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Janus kinase (JAK) inhibitor-induced acne in inflammatory bowel disease – an international, multicenter, retrospective cohort study
No full textInternational audienceBackground and AimsJAK inhibitor-associated acne is a common but poorly understood adverse event. This study aimed to investigate the epidemiology, clinical characteristics, and treatment outcomes of this condition in patients with inflammatory bowel disease (IBD).MethodsThis international, multicenter, retrospective cohort study consecutively enrolled JAK-inhibitor-treated IBD patients who subsequently developed acne. The primary objective was to evaluate the clinical characteristics of acne. Secondary objectives included determining acne prevalence, impact on quality of life, and anti-acne treatment effectiveness.ResultsAmong 2,183 JAK inhibitor-treated patients with IBD, 272 developed acne. The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib. Acne predominantly affected patients aged 30–50 years; most cases were mild-moderate in severity. A prior history of acne vulgaris was associated with significantly increased odds of developing severe JAK inhibitor–associated acne (OR 4.88, 95% CI 2.88–31.7;p=0.0003) and acne-related skin complications (OR 3.92, 95% CI 1.56–10.11;p=0.004). One-third of patients reported a negative psychosocial impact, and 40% received pharmacological intervention. Eighteen percent of patients who developed acne required JAK inhibitor dose reduction or discontinuation, although most did not have severe disease.ConclusionThis is the first study characterizing this adverse event in JAK inhibitor-treated IBD patients and presents the largest cohort of JAK inhibitor-induced acne cases across all immune-mediated diseases. Acne is a common adverse effect resulting in significant psychological burden. Early identification, proactive counseling, and timely interventions, such as dose reduction or referral to dermatology, are crucial in managing this side effect
Association between Helicobacter pylori, reflux and chronic rhinosinusitis: a systematic review
No full textInternational audienceBackgroundThe prevalence, role, and clinical relevance of Helicobacter Pylori (HP) in sinonasal tissues of patients with chronic rhinosinusitis remain unclear.ObjectiveTo investigate the prevalence and clinical relevance of Helicobacter Pylori (HP) in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSSNP).MethodsThree investigators conducted a PubMed, Scopus, and Cochrane Library systematic review of the prevalence and clinical relevance of HP infection in CRS patients through the PRISMA framework. A bias analysis was conducted to identify potential heterogeneity and biases across studies.ResultsOf the 42 identified studies, 20 met the inclusion criteria, accounting for 741 CRS patients and 368 controls. HP was detected in 37.1% (n = 127/342) of polyps of CRSwNP patients with the polymerase chain reaction (PCR) and 32.7% (n = 37/113) of polyp tissue with the immunohistochemistry (IHC). Controls reported a nasal PCR and IHC detection rates of 14.8% (n = 36/243) and 3.6% (n = 3/84), respectively. The HP rate did not differ between CRSwNP and CRSsNP. Among patients with CRS, the enzyme-linked immunosorbent assay testing detected blood HP antigens in 48.7% (n = 74/152) of CRS patients and 41.6% (n = 37/89) of controls. The detection of HP in polyps was associated with the severity of gastroesophageal reflux disease (GERD). There was an important heterogeneity between studies for the inclusion criteria, methods of HP detection, and reflux outcomes.ConclusionHelicobacter Pylori can be detected in one-third of sinonasal tissues from patients with CRS and can be considered a biomarker of GERD. The potential role of HP in the development of CRS remains unclear. The heterogeneity between studies limits the drawing of valid conclusions
Ventriculitis characteristics and outcomes (VELCRO): an international retrospective cohort study
No full textInternational audienceVentriculitis is a dreaded complication of central nervous system infections, which has been scarcely described in the literature. We aimed to present a contemporary picture of ventriculitis, describing its characteristics and outcomes across the spectrum of aetiologies that may lead to ventriculitis. VELCRO is an international retrospective multicentre cohort study conducted at 34 hospitals in six countries. Adult patients fulfilling clinical, microbiological and imaging criteria of ventriculitis between 2010 and 2021 were included. Survival analyses were performed using a multivariable Cox proportional hazards regression model to identify risk factors for 1-year all-cause mortality. Overall, 436 patients with ventriculitis were included: 274 (62.8%) males, median age 58 years [interquartile range 48-68], 68 (15.6%) had diabetes mellitus and 62 (14.2%) were immunocompromised. The most common neuroimaging features of ventriculitis were ependymal enhancement (n=310/436, 71.1%), intraventricular pus (n=286/436, 65.6%) and intraventricular septations (n=85/436, 19.5%). To describe the cohort, patients were divided into three groups: ventriculitis with brain abscess(es) (V-BA, n=181), community-acquired ventriculitis without brain abscess (CA-V, n=88), and healthcare-associated ventriculitis without brain abscess (HCA-V, n=167). Intensive care unit admission was required for 351 patients (80.5%) and the median hospital length of stay was 45 days [26-74]. One-year mortality rate was 33.7% (n=147/436), with a lower rate in patients with V-BA (n=50/181, 27.6%) than in patients with CA-V (n=30/88, 34.1%) and HCA-V (n=67/167, 40.1%). On multivariable analysis, the predictive factors for 1-year mortality were: age > 60 years, immunosuppression, diabetes mellitus, Glasgow Coma Scale score < 13 at presentation, infection involving Enterobacterales or fungi, acute hydrocephalus, cerebral ischemia and intraventricular septations. Staphylococcal ventriculitis was associated with a lower 1-year mortality. Long-term unfavourable outcome (modified Rankin score (mRS) > 2 after 6 months of follow-up) occurred in 43.3% (n=91/210), considering that 26.7% (n=56) had a mRS > 2 before the onset of ventriculitis. Ventriculitis is associated with high mortality and neurological morbidity. Further large prospective studies are needed in this area of research
Efficient generation of germline chimeras in a non-rodent species using rabbit induced pluripotent stem cells
No full textInternational audiencePluripotent stem cells have long been used to produce knockout mice via germline chimera technology. However, aside from the rat, this approach has not been successfully applied to other mammals. Here, we demonstrate that rabbit induced pluripotent stem cells (iPSCs) can be reprogrammed using KLF2, ERAS and PRMT6, enabling them to efficiently colonize embryos. These chimeric embryos can develop into fetuses and newborn rabbits, with iPSCs contributing up to 100 % to certain organs. Notably, female rabbits generated through this method are healthy and transmit the iPSC genome to their offspring with a high efficiency, demonstrating germline chimerism. This advancement establishes a foundation for developing rabbit models of human disease with complex genetic traits
Motor and Non-motor Complications Following Different Early Therapies in Parkinson’s Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort
No full textInternational audienceBackground: Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.Methods: NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.Results: We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.Conclusions: In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.Gov identifier: NCT04888364. Registered June 2021
Real‐World Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated Before the Era of Anti‐CD38 Antibodies: The EMMY Cohort From 2017 to 2020
No full textInternational audienceAims/Background: Recent agents have profoundly reshaped the multiple myeloma (MM) landscape. Their real-world impacts need to be assessed over the long term.Methods: EMMY is a non-interventional, prospective dynamic cohort, conducted in France, since 2017, with 900 patients enrolled each year. Newly diagnosed MM (NDMM) who initiated a treatment from 2017 to 2020 are here described.Results: A total of 1036 non-transplant eligible (NTE) patients (median age: 74.9 years) and 561 patients who received autologous stem cell transplantation (ASCT) (median age: 60.6 years) were enrolled. For ASCT patients, a shift in induction treatment from bortezomib-thalidomide-dexamethasone (VTd) (29.1%) to bortezomib-lenalidomide-dexamethasone (VRd) (55.1%) marked the period. Maintenance treatment with R after ASCT became a standard (75% of patients). In NTE patients, R-based regimens were increasingly used from 29.4% in 2017 (of whom Rd.: 17.0%, VRd: 10.6%) to 73.3% in 2020 (of whom Rd.: 21.8%, VRd: 48.5%). Median progression-free survival (mPFS) was 46.5 months (95% CI: 37.8-50.6) and 18.7 months (95% CI: 16.3-20.8) in ASCT and NTE patients, respectively. In the ASCT group, patients treated with and without R maintenance had a mPFS of 51.8 (95% CI: 44.1-NA) and 29.6 months (95% CI: 21.8-40.9), respectively. In the NTE group, the mPFS was 26.3 (95% CI: 21.9-30.9) and NTE patients, respectively.wbr/>Conclusions: The 2017-2020 period was marked by the expansion of R use in both NDMM ASCT and NTE patients
Neurosurgical management of the acute phase of adult and pediatric traumatic brain injury
No full textInternational audienceObjectiveTo develop a multidisciplinary French framework addressing neurosurgical management in the initial phase of traumatic brain injury (TBI) in adults and children.DesignA panel of 29 experts was formed at the request of the French Society of Neurosurgery (SFNC), with the participation of the French Society of Pediatric Neurosurgery (SFNCP), French Society of Private-Practice Neurosurgeons (SFNCL), French-Speaking Neurocritical Care and Neuro-Anesthesiology Society (ANARLF), French Society of Anesthesia, Critical Care and Perioperative Medicine (SFAR), French-Speaking Pediatric Emergency and Intensive Care Group (GFRUP), French Society of Neuroradiology (SFNR), French-Speaking Infectious Diseases Society (SPILF), and the French Society of Physical Medicine and Rehabilitation (SOFMER).MethodsQuestions were formulated using the PICO (Patients, Intervention, Comparison, Outcome) format, grouped into 7 categories: 1. Factors of poor prognosis, 2. Extradural hematoma, 3. Acute subdural hematoma, 4. Skull-base fracture and dural tear, 5. Penetrating traumatic brain injury, 6. Post-traumatic cerebrospinal fluid disorder, and 7. Pediatric specificities.ResultsSynthesis by the experts and application of the GRADE® method resulted in the formulation of 45 recommendations. Strong consensus was reached for all recommendations at the first round of rating,ConclusionThere was a strong consensus among the experts on important interdisciplinary recommendations to improve the neurosurgical management of patients with TBI
Development of Tungsten-based contrast agents for Spectral Photon counting computed Tomography (SPCCT) scanner
No full textInternational audienc
Epidemiological changes in Toxoplasma infection: a 7-year longitudinal study in pregnant women in Lyon, France, 2017–2023
No full textInternational audienceThe epidemiology of Toxoplasma infection is known to vary geographically, but is also likely to vary over time, under the influence of many contributing factors. Monitoring is particularly useful in the context of preventing congenital toxoplasmosis. We took advantage of the French prenatal prevention programme to retrospectively assess changes between 2017 and 2023 in seroprevalence and incidence rates of Toxoplasma infection in pregnant women and the incidence of congenital infections. We conducted a longitudinal retrospective study including all pregnancies with known Toxoplasma status followed up at Lyon’s public maternity hospitals between 2017 and 2023 (71,922 pregnancies). We used a multivariable logistic regression model to identify factors (age-group, WHO region of origin, population density of the area of residence and parity) associated with seropositivity. The seroprevalence of toxoplasmosis decreased consistently from 26.4% in 2017 to 22.1% in 2023 ( p = 0.003), while maternal infection incidence remained stable at 1.3/1,000 pregnancies at risk. Notably, the seroprevalence showed a linear increase with age from 18.9% in women aged 25–29 years to 38.0% in women aged ≥40 years ( p < 0.001). The seroprevalence was lower in pregnant women living in rural areas [adjusted seroprevalence ratio (aPR) = 0.87, 95% CI: 0.82–0.92] and higher in multiparous women (aPR = 1.08, 95% CI: 1.04–1.12). This study confirms the ongoing decline in toxoplasmosis seroprevalence while seroconversions remained stable, indicating a need for more tests in seronegative women in the future. These findings highlight the need for ongoing monitoring and refinement of congenital toxoplasmosis prevention strategies in high-income countries.Il est connu que l’épidémiologie de l’infection à Toxoplasma varie selon les zones géographiques, mais elle est également susceptible de varier au fil du temps, sous l’influence de nombreux facteurs contributifs. La surveillance est particulièrement utile dans le cadre de la prévention de la toxoplasmose congénitale. Nous avons exploité le programme français de prévention prénatale pour évaluer rétrospectivement l’évolution entre 2017 et 2023 de la séroprévalence et des taux d’incidence de l’infection à Toxoplasma chez les femmes enceintes, ainsi que de l’incidence des infections congénitales. Nous avons mené une étude rétrospective longitudinale incluant toutes les grossesses dont le statut toxoplasmique était connu, suivies dans les maternités publiques de Lyon entre 2017 et 2023 (71 922 grossesses). Nous avons utilisé un modèle de régression logistique multivariée pour identifier les facteurs (tranche d’âge, région d’origine OMS, densité de population du lieu de résidence et parité) associés à la séropositivité. La séroprévalence de la toxoplasmose a diminué de façon constante, passant de 26,4 % en 2017 à 22,1 % en 2023 ( p = 0,003), tandis que l’incidence de l’infection maternelle est restée stable à 1,3/1 000 grossesses à risque. Il est à noter que la séroprévalence a montré une augmentation linéaire avec l’âge, passant de 18,9 % chez les femmes âgées de 25 à 29 ans à 38,0 % chez les femmes âgées de plus de 40 ans ( p < 0,001). La séroprévalence était plus faible chez les femmes enceintes vivant en zone rurale [rapport de séroprévalence ajusté (aPR) = 0,87, IC à 95 % : 0,82-0,92] et plus élevée chez les femmes multipares (aPR = 1,08, IC à 95 % : 1,04-1,12). Cette étude confirme la baisse continue de la séroprévalence de la toxoplasmose, tandis que les séroconversions sont restées stables, ce qui indique la nécessité de réaliser davantage de tests chez les femmes séronégatives à l’avenir. Ces résultats soulignent la nécessité d’une surveillance continue et d’un perfectionnement des stratégies de prévention de la toxoplasmose congénitale dans les pays à revenu élevé
Causal Inference in Presence of Intra‐Patient Correlation due to Repeated Measurements of Exposure and Outcome in Longitudinal Settings
No full textInternational audienceABSTRACT Introduction In causal inference with time‐dependent confounding between an exposure and an outcome, the repeated nature of measures is likely to lead to intra‐patient correlation and introduces bias in the estimation of the causal effect, even in the absence of unmeasured confounders. Method We evaluated the impact of intra‐patient correlation on causal effect estimation with g‐computation, inverse probability weighting (IPW) and longitudinal targeted maximum likelihood estimator (LTMLE), and compared two ways of accounting for it, using a fixed‐effects or a mixed‐effects approach. We conducted a simulation analysis under different scenarios for numerous time points and a real‐life analysis to investigate the causal effect of pregnancy on neurological disability in multiple sclerosis. Results In simulation analyses, the presence of intra‐patient correlation led to bias in the causal effect estimation with g‐computation, IPW, and LTMLE when this was not accounted for; the bias was smaller for LTMLE. Taking into account intra‐patient correlation with fixed‐effects and mixed‐effects approaches reduced the bias in g‐computation, with lower standard errors for the mixed‐effects approach. Regarding IPW, the fixed‐effects approach suffered from weight stability issues when the number of time points increased, and the mixed‐effects approach provided inconsistent estimates of the intra‐patient correlation in the exposure model. Application to real‐life data yielded results consistent with the simulation study, highlighting the importance of accounting for intra‐patient correlation. Conclusion When analyzing longitudinal data in the presence of time‐dependent confounding using g‐methods, intra‐patient correlation due to repeated measurements of exposure and outcome should be accounted for in the causal reasoning