Mismatch negativity (MMN) is the neurophysiological correlate of cognitive integration of novel stimuli. Although MMN is a well-established predictor of awakening in non-sedated comatose patients, ...its prognostic value in deeply sedated critically ill patients remains unknown. The aim of this prospective, observational pilot study was to investigate the prognostic value of MMN for subsequent awakening in deeply sedated critically ill patients.
MMN was recorded in 43 deeply sedated critically ill patients on Day 3 of ICU admission using a classical ‘odd-ball’ paradigm that delivers rare deviant sounds in a train of frequent standard sounds. Individual visual analyses and a group level analysis of recordings were performed. MMN amplitudes were then analysed according to the neurological status (awake vs not awake) at Day 28.
Median (inter-quartile range) Richmond Assessment Sedation Scale (RASS) at the time of recording was −5 (range, from −5 to −4.5). Visual detection of MMN revealed a poor inter-rater agreement kappa=0.17, 95% confidence interval (0.07–0.26). On Day 28, 30 (70%) patients had regained consciousness while 13 (30%) had not. Quantitative group level analysis revealed a significantly greater MMN amplitude for patients who awakened compared with those who had not mean (standard deviation) = −0.65 (1.4) vs 0.08 (0.17) μV, respectively; P=0.003).
MMN can be observed in deeply sedated critically ill patients and could help predict subsequent awakening. However, visual analysis alone is unreliable and should be systematically completed with individual level statistics.
The master biological clock situated in the suprachiasmatic nuclei of the anterior hypothalamus plays a vital role in orchestrating the circadian rhythms of multiple biological processes. Increasing ...evidence points to a role of the biological clock in the development of depression. In seasonal depression and in bipolar disorders it seems likely that the circadian system plays a vital role in the genesis of the disorder. For major unipolar depressive disorder (MDD) available data suggest a primary involvement of the circadian system but further and larger studies are necessary to conclude. Melatonin and melatonin agonists have chronobiotic effects, which mean that they can readjust the circadian system. Seasonal affective disorders and mood disturbances caused by circadian malfunction are theoretically treatable by manipulating the circadian system using chronobiotic drugs, chronotherapy or bright light therapy. In MDD, melatonin alone has no antidepressant action but novel melatoninergic compounds demonstrate antidepressant properties. Of these, the most advanced is the novel melatonin agonist agomelatine, which combines joint MT1 and MT2 agonism with 5-HT(2C) receptor antagonism. Adding a chronobiotic effect to the inhibition of 5-HT(2C) receptors may explain the rapid impact of agomelatine on depression, since studies showed that agomelatine had an early impact on sleep quality and alertness at awakening. Further studies are necessary in order to better characterize the effect of agomelatine and other novel melatoninergic drugs on the circadian system of MDD patients. In summary, antidepressants with intrinsic chronobiotic properties offer a novel approach to treatment of depression.
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 PaCO
2
. 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 (HLV
T
; 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/kg
PBW
or 9.0 cmH
2
O, respectively). Primary outcome was mean nocturnal transcutaneous CO
2
pressure (PtcCO
2
). Secondary outcomes included adherence to NIV, leaks, and side effects.
Results
Of a total of 26 patients, 13 were exposed to HLV
T
, with significantly lower nocturnal PtcCO
2
(respectively 40.5 ± 4.2 vs. 46.3 ± 3.9 mmHg,
p
= 0.002). A linear correlation between V
T
(mL/kg
PBW
) and mean nocturnal PtcCO
2
was evidenced (
r
= − 0.59, 95%CI − 0.80; − 0.25,
p
= 0.002). No significant impact of HLV
T
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 PtcCO
2
in patients with NMD. Further studies are desirable to assess the extent to which the level of assistance influences PaCO
2
evolution in patients with slowly progressive NMD, as well as in restrictive thoracic disorders.
Most pressure-support devices use a single circuit with an exhalation port integrated in the mask. The aim of the current study was to compare the effects of masks having different ...manufacturer-inserted leaks on ventilator performance. We simulated chronic obstructive pulmonary disease and restrictive disease. Four ventilators (VENTImotion (Weinmann, Hamburg, Germany), VPAP III STA (ResMed, Saint Priest, France), Synchrony 2 (Respironics, Nantes, France) and Vivo 40 (Breas, Saint Priest)) were tested with the recommended masks and with the masks having the largest and smallest leaks. Tests were performed with pressure support levels of 10, 15 and 20 cmH(2)O. The in vivo evaluation compared two ventilators using recommended masks opposed in terms of exhaled port resistance. The ventilators were tested with their recommended mask, and after mask exchange. The mask with the largest leak induced auto-triggering and/or increased inspiratory-trigger sensitivity was the VENTImotion under both simulated conditions and VPAP III STA under the simulated obstructive-disease condition. The mask with the smallest leak-increased inspiratory-trigger delay was Synchrony 2 in the simulated obstructive-disease condition and increased rebreathing. The in vivo study confirmed the bench results. When switching to a mask that has a different leak, evaluation is needed to adjust trigger sensitivity and pressurisation level and to check the absence of rebreathing.
The aim of the present study was to evaluate the performance characteristics of all the ventilators proposed for home noninvasive positive-pressure ventilation in children in France. The ventilators ...(one volume-targeted, 12 pressure-targeted and four dual) were evaluated on a bench which simulated six different paediatric ventilatory patterns. For each ventilator, the quality of the inspiratory and expiratory trigger and the ability to reach and maintain the preset pressures and volumes were evaluated with the six patient profiles. The performance of the ventilators showed great variability, and depended upon the type of trigger (flow or pressure), type of circuit and patient profile. Differences were observed between the preset and measured airway pressure and between the tidal volume measured by the ventilator and on the bench. Leaks were associated with an inability to detect the patient's inspiratory effort or autotriggering. No single ventilator was able to adequately ventilate the six paediatric profiles. Only a few ventilators were able to ventilate the profiles simulating the youngest patients. A systematic paediatric bench evaluation is recommended for every ventilator proposed for home ventilation, in order to detect any dysfunction and guide the choice of the appropriate ventilator for a specific patient.
Sniff nasal inspiratory pressure (SNIP) measurement is a volitional noninvasive assessment of inspiratory muscle strength. A maximum of 10 sniffs is generally used. The purpose of the present study ...was to investigate whether the maximum SNIP improved after the tenth sniff. In total, 20 healthy volunteers and 305 patients with various neuromuscular and lung diseases were encouraged to perform 40 and 20 sniffs, respectively. The best SNIP among the first 10 sniffs was lower than the best SNIP among the next 10 sniffs in the healthy volunteers and patients. The SNIP improvement after the twentieth sniff was marginal. In conclusion, a learning effect persists after the tenth sniff. The current authors suggest using 10 additional sniffs when the best result of the first 10 sniffs is slightly below normal, or when sniff nasal inspiratory pressure is used to monitor a progressive decline in inspiratory muscle strength.
Sniff nasal inspiratory pressure is proposed as a noninvasive test of inspiratory muscle strength. During this manoeuvre, the nasal pressure is supposed to reflect oesophageal pressure. The aim of ...the present study was to compare the nasal pressure with the oesophageal pressure during a maximal sniff in children with neuromuscular disease (NM, n = 78), thoracic scoliosis (n = 12) and cystic fibrosis (CF, n = 23). A significant correlation was observed between the sniff nasal and oesophageal pressure. The ratio of the sniff nasal/oesophageal pressure was lower in patients with CF (0.72+/-0.13) than in NM patients (0.83+/-0.17) or patients with thoracic scoliosis (0.86+/-0.10). In patients with CF and NM disease, this ratio was not correlated to age or spirometric data. The difference between the sniff oesophageal and nasal pressure exceeded 15 cm H(2)O in 17, 33 and 87% of the NM, thoracic scoliosis and CF patients, respectively. Sniff nasal pressure often underestimates the strength of inspiratory muscles in cystic fibrosis. Such an underestimation occurs more rarely in neuromuscular disease disorders and thoracic scoliosis. A normal value excludes inspiratory muscle weakness but a low value requires the measurement of the oesophageal pressure.
The objective of the present study was to prospectively evaluate relationships linking age, respiratory function and locomotor function in 29 outpatients with late-onset Pompe's disease and to ...retrospectively determine clinical outcomes. Using univariate regression analysis, vital capacity (VC) was weakly, but significantly, correlated to shoulder motility, Walton score and lower-limb Modified Medical Research Council score. Six patients were able to walk without a walking aid and with only the help of a handrail on the stairs (Walton score=3), although VC was <50%. No parameters were significantly correlated with age. As assessed retrospectively, VC and locomotion deteriorated over time in most patients. In contrast, among the 16 patients started on invasive or noninvasive ventilation with VC monitoring, eight had a VC increase at the first measurement time-point. The absence of correlation with age and the presence, in some patients, of severe respiratory insufficiency without severe limb girdle muscle weakness indicate that respiratory function should be monitored independently from the degree of peripheral muscle weakness. Mechanical ventilation and tracheostomy may improve vital capacity and should, therefore, be taken into account when evaluating treatments for the adult form of Pompe's disease.
Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected ...breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.
Mycobacterium abscessus (Mabs), a non-tuberculous mycobacterium, is an emerging and rapidly growing opportunistic pathogen that is frequently found in patients with cystic fibrosis and in ...immunosuppressed patients. Its high tolerance to antibiotics is of great concern for public health. In this study, our results showed that human THP-1-derived macrophages infected with M. abscessus presented an increase in ROS production and cell necrosis. In addition, M. abscessus infection triggered activation of the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and the induction of HO-1 and NQO1 expression levels. Interestingly, pretreatment of macrophages with sulforaphane (SFN), an activator of the antioxidant key regulator Nrf2, followed by M. abscessus infection significantly decreased mycobacterial burden. We demonstrated that this reduction in mycobacterial growth was due to an activation in cell apoptosis in SFN-pretreated and M. abscessus-infected macrophages. Pretreatment with specific MAPK inhibitors, PD98059, SP600125, and SB203580 to ERK, JNK, and p38 respectively, failed to inhibit induction of Nrf2 expression, suggesting that Nrf2 signaling pathway was upstream of MAPK signaling. Activation of cell apoptosis was caspase 3/7 independent but p38 MAPK dependent. Moreover, p38 MAPK induction was abolished in macrophages transfected with Nrf2 siRNA. In addition, p38 inhibitor abolished Nrf2-dependent apoptosis in infected macrophages. Taken together, our results indicate that modulation of the Nrf2 signaling using Nrf2 activators may help potentiate the actual drug therapies used to treat mycobacterial infection.
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