Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm ...activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes.
To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support.
In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured.
Rocuronium titration resulted in significant declines of Vt (mean ± SEM, 9.3 ± 0.6 to 5.6 ± 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 ± 2.5 to 10.7 ± 1.2 cm H
O; P < 0.0001), and diaphragm electrical activity (17.4 ± 2.3 to 4.5 ± 0.7 μV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 ± 0.02 to 7.35 ± 0.02; P < 0.0001), and mean arterial blood pressure increased (84 ± 6 to 99 ± 6 mm Hg; P = 0.0004), as did heart rate (83 ± 7 to 93 ± 8 beats/min; P = 0.0004).
Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.
Over the years, the scope of outcomes assessment in chronic obstructive pulmonary disease (COPD) has broadened, allowing for the evaluation of various patient-reported outcomes (PROs). As it still ...remains unclear whether and to what extent PROs mirror the exercise performance of patients with COPD, the current study aimed to assess the association between different exercise test outcomes and PROs, before and after pulmonary rehabilitation (PR). Correlations between PROs used to describe health-related quality of life (HRQoL), mood status, level of care dependency and dyspnea in patients with COPD and commonly used laboratory- and field-based exercise test outcomes were evaluated in 518 individuals with COPD attending PR. Overall, correlations between PROs and exercise test outcomes at baseline were statistically significant. The correlation between modified Medical Research Council (mMRC) dyspnea score and 6-min walking distance (6MWD) was strongest (rho:-0.65; p<0.001). HRQoL related PROs showed weak correlations with exercise outcomes at baseline. Moderate correlations were found between St George's Respiratory Questionnaire total score and 6MWD (r:-0.53; p<0.001) and maximal workload achieved during cardiopulmonary exercise testing (rho:-0.48; p<0.001); and between Clinical COPD Questionnaire (CCQ) total score and 6MWD (r:-0.48; p<0.001) and maximal workload (rho:-0.43; p<0.001). When significant, correlations between changes in exercise test outcomes and changes in PROs after PR were generally very weak or weak. The highest correlation was found between changes in CCQ total score and changes in 6MWD (rho: - 0.36; p<0.001). PROs and exercise test outcomes, although significantly correlated with each other, assess different disease features in patients with COPD. Individual PROs need to be supported by additional functional measurements whenever possible, in order to get a more detailed insight in the effectiveness of a PR program.
Saproxylic organisms are among the most threatened species in Europe and constitute a major conservation problem because they depend on the most important forestry product – dead wood. Diversity of ...fungal and bryophyte communities occurring on dead beech trees was analyzed in five European countries (Slovenia, Hungary, The Netherlands, Belgium and Denmark) considering tree level species richness (TLSR), country level species richness (CLSR), frequency distributions of species, occurrence of threatened species and relations between TLSR and decay stage, tree size and countries. Altogether 1009 trees were inventoried in 19 beech dominated forest reserves.
The number of fungi in the full dataset was approximately three times larger (456 versus 161 species) and the proportion of low frequent species was higher than among bryophytes. The species richness of bryophytes and fungi was significantly different among countries considering both TLSR and CLSR. In addition the diversity patterns deviated considerably between the two groups of organisms. Slovenian sites appeared to be biodiversity hotspots for bryophytes characterized by high TLSR and CLSR and a high fraction of threatened species. Hungarian sites had somewhat lower bryophyte diversity, while the Atlantic region had deteriorated assemblages. Fungal species richness was very high in Denmark, but the Hungarian and Slovenian sites were richer in threatened and low frequency species. Tree size was better able to explain variation in TLSR in both organism groups than decay stage. TLSR was found to vary significantly between countries but the difference was most considerable in the case of bryophytes.
The diversity patterns of both organism groups along the investigated geographical gradient appear to be influenced by both climatic and management related factors (forest history, dead wood availability and continuity, habitat fragmentation). There is no doubt that an increase in the abundance of dead wood in European beech forests will benefit diversity of saproxylic fungi and bryophytes, especially if a continuous presence of large diameter logs are secured within individual stands.
Many prodromal Alzheimer's disease trials collect two types of data: the time until clinical diagnosis of dementia and longitudinal patient information. These data are often analysed separately, ...although they are strongly associated. By combining the longitudinal and survival data into a single statistical model, joint models can account for the dependencies between the two types of data.
We illustrate the major steps in a joint modelling approach, motivated by data from a prodromal Alzheimer's disease study: the LipiDiDiet trial.
By using joint models we are able to disentangle baseline confounding from the intervention effect and moreover, to investigate the association between longitudinal patient information and the time until clinical dementia diagnosis.
Joint models provide a valuable tool in the statistical analysis of clinical studies with longitudinal and survival data, such as in prodromal Alzheimer's disease trials, and have several added values compared to separate analyses.
Commercial pre-weaning diets are formulated to be highly digestible and nutrient-dense and contain low levels of dietary fibre. In contrast, pigs in a natural setting are manipulating fibre-rich ...plant material from a young age. Moreover, dietary fibre affects gastrointestinal tract (GIT) development and health in older pigs. We hypothesised that supplemental diets that contain vegetal fibres are accelerating GIT development in suckling piglets in terms of size and functionality. From d 2 of life, sow-suckled piglets had access to a low fibre diet (CON), a diet with a fermentable long-chain arabinoxylan (lc-AXOS), a diet with a largely non-fermentable purified cellulose (CELL), or a diet containing both fibres. During the initial 2 weeks, the control diet was a high-density milk replacer, followed by a dry and highly digestible creep meal. Upon weaning at 25 d, 15 piglets from each treatment group, identified as eaters and originating from six or seven litters, were sacrificed for post-mortem examination of GIT morphology, small intestinal permeability and metabolic profile of the digesta. The microbiota composition of the mid-colon was evaluated in a sub-set of ten piglets.
No major statistical interactions between the fibre sources were observed. Piglets consumed the fibre-containing milk supplements and creep diets well. Stomach size and small intestinal permeability was not affected. Large intestinal fill was increased with lc-AXOS only, while relative large intestinal weight was increased with both fibre sources (
< 0.050). Also, CELL decreased ileal pH and tended to increase ileal DM content compared to CON (
< 0.050). Moreover, the concentration of volatile fatty acids was increased in the caecum (
< 0.100) and mid-colon (
< 0.050) by addition of CELL. lc-AXOS only stimulated caecal propionate (
< 0.050). The microbiota composition showed a high individual variation and limited dietary impact. Nonetheless, CELL induced minor shifts in specific genera, with notable reductions of
-
.
Adding dietary fibres to the supplemental diet of suckling piglets altered large intestinal morphology but not small intestinal permeability. Moreover, dietary fibre showed effects on fermentation and modest changes of microbial populations in the hindgut, with more prominent effects from the low-fermentable cellulose.
Videobronchoscopy is an essential diagnostic procedure for evaluation of the central airways and pivotal for the diagnosis and staging of lung cancer. Technological improvements have resulted in high ...definition (HD) images with advanced real time image enhancement techniques (i-scan).
In this study we aimed to explore the sensitivity of HD+ i-scan bronchoscopy for detection of epithelial changes like vascular abnormalities and suspicious preinvasive lesions, and tumors.
In patients scheduled for a therapeutic or diagnostic procedure under general anesthesia videos of the bronchial tree were made using 5 videobronchoscopy modes in random order: normal white light videobronchoscopy (WLB), HD-bronchoscopy (HD), HD bronchoscopy with surface enhancement technique (i-scan1), HD with surface- and tone enhancement technique (i-scan2) and dual mode autofluorescence videobronchoscopy (AFB). The videos were scored in random order by two independent and blinded expert bronchoscopists.
In 29 patients all videos were available for analysis. Vascular abnormalities were scored most frequently in HD + i-scan2 bronchoscopy (1.33 ± 0.29 abnormal or suspicious sites per patient) as compared to 0.12 ± 0.05 site for AFB (P = 0.003). Sites suspicious for preinvasive lesions were most frequently reported using AFB (0.74 ± 0.12 sites per patient) as compared to 0.17 ± 0.06 for both WLB and HD bronchoscopy (P = 0.003). Tumors were detected equally by all modalities. The preferred modality was HD bronchoscopy with i-scan (tone- plus surface and surface enhancement in respectively 38% and 35% of cases P = 0.006).
This study shows that high definition bronchoscopy with image enhancement technique may result in better detection of subtle vascular abnormalities in the airways. Since these abnormalities may be related to preneoplastic lesions and tumors this is of clinical relevance. Further investigations using this technique relating imaging to histology are warranted.
Volitional assessment of quadriceps muscle endurance is clinically relevant in patients with chronic obstructive pulmonary disease (COPD). However, studies that determine the construct validity of ...volitional tests by comparing them to non-volitional measures are lacking. Therefore, the aim of the current study is to evaluate the correlation between volitional and non-volitional quadriceps muscle endurance in patients with COPD. Quadriceps muscle endurance was evaluated in twenty-six patients with COPD. A volitional isometric and a volitional isokinetic protocol were performed on a computerised dynamometer to determine the isometric time and isokinetic work fatigue index, respectively. Non-volitional assessment of quadriceps muscle endurance was evaluated using repetitive electrical stimulations to establish the isometric muscle force decline. Sixteen patients (61 ± 8 years, 63% male, FEV
47 (32-53)%) performed all three quadriceps endurance tests conforming to pre-defined test criteria. Both volitional isometric time and isokinetic work fatigue index did not significantly correlate with non-volitional muscle force decline (both
> 0.05). There was a strong correlation between volitional isometric time and isokinetic work fatigue index (rho = -0.716,
= 0.002). To conclude, this study suggests that volitional measures evaluate partly different aspects of quadriceps muscle endurance compared to non-volitional measures. Accordingly, these outcome measures cannot be used interchangeably.
Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined ...whether the administration of a proteasome inhibitor, bortezomib, would have a protective effect against ventilator-induced diaphragm dysfunction.
Randomized, controlled experiment.
Basic science animal laboratory.
Anesthetized rats were submitted for 24 hrs to controlled mechanical ventilation while receiving 0.05 mg/kg bortezomib or saline. Control rats were acutely anesthetized.
After 24 hrs, diaphragm force production was significantly lower in mechanically ventilated animals receiving an injection of saline compared to control animals (-36%, p<.001). Importantly, administration of bortezomib improved the diaphragmatic force compared to mechanically ventilated animals receiving an injection of saline (+15%, p<.01), but force did not return to control levels. Compared to control animals, diaphragm cross-sectional area of the type IIx/b fibers was significantly decreased by 28% in mechanically ventilated animals receiving an injection of saline (p<.01) and by 16% in mechanically ventilated animals receiving an injection of bortezomib (p<.05). Diaphragmatic calpain activity was significantly increased in mechanically ventilated animals receiving an injection of saline (+52%, p<.05) and in mechanically ventilated animals receiving an injection of bortezomib (+36%, p<.05). Caspase-3 activity was increased after controlled mechanical ventilation with saline by 55% (p<.05), while it remained similar to control animals in mechanically ventilated animals receiving an injection of bortezomib. Diaphragm 20S proteasome activity was slightly increased in both ventilated groups, and the amount of ubiquitinated proteins was significantly and similarly enhanced in mechanically ventilated animals receiving an injection of saline and mechanically ventilated animals receiving an injection of bortezomib.
These data show that the administration of bortezomib partially protects the diaphragm from controlled mechanical ventilation-induced diaphragm contractile dysfunction without preventing atrophy. The fact that calpain activity was still increased after bortezomib treatment may explain the persistence of atrophy. Part of bortezomib effects might have been due to its ability to inhibit caspase-3 in this model.
Large epidemiological studies that use accelerometers for physical behavior and sleep assessment differ in the location of the accelerometer attachment and the signal aggregation metric chosen. This ...study aimed to assess the comparability of acceleration metrics between commonly-used body-attachment locations for 24 hours, waking and sleeping hours, and to test comparability of PA cut points between dominant and non-dominant wrist. Forty-five young adults (23 women, 18-41 years) were included and GT3X + accelerometers (ActiGraph, Pensacola, FL, USA) were placed on their right hip, dominant, and non-dominant wrist for 7 days. We derived Euclidean Norm Minus One g (ENMO), Low-pass filtered ENMO (LFENMO), Mean Amplitude Deviation (MAD) and ActiGraph activity counts over 5-second epochs from the raw accelerations. Metric values were compared using a correlation analysis, and by plotting the differences by time of the day. Cut points for the dominant wrist were derived using Lin's concordance correlation coefficient optimization in a grid of possible thresholds, using the non-dominant wrist estimates as reference. They were cross-validated in a separate sample (N = 36, 10 women, 22-30 years). Shared variances between pairs of acceleration metrics varied across sites and metric pairs (range in r
: 0.19-0.97, all p < 0.01), suggesting that some sites and metrics are associated, and others are not. We observed higher metric values in dominant vs. non-dominant wrist, thus, we developed cut points for dominant wrist based on ENMO to classify sedentary time (<50 mg), light PA (50-110 mg), moderate PA (110-440 mg) and vigorous PA (≥440 mg). Our findings suggest differences between dominant and non-dominant wrist, and we proposed new cut points to attenuate these differences. ENMO and LFENMO were the most similar metrics, and they showed good comparability with MAD. However, counts were not comparable with ENMO, LFENMO and MAD.
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