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Abstract: Although broadly used, consolidative autologous hematopoietic stem cell transplantation (auto-HCT) for relapsed/refractory (R/R) T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) has never been specifically investigated. Here, we have analyzed outcomes of auto-HCT for THRLBCL compared with diffuse large cell B-cell lymphoma not otherwise specified (DLBCL). Eligible for this retrospective registry study were adult patients with R/R THRLBCL and DLBCL, respectively, who underwent a first auto-HCT in a salvage-sensitive disease status as assessed by positron emission tomography-computed tomography between 2016 and 2021 and were registered with the European Society for Blood and Marrow Transplantation database. The primary end point was progression-free survival (PFS) 2 years after transplantation. A total of 201 patients with THRLBCL and 5543 with DLBCL were included. There were no significant differences in terms of disease status at HCT, pretreatment lines, and interval from diagnosis to transplant between the cohorts, but patients with THRLBCL were significantly younger, contained a higher proportion of men, and had a better performance status. Compared with DLBCL, THRLBCL was associated with significantly better 2-year PFS (78% vs 59%; P < .001) and overall survival (OS, 81% vs 74%; P = .02) because of a significantly lower 2-year relapse incidence (16% vs 35%; P < .001). On multivariate analysis, favorable relapse risk (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.31-0.7) and PFS (HR, 0.58; 95% CI, 0.41-0.82) of patients with THRLBCL remained significant, whereas OS benefits (HR, 0.78; 95% CI, 0.54-1.12) did not. These results were validated in a propensity score-matched analysis. These data prove auto-HCT as an effective treatment option for salvage-sensitive R/R THRLBCL., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: A significant proportion of trans women is demanding for a genital gender-affirming surgery, with vulvo-vaginoplasty being the most frequently requested procedure. The gold standard for primary vaginoplasty in trans women is the penile skin inversion technique with scrotal skin graft, which allows for increased depth of the vaginal cavity., Aims: The assessment of vulvo-vaginoplasty outcomes utilizing penile skin inversion and scrotal skin graft in individuals assigned male at birth in the surgeon's learning curve involves evaluating aesthetics, functionality, and sexual aspects., Methods: A total of 76 individuals assigned male at birth were included in 2 French university hospitals from 2020 to 2022. They underwent vulvo-vaginoplasty following 8 key steps: scrotal skin excision; bilateral orchiectomy; dissection between the rectum, bladder, and prostate; penile dissection; clitoroplasty; urethroplasty; penile skin inversion with scrotal skin graft; labioplasty. The average follow-up period was 12.4 months, with participants averaging 35.7 years of age. Each patient was invited to complete a questionnaire during follow-up., Outcomes: The study's outcomes encompassed the assessment of both early and late surgical complications, postoperative sexuality, aesthetic results, and voiding satisfaction., Results: Of the total patients, 15.8% experienced major early postoperative complications, while 3% encountered major late postoperative complications. No complication was classified 4 or 5 in Clavien-Dindo scale. Most early complications were related to issues in vulvar healing, which did not compromise long-term aesthetic results. Patients-reported satisfaction was 82% after the procedure., Clinical Implications: Vulvo-vaginoplasty utilizing penile skin inversion and scrotal skin graft for individuals assigned male at birth is a reproductive surgery procedure that can be successfully performed by experienced urologist. It achieves high patient-reported satisfaction even during the learning curve., Strengths and Limitations: The surgical procedures were consistent, and the sizable cohort of patients accurately reflects the learning curve of both surgeons. However, extrapolating long-term complications is challenging due to the relatively brief follow-up period. Additionally, there is a lack of self-reported sexual function data, and the scales used to assess patient-reported quality of life and urinary satisfaction are not specifically validated for transgender patients., Conclusion: Vulvo-vaginoplasty utilizing penile skin inversion and scrotal skin graft for individuals assigned male at birth is a complex surgical procedure. It appears to be achievable by experienced urologists during their learning curve, resulting in similar functional and surgical outcomes, along with high patient satisfaction., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Large pharmacokinetic (PK) variability of fluconazole has been reported in critically ill patients, but the implications for fluconazole dosing remain unclear. The objectives of this study were to evaluate the population PK of fluconazole and identify appropriate dosage regimens by simulations. This was a retrospective analysis of fluconazole PK data from patients hospitalized in critical care and infectious disease departments. Both parametric and nonparametric population approaches were used. Various loading and maintenance fluconazole doses were evaluated by simulations, with computation of the probabilities of PK/pharmacodynamic (PD) target attainment (PTA) and cumulative fractions of response (CFR) based on international and local minimum inhibitory concentration (MIC) distributions of Candida sp. Data from 36 critically ill patients and 16 non-critically ill patients were available for model building ( n = 202 concentrations). The final model adequately described the data, including the external data set (13 patients). After 24 h of therapy, 65% and 74% of patients had trough and area under the concentration-time curve values below the usual targets. Standard dosages were associated with low PTA for MIC >1 mg/L at 24 h. Higher loading doses administered two times daily improved PTA. CFR were >90% for C. albicans with standard dosages, while they were very low for C. glabrata , even with high dosages. Candida species and associated MIC distributions strongly influence fluconazole dosage requirements. Higher loading doses may be necessary for the achievement of PK/PD targets up to MIC breakpoints. The use of fluconazole for invasive C. glabrata infection should be discouraged because of poor PK/PD target attainment., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Enrique M. Ocio received honoraria from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Pfizer, Regeneron, Sanofi, and Takeda; disclosed consulting/advisory role for AbbVie, Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Menarini/Stemline Therapeutics, Oncopeptides, Pfizer, Sanofi, and Takeda, and participation in speakers' bureau for Janssen; received travel/accommodation expenses from Bristol Myers Squibb, GlaxoSmithKline, Janssen, and Lilly. Aurore Perrot: received honoraria from AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Pfizer, Sanofi, and Takeda; research funding from Takeda; and support for attending meetings and/or travel from Amgen, Janssen. Philippe Moreau: disclosed honoraria and consulting/advisory role for AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Roche, and Sanofi. Maria‐Victoria Mateos: received honoraria from AbbVie, Adaptive, Amgen, Bluebird bio, Celgene, GSK, Janssen, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Sea‐Gen, and Takeda, and is on the Editorial Board of HemaSphere. Sara Bringhen: received honoraria from Amgen, BMS/Celgene, and Janssen, and consulting fees from BMS/Celgene, Janssen, and Takeda; disclosed participation on a data safety monitoring board or advisory board for Amgen, Celgene, GSK, Janssen, Karyopharm, and Sanofi. Joaquín Martínez‐López received honoraria and consulting fees from BMS/Celgene, Incyte, Janssen, Novartis, Roche, and Sanofi; travel and accommodation support from BMS, Janssen, Novartis, Roche, and Sanofi. Lionel Karlin: received honoraria from AbbVie, Amgen, Celgene, Janssen, Sanofi, and Takeda; disclosed advisory role for Amgen, Celgene, GSK, Janssen, and Takeda. Song‐Yau Wang: disclosed no conflicts. Corina Oprea, Yi Li, and Ercem Kodas are employed by Sanofi and may hold stock and/or stock options in the company. Jesus San‐Miguel: received honoraria and consulting fees from Amgen, BMS/Celgene, GSK, Janssen, Karyopharma, Sanofi, and Takeda.

Objectives: Diagnostic imaging of peritoneal metastases in ovarian and colorectal cancer remains pivotal in selecting the most appropriate treatment and balancing clinical benefit with treatment-related morbidity and mortality. To address the challenges related to diagnostic imaging and detecting and reporting peritoneal metastatic spread, a joint guideline was created by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Society of Urogenital Radiology (ESUR), Peritoneal Surface Oncology Group International (PSOGI), and European Association of Nuclear Medicine (EANM)., Methods: A targeted literature search was performed and consensus recommendations were proposed using Delphi questionnaires and a five-point Likert scale., Results: A total of three Delphi rounds were performed. Consensus was reached on the position of diagnostic imaging for assessment of operability, treatment response monitoring, and follow-up of peritoneal metastases, optimal imaging modality and their technical imaging requirements depending on the indication and how to optimise communication of imaging results by the report and multidisciplinary board discussion. The complete list of recommendations is provided., Conclusion: These expert consensus statements aim to guide appropriate indications, acquisition, interpretation, and reporting of imaging for operability assessment, treatment response monitoring, and follow-up of peritoneal metastases in ovarian and colorectal cancer patients., Key Points: Question Staging peritoneal metastases (PM) helps to guide clinical decision-making for colorectal and ovarian cancer patients. How can we optimise the use of imaging techniques to assess PM? Findings Imaging plays a crucial role in the detection, operability assessment, treatment response monitoring, and follow-up of peritoneal metastases in colorectal and ovarian cancer patients. Clinical relevance These expert consensus statements aim to guide appropriate indication, acquisition, interpretation, and reporting of imaging for operability assessment, treatment response monitoring, and follow-up of peritoneal metastases in ovarian and colorectal cancer patients., (© 2024. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Objective: Trigeminal schwannoma (TS), though a rare and benign tumor, becomes a significant surgical challenge due to its intricate location. This study aims to detail the long-term functional outcomes and tumor control post-surgical resection., Method: We analyzed a multicentric retrospective cohort of 39 patients operated on for a TS in five tertiary centers between January 1993 and July 2022., Results: Six TS (15%) were in the middle fossa (type M), two (5%) in the posterior fossa (type P), and two (5%) were extracranial (type E). Twenty-nine (75%) were Dumbbell shape: Eighteen (47%) were MP type, seven (18%) were MPE type, and four (10%) were ME type. Fifth nerve symptoms were the foremost preoperative complaint: hypesthesia (51%), trigeminal neuralgia (36%), and paresthesia (30%). We report a favorable evolution course for 61% of preexisting deficits (half of patients with preoperative paresthesia and neuralgia improved while only 5% of preoperative hypesthesia improved). Postoperative hypesthesia was the most frequent de novo deficit 14 (74%) and resolved in solely half the cases. Various approaches were used according to tumor type. Gross total resection (GTR), Subtotal resection (STR), and partial resection (PR) were achieved in respectively 33% (N = 13), 10% (N = 4), and 56% (N = 22) of patients. The mean clinical and radiological FU was 63 months (12 - 283 months). GTR led to no sign of recurrence (mean FU: 60 months - range: 12-283 months). For STR or PR (67%): 23 (88%) were assigned to a Wait-&-rescan policy (WS group) which offered stability in 70% (N = 16). Three cases (8%) underwent a complementary GKS (GammaKnife) on the residual lesion (GK group) without tumor change., Conclusion: For large TS, the completeness of resection must consider the potential functional burden of surgery. With giant infiltrating lesions, a strategy of planned subtotal resection, complemented by radiosurgery, either complementary or uppon regrowth, may provide similar oncological outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: An updated revision of the 2016 recommendations from the French Study Group for Large Vessel Vasculitis (GEFA) was needed to better delineate the place and management of immunosuppressants or biologics in giant cell arteritis (GCA)., Methods: A panel of 18 physicians, including internists and rheumatologists, constituted the task force of this project and drafted the recommendations. Twelve additional readers were asked to analyse and comment on the recommendations. Two face-to-face virtual meetings were held to discuss and validate the recommendations. Each member voted individually, and a>85% consensus was required to validate each recommendation., Results: From the initial 6 questions, 26 recommendations were validated. The following main recommendations were validated. (1) Subcutaneous 162mg tocilizumab (TCZ) for at least 12months should be used first when glucocorticoid (GC)-sparing treatment is needed with the objective of discontinuing GCs within the subsequent 6months. (2) GCA patients who have experienced any of the following conditions must receive TCZ at GCA diagnosis with 6months of GC therapy: major cardiovascular event, osteoporosis with fracture, psychiatric event with GC use, complicated diabetes mellitus, or any previous>6months of GC treatment. (3) In patients in whom GC discontinuation is not possible after 12months of treatment because of persistent disease activity or in patients in whom GC-related adverse events are unacceptable, TCZ (or alternatively methotrexate) may be proposed., Conclusions: These recommendations were constructed based on the results of the published literature and the experts' experiences to standardise therapeutic practices in France. Further updates will likely be necessary following new publications., Competing Interests: Disclosure of interest HdB, MS and VDP received fees from Roche Chugai, Novartis and Fresenius Kabi. The other authors declare that they have no competing interest., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Context: Spasticity is characterized by muscle hypertonia due to a velocity-dependent increase in tonic stretch reflexes, mostly related to hyperactive spinal reflexes. After spinal cord injury, the impact of noxious stimuli on autonomic dysreflexia is well documented. It is admitted in clinical practice that sublesional noxious stimuli can also increase spasticity. However, this has never been reported in the literature. In this single case study, we describe the impact of a noxious stimulus (bladder stone) on the spasticity of lower limbs in a male with spinal cord injury, using quantitative gait analysis before and after stone removal., Findings: : Clinical evaluation was performed on the subject before and after bladder lithiasis removal, by two physiotherapists using ASIA score and the Modified Ashworth scale. Quantitative gait analyses were compared before and 3 months after lithiasis resection.Regarding gait kinematics, there was a reduction of the right knee recurvatum, and of the successive increases of flexion (double bump) of flexion in the swing phase. In the stance phase, the right ankle maximum dorsiflexion increased. In the swing phase, the double bump of ankle dorsiflexion disappeared. Surface electromyography showed a reduction of the triceps surae hypertonia, especially in the right gastrocnemius muscle at the swing., Conclusion: We propose that lithiasis created a noxious stimulus regarding the S2, S3 and S4 metamers with a diffusion of the spinal reflex to the metamers S1, S2, S3 and S4. This highlights a potential causal link between an intravesical noxious stimulus and an increase in the subject's spasticity, through a disinhibited spinal nociceptive reflex.

Background: Assessing the potential increased risk of viral rebound (VR) in migrants requires adequate control for sex and acquisition risk groups., Methods: People living with HIV1, enrolled in the ANRS CO4-French Hospital Database on HIV, who achieved virological suppression with antiretroviral therapy (ART) initiated between 2006 and 2016 were included. We first compared the risk of VR, with loss to follow-up and death considered as competing events, across origin among the HIV acquisition groups, then across acquisition groups among the different origins, and finally across modality of a variable combining sex, acquisition group, and origin. Models were adjusted for clinical and biological confounding factors., Results: We included 21 571 French natives (FRA), 10 148 migrants from sub-Saharan Africa (SSA), 1137 migrants from the non-French West Indies (NFWI), and 4205 other migrants (OTHER). The 5-year probability of VR was 19% (95% confidence interval [CI] 19-20) overall, 15% in FRA, 21% in OTHER, 26% in SSA, and 34% in NFWI (p < 0.0001). It was 14% in men who have sex with men (MSM), 23% in heterosexual men, and 23% in women (p < 0.0001). After adjustment, all acquisition groups had a higher risk of VR than MSM from FRA, with men and women from NFWI having the highest risk (adjusted hazard ratio [aHR] 2.46; 95% CI 2.12-2.86 and aHR 2.59; 95% CI 2.20-3.04, respectively). Within each acquisition group, all groups of origin had a higher risk of VR than FRA. Within each region of origin, except the NFWI, heterosexual men had a higher risk of VR than MSM., Conclusions: After accounting for sex and acquisition group, migration, especially from NFWI, remains prognostic of VR., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Phage therapy is a highly promising approach to address the challenge that is presented by the global burden of antimicrobial resistance. Given the natural specificity of phages, phage susceptibility testing (PST) is a prerequisite for successful personalized therapy, allowing the selection of active phages from large and diverse collections. However, the issue of an easy-to-use and standardized technique remains. In this review, we describe the principles, advantages and drawbacks of two routinely used PST techniques: plaque and growth kinetic assays. These are labour-intensive and time-consuming methods that require automation of one or more steps, including preparation of test panels, incubation, reading and analysis of results. In addition to automation, there is an urgent need to establish a reference method to enable efficient of PST techniques selection of therapeutic phages. We discuss knowledge gaps and parameters that need to be investigated to work towards this goal., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown., Methods: We analysed the evolution of both the nasopharyngeal viral load and the serum neutralization activity against the variant of infection in 199 hospitalized patients (109 treated with Evusheld, 90 treated with placebo) infected with the SARS-CoV-2 virus and included in the randomized, double-blind, trial DisCoVeRy (NCT04315948). Using a mechanistic mathematical model, we reconstructed the trajectories of viral kinetics and how they are modulated by the increase in serum neutralization activity during Evusheld treatment., Results: Our model identified that the neutralization activity was associated with viral kinetics. Reflecting the variant-dependent neutralization activity of Evusheld, the antiviral activity of Evusheld was larger in patients infected with pre-Omicron or Omicron BA.2 variants than in patients infected with Omicron BA.1 variant. More specifically, the model predicted that Evusheld reduced the median time to viral clearance compared with placebo-treated patients by more than 5 days in patients infected by pre-Omicron (median: 5.9; 80% PI: 2.1-13.6) or Omicron BA.2 (median: 5.4; 80% PI: 2.0-12.4), respectively. The effect was more modest in patients infected by the Omicron BA.1 variant, reducing the median time to viral clearance by 2 days (median: 2.2; 80% PI: 0.4-8.9)., Conclusions: Hospitalized patients treated with Evusheld had a shorter median time to SARS-CoV-2 viral clearance. As Evusheld antiviral activity is mediated by the level of neutralization activity, its impact on viral clearance varies largely according to the variant of infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous diseases caused by mutations affecting neuromuscular transmission. Even if the first symptoms mainly occur during childhood, adult neurologists must confront this challenging diagnosis and manage these patients throughout their adulthood. However, long-term follow-up data from large cohorts of CMS patients are lacking, and the long-term prognosis of these patients is largely unknown. We report the clinical features, diagnostic difficulties, and long-term prognosis of a French nationwide cohort of 235 adult patients with genetically confirmed CMS followed in 23 specialized neuromuscular centres. Data were retrospectively analysed. Of the 235 patients, 123 were female (52.3%). The diagnosis was made in adulthood in 139 patients, 110 of whom presented their first symptoms before the age of 18. Mean follow-up time between first symptoms and last visit was 34 years [standard deviation (SD) = 15.1]. Pathogenic variants were found in 19 disease-related genes. CHRNE-low expressor variants were the most common (23.8%), followed by variants in DOK7 (18.7%) and RAPSN (14%). Genotypes were clustered into four groups according to the initial presentation: ocular group (CHRNE-LE, CHRND, FCCMS), distal group (SCCMS), limb-girdle group (RAPSN, COLQ, DOK7, GMPPB, GFPT1), and a variable-phenotype group (MUSK, AGRN). The phenotypical features of CMS did not change throughout life. Only four genotypes had a proportion of patients requiring intensive care unit admission that exceeded 20%: RAPSN (54.8%), MUSK (50%), DOK7 (38.6%) and AGRN (25.0%). In RAPSN and MUSK patients most ICU admissions occurred before age 18 years and in DOK7 and AGRN patients at or after 18 years of age. Different patterns of disease course (stability, improvement and progressive worsening) may succeed one another in the same patient throughout life, particularly in AGRN, DOK7 and COLQ. At the last visit, 55% of SCCMS and 36.3% of DOK7 patients required ventilation; 36.3% of DOK7 patients, 25% of GMPPB patients and 20% of GFPT1 patients were wheelchair-bound; most of the patients who were both wheelchair-bound and ventilated were DOK7 patients. Six patients died in this cohort. The positive impact of therapy was striking, even in severely affected patients. In conclusion, even if motor and/or respiratory deterioration could occur in patients with initially moderate disease, particularly in DOK7, SCCMS and GFPT1 patients, the long-term prognosis for most CMS patients was favourable, with neither ventilation nor wheelchair needed at last visit. CHRNE-LE patients did not worsen during adulthood and RAPSN patients, often severely affected in early childhood, subsequently improved., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: To describe the set-up in 2022 of the PHAGEinLYON Clinic program dedicated to improve access to phage therapy in France using pharmaceutical-grade phages., Methods: We described the process, prospectively collected all phage therapy requests received during 2022 and reviewed them retrospectively to analyze the decision and also the patient care pathway (NCT05883995)., Results: Among 143 phage therapy requests, the indication was confirmed by multidisciplinary team meetings for 57 (40%) of them, and 44 were infected with bacteria that could be easily targeted by phages in France. Finally, 33 patients were treated, including 26 at our institution as compassionate use or in a clinical trial. Main indications were complex bone and joint infections, endovascular infections and lung infections. To manage these patients, 172 pharmaceutic phage cocktails targeting S. aureus and/or P. aeruginosa were prepared; 57 were dedicated to local, and 99 to intravenous injections. During the follow-up, 18 (69%) patients had a favorable clinical evolution, 6 (23%) required subsequent phage therapy, with the same phages with a greater phage exposition, or with different phages from elsewhere., Conclusions: The implementation of the PHAGEinLYON Clinic program in 2022 was associated with a groundbreaking access of phage therapy in France., (Copyright © 2024. Published by Elsevier Ltd.)

In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC., (© 2024. The Author(s).)

Background: Aromatase inhibitor is associated with a high incidence of Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS) in postmenopausal women with hormone-sensitive breast cancer., Objective: This scoping review aims to identify available information regarding the frameworks, models, or strategies of adapted physical activity (APA) programs implemented for the prevention and management of AIMSS., Methods: Search was realized by two independent reviewers in six databases following PRISMA-ScR guidelines. Data of included articles were extracted, and risk of bias analyzed., Results: Finally, 14 were included. No study has examined APA in the prevention of AIMSS. There is no solid evidence supporting the impact of APA on the management of AIMSS. However, evidence suggests that an APA program can reduce the worst joint pain and improve the quality of life., Conclusion: Future research will enlighten clinical practices with the development of personalized APA programs in hormone-sensitive breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Hematological involvement (HI) is one of the life-threatening risk organs (ROs) in Langerhans cell histiocytosis (LCH). Lahey criteria have defined HI since 1975 as hemoglobin <10 g/dL and/or platelets <100 G/L and/or leukopenia (white blood cell count <4 G/L) and/or neutrophils <1.5 G/. Among the 2313 patients <18 years old enrolled in the French National Histiocytosis Registry (1983-2023), 331 developed HI (median age at diagnosis: 1 year); median follow-up lasted 8.1 years. Bone-marrow aspirate smears and biopsies may show reactive histiocytes, hemophagocytosis or myelofibrosis but never confirm the diagnosis. Fifty-eight (17%) patients developed macrophage-activation syndrome, sometimes related to acute Epstein-Barr virus or cytomegalovirus infection, sometimes months before typical LCH manifestations appeared. Hemoglobin and platelet thresholds for initiating transfusion(s) appear to accurately distinguish 2 groups: mild HI (MHI; >7 g/dL and >20 G/L, respectively) and severe HI (SHI; ≤7 g/dL and ≤20 G/L). Each entity has different organ involvements, laboratory parameters, mutational status, blood BRAFV600E loads, drug sensitivities and outcomes (respective MHI and SHI 10-year survival rates: 98% and 73%). Since 1998, mortality first declined with combination Cladribine-cytarabine therapy, and then with mitogen-activated protein-kinase inhibitors since 2014. Forty-one (12%) patients developed neurodegenerative complications that have emerged as a risk for long-term survivors. These results suggest limiting the HI-RO definition to SHI, as it encompasses almost all medical complications of LCH. Future clinical trials might demonstrate that targeted-therapy approaches would be better adapted for these patients, while MHI can be managed with classic therapies., (Copyright © 2024 American Society of Hematology.)

Background: It is uncertain whether fluid administration can improve patients with systemic venous congestion and haemodynamic instability. This study aimed to describe the changes in systemic venous congestion and peripheral perfusion parameters induced by a fluid challenge in these patients, and to analyse the influence of the fluid responsiveness status on these changes., Methods: The study is a single-centre prospective cohort study of 36 critically ill ICU patients with haemodynamic instability and a maximum vena cava diameter ≥ 20 mm. Changes in cardiac index during a fluid challenge (4 mL/kg of lactated Ringer's solution during 5 min) assessed by pulse contour analysis, central venous pressure, ultrasound systemic congestion parameters (portal venous flow pulsatility index, supra hepatic and intrarenal venous Doppler), and peripheral perfusion parameters (capillary refill time and peripheral perfusion index) were assessed in the overall population. All these data were compared between patients presenting a cardiac index increase > 10% during the fluid challenge (fluid responders) and the others (fluid non-responders)., Results: Twenty-eight (78%) patients were admitted for postoperative care following cardiac surgery; their mean ± SD left ventricular ejection fraction was 42 ± 9% and right ventricular dysfunction was found in at least 61% of the patients. The mean ± SD SOFA score was 9 ± 3. Thirteen (36%) patients were fluid responders. The fluid challenge administration induced a significant increase in portal pulsatility index, VExUS score, and central venous pressure without significant difference of these changes between fluid responders and non-responders. No significant change in perfusion parameters was observed., Conclusion: Fluid administration in patients with haemodynamic instability and systemic venous congestion worsens venous congestion regardless of the fluid responsiveness status, without improving perfusion parameters., (© 2024. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.

Competing Interests: The authors declare no funding or conflicts of interest.

In recent years, it has become clear that artificial intelligence (AI) models can achieve high accuracy in specific pathology-related tasks. An example is our deep-learning model, designed to automatically detect serous tubal intraepithelial carcinoma (STIC), the precursor lesion to high-grade serous ovarian carcinoma, found in the fallopian tube. However, the standalone performance of a model is insufficient to determine its value in the diagnostic setting. To evaluate the impact of the use of this model on pathologists' performance, we set up a fully crossed multireader, multicase study, in which 26 participants, from 11 countries, reviewed 100 digitalized H&E-stained slides of fallopian tubes (30 cases/70 controls) with and without AI assistance, with a washout period between the sessions. We evaluated the effect of the deep-learning model on accuracy, slide review time and (subjectively perceived) diagnostic certainty, using mixed-models analysis. With AI assistance, we found a significant increase in accuracy (p < 0.01) whereby the average sensitivity increased from 82% to 93%. Further, there was a significant 44 s (32%) reduction in slide review time (p < 0.01). The level of certainty that the participants felt versus their own assessment also significantly increased, by 0.24 on a 10-point scale (p < 0.01). In conclusion, we found that, in a diverse group of pathologists and pathology residents, AI support resulted in a significant improvement in the accuracy of STIC diagnosis and was coupled with a substantial reduction in slide review time. This model has the potential to provide meaningful support to pathologists in the diagnosis of STIC, ultimately streamlining and optimizing the overall diagnostic process., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Glucose (GBT) and lactulose (LBT) breath tests have been recommended for the diagnosis of small intestinal bacterial overgrowth (SIBO). LBT may yield a higher prevalence of SIBO diagnosis, because of its limited small bowel absorption, and therefore colonic fermentation. The aim of this retrospective study was to confirm this hypothesis, in irritable bowel syndrome patients (IBS)., Methods: Among a cohort of 995 patients who underwent GBT or LBT, 287 with typical IBS according to Rome IV criteria, without past digestive surgery or significant medical comorbidities, were included., Results: 155 IBS patients underwent GBT, and 132 LBT (71% women, mean age 45±15, mean BMI: 22.6±4.3 kg/m 2 ). There were no difference between both groups in terms of demographics, IBS type and severity of symptoms. The prevalence of SIBO according to LBT was 47%, versus 4.5% only with GBT (p<0.001). The prevalence of methane values ≥ 10 ppm were similar in both groups (34%)., Conclusion: LBT is very frequently positive in IBS patients, as compared to GBT. The 2 tests are thus not interchangeable for the diagnosis of SIBO. Furthermore, the positivity of both tests was not correlated with symptoms, which may indicate a poor clinical interest of these tests in IBS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Cladophialophora bantiana is one of the most virulent phaeohyphomycetes, typically causes non-angiogenic single (or sometimes multiple) cystic brain lesions, and has resulted in a mortality rate of up to 70%. Most C bantiana cases are described either in a series of isolated reports or in very small cohorts. The aim of this retrospective nation-based study was to share the data on C bantiana phaeohyphomycosis cases reported in France and French overseas territories over the past two decades to improve understanding of this disease., Methods: Patients with C bantiana infection were processed through the active surveillance programme of invasive fungal infections launched by the National Reference Center for Mycoses and Antifungals, Institut Pasteur (Paris, France), and the French Surveillance Network of Invasive Fungal Infections, which involved 29 hospitals from mainland France and overseas French territories. Only proven and probable cases of infection, according to the revised and updated consensus definitions from the European Organization for Research and Treatment of Cancer and Mycoses Study Group, were included in the study. Patients were diagnosed or confirmed, or both, using a polyphasic approach at the Institut Pasteur between 2002 and 2022. Patients were separated into two groups: those with CNS involvement and those with no CNS involvement. The primary outcome was the survival rate., Findings: A total of 23 patients with a C bantiana invasive infection were included during the study period (Jan 1, 2002, to Dec 31, 2022). The median age was 56 years in the CNS involvement group and 65 years in the non-CNS involvement group. Until 2021, the annual number of cases varied between zero and two, with six cases observed in 2022, the warmest year recorded in France since 1900. CNS involvement was observed in 15 (65%) patients, including three disseminated cases; skin and soft tissue involvement in seven (30%) patients and an isolated lung infection in one case. Diabetes was observed in five patients, and any immunodepression factor was observed in 14 (61%) of 23 patients. When considering only patients with CNS involvement, 9-month survival appeared higher in patients who underwent exeresis or large drainage (three [75%] of four patients vs three [27%] of 11 patients; p=0·24) and significantly higher in those treated for 2 or more weeks with triple antifungal therapy (liposomal amphotericin B plus posaconazole and flucytosine; seven [78%] of nine patients vs one [17%] of six patients; p=0·040). Two patients were treated with excision surgery alone (one patient with success, and the other patient lost to follow-up)., Interpretation: This study shows that the clinical presentations and underlying medical conditions of C bantiana infections are more diverse than previously described. It also emphasises a significant difference in mortality rate between those with and without CNS involvement. The prognosis improved when surgery was performed and triple antifungal therapy was administered. Such rare and devastating invasive fungal infections should be managed by a multidisciplinary team., Funding: Santé Publique France., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Gilles de la Tourette syndrome (GTS) and dystonia (DYS) are both hyperkinetic movement disorders effectively treated by deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi). In this study, we compared single-neuron activity in the GPi between 18 GTS patients (with an average of 41 cells per patient) and 17 DYS patients (with an average of 54 cells per patient), all of whom underwent bilateral pallidal stimulation surgery, under general anesthesia or while awake at rest. We found no significant differences in GPi neuronal activity characteristics between patients operated on under general anesthesia versus those who were awake, irrespective of their diagnosis (GTS or DYS). We found higher firing rates, firing rate in bursts, pause duration and interspike interval coefficient of variation in GTS patients compared to DYS patients. On the opposite, we found higher number of pauses and bursts frequency in DYS patients. Lastly, we found a higher proportion of GPi oscillatory activities in DYS compared to GTS patients, with predominant activity within the low-frequency band (theta/alpha) in both patient groups. These findings underscore the complex relationship between the different neuronal discharge characteristic such as oscillatory or bursting activity within the GPi in shaping the clinical phenotypes of hyperkinetic disorders. Further research is warranted to deepen our understanding of how neuronal patterns are transmitted within deep brain structures and to develop strategies aimed at normalizing these pathological activities, by refining DBS techniques to enhance treatment efficacy and individual outcomes., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: In acute stroke, diffusion-weighted imaging (DWI) is used to assess the ischemic core. Dynamic-susceptibility contrast perfusion magnetic resonance imaging allows an estimation of the oxygen extraction fraction (OEF), but the outcome of DWI lesions with increased OEF postrecanalization is unclear. This study investigated the impact of OEF on the fate of DWI lesions in patients achieving recanalization after thrombectomy., Methods: This was a retrospective analysis of the HIBISCUS-STROKE cohort (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke; NCT: 03149705), a single-center observational study that prospectively enrolled patients who underwent magnetic resonance imaging triage for thrombectomy and a day-6 T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging. Automated postprocessing of admission dynamic-susceptibility contrast perfusion magnetic resonance imaging generated OEF maps. At visual analysis, the OEF status within DWI lesions was assessed in comparison to the contralateral side and correlated with volume changes (difference of ischemic lesion between admission DWI and registered day-6 T2-FLAIR). At voxel-based analysis, recovered DWI regions (lesions present on the admission DWI but absent on the registered day-6 T2-FLAIR) and nonrecovered regions were segmented to extract semiquantitative OEF values., Results: Of the participants enrolled from 2016 to 2022, 134 of 321 (41.7%) were included (median age, 71.0 years; 58.2% male; median baseline National Institutes of Health Scale score, 15.0). At visual analysis, 46 of 134 (34.3%) patients had increased OEF within DWI lesions. These patients were more likely to show a reduction in ischemic lesion volumes compared with those without increased OEF (median change, -4.0 versus 4.8 mL; P <0.0001). Multivariable analysis indicated that increased OEF within DWI lesions was associated with a reduction in ischemic lesion volumes from admission DWI to day-6 T2-FLAIR (odds ratio, 0.68 [95% CI, 0.49-0.87]; P =0.008). At voxel-based analysis, recovered DWI regions had increased OEF, while nonrecovered regions had decreased OEF (median, 126.9% versus -27.0%; P <0.0001)., Conclusions: Increased OEF within hyperacute DWI lesions was associated with ischemic lesion recovery between admission DWI and day-6 T2-FLAIR in patients achieving recanalization after thrombectomy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03149705., Competing Interests: None.

Background and Objectives: To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC)., Methods: Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; p = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, p = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; p = 0.02)., Discussion: MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. The POLO trial showed that olaparib (PARP inhibitor) improved progression-free survival (PFS) but not overall survival (OS), when used as maintenance therapy after ≥ 16 weeks of disease control with first-line platinum-based chemotherapy in patients with germline (g) BRCA 1 or 2 pathogenic variants (PV) metastatic PDAC. However, real-world data on the effectiveness of olaparib are missing., Methods: Patients with unresectable PDAC associated with somatic (s) or (g)BRCA1/2 and (g)non-BRCA-HRD PV (i.e. other homologous recombination deficiency/HRD genes) who were treated with olaparib between 2020-2023 were included. The primary objective was to describe treatment patterns. Secondary exploratory objectives included OS and PFS in patients treated with olaparib according to the POLO trial or not, OS and PFS in patients with (g)HRD PV-associated PDAC versus (s)PVs, olaparib safety profile and factors associated with olaparib poor outcomes., Results: Among 85 patients, 45.9 % received olaparib as defined by the POLO trial. No difference in OS and PFS was observed between patients who received olaparib according to the POLO trial versus not. Patients with (g)HRD PV-associated PDAC had better OS compared to others (22.3 versus 10.5 months, p = 0.038). Factors associated with olaparib poor outcomes included a high neutrophil-to-lymphocyte ratio and the use of olaparib outside the recommendations of the POLO trial. Few grade ≥ 3 adverse events were reported (9.4 %)., Conclusion: Patients with (g)HRD PV-associated PDAC had longer OS than those with (s)HRD PV. Olaparib use beyond the scope of the POLO trial was associated with poor outcomes., Competing Interests: Declaration of Competing Interest APe declares speaker’s engagement from Servier; consulting/advisory role for Amgen; travel grant from Ipsen, Merk and Servier. DT reports consultancy, advisory fees, honoraria from Servier, Pierre Fabre, Merck Serono, MSD, BMS, AZ, Roche, Sanofi; research funding from Sandoz, Astra Zenenca, Servier, MSD; travel grants from Pierre Fabre, MSD, Servier, Roche. JT has received honoraria as a speaker and/or in an advisory role from: AMGEN, Astellas, Astra Zeneca, BMS, Boehringer Ingelheim, Merck KGaA, MSD, Novartis, ONO pharmaceuticals, Pierre Fabre, Roche Genentech, Sanofi, Servier, Takeda. MM reports consultancy, advisory fees, honoraria from Pierre Fabre, Merck Serono, MSD, Takeda; travel grants from Pierre Fabre, Servier. OB reports consultancy, advisory fees, honoraria from Servier, Amgen, Pierre Fabre, Merck Serono, MSD, Takeda, Deciphera; travel grants from Pierre Fabre, Servier, MSD., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Thesaurismosis or storage diseases are rare genetic disorders due to an abnormal accumulation of an organic compound or its metabolite within cells. These conditions are either secondary to a defect in catabolism caused by enzymatic dysfunction or to a deficiency in transport proteins. They encompass lysosomal storage diseases, lipid storage diseases or dyslipidemias, and glycogen storage disorders or glycogenoses. Diagnosis is typically based on clinical and biological anomalies but may be made or suggested by the pathologist when symptoms are atypical or when biochemical or genetic tests are challenging to interpret. For accurate diagnosis, it is crucial to freeze a portion of the samples. Special staining and electronic microscopy can also aid in the diagnostic process. As the diagnosis is multidisciplinary, collaboration with clinicians, biochemists and geneticists is essential., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Real life data about the long-term efficacy of darvadstrocel for treating perianal fistulas in Crohn's disease (CD) remain scarce., Aim: To report the effectiveness and safety of darvadstrocel therapy to close perianal fistula in a real-life cohort of CD patients., Methods: All patients with CD suffering complex draining perianal fistulas who consecutively underwent administration of a single local injection of darvadstrocel at two centres were followed up and evaluated. The primary endpoint was clinical remission (closure of all external openings with no discharge at pressure) at week 24. Combined remission (defined as clinically plus MRI-assessed fistula closure) were also assessed at week 24 and 52., Results: A total of 36 CD patients (19 Male, mean age 38.5 years) were included with a median follow up of 16 months. Clinical remission was achieved in 17 out of 36 patients (47.2 %) and combined remission in 15 out of 36 patients (41.6 %) at week 24. At week 52, clinical and combined remission was achieved in 17 out of 36 patients (47.2 %) and in 15 out of 33 evaluable patients (45.4 %), respectively., Conclusion: In this real-world setting, a successful response to darvadstrocel therapy based on clinical remission was reported in around half of the patients and combined remission including radiological assessment in more than 4 out of 10 patients., Competing Interests: Declaration of competing interest R Altwegg, Maria Alonso-Gomez, declares no conflict of interest related to this work. S Nancey declares counseling, boards, transports or fees from Abbvie, Biogen, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Takeda, Tillots, BMS, Amgen, and Fresenius. E Cotte declares fees from Abbvie, Takeda G Boschetti declares fees from Abbvie, Takeda, Janssen Anne Laure Charlois: None Claire Gay: Takeda, Abbvie, Janssen. Pauline Danion: none Emilie Malezieux: Nonea, (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

CASPR2-associated neurological disorders encompass a wide clinical spectrum broadly divided into overlapping three autoimmune syndromes: CASPR2 limbic encephalitis, Morvan syndrome, and Isaacs syndrome. CASPR2 is a neuronal protein expressed at different sites in the central and peripheral nervous system and has a variety of roles and functions regarding neuronal excitability, synaptic plasticity, and homeostasis of inhibitory networks, most of which are only partially understood. CASPR2 antibodies have various pathogenic effects including internalization of CASPR2, disruption of protein-protein interactions, and, possibly, complement activation. Their pathogenic effect is well demonstrated in the limbic encephalitis phenotype, but the role of pathogenic antibodies in the development of other clinical manifestations is less clear. CASPR2 limbic encephalitis also differ from the other CASPR2-associated disorders in regard to HLA allele and paraneoplastic associations, suggesting it has immunological mechanisms distinct from the other clinical forms. Future studies are needed to better understand how the immunological alterations lead to the different phenotypes associated with CASPR2 antibodies., (Copyright © 2024. Published by Elsevier Masson SAS.)

T-lymphoblastic lymphoma (T-LBL) and thymoma are two rare primary tumors of the thymus deriving either from T-cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase-positive (TdT + ) T-cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T-LBL and TdT + T-lymphocyte-rich thymoma could be challenging, especially in the case of needle biopsy. To distinguish between T-LBL and thymoma-associated lymphoid proliferations, we analyzed the global DNA methylation using two different technologies, namely MeDIP array and EPIC array, in independent samples series [17 T-LBLs compared with one TdT + lymphocyte-rich thymoma (B1 subtype) and three normal thymi, and seven lymphocyte-rich thymomas compared with 24 T-LBLs, respectively]. In unsupervised principal component analysis (PCA), T-LBL and thymoma samples clustered separately. We identified differentially methylated regions (DMRs) using MeDIP-array and EPIC-array datasets and nine overlapping genes between the two datasets considering the top 100 DMRs including ZIC1, TSHZ2, CDC42BPB, RBM24, C10orf53, and MACROD2. In order to explore the DNA methylation profiles in larger series, we defined a classifier based on these six differentially methylated gene promoters, developed an MS-MLPA assay, and demonstrated a significant differential methylation between thymomas (hypomethylated; n = 48) and T-LBLs (hypermethylated; n = 54) (methylation ratio median 0.03 versus 0.66, respectively; p < 0.0001), with MACROD2 methylation status the most discriminating. Using a machine learning strategy, we built a prediction model trained with the EPIC-array dataset and defined a cumulative score taking into account the weight of each feature. A score above or equal to 0.4 was predictive of T-LBL and conversely. Applied to the MS-MLPA dataset, this prediction model accurately predicted diagnoses of T-LBL and thymoma. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

In line with the digital transformation trend in medical training, students may resort to artificial intelligence (AI) for learning. This study assessed the interaction between obstetrics residents and ChatGPT during clinically oriented summative evaluations related to acute hepatic steatosis of pregnancy, and their self-reported competencies in information technology (IT) and AI. The participants in this semi-qualitative observational study were 14 obstetrics residents from two university hospitals. Students' queries were categorized into three distinct types: third-party enquiries; search-engine-style queries; and GPT-centric prompts. Responses were compared against a standardized answer produced by ChatGPT with a Delphi-developed expert prompt. Data analysis employed descriptive statistics and correlation analysis to explore the relationship between AI/IT skills and response accuracy. The study participants showed moderate IT proficiency but low AI proficiency. Interaction with ChatGPT regarding clinical signs of acute hepatic steatosis gravidarum revealed a preference for third-party questioning, resulting in only 21% accurate responses due to misinterpretation of medical acronyms. No correlation was found between AI response accuracy and the residents' self-assessed IT or AI skills, with most expressing dissatisfaction with their AI training. This study underlines the discrepancy between perceived and actual AI proficiency, highlighted by clinically inaccurate yet plausible AI responses - a manifestation of the 'stochastic parrot' phenomenon. These findings advocate for the inclusion of structured AI literacy programmes in medical education, focusing on prompt engineering. These academic skills are essential to exploit AI's potential in obstetrics and gynaecology. The ultimate aim is to optimize patient care in AI-augmented health care, and prevent misleading and unsafe knowledge acquisition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Biosimilars are cost-effective alternatives to reference products for patients with inflammatory bowel diseases (IBD) and chronic inflammatory rheumatic diseases (CIRD), but patient beliefs can affect adherence to the transition. This study aimed to explore patient experience and satisfaction after switching to CT-P17, a high-concentration (100 mg/mL), citrate-free adalimumab biosimilar., Patients and Methods: This observational, multicenter, prospective French study included adult patients with IBD or CIRD who switched to CT-P17 from reference adalimumab (R-ADA; 100 mg/mL) or a low-concentration adalimumab biosimilar (ADA-BioS; 50 mg/mL). Patients completed online questionnaires to assess treatment perceptions, satisfaction, and tolerance at study inclusion (under previous treatment) and over 3 months of CT-P17 treatment. The primary criterion was overall patient satisfaction, which was assessed with the question, "What is your global satisfaction with the CT-P17 injection?", using a 7-point Likert scale. Multivariate logistic regression analysis was performed to identify factors associated with increased treatment satisfaction after switching to CT-P17., Results: The total analysis population included 232 patients (IBD 72.0%, CIRD 28.0%). Median patient age was 57.0 years (interquartile range [IQR] 46.0-63.0), 50.4% were men, and median disease duration was 9 years (IQR 5-16). Approximately half of the cohort (51.2%) switched to CT-P17 from an ADA-BioS (including 19.4% from an ADA-BioS with citrate) and half (48.7%) from R-ADA. The proportion of patients who were satisfied with treatment was stable between baseline (under previous treatment) and 3 months (under CT-P17). More patients reported increased satisfaction after switching to CT-P17 from an ADA-BioS (22.7% vs 8.0% when switching from R-ADA; p = 0.002), or from an ADA-BioS containing citrate (28.9% vs 12.3% when switching from a citrate-free ADA-BioS; p = 0.008). Independent prognostic factors for increased satisfaction were previous treatment with an ADA-BioS (odds ratio [OR] 2.88 [95% confidence interval 1.17-7.08]; p = 0.021) and pain at the injection site under previous treatment (OR 1.26 [1.08-1.47]; p = 0.004). Significantly fewer patients reported pain, redness, itching, and hematoma after 3 months of CT-P17 treatment versus baseline (p < 0.001)., Conclusions: The majority of patients had stable or increased treatment satisfaction after switching from R-ADA or an ADA-BioS to CT-P17. In particular, switching to CT-P17 from a low-concentration ADA-BioS or an ADA-BioS containing citrate was associated with increased patient satisfaction. An improvement in overall tolerance with CT-P17 versus previous adalimumab treatment was also reported., Trial Registration: ClinicalTrials.gov identifier NCT05427942, registered June 22, 2022., (© 2024. The Author(s).)

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor T-cell therapies that were evaluated in third and later line (3L+) relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the ZUMA-1 and JULIET trials, respectively. As of October 2021, the DESCAR-T registry included 729 French patients with 3L+ r/r DLBCL who received axi-cel or tisa-cel. Using these data, propensity score matching was used to conduct an adjusted comparison between axi-cel and tisa-cel. Axi-cel was associated with statistically significant improvements in overall survival (OS) and progression-free survival (PFS), and significantly more frequent Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS), compared with tisa-cel. There was no significant difference in Grade ≥ 3 cytokine release syndrome (CRS). The current analysis assessed the cost-effectiveness of axi-cel versus tisa-cel in the treatment of 3L+ r/r DLBCL using propensity score-matched data from the DESCAR-T registry., Methods: A partitioned survival model was used to extrapolate costs and quality-adjusted life years (QALYs) over a lifetime. Survival curves for PFS and OS were based on independent mixture cure models fitted to digitized Kaplan-Meier data for the propensity score-matched DESCAR-T populations. Average duration of intensive care unit stays for each of axi-cel and tisa-cel in DESCAR-T were used to inform adverse event costs. Selected parametric survival distributions were based on clinical expert validation. Utility values were derived from ZUMA-1, and costs were obtained from French registries and published sources. List prices were used for both axi-cel and tisa-cel. Costs and outcomes were discounted at an annual rate of 2.5%., Results: Axi-cel is associated with an incremental cost-effectiveness ratio of €15,520 per QALY compared with tisa-cel., Conclusion: Based on explicit willingness-to-pay thresholds applied in Europe, axi-cel is expected to be a cost-effective use of healthcare resources in real-world clinical settings compared with tisa-cel in 3L+ r/r DLBCL., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Immune checkpoint inhibitors lead to effective antitumour responses but also to immune-related adverse events (irAEs), which affect the nervous system in 1-5% of patients. Encephalitis is the most frequent central nervous system irAE and is clinically relevant due to its high severity and mortality. Early diagnosis is crucial but is hampered by the broad list of alternative diagnoses, the lack of established diagnostic criteria, and the need of extensive diagnostic procedures (e.g., spinal tap, brain MRI) alongside expert neurological evaluation. Additionally, the response to corticosteroids is inconsistent, and the management of corticosteroid-refractory patients remains poorly defined. This mini-review discusses the role of various soluble biomarkers in the diagnosis, prognostication, and management of ICI-encephalitis. Neural antibodies, which are well-established biomarkers of autoimmune and paraneoplastic encephalitis, are found in only a subset of ICI-encephalitis, in which they can aid to establish the diagnosis. The most prevalent are paraneoplastic neurological syndromes (PNS)-associated antibodies, which are found almost exclusively in focal ICI-encephalitis syndromes and are associated with poor outcomes, possibly due to predominantly cytotoxic T cell involvement leading to irreversible neuronal loss. Beside antibodies, serum brain injury biomarkers such as NfL and S100B are elevated in ICI-encephalitis and, even if non-specific, may be useful as a routine test to quickly identify patients in whom neurological evaluation and second-level diagnostic procedures should be prioritized. Additionally, higher serum and CSF NfL levels have been associated with lack of treatment response in ICI-encephalitis, suggesting they may have a prognostic role. Among cytokines, elevated interleukin 6 (IL6) levels have been observed in serum and/or CSF samples of some patients with ICI-encephalitis, but the role of IL6 as a biomarker for response to IL6-directed therapies requires further investigation. Likewise, the value of other biomarkers, including T cells markers and HLA haplotypes, still needs to be evaluated in large cohorts. Overall, neural antibodies are important diagnostic and prognostic biomarkers in ICI-encephalitis, and other soluble biomarkers, especially NfL, deserve further investigation since they have a promising application in clinical practice., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Paediatric CSF shunt infection rate remains a well-known complication that is not only responsible of potentially severe sequels for patients but also for economical expenses. In that study, we questioned if it is possible to attain the zero percent rate of infection that should be the goal of every paediatric neurosurgeon., Methods: We report our series of patients treated with a CSF device from January the first 2016 to December 31 2018., Results: In all 147 patients treated for hydrocephalus, the follow-up was of at least of 2 years from the implantation. Antibiotic-coated tubes were always used with a differential pressure valve system. A total of 172 surgical procedures were performed for 147 patients. In the follow-up time period, 4 patients presented a post-operative infection (2.3%). Two infections appeared early after the surgical procedure one after 24 h and the other after 6 days; the other two infections were diagnosed after 53 days and the other after 66 days. The germs responsible of the infections were a Staphylococcus capitals, an Escherichia coli, a Klebsiella pneumonia, and a Staphylococcus aureus., Conclusions: Shunts will always be implanted especially in new-borns and for particular aetiologies of hydrocephalus. To reduce the rate of infection, the best thing to do is to adopt adapted protocols. Our low incidence of infection rate for shunts represent a long history to research preventive factors that helped us to improve our results during the time., (© 2024. The Author(s).)