Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis.

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development. Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI). Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection. Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise. Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated. Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs. Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Long-Term Outcomes of Birdshot Chorioretinopathy Treated with Corticosteroids: A Case Reports.

PURPOSE: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. METHODS: We included 39 BSCR patients that were followed for ≥1 year. We analyzed their progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. In order to determine the efficiency of initial loading doses, patients were classified into two groups according to their initial treatment: methylprednisolone followed by prednisone (n = 28) and prednisone alone (n = 11). RESULTS: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. CONCLUSIONS: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Kappa Free Light Chain Index Predicts Disease Course in Clinically and Radiologically Isolated Syndromes.

BACKGROUND AND OBJECTIVES: To evaluate whether the kappa free light chain index (K-index) can predict the occurrence of new T2-weighted MRI lesions (T2L) and clinical events in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). METHODS: All consecutive patients presenting for the diagnostic workup, including CSF analysis, of clinical and/or MRI suspicion of multiple sclerosis (MS) since May 1, 2018, were evaluated. All patients diagnosed with CIS and RIS with at least 1-year follow-up were included. Clinical events and new T2L were collected during follow-up. The K-index performances in predicting new T2L and a clinical event were evaluated using time-dependent ROC analyses. The time to clinical event or new T2L was estimated using survival analysis according to the binarized K-index using an independent cutoff of 8.9, and the ability of each variable to predict outcomes was compared using the Harrell c-index. RESULTS: One hundred and eighty two patients (146 CIS and 36 RIS, median age 39 [30; 48] y-o, 70% females) were included with a median follow-up of 21 [13, 33] months. One hundred five (58%) patients (85 CIS and 20 RIS) experienced new T2L, and 28 (15%; 21 CIS and 7 RIS) experienced a clinical event. The K-index could predict new T2L over time in CIS (area under the curve [AUC] ranging from 0.86 to 0.96) and in RIS (AUC ranging from 0.84 to 0.54) but also a clinical event in CIS (AUC ranging from 0.75 to 0.87). Compared with oligoclonal bands (OCBs), the K-index had a better sensitivity and a slight lower specificity in predicting new T2L and clinical events in both populations. In the predictive model, the K-index was the variable that best predict new T2L in both CIS and RIS but also clinical events in CIS (c-index ranging from 0.70 to 0.77), better than the other variables, including OCB. DISCUSSION: This study provides evidence that the K-index predicts new T2L in CIS and RIS but also clinical attack in patients with CIS. We suggest adding the K-index in the further MS diagnosis criteria revisions as a dissemination-in-time biomarker.

Peripheral but not axial muscle mass is associated with early mortality in bone metastatic lung cancer patients at diagnosis.

OBJECTIVES: Identification of sarcopenia is a key issue in oncology. Several methods may be used to evaluate muscle mass in patients. Routine cancer follow-up computed tomography (CT) provides axial muscle mass whereas whole-body densitometry (DEXA) measures appendicular lean mass (ALM). Up to now, no studies have assessed, in cancer patients, the correlation between CT and DEXA muscle mass indicators and compared their prognostic value. METHODS: We included patients with synchronous bone metastases from lung adenocarcinoma at diagnosis. Diagnosis was confirmed by bone biopsy. Skeletal muscle area was determined semi-automatically on initial CT scan at the T7, T12, and L3 vertebral level using Osirix® software. The skeletal muscle index (SMI) was calculated as the ratio of muscle area to height squared. Standardised ALM/height squared data were obtained by DEXA assessment within a 30-day window of CT. RESULTS: A total of 65 patients were included; 47 (72%) were male. Mean±SD age was 65±11.4years. DEXA was available for 46 patients. The performance status was good (<1) for 39 patients. SMI indicators were significantly correlated with each other (rho from 0.3 to 0.7) but moderately correlated with ALM (rho from 0.1 to 0.7). ALM had a good discriminatory ability on 6-month survival (AUC 0.87 [0.76; 0.97]). ALM was associated with early mortality (<6months) (HR=0.29, 95% CI [0.15; 0.57]; P<0.001) but not with later mortality (>6months). In contrast, no significant effect was found for SMI. CONCLUSIONS: Peripheral muscle mass (standardized ALM by DEXA) but not axial muscle mass (SMI assessed by CT) was associated with early mortality (<6months) suggesting that cancer-induced muscle loss would affect differently appendicular muscles and axial muscles.

Axillary vein catheterization using ultrasound guidance: A prospective randomized cross-over controlled simulation comparing standard ultrasound and new needle-pilot device.

BACKGROUND: Real-time ultrasound (US) guidance facilitates central venous catheterization in intensive care unit (ICU). New magnetic needle-pilot devices could improve efficiency and safety of central venous catheterization. This simulation trial was aimed at comparing venipuncture with a new needle-pilot device to conventional US technique. METHODS: In a prospective, randomized, simulation trial, 51 ICU physicians and residents cannulated the right axillary vein of a human torso mannequin with standard US guidance and with a needle-pilot system, in a randomized order. The primary outcome was the time from skin puncture to successful venous cannulation. The secondary outcomes were the number of skin punctures, the number of posterior wall puncture of the axillary vein, the number of arterial punctures, the number of needle redirections, the failure rate, and the operator comfort. RESULTS: Time to successful cannulation was shorter with needle-pilot US-guided technique (22 s (interquartile range (IQR) = 16-42) vs 25 s (IQR = 19-128); median of difference (MOD) = -9 s (95%-confidence interval (CI) -5, -22), p < 0.001). The rates of skin punctures, posterior wall puncture of axillary vein, and needle redirections were also lower (p < 0.01). Comfort was higher in needle-pilot US-guided group on a 11-points numeric scale (8 (IQR = 8-9) vs 6 (IQR = 6-8), p < 0.001). CONCLUSIONS: In a simulation model, US-guided axillary vein catheterization with a needle-pilot device was associated with a shorter time of successful cannulation and a decrease in numbers of skin punctures and complications. The results plea for investigating clinical performance of this new device.

Investigating the Long-term Effect of Pregnancy on the Course of Multiple Sclerosis Using Causal Inference.

BACKGROUND AND OBJECTIVES: The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery). METHODS: We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up). RESULTS: We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [-0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93-1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate. DISCUSSION: Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias.

Management and Outcome of COVID-19 Positive and Negative Patients in French Emergency Departments During the First COVID-19 Outbreak: A Prospective Controlled Cohort Study.

INTRODUCTION: Few studies have investigated the management of COVID-19 cases from the operational perspective of the emergency department (ED), We sought to compare the management and outcome of COVID-19 positive and negative patients who presented to French EDs. METHODS: We conducted a prospective, multicenter, observational study in four EDs. Included in the study were adult patients (≥18 years) between March 6-May 10, 2020, were hospitalized, and whose presenting symptoms were evocative of COVID-19. We compared the clinical features, management, and prognosis of patients according to their confirmed COVID-19 status. RESULTS: Of the 2,686 patients included in this study, 760 (28.3%) were COVID-19 positive. Among them, 364 (48.0%) had hypertension, 228 (30.0%) had chronic cardiac disease, 186 (24.5%) had diabetes, 126 (16.6%) were obese, and 114 (15.0%) had chronic respiratory disease. The proportion of patients admitted to intensive care units (ICU) was higher among COVID-19 positive patients (185/760, 24.3%) compared to COVID-19 negative patients (206/1,926, 10.7%; P <0.001), and they required mechanical ventilation (89, 11.9% vs 37, 1.9%; P <0.001) and high-flow nasal cannula oxygen therapy (135, 18.1% vs 41, 2.2%; P < 0.001) more frequently. The in-hospital mortality was significantly higher among COVID-19 positive patients (139, 18.3% vs 149, 7.7%; P <0.001). CONCLUSION: Emergency departments were on the frontline during the COVID-19 pandemic and had to manage potential COVID-19 patients. Understanding what happened in the ED during this first outbreak is crucial to underline the importance of flexible organizations that can quickly adapt the bed capacities to the incoming flow of COVID-19 positive patients.

Usefulness and prognostic value of diagnostic tests in patients with possible chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Recent guidelines define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and possible CIDP. The aims of our study were to evaluate the value of diagnostic tests to support the diagnosis of CIDP in patients with possible CIDP and to identify prognostic factors of therapeutic success. METHODS: We conducted an observational retrospective two-center study between 2014 and 2019. We selected patients with a clinical presentation suggesting CIDP, but whose electrodiagnostic (EDX) test results did not meet the EFNS/PNS 2021 criteria. We analyzed epidemiologic and clinical features, axonal loss on EDX, cerebrospinal fluid (CSF), somatosensory evoked potentials (SSEPs), plexus magnetic resonance imaging (MRI), nerve biopsy, and therapeutic response. RESULTS: We selected 75 patients, among whom 30 (40%) responded to treatment. The positivity rates of CSF analysis, MRI and SSEPs were not influenced by the clinical presentation or by the delay between symptom onset and medical assessment. A high protein level in CSF, female gender, and a relapsing-remitting course predicted the therapeutic response. DISCUSSION: It is important to properly diagnose suspected CIDP not meeting EFNS/PNS 2021 EDX criteria by using supportive criteria. Specific epidemiological factors and a raised CSF protein level predict a response to treatment. Further prospective studies are needed to improve diagnosis and the prognostic value of diagnostic tests in CIDP.

Prognostic Factors and Treatment Efficacy in Spinal Cord Sarcoidosis: An Observational Cohort With Long-term Follow-up.

BACKGROUND AND OBJECTIVES: Spinal cord sarcoidosis is a rare manifestation of sarcoidosis with a consequent risk of neurologic 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 7 centers in France. Patients with definite, probable, or possible spinal cord sarcoidosis according to the Neurosarcoidosis Consortium Consensus Group criteria and with 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 Expanded Disability Status Scale. Tumor necrosis factor-α (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.

Ependyma: a new target for autoantibodies in neuromyelitis optica?

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 focused 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 and CSF flow, and are a niche for sub-ventricular 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 cultures of rat ependymal cells and explant cultures of rat lateral ventricular wall whole mounts, to purified IgG of NMO patients (NMO-IgG) for 24 hours. We then evaluated the treatment effect using immunolabelling, functional assays, ependymal flow analysis and bulk RNA sequencing. For each experiment, the effects were compared with those of purified IgG from a healthy donors and non-treated cells. We found that: (i) NMO-IgG induced aquaporin-4 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 sub-ventricular neural stem cells; (iv) treatment with NMO-IgG up-regulated 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 sub-ventricular 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.

Otoskills training during covid-19 pandemic: a before-after study.

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.

Results of in vitro fertilization versus intrauterine insemination in patients with low anti-Müllerian hormone levels. A single-center retrospective study of 639 + 119 cycles.

OBJECTIVES: The aim of this study was to evaluate the results of in vitro fertilization (IVF) and intrauterine insemination (IUI) in a population of infertile women with low AMH levels, in whom both techniques were possible. METHODS: This was a retrospective analysis of 462 patients treated over 24 months in a single center comparing the live birth rates after 176 IUI and 639 IVF attempts in infertile couples. The women had AMH levels ≤ 1.2 ng/mL and at least one patent tube and their partner's sperm was of sufficient quality for IUI. RESULTS: The live birth rate after IVF was not sufficiently higher than after IUI, or than after IVF attempts converted to IUI for low response (odds ratios in multivariate analysis with respect to IVF: 0.61, p = 0.15 for IUI and 0.73, p = 0.6 for conversions). The pregnancy rates after IVF (13.0 %) and IUI (13.3 %) were similar (p = 0.4), and were non-significantly higher than the pregnancy rate in the IUI conversion group (8.8 %, p = 0.9). Nearly half (43.8 %) of all IVF cycles did not lead to embryo transfer. CONCLUSION: In this group of women with AMH levels ≤ 1.2 ng/mL, IVF did not lead to a higher live birth rate than IUI, and more than 40 % of all IVF attempts did not lead to embryo transfer, suggesting that diminished ovarian reserve is not an indication for IVF over IUI.