Search

Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors.We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally.Between January 2021 and March 2022, nine women and one man, aged 50-90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis.BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon.

Le syndrome des antisynthétases est une pathologie auto-immune caractérisée cliniquement par une atteinte pulmonaire (pneumopathie interstitielle diffuse), une myopathie inflammatoire, des manifestations articulaires et biologiquement par la présence d’autoanticorps spécifiques dirigés contre différentes anti-synthétases. L’atteinte clinique est hétérogène, rendant parfois difficile le diagnostic de cette pathologie. La présentation initiale, subaiguë ou chronique, a un spectre de gravité large. L’évolution est variable selon les individus, mais le pronostic est conditionné par l’atteinte pulmonaire. Le dépistage précoce de cette atteinte pourrait permettre une meilleure prise en charge et ainsi améliorer le pronostic. Les thérapeutiques ne sont pas consensuelles du fait d’un manque cruel d’études randomisées. Les corticoïdes correspondent au traitement de première intention. Un traitement immunosuppresseur sera dans la grande majorité des cas associé afin d’éviter échec ou rechute, ou encore à à visée d’épargne cortisonée. La durée du traitement et le suivi ne sont pas bien définis, mais sont le plus souvent prolongés plusieurs années.

International audience; Objective: To investigate whether the initiation of treatment with an interleukin-17 inhibitor (IL-17i) in real life is associated with a higher risk of inflammatory bowel disease (IBD) in patients who had both psoriasis (PsO) and psoriatic arthritis (PsA)/ankylosing spondylitis (AS). Methods: This nationwide cohort study was conducted using the French National Health Data System database. All adult patients with PsO and PsA/AS who were identified as having newly initiated treatment with an IL-17i during 2016–2019 were included. As controls, patients with PsO and PsA/AS who had newly initiated either 1) apremilast or 2) etanercept (ETN) during this period but had not received IL-17i were included. The follow-up end date was September 30, 2019. The primary end point was the risk of occurrence of IBD associated with exposure to an IL-17i compared to exposure to the other treatments, as determined in a time-to-event analysis with propensity score–weighted Cox and Fine-Gray proportional hazards models. Results: The study included a total of 16,793 new IL-17i users (mean ± SD age 48.4 ± 13 years, 45% men), 20,556 new apremilast users (age 52.6 ± 15 years, 54% men), and 10,294 new ETN users (age 46.3 ± 15 years, 44% men). New IL-17i users and new ETN users had received more biologics for their underlying disease compared to new apremilast users. IBD occurred in 132 patients: 72 new IL-17i users (0.43%), 11 new apremilast users (0.05%), and 49 new ETN users (0.48%). Most IBD cases occurred after 6 months of exposure (82%, 55%, and 76%, respectively). After propensity score weighting, the risk of IBD was significantly greater among patients initiating an IL-17i compared to those initiating apremilast (weighted hazard ratio [HR] 3.8 [95% confidence interval (95% CI) 2.1–6.8]). No difference in the risk of IBD between new IL-17i users and new ETN users was observed (weighted HR 0.8 [95% CI 0.5–1.2]). Conclusion: Patients with PsO and PsA/AS who initiate treatment with an IL-17i do not have a higher risk of developing IBD when compared to patients initiating ETN who display the same severity of underlying disease. These results need to be confirmed in other large studies of patients with PsO and PsA/AS.

Convection in a silicone oil with a temperature dependant fluid property is investigated experimentally in a differentially heated cylindrical annulus. A convective flow is induced by terrestrial gravity in axial direction and combined with an electrical tension applied between both cylinders to induce thermo-electrohydrodynamic convection. To capture the evolving velocity and temperature fields a novel combination of simultaneous PIV and shadowgraph technique is utilized. Results reveal azimuthal modes with cold and hot jets from inner and outer cylinder that are referred to the electric tension. The lack of information in the shadowgraph pictures were recovered by the PIV technique providing a deeper understanding in the nature of the development of the azimuthal mode number and the surrounding axial flow of natural convection. In addition, the results provide a robust framework in the capability of combining both techniques to investigate complex flow patterns that are non-axisymmetric.

Background Ustekinumab and vedolizumab are commonly used after anti-tumour necrosis factor (TNF) failure in patients with Crohn's disease (CD). No randomised controlled trial has compared these drugs. Aims To compare the effectiveness of ustekinumab and vedolizumab in CD patients refractory to anti-TNF. Methods From PubMed, EMBASE and the Cochrane Library, through March 27, 2021, we identified studies that compared ustekinumab and vedolizumab in patients with CD refractory to anti-TNF. The main outcomes were clinical remission and steroid-free clinical remission at weeks 14 and 52. Secondary outcomes were biological remission and treatment persistence. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) using random effects meta-analysis. Results We identified 1513 reports. Among them, 38 studies were assessed for eligibility and five studies were included. All studies included were of high quality: four were retrospective and one was prospective. Among 1026 patients, 659 received ustekinumab and 367 received vedolizumab. At week 14, clinical remission (OR 1.36; 95%CI: 0.74-2.47; I2 = 50%), steroid-free clinical remission (OR 1.24; 95%CI: 0.79-1.92; I2 = 52%) and biological remission (OR 0.80; 95%CI: 0.50-1.28; I2 = 0%) rates were similar between the two treatments. At week 52, ustekinumab was associated with higher rates of clinical remission (OR 1.87; 95% CI: 1.18-2.98; I2 = 0%), steroid-free clinical remission (OR 1.56; 95% CI: 1.23-1.97; I2 = 0%), biological remission (OR 1.86; 95% CI: 1.03-3.37; I2 = 29%) and treatment persistence (OR 2.37; 95% CI: 1.56-3.62; I2 = 0%). Conclusion In patients with CD refractory to anti-TNF, ustekinumab and vedolizumab are similarly effective in induction, but as maintenance treatment, ustekinumab appears to be more effective than vedolizumab.

Continuation of biologics for inflammatory disorders during pregnancy is still a difficult decision. Many women with inflammatory bowel diseases (IBDs) stop anti-tumor necrosis factor (anti-TNF) treatment after 24 weeks.To evaluate the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy for mothers with IBD and their offspring.Target trial emulation between 2010 and 2020.Nationwide population-based study using the Système National des Données de Santé.All pregnancies with birth exposed to anti-TNF between conception and 24 weeks of pregnancy in women with IBD.Continuation of anti-TNF after 24 weeks of pregnancy.Occurrence of maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in the offspring during the first 5 years of life was compared according to anti-TNF continuation after 24 weeks of pregnancy using inverse probability-weighted marginal models.A total of 5293 pregnancies were included; among them, anti-TNF treatment was discontinued before 24 weeks for 2890 and continued beyond 24 weeks for 2403. Continuation of anti-TNF was associated with decreased frequencies of maternal IBD relapse (35.8% vs. 39.0%; adjusted risk ratio [aRR], 0.93 [95% CI, 0.86 to 0.99]) and prematurity (7.6% vs. 8.9%; aRR, 0.82 [CI, 0.68 to 0.99]). No difference according to anti-TNF continuation was found regarding stillbirths (0.4% vs. 0.2%; aRR, 2.16 [CI, 0.64 to 7.81]), small weight for gestational age births (13.1% vs. 12.9%; aRR, 1.01 [CI, 0.88 to 1.17]), and serious infections in the offspring (54.2 vs. 50.2 per 1000 person-years; adjusted hazard ratio, 1.08 [CI, 0.94 to 1.25]).Algorithms rather than clinical data were used to identify patients with IBD, pregnancies, and serious infections.Continuation of anti-TNF after 24 weeks of pregnancy appears beneficial regarding IBD activity and prematurity, while not affecting neonatal outcomes and serious infections in the offspring.None.

Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort.Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption.During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35-0.93; P trend.01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34-0.87 and 0.55; 95% CI, 0.34-0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks.In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found.

International audience; INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p\,=\,.21 and 0.94 [0.40-2.22], p\,=\,.89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Background: Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn's disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD.Methods: From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw [HB] score

ObjectiveTo describe and identify factors associated with articular manifestations occurring in patients treated with anti-tumour necrosis factor (TNF) for inflammatory bowel diseases (IBDs).MethodsRetrospective monocentric study, including all patients who received an anti-TNF for an IBD in our hospital. All incident articular manifestations occurring during treatment were analysed. Characteristics of patients with paradoxical articular manifestations were compared with that of patients without inflammatory articular manifestations.ResultsBetween February 2013 and May 2017, we identified 442 patients (36.2±15 years, 50.5% men) who had ever received an anti-TNF for an IBD: Crohn’s disease (n=277), ulcerative colitis (n=154) and undetermined colitis (n=11). 115 (26%) patients developed new articular manifestations after a mean of 20 (±22) months of treatment. Among them, 59 (13.3%) had inflammatory manifestations: paradoxical in 39%, concomitant of an IBD flare in 27%, linked to an immunisation against anti-TNF in 27% and 7% to another diagnosis. Among paradoxical articular manifestations, 19 (83%) were new articular symptoms, including 8 (35%) de novo spondyloarthritis. There were no predictive factors of paradoxical articular manifestation. Paradoxical manifestations spontaneously resolved in 16 (70%) patients despite continuation of anti-TNF.ConclusionInflammatory articular manifestations occurred in about 13% of patients treated with anti-TNF for IBD. More than a quarter were linked to an immunisation against anti-TNF, which has to be searched in this situation. About 40% were paradoxical. In most of cases, they were transitory and did not require anti-TNFs discontinuation.

BACKGROUND The long-term outcome of patients with acute severe ulcerative colitis (ASUC) responding to intravenous steroids (IVS) has been poorly reported. AIMS To assess relapse-free survival in patients with ASUC responding to IVS. METHODS Between January 2006 and December 2017, 142 consecutive patients with ASUC (according to modified Truelove-and-Witts criteria) responding to IVS were included in this multicentre retrospective study. Relapse was defined by a partial Mayo Clinic score >4 and/or the need for another maintenance therapy. RESULTS Among the 142 included patients (100 naive of immunomodulator and/or biological agent) hospitalised for ASUC, 59 (41.5%) were treated at discharge with 5-aminosalicylic acid, 60 (42%) with immunomodulators, 18 (13%) with anti-tumour necrosis factor (TNF) agents and 5 (3.5%) with vedolizumab. After a median follow-up of 4.8 (2.6-7.3) years, 90 (63.4%) had relapsed and 12 (8.5%) had required colectomy. The probabilities of relapse-free survival were 58%, 48% and 40% at 1, 2 and 5 years respectively. The multivariate analysis demonstrated that patients with

International audience; Background: Recently, the SECURE-IBD study, based on a physician-reported registry, suggested that thiopurines, either alone or combined with anti-TNF, may increase risk of severe COVID-19. Aims: To compare the risk of severe COVID-19 according to IBD medications in a large and unselected population. Methods: Using the French national health data system, the risks of hospitalisation and of death or mechanical ventilation for COVID-19 from 15 February 2020 to 31 August 2020 in IBD patients were compared according to IBD treatment (immunomodulators and biologics), using multivariable Cox models adjusted for socio-demographic characteristics, budesonide/corticosteroids and aminosalicylates use, and comorbidities. Results: Among 268 185 IBD patients, 600 were hospitalised for COVID-19 and 111 of them died or were mechanically ventilated (including 78 deaths). In multivariable analysis, the risk of hospitalisation for COVID-19 did not differ according to IBD treatment category, with adjusted Hazard Ratios (aHR, unexposed patients used as reference) of 0.94 (95%CI: 0.66-1.35) for immunomodulator monotherapy, 1.05 (0.80-1.38) for anti-TNF monotherapy, 0.80 (0.38-1.69) for anti-TNF combination therapy, 1.06 (0.55-2.05) for vedolizumab and 1.25 (0.64-2.43) for ustekinumab. Similarly, the risk of death or mechanical ventilation for COVID-19 did not differ according to IBD treatment. Conclusions: Immunomodulators and biologics prescribed in patients with IBD do not appear to increase the severity of COVID-19 infection.

The dielectrophoretic force is applied between two differentially heated cylinders under microgravity conditions obtained during parabolic flight. The electric field is activated at various moments of the microgravity phase in order to control the initial condition at which the dielectrophoretic force intervenes. The time evolution of the flow is measured by particle image velocimetry and that of thermal plumes is captured by shadowgraphy. The growth rate of the instability during microgravity conditions is determined from these measurements. It is found that the closer the initial condition to the purely conductive state is, the faster the instability grows.

We appreciate the comments from Dr. Cheng-Ruei Yang et al. about our recent article that investigated whether IL17-inhibitors (IL17i) initiation is associated with a higher risk of inflammatory bowel disease (IBD) in patients with psoriasis (PsO), psoriatic arthritis and ankylosing spondylitis (PsA/AS).(1) We demonstrated that treatment with IL17i was not associated with a higher risk of IBD in patients with PsO, or PsA/AS when taking into account the severity of the underlying disease i.e. when using etanercept as a comparator. The main strength of this study was the use of a large sample from a nationally representative database, the French national health data system (Systeme National des Donnees de Sante [SNDS]) which has contained comprehensive data on all reimbursements for health-related expenditures, on ambulatory care and hospitalizations since 2006.(2,3).

Background Data about thiopurines or anti-TNF use during pregnancy in women with inflammatory bowel diseases (IBD) are reassuring. However, many studies are based upon small sample sizes. Aims To assess IBD medication safety during pregnancy. Methods Using the French national health database, which covers more than 99% of the French population, around 65 000 000 people, we identified pregnancies ending with a birth in IBD patients in France between 2010 and 2018. Pregnancy outcomes (vital status at birth, birth term, and weight for gestational age) were compared according to treatment exposure during pregnancy using propensity score-weighted marginal logistic regression models. Results 27 729 pregnancies were included: 3554 were exposed to thiopurines monotherapy, 3525 to anti-TNF monotherapy, 839 to combination therapy, and 19 811 unexposed. Pregnancies exposed to thiopurines monotherapy compared to unexposed pregnancies more frequently resulted in stillbirths (1.0% vs 0.5%, aOR 2.04; 95%CI: 1.18-3.55), preterm birth (12.3% vs 7.1%, aOR 1.76; 95%CI: 1.55-2.00), large for gestational age (10.6% vs 8.4%, aOR 1.32; 95%CI: 1.13-1.53) and less frequently in small for gestational age (9.6% vs 11.1%, aOR 0.79; 95%CI: 0.67-0.92). By contrast, pregnancies exposed to anti-TNF monotherapy were not different from unexposed pregnancies as regards to these outcomes. Compared to unexposed pregnancies, those exposed to combination therapy more frequently resulted in preterm births (aOR 1.55; 95%CI: 1.15-2.11) and larger for gestational age (aOR 1.61; 95%CI: 1.13-2.29) but did not differ as regards to stillbirths. Conclusions Pregnancies exposed to thiopurines more frequently resulted in stillbirths, preterm births and large for gestational age compared to pregnancies exposed to anti-TNF or unexposed pregnancies. By contrast, pregnancies exposed to anti-TNF monotherapy were not associated with these outcomes.

International audience; Discrete mathematics, roughly defined as concerning countable objects, recently gained importance both in research and education, mainly due to its foundational role in large parts of computer science. This chapter provides a synthesis of recent INDRUM research concerning the educational side of this “border area” between university mathematics and computer science, and especially the actual and potential significance of logic in both disciplines. The authors demonstrate the potential and interest of interdisciplinary didactical engineering in this area, and the need to pursue and deepen the epistemological analysis on which such research could be founded.

Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn’s disease (CD) refractory to anti-TNF. In France between May 2014 and November 2016, vedolizumab (and not ustekinumab) was reimbursed for patients who had failed anti-TNF. Then, between December 2016 and August 2018, ustekinumab (and not vedolizumab) was reimbursed for this category of patients. Since September 2018, both ustekinumab and vedolizumab are reimbursed in patients who are refractory to anti-TNF. The aim of this study was to compare effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF. Methods We studied all consecutive patients with active CD who were refractory to at least one anti-TNF, and were treated either with vedolizumab or ustekinumab, in five university hospitals of the Paris area, between May 2014 and August 2018. The primary endpoint was clinical remission rate at week 48. Adjustment according to propensity scores with inverse probability of treatment weighting was performed. Results 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. After propensity scoring with IPTW, there was no difference between the two groups (Figure 1). At week 48, the clinical remission rate was higher with ustekinumab than with vedolizumab (54.4% vs. 38.3%; OR =1.92, 95% CI [1.09–3.39]). At week 48, corticosteroid-free remission rate tended to be numerically higher with ustekinumab than with vedolizumab (44.7% vs. 34.0%; OR = 1.57, 95% CI [0.88–2.79]). Treatment persistence was significantly more frequent in the ustekinumab group (71.5% vs. 49.7%; OR = 2.54, 95% CI [1.40–4.62]). The dose optimisation rate at week 48 was higher with vedolizumab than with ustekinumab (53.5% vs. 30.1%; OR = 0.37, 95% Cl [0.21–0.67]). Subgroup analyses showed that ustekinumab was associated with higher clinical remission rates at week 48 in patients with ileal CD (OR = 3.49; 95% CI [1.33–9.17]), a penetrating phenotype (OR = 6.58; 95% CI [1.91–22.68]) and a history of perianal disease (OR = 2.48; 95% CI [1.04–5.93]). Regardless of treatment group, combotherapy was associated with a higher clinical remission rate at week 48 (OR = 1.93; 95% CI [1.09–3.43]). Conclusion This study suggests that, after 1 year of follow-up, ustekinumab is associated with a higher rate of clinical remission than vedolizumab in CD patients refractory to anti-TNF, particularly in those with ileal and penetrating disease.

The main objective of the AtmoFlow experiment is the investigation of convective flows in the spherical gap geometry. Gaining fundamental knowledge on the origin and behavior of flow phenomena such as global cells and planetary waves is interesting not only from a meteorological perspective. Understanding the interaction between atmospheric circulation and a planet’s climate, be it Earth, Mars, Jupiter, or a distant exoplanet, contributes to various fields of research such as astrophysics, geophysics, fluid physics, and climatology. AtmoFlow aims to observe flows in a thin spherical gap that are subjected to a central force-field. The Earth’s own gravitational field interferes with a simulated central force-field with the given parameters of the model which makes microgravity conditions of $\mathrm {g}

Summary Background CT‐P13, a biosimilar of the reference product infliximab, has been approved for the treatment of ulcerative colitis on the basis of the results of trials conducted in patients with spondyloarthritis and rheumatoid arthritis. Aim To compare the effectiveness and safety of CT‐P13 and the reference product in infliximab‐naive patients with ulcerative colitis Methods A comparative real‐life equivalence cohort study was conducted using the French nationwide health administrative database. Infliximab‐naive patients with ulcerative colitis over 15 years of age who started infliximab with no other indications for infliximab were included. The primary outcome was a composite endpoint (death, ulcerative colitis‐related surgery, all‐cause hospitalisation and reimbursement for other biologics). Equivalence was defined as a 95% CI of the hazard ratio (HR) of CT‐P13 vs the reference product, in a multivariable marginal Cox model situated within prespecified margins of (0.80‐1.25). Results A total of 3112 patients were included between 1 January 2015 and 30 June 2017: 1434 received the reference product, 1678 received CT‐P13. Overall, 710 patients in the reference product group and 743 patients in the CT‐P13 group met the composite endpoint. In multivariable analysis of the primary outcome, CT‐P13 was equivalent to the reference product (HR 1.04; 95% CI: 0.94‐1.15). The number of serious infections was lower in the CT‐P13 group (HR 0.65; 95% CI: 0.48‐0.88). There was no difference in the incidence of solid or haematologic malignancy (HR 0.81; 95% CI: 0.41‐1.60). Conclusions The effectiveness of CT‐P13 is equivalent and the risk of serious infections could be lower than that of the reference product for infliximab‐naive patients with ulcerative colitis.