Differential contractile response of critically ill patients to neuromuscular electrical stimulation

BACKGROUND: Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response. METHODS: This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge. RESULTS: One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA, p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score, p = 0.036). CONCLUSION: Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits. TRIAL REGISTRATION: ISRCTN ISRCTN19392591 , registered 17 February 201

Introduction of the Charité Mobility Index (CHARMI) - A Novel Clinical Mobility Assessment for Acute Care Rehabilitation.

Mobility is an essential part of a person's functioning and independence. It encompasses locomotive functions, but also the more basic functions of positioning and transferring. Despite the availability of several mobility-related assessment instruments to date, there is a need for assessment instruments with the specific capability to display the full range of mobilisation. Our aim was to develop and validate a scoring instrument with hierarchical composition where every score value stands for a defined mobility level.A previously developed and validated pilot instrument was applied to assess patients (n = 113) admitted to an acute rehabilitation programme. Mobility was assessed during admission, subsequently at weekly intervals and at discharge to acquire a detailed status of mobility at multiple time points and individual mobilisation profiles over time. The scoring instrument was then remodelled based on clinical criteria to establish an easy-to-use scoring system with hierarchical composition. Psychometric properties were calculated using an independent sample of 87 consecutive patients.Content validity could be affirmed. The psychometric tests demonstrated excellent convergent validity with the three mobility items of the Barthel Index (r = 0.93), despite an adequately lower correlation with the whole Barthel Index (r = 0.63). Adequate floor and ceiling effects (20%) and a large responsiveness to change (ǀdǀ = 1.7, p < 0.001) between admission and discharge values were demonstrated. Inter-rater reliability was excellent (κ = 0.88).The Charité Mobility Index (CHARMI) is a promising, easy-to-use hierarchical scoring instrument assessing the full individual spectrum from immobility to unlimited mobility, including positioning, transfer and locomotion items. It allows for monitoring of mobilisation

Characterization of the Peptide-Binding Specificity of Mamu-B*17 and Identification of Mamu-B*17-Restricted Epitopes Derived from Simian Immunodeficiency Virus Proteins

The SIV-infected rhesus macaque is an excellent model to examine candidate AIDS virus vaccines. These vaccines should elicit strong CD8(+) responses. Previous definition of the peptide-binding motif and optimal peptides for Mamu-A*01 has created a demand for Mamu-A*01-positive animals. We have now studied a second MHC class I molecule, Mamu-B*17, that is present in 12% of captive-bred Indian rhesus macaques. The peptide-binding specificity of the Mamu-B*17 molecule was characterized using single substitution analogs of two Mamu-B*17-binding peptides and libraries of naturally occurring sequences of viral or bacterial origin. Mamu-B*17 uses position 2 and the C terminus of its peptide ligands as dominant anchor residues. The C terminus was found to have a very narrow specificity for the bulky aromatic residue W, with other aromatic residues (F and Y) being only occasionally tolerated. Position 2 is associated with a broad chemical specificity, readily accommodating basic (H and R), bulky hydrophobic (F and M), and small aliphatic (A) residues. Using this motif, we identified 50 peptides derived from SIV(mac)239 that bound Mamu-B*17 with an affinity of 500 nM or better. ELISPOT and intracellular cytokine-staining assays showed that 16 of these peptides were antigenic. We have, therefore, doubled the number of MHC class I molecules for which SIV-derived binding peptides have been characterized. This allows for the quantitation of immune responses through tetramers and analysis of CD8(+) function by intracellular cytokine-staining assays and ELISPOT. Furthermore, it is an important step toward the design of a multiepitope vaccine for SIV and HIV

Basic requirements for the final assessment instrument.

<p>Basic requirements for the final assessment instrument.</p

Sample characteristics and normative data of ACR sample for CHARMI.

<p>Sample characteristics and normative data of ACR sample for CHARMI.</p

Differentiation of CHARMI items by ICF subcategories.

<p>Differentiation of CHARMI items by ICF subcategories.</p

Charité Mobility Index [43].

<p>Charité Mobility Index [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169010#pone.0169010.ref043" target="_blank">43</a>].</p