiology procedures must still be determined., Level of Evidence: IV, retrospective study without control group., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Intraperitoneal chemoperfusion (IPEC) of cisplatin is a popular treatment for advanced ovarian cancer, typically under hyperthermia (HIPEC). The use of cisplatin under (H)IPEC is off-label, and the role of hyperthermia is unknown. The aim of this study was to characterize the pharmacokinetic/pharmacodynamic (PKPD) properties of cisplatin under (H)IPEC and to predict the optimal treatment regimen. Using a randomized design, data on intact cisplatin perfusate and plasma concentrations, leukocyte counts-a hematotoxicity marker-and serum creatinine-a nephrotoxicity marker-were collected from 50 patients treated with a combination of cytoreductive surgery (CRS) and either normothermic or hyperthermic IPEC of cisplatin dosed at 75, 100, and 120 mg/m 2 . The non-linear mixed effects modeling technique was used to construct the PKPD models. The PK of intact cisplatin was characterized by a two-compartment model. A semi-physiological myelosuppression model for the leukopenia was modified to account for the CRS-induced leukocytosis and the residual myelosuppression effect of neoadjuvant chemotherapy. The incidence and severity of nephrotoxicity were described by a discrete-time Markov model. Hyperthermia increased the absorption rate of cisplatin by 16.3% but did not show a clinically relevant impact on the investigated toxicities compared with normothermia. Leukopenia was not severe, but nephrotoxicity can become severe or life-threatening and was affected by the dose and IPEC duration. The model predicted that nephrotoxicity is minimal at a cisplatin dose of 75 mg/m 2 with an IPEC duration of 1-2 h and an 1-h duration is favored for doses between 100 and 120 mg/m 2 . Graphical abstract.

Objective: To assess the short-term incidence of serious complications of surgery for urinary incontinence or pelvic organ prolapse., Design: Prospective longitudinal cohort study using a surgical registry., Setting: Thirteen public hospitals in France., Population: A cohort of 1873 women undergoing surgery between February 2017 and August 2018., Methods: Preliminary analysis of serious complications after a mean follow-up of 7 months (0-18 months), according to type of surgery. Surgeons reported procedures and complications, which were verified by the hospitals' information systems., Main Outcome Measures: Serious complication requiring discontinuation of the procedure or subsequent surgical intervention, life-threatening complication requiring resuscitation, or death., Results: Fifty-two women (2.8%, 95% CI 2.1-3.6%) experienced a serious complication either during surgery, requiring the discontinuation of the procedure, or during the first months of follow-up, necessitating a subsequent reoperation. One woman also required resuscitation; no women died. Of 811 midurethral slings (MUSs), 11 were removed in part or totally (1.4%, 0.7-2.3%), as were two of 391 transvaginal meshes (0.5%, 0.1-1.6%), and four of 611 laparoscopically placed mesh implants (0.7%, 0.2-1.5%). The incidence of serious complications 6 months after the surgical procedure was estimated to be around 3.5% (2.0-5.0%) after MUS alone, 7.0% (2.8-11.3%) after MUS with prolapse surgery, 1.7% (0.0-3.8%) after vaginal native tissue repair, 2.8% (0.9-4.6%) after transvaginal mesh, and 1.0% (0.1-1.9%) after laparoscopy with mesh., Conclusions: Early serious complications are relatively rare. Monitoring must be continued and expanded to assess the long-term risk associated with mesh use and to identify its risk factors., Tweetable Abstract: Short-term serious complications are rare after surgery for urinary incontinence or pelvic organ prolapse, even with mesh., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Although intraperitoneal chemotherapy (IPC) has evolved into an established treatment modality for patients with peritoneal metastasis (PM), drug penetration into tumor nodules remains limited. Drug transport during IPC is a complex process that depends on a large number of different parameters (e.g. drug, dose, tumor size, tumor pressure, tumor vascularization). Mathematical modeling allows for a better understanding of the processes that underlie drug transport and the relative importance of the parameters influencing it. In this work, we expanded our previously developed 3D Computational Fluid Dynamics (CFD) model of the drug mass transport in idealized tumor nodules during IP chemotherapy to include realistic tumor geometries and spatially varying vascular properties. DCE-MRI imaging made it possible to distinguish between tumorous tissues, healthy surrounding tissues and necrotic zones based on differences in the vascular properties. We found that the resulting interstitial pressure profiles within tumors were highly dependent on the irregular geometries and different zones. The tumor-specific cisplatin penetration depths ranged from 0.32 mm to 0.50 mm. In this work, we found that the positive relationship between tumor size and IFP does not longer hold in the presence of zones with different vascular properties, while we did observe a positive relationship between the percentage of viable tumor tissue and the maximal IFP. Our findings highlight the importance of incorporating both the irregular tumor geometries and different vascular zones in CFD models of IPC.

This study investigates how catchment properties influence low-flow dynamics. With 496 synthetic models composed of a bedrock and an alluvial aquifer, we systematically assess the impact of the hydraulic conductivity of both lithologies, of the hillslope and of the river slope on catchment dynamics. The physically based hydrogeological simulator HydroGeoSphere is employed, which allows obtaining a range of low-flow indicators. The hydraulic conductivity of the bedrock K bedrock , a proxy for transmissivity, is the only catchment property exerting an overall control on low flows and explains 60% of the variance of Q95/Q50. The difference in dynamics of catchments with same K bedrock depends on hillslope gradients and the alluvial aquifer properties. The buffering capacity of the bedrock is mainly related to K bedrock and the hillslope gradient. We thus propose the dimensionless bedrock productivity index (BPI) that combines these characteristics with the mean net precipitation. For bedrock only models, the BPI explains 82% of the variance of the ratio of Q95 to mean net precipitation. The alluvial aquifer can significantly influence low flows when the bedrock productivity is limited. Although our synthetic catchment setup is simple, it is far more complex than the available analytical approaches or conceptual hydrological models. The direct application of the results to existing catchments requires nevertheless careful consideration of the local geological topographic and climatic conditions. This study provides quantitative insight into the complex interrelations between geology, topography and low-flow dynamics and challenges previous studies which neglect or oversimplify geological characteristics in the assessment of low flows., (© 2018, National Ground Water Association.)

The presence of a peritoneal barrier results in a pharmacokinetic advantage associated with intraperitoneal (IP) delivery of anticancer drugs. The anticancer efficacy of IP chemotherapy depends, however, on its ability to penetrate the tumor stroma. Tumor tissue transport is governed by diffusion and convection and is affected by numerous physical, biological, and pharmaceutical variables. From preclinical and clinical studies, it appears that tissue penetration after IP chemotherapy delivery is very limited. Several approaches are studied in order to improve tissue penetration of small molecular and macromolecular anticancer drugs after IP instillation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Diogenes syndrome is a chronic condition often affecting elderly people, especially those living in isolation. It is characterised by self-neglect and compulsive hoarding. Medico-social professionals working with people in their home, have reflected on levers to help improve the complex support of these patients., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Intraperitoneal (IP) drug delivery, either as an intraoperative chemoperfusion or as an adjuvant, repeated instillation, is an established treatment modality in patients with peritoneal carcinomatosis. The efficacy of IP drugs depends on its ability to penetrate the tumour stroma in order to reach their (sub)cellular target. It is known, that drug penetration after IP delivery is limited to a few millimetres. Here, we review the basic tissue transport mechanisms after IP delivery and discuss the biophysical barriers and obstacles that limit penetration distance. In addition, we review the physical and pharmaceutical interventions that have been studied in order to improve delivery of small molecular and macromolecular drugs after IP instillation. These interventions could inform the design of future clinical trials aiming at an improved efficacy of IP-based drug delivery in carcinomatosis patients.

There is increasing interest in the treatment of advanced stage ovarian cancer (OC) using intraperitoneal (IP) delivery of platinum (Pt)-based chemotherapy. The antitumor efficacy of IP chemotherapy is determined by efficient tumor tissue penetration. Although it is assumed that Pt penetration is limited to a few millimeters after IP delivery, little is known on the distribution of Pt in different tumor compartments at the ultrastructural level following IP administration. Here, using synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), Pt distribution and penetration in OC peritoneal xenografts were determined at nanometer scale after IP chemoperfusion of cisplatin at 37-38°C or 40-41°C (hyperthermic). Using principal component analysis (PCA) the presence of phosphorus, manganese, calcium, zinc, iron, bromine, and sulfur was correlated with the distribution of Pt, while k-means analysis was used to quantify the amount of Pt in weight% in tumor stroma and in tumor cells. The results showed a heterogeneous distribution of Pt throughout the tumor, with an accumulation in the extracellular matrix. LA-ICP-MS mappings indicated significantly higher concentrations of Pt (P=0.0062) after hyperthermic chemoperfusion of cisplatin, while SR-XRF demonstrated a deeper tissue Pt penetration after hyperthermic treatment. Using PCA, it was showed that Pt co-localizes with bromine and sulfur. No differences were observed in Pt distribution regarding tumor cells and stroma, when comparing normo- vs. hyperthermic treatment. In conclusion, SR-XRF and LA-ICP-MS are suitable and highly sensitive techniques to analyze the penetration depth and distribution of Pt-based drugs after IP administration. To the best of our knowledge, this is the first experiment in which the distribution of Pt is analyzed at the cellular level after IP administration of cisplatin., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

Objective: The study describes the most common reasons for using vaporizers (such as e-cigarettes) among US adolescents and investigates how reasons for use differ by grade, lifetime cigarette use, frequency of vaporizer use, gender, race/ethnicity, and parent education., Method: Data were collected from 4066 students in the 8th, 10th, and 12th grades in 2015 as part of the Monitoring the Future study, a cross-sectional and nationally representative US survey., Results: Common reasons for vaporizer use reported by respondents who had ever used a vaporizer were experimentation (53.0%), taste (37.2%), boredom (23.5%), having a good time (22.4%), and relaxation (21.6%). Reasons differed little across grades or parent education; reasons differed by lifetime use of regular cigarettes, frequency of vaping, gender, and race/ethnicity., Conclusions: Overall, results suggest that decisions to vape are based on curiosity, taste, and pleasure, rather than for reasons such as quitting regular cigarettes or substituting for regular cigarette smoking., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ovarian cancer is amongst the most common types of cancer in women, with a relatively low overall cure rate of approximately 30%. This is therefore an important incentive to urge for further research in order to maximize the chances of survival for these patients. Intraperitoneal chemotherapy with Cisplatin is an effective treatement for ovarian cancer; however, many questions still remain concerning the ideal treatment protocol and tumor resistance towards the drug, which should be resolved for optimal application of this therapy. For the first time in-vivo grown tumors treated with both hyper- and normothermic intraperitoneal chemotherapy have been studied using nano-XRF spectroscopy to examine the platinum (Pt) distribution within the analyzed tissues. These measurements prove Pt resides predominantly outsides the cancer cells in the stroma of the tissue. These findings indicate the resistance mechanism of the cancer cells prevents Cisplatin from diffusing through their cell membranes. This is an important addition to the existing knowledge on the resistance mechanism providing insights which might help to overcome this effect. In our aim to find the optimal treatment protocol, no significant differences were found between the two examined procedures. A more extensive data set will be needed to draw definite conclusions.

Objectives: The aim of this study was to assess long-term pelvic floor symptoms after an obstetric anal sphincter injury (OASI)., Methods: This retrospective cohort study included 237 cases of OASI (0.86% of deliveries) identified at Poitiers University Hospital between 2000 and 2011. Symptoms were assessed using validated self-administered questionnaires, including Female Pelvic Floor Questionnaire, Pescatori anal incontinence score, EuroQoL five-dimension score, and pain visual analogue scale (VAS)., Results: One hundred and sixty women (67%) filled out the questionnaires, on average 46 months after delivery (8-152). Among them, 93 (54%) reported at least one symptom occurring "frequently" (the most common being dyspareunia), and 45 (28%) a symptom occurring "daily" (the most common being flatus incontinence). Anal incontinence was reported by 32 (20%) women, flatus incontinence "frequently" or "daily" by 28 (18%), and stool incontinence "frequently" or "daily" by 9 (6%). Urinary incontinence was reported "frequently" or "daily" by 27 women (17%) at stress, 17 (11%) at urge, and 11 (7%) at mixed circumstances. Prolapse symptoms were reported "frequently" or "daily" by 6 women (4%). Pain during intercourse was reported "frequently" or "daily" by 17 women (11%). Twenty-four women (18%) reported chronic pelvic pain (VAS score≥4/10). Ninety-five percent of women reported a normal quality of life for mobility, self-care, and usual activities; however, alterations in pain/discomfort (32%) and anxiety/depression (33%) domains were frequently reported., Conclusion: Pelvic floor symptoms 4 years after OASI were highly prevalent., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

This data paper contains information about the in vivo model for peritoneal implants used in the paper "Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells" (De Vlieghere et al., 2015) [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included.

Breastfeeding induces a different metabolic and endocrine response than feeding conventional infant formula, and it has also been associated with slower weight gain and reduced disease risk in later life. The underlying programming mechanisms remain to be explored. Breastfeeding has been reported to induce lower levels of insulin, insulin-like growth factor-1 and some amino acids (AAs) than formula feeding. In the Childhood Obesity Project (CHOP), infants fed a conventional protein-rich formula had a higher BMI at 2 and 6 years than those fed a protein-reduced formula. At 6 months, higher protein intakes induced increased plasma concentrations of branched-chain AAs (BCAAs) and their oxidation products, short-chain acylcarnitines. With increasing BCAA levels, these short-chain acylcarnitines increased proportionally only until a break point was reached, after which BCAAs seemed to escape their degradation. The resulting marked elevation in BCAA levels with high-protein (HP) intakes appears to contribute to increased insulin levels and to affect β-oxidation of fatty acids. The ratios of long-chain acylcarnitines to free carnitine decreased in infants who received a HP formula, which indicates a reduced initiation of β-oxidation. We conclude that HP intakes inducing high BCAA plasma levels may inhibit fat oxidation and thereby enhance body fat deposition and adiposity., (© 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Background: Nutrition in childhood has an influence on the cardiovascular function later on in life. European Childhood Obesity Project is a multicenter, randomized clinical intervention trial examining the effect of early protein intake on later health outcomes, particularly adiposity and related disorders. The aim of the study was to examine the effect of nutritional intervention--different protein intake in infancy on carotid intima-media thickness (cIMT) at 5 years. The association of cardiovascular risk factors with cIMT was also assessed., Methods: Healthy term formula-fed infants in five European countries were enrolled either to the higher (HP) or to the lower (LP) protein group. Observational group consisted of breastfed infants. Plasma insulin, glucose, lipid profile, IGF-1, apolipoprotein A1 and B were measured as well as anthropometric parameters of parents and a child, blood pressure and physical activity., Results: No difference in cIMT between HP and LP group was observed. Insulin, HOMA-IR index and total IGF-1 were positively associated with cIMT but after adjustment for confounders only an inverse association between ApoA1 and positive between ApoB/ApoA1 and cIMT were significant., Conclusion: High versus low protein intake in infancy does not influence cIMT at 5 years. cIMT in healthy children at 5 years is associated with their apolipoprotein profile., (© 2015 S. Karger AG, Basel.)

Context: The protective effect of breast-feeding against later obesity may be explained by the lower protein content compared with formula milk. However, the metabolic mechanisms remain unknown., Objective: We studied the metabolic response to a higher or lower protein supply in infancy., Design and Setting: The Childhood Obesity Project study is a double-blind, randomized, multicenter intervention trial. Infants were randomized to receive a higher (HP) or lower protein (LP) content infant formula or were breast-fed., Patients and Interventions: Plasma samples of 691 infants who received formula milk with different protein content (HP, 2.05 g per 100 mL; LP, 1.25 g per 100 mL) or were breast-fed were collected., Main Outcome Measures: Changes in plasma amino acid and acylcarnitine concentrations of 6-month-old infants according to different dietary protein supply were determined by liquid chromatography coupled to tandem mass spectrometry., Results: Twenty-nine metabolites differed significantly between the formula groups. Branched-chain amino acids (BCAAs) were the most discriminant metabolites. Their degradation products, the short-chain acylcarnitines C3, C4, and C5, were also significantly elevated in the HP group. A breakpoint analysis confirmed that with increasing BCAAs, the ratio between acylcarnitines and BCAAs decreases. Long-chain acylcarnitines were decreased in HP infants., Conclusions: BCAAs seem to play a pivotal role in the effect of a high-protein diet on β-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high-protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the β-oxidation, thus leading to high early weight gain and body fat deposition.

Objective(s): Assess the efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of postpartum haemorrhage., Study Design: Systematic review with meta-analysis., Material and Methods: Systematic review of the literature with the aim of identifying prospective, randomised, controlled trials that assessed the effect of tranexamic acid on peripartum blood loss and transfusion requirement in three clinical contexts: (i) prevention of post-partum haemorrhage in case of elective caesarean section, (ii) prevention of post-partum haemorrhage in case of vaginal delivery, (iii) treatment of post-partum haemorrhage., Results: Prophylactic administration of tranexamic acid reduced blood loss (mean difference for intraoperative blood loss: -177.9mL, IC 95%: -189.51 to -166.35, total blood loss: -183.94, IC 95%: -198.29 to -169.60), and the incidence of severe post-partum haemorrhage (OR: 0.49, IC 95%: 0.33 to 0.74). None of the published trials assessed the effect of tranexamic acid on blood products administration or transfusion requirement. Only one study assessed and reported the efficacy of tranexamic acid when administered as a treatment for postpartum haemorrhage. A significant reduction in blood loss was reported within 30 minutes after randomisation (P=0.03) and confirmed after 6 hours (median: 170mL (58-323) vs 221mL (110-543), P=0.04). None of the included studies adequately studied the incidence of side effects after tranexamic acid administration., Conclusion: Although tranexamic acid administration seemed to significantly reduce blood loss and the incidence of severe post-partum haemorrhage, further prospective trials are needed to confirm the efficacy and safety of tranexamic administration in the treatment of postpartum haemorrhage. Those studies should assess the pharmacokinetic profile and the safety of this drug in pregnant women., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Falls in geriatry are associated with important morbidity, mortality and high healthcare costs. Because of the large number of variables related to the risk of falling, determining patients at risk is a difficult challenge. The aim of this work was to validate a tool to detect patients with high risk of fall using only bibliographic knowledge. Thirty articles corresponding to 160 studies were used to modelize fall risk. A retrospective case-control cohort including 288 patients (88 ± 7 years) and a prospective cohort including 106 patients (89 ± 6 years) from two geriatric hospitals were used to validate the performances of our model. We identified 26 variables associated with an increased risk of fall. These variables were split into illnesses, medications, and environment. The combination of the three associated scores gives a global fall score. The sensitivity and the specificity were 31.4, 81.6, 38.5, and 90 %, respectively, for the retrospective and the prospective cohort. The performances of the model are similar to results observed with already existing prediction tools using model adjustment to data from numerous cohort studies. This work demonstrates that knowledge from the literature can be synthesized with Bayesian networks.