Predictive factors and screening strategy for obstructive sleep apnea in patients with advanced multiple sclerosis.

BACKGROUND: Obstructive sleep apnea (OSA) screening questionnaires have been evaluated in Multiple Sclerosis (MS) but not yet validated in patients with advanced disease. The aim of this study is to identify OSA predictive factors in advanced MS and to discuss screening strategies. METHODS: Oximetry data from 125 patients were retrospectively derived from polysomnographic reports. Univariate and multivariate analysis were used to determine predictive factors for OSA. A two-level screening model was assessed combining the oxygen desaturation index (ODI) and a method of visual analysis. RESULTS: multivariate analysis showed that among the clinical factors only age and snoring were associated with OSA. Usual predictive factors such as sleepiness, Body mass index (BMI) or sex were not significantly associated with increased Apnea Hypopnea Index (AHI). The ODI was highly predictive (p < 0.0001) and correctly identified 84.1 % of patients with moderate OSA and 93.8 % with severe OSA. The visual analysis model combined with the ODI did not outperform the properties of ODI used alone. CONCLUSION: As the usual clinical predictors are not associated with OSA in patients with advanced MS, questionnaires developed for the general population are not appropriate in these patients. Nocturnal oximetry seems a pertinent, ambulatory and accessible method for OSA screening in this population.

Non-invasive ventilation in neuromuscular diseases: should we use higher levels of ventilatory support?

PURPOSE: In patients with COPD, one of the leading indications for domiciliary non-invasive ventilation (NIV), a major paradigm shift has been observed over the past decade in the method for adjusting NIV settings, with the use of sufficient ventilatory support to achieve a significant reduction in PaCO2. Whether this approach may be relevant to other populations, especially slowly progressive neuromuscular diseases (NMD), is unknown. METHODS: This study was conducted as a post hoc analysis from a previously published randomized controlled trial (NCT03458507). Patients with NMD treated with domiciliary NIV were stratified according to the level of ventilatory support: high-level tidal volume (HLVT; mL/kg of predicted body weight [PBW]) or high-level pressure support (HLPS), defined as a value above median value of the whole population (> 6.8 mL/kgPBW or 9.0 cmH2O, respectively). Primary outcome was mean nocturnal transcutaneous CO2 pressure (PtcCO2). Secondary outcomes included adherence to NIV, leaks, and side effects. RESULTS: Of a total of 26 patients, 13 were exposed to HLVT, with significantly lower nocturnal PtcCO2 (respectively 40.5 ± 4.2 vs. 46.3 ± 3.9 mmHg, p = 0.002). A linear correlation between VT (mL/kgPBW) and mean nocturnal PtcCO2 was evidenced (r = - 0.59, 95%CI [- 0.80; - 0.25], p = 0.002). No significant impact of HLVT was found on secondary outcomes. CONCLUSION: Despite the lack of power of this post hoc analysis, our results suggest that higher levels of ventilatory support are correlated with lower PtcCO2 in patients with NMD. Further studies are desirable to assess the extent to which the level of assistance influences PaCO2 evolution in patients with slowly progressive NMD, as well as in restrictive thoracic disorders.

[Factors associated with the type of mask used during nocturnal NIV in patients with neuromuscular disorders]. / Facteurs associés au masque de ventilation non invasive nocturne chez les patients neuromusculaires adultes.

In subjects with neuromuscular diseases (NMD), the choice of facemask is essential for successful long-term noninvasive ventilation (NIV). While nasal masks usually represent the first line of treatment, almost a third of our subjects with NMD use an oro-nasal interface. Factors associated with the choice of mask remain poorly understood. We provide an original analysis of a previous prospective, multi-centric, Franco-Belgian survey investigating the factors associated with the type of nocturnal mask used in 116 adult NMD subjects treated with NIV. In these patients oro-nasal mask use was more often associated with non-Duchenne muscular dystrophy, older subjects, higher body mass index, better upper limb autonomy allowing independent mask removal and shorter periods of ventilation. Controlled prospective studies are needed to compare the efficacy and tolerance of different interfaces in this specific population.

Role of nitric oxide in the anti-tumoral effect of retinoic acid and 1,25-dihydroxyvitamin D3 on human promonocytic leukemic cells.

All trans retinoic acid and vitamin D3 derivatives are well known for their antileukemic activity, while the precise mechanism of this effect remains to be clarified. Using human leukemic U937 and THP-1 promonocytic cell lines, we analyzed the effect of all-trans retinoic acid (RA) and/or 1,25-dihydroxyvitamin D3 (VD) on the generation of nitric oxide (NO), a potent antitumoral mediator. U937 cell differentiation with VD or with both RA and VD (RA/VD) correlated with gene transcription and functional expression of inducible nitric oxide synthase (iNOS). Nitrites and L-citrulline were also detected in U937 cell supernatants as soon as 24 hours following cell incubation with VD or RA/VD, but not in cells treated with RA alone. Inhibition of iNOS activity by NG-monomethyl-L-arginine (LNMMA) significantly decreased in vitro U937 cell differentiation with VD and RA/VD as shown by the expression of cell differentiation markers (CD14 and CD68) and by the capacity of these cells to undergo a luminol-dependent chemiluminescence in response to opsonized zymosan. Similar results were obtained using the THP-1 cell line strengthening the role of NO in the VD- and RA/VD-induced growth arrest and terminal differentiation of promonocytic leukemia cells.