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Background and objectives:Spinal cord sarcoidosis is a rare manifestation of sarcoidosis with a consequent risk of neurological sequelae for the patient. We investigated prognostic factors and efficacy of immunosuppressive treatments in a longitudinal cohort.Methods:We retrospectively studied patients with spinal cord sarcoidosis followed between 1995 and 2021 in seven centers in France. Patients with a definite, probable or possible spinal cord sarcoidosis according to the Neurosarcoidosis Consortium Consensus Group criteria and with a spinal cord involvement confirmed by MRI were included. We analyzed relapse or progression rate with a Poisson model, initial Rankin score with a linear model and change in the Rankin score during follow-up with a logistic model.Results:A total of 97 patients were followed for a median of 7.8 years. Overall mean relapse or progression rate was 0.17 per person-year and decreased over time. At last visit, 46 (47.4%) patients had a loss of autonomy (Rankin score ≥ 2). The main prognostic factors significantly associated with relapse or progression rate were gadolinium enhancement (relative rate [95% CI]: 0.61 [0.4, 0.95]) or meningeal involvement (relative rate [95% CI]: 2.05 [1.31, 3.19]) on spinal cord MRI, and cell count (relative rate [95% CI] per 1 log increase: 1.16 [1.01, 1.33]) on CSF analysis. Relapse or progression rate was not significantly associated with initial Rankin score or EDSS. TNF α antagonists significantly decreased relapse or progression rate compared with corticosteroids alone (relative rate [95% CI]: 0.33 [0.11, 0.98]). Azathioprine was significantly less effective than methotrexate on relapse or progression rate (relative rate [95% CI]: 2.83 [1.04, 7.75]) and change in Rankin score (mean difference [95% CI]: 0.65 [0.23, 1.08]).Discussion:Regarding the relapse or progression rate, meningeal localization of sarcoidosis was associated with a worse prognosis; TNF α antagonists resulted in a significant decrease compared to corticosteroids alone; and methotrexate was more effective than azathioprine.Classification of Evidence:This study provides Class IV evidence that in individuals with spinal cord neurosarcoidosis, TNF α antagonists were associated with decreased relapse or progression rate compared to corticosteroids alone, but other therapies showed no significant benefit.

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Background The ongoing COVID-19 pandemic has disrupted the surgical training of residents. There is a real concern that trainees will not be able to meet their training requirements. Low-fidelity surgical simulation appears to be an alternative for surgical training. The educational benefits of repeating ossiculoplasty simulations under a microscope have never been evaluated. With this study we aimed to evaluate the differences in performance scores and on a global rating scale before and after training on an ossiculoplasty simulator. Methods In this quasi-experimental, prospective, single-centre, before-after study with blinded rater evaluation, residents performed five microscopic ossiculoplasty tasks with a difficulty gradient (sliding beads onto rods, the insertion of a partial prosthesis, the insertion of a total prosthesis, and the insertion of a stapedotomy piston under microscopic or endoscopic surgery) before and after training on the same simulator. Performance scores were defined for each task, and total performance scores (score/min) were calculated. All data were collected prospectively. Results Six out of seven intermediate residents and 8/9 novices strongly agreed that the simulator was an effective training device and should be included in the ENT residency program. The mean effect of training was a significant increase in the total performance score (+ 0.52 points/min, [95 % CI, 0.40–0.64], p < 0.001), without a significant difference between novice and intermediate residents. Conclusions This preliminary study shows that techniques for middle-ear surgery can be acquired using a simulator, avoiding any risk for patients, even under lockdown measures.

Neuromyelitis Optica (NMO) is an autoimmune demyelinating disease of the central nervous system characterized by the presence of autoantibodies (called NMO-IgG) targeting aquaporin-4. Aquaporin-4 is expressed at the perivascular foot processes of astrocytes, in the glia limitans but also at the ependyma. Most studies have focus on studying the pathogenicity of NMO-IgG on astrocytes and NMO is now considered an astrocytopathy. However, periependymal lesions are observed in NMO suggesting that ependymal cells could also be targeted by NMO-IgG. Ependymal cells regulate CSF-parenchyma molecular exchanges, CSF flow and is a niche for subventricular neural stem cells. Our aim was to examine the effect of antibodies from NMO patients on ependymal cells. We exposed two models, i.e., primary culture of rat ependymal cells and explant cultures of rat lateral ventricular wall wholemounts, to purified IgG of NMO patients (NMO-IgG) for 24 hours. We then evaluated the treatment effect using immunolabeling, functional assays, ependymal flow analysis and bulk RNA sequencing. For each experiment, the effects were compared to purified IgG of healthy donor and to non-treated cells. We found that: i) NMO-IgG patients induced AQP4 agglomeration at the surface of ependymal cells, and induced cell enlargement in comparison to controls. In parallel, it induced an increase in gap junction connexin-43 plaque size; ii) NMO-IgG altered the orientation of ciliary basal bodies and functionally impaired cilia motility; iii) NMO-IgG activated the proliferation of subventricular neural stem cells; and iv) treatment with NMO-IgG upregulated the expression of pro-inflammatory cytokines and chemokines in the transcriptomic analysis. Our study showed that NMO-IgG can trigger an early and specific reactive phenotype in ependymal cells, with functional alterations of intercellular communication and cilia, activation of the subventricular stem cell proliferation and the secretion of pro-inflammatory cytokines. These findings suggest a key role for ependymal cells in the early phase of NMO lesion formation.

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The aim of the present study was to evaluate the effect of activin A on the activation of in vitro folliculogenesis of human ovarian tissues from transgender men with or without our new compartmented chitosan hydrogel microbioreactor (“three-dimensional (3D)-structure”) enabling a three-dimensional tissue culture. Five fresh ovarian human tissues were cultured in vitro for 20 or 22 days in four groups with 100 ng/mL activin A or without activin A during the last six to eight days of culture, and within a 3D-structure or without the 3D-structure in standard conditions. Follicular density and quality were evaluated, and follicular diameters were measured. Estradiol secretion was quantified. Proliferation and apoptosis through immunostaining were also performed. The proportion of primordial follicles was significantly reduced, and the proportion of primary and secondary follicles was significantly increased in all four groups (p < 0.001). Tertiary follicles were observed in the four culture groups. Activin A supplementation did not significantly affect the follicular density, follicular quality, follicular growth, or estradiol secretion (p > 0.05). The 3D-structure increased the density of primary follicles and decreased the estradiol secretion (p < 0.001). Follicular proliferation was significantly lower in the 3D-structure group compared to the non-3D-structure group (p = 0.008). Regarding follicular apoptosis, it was significantly higher in the activin group compared to the non-activin group (p = 0.006). Activin A did not seem to play a key role in the in vitro folliculogenesis activation in our culture conditions. However, the results may indicate that the 3D-structure could be more physiological and could prevent a detrimental in vitro folliculogenesis flare-up.