The effects of shock wave therapy applied on hypertrophic burn scars: a randomised controlled trial.

INTRODUCTION: A wide variety of non-invasive treatments has been proposed for the management of hypertrophic burn scars. Unfortunately, the reported efficacy has not been consistent, and especially in the first three months after wound closure, fragility of the scarred skin limits the treatment options. Extracorporeal shock wave therapy (ESWT) is a new non-invasive type of mechanotherapy to treat wounds and scars. The aim of the present study was to examine the objective and subjective scar-related effects of ESWT on burn scars in the early remodelling phase. MATERIAL AND METHODS: Evaluations included the Patient and Observer Scar Assessment Scale (POSAS) for scar quality, tri-stimulus colorimetry for redness, tewametry for trans-epidermal water loss (TEWL) and cutometry for elasticity. Patients were randomly assigned to one of two groups, the low-energy intervention group or the placebo control group, and were tested at baseline, after one, three and six months. All patients were treated with pressure garments, silicone and moisturisers. Both groups received the ESWT treatment (real or placebo) once a week for 10 weeks. RESULTS: Results for 20 patients in each group after six months are presented. The objective assessments showed a statistically significant effect of ESWT compared with placebo on elasticity (P = 0.011, η2P=0.107) but revealed no significant effects on redness and TEWL. Results of the clinical assessments showed no significant interactions between intervention and time for the POSAS Patient and Observer scores. CONCLUSION: ESWT can give added value to the non-invasive treatment of hypertrophic scars, more specifically to improve elasticity when the treatment was already started in the first three months after wound closure. LAY SUMMARY: Pathological scarring is a common problem after a burn injury. A wide variety of non-invasive treatments has been proposed for the management of these scars. Unfortunately, the reported efficacy of these interventions has not been consistent, and especially in the first three months after wound closure, fragility of the scarred skin limits the treatment options. Extracorporeal shock wave therapy (ESWT) is a relatively new non-invasive therapy to treat both wounds and scars. The aim of the present study was to examine the scar-related effects of ESWT on burn scars in the early phase of healing.The scars were subjectively assessed for scar quality by the patient and an observer using the Patient and Observer Scar Assessment Scale (POSAS). Objective assessments included measurements to assess redness, water loss and elasticity. Forty patients were randomly assigned to one of two groups, the low-energy intervention group or the placebo control group (the device simulated the sound of an ESWT treatment but no real shocks were applied), and were tested at four timepoints up to six months. All patients were treated with pressure garments, silicone and moisturisers. Both groups received the ESWT treatment (real or placebo) once a week for 10 weeks.The objective assessments showed a significant improvement of elasticity in the intervention group when compared with placebo but revealed no significant effects on redness and water loss. Results of the clinical assessments showed no differences between the groups for the POSAS Patient and Observer scores.ESWT can give added value to the non-invasive treatment of pathological scars more specifically to improve elasticity in the early phase of healing.

Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU.

PURPOSE: Muscle weakness in long-stay ICU patients contributes to 1-year mortality. Whether electrophysiological screening is an alternative diagnostic tool in unconscious/uncooperative patients remains unknown. We aimed to determine the diagnostic properties of abnormal compound muscle action potential (CMAP), sensory nerve action potential (SNAP), and spontaneous electrical activity (SEA) for Medical Research Council (MRC)-defined weakness and their predictive value for 1-year mortality. METHODS: Data were prospectively collected during the EPaNIC trial (ClinicalTrials.gov: NCT00512122). First, sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of abnormal CMAP, SNAP, and SEA for weakness were determined. Subsequently, association between 1-year mortality and abnormal findings on electrophysiological screening was assessed by univariate and multivariate analyses correcting for weakness and other risk factors and the prediction model involved only a development phase. RESULTS: A total of 730 patients were electrophysiologically screened of whom 432 were tested for weakness. On day 8, normal CMAP excluded weakness with a high NPV (80.5 %). By day 15, abnormal SNAP and the presence of SEA had a high PPV (91.7 and 80.0 %, respectively). Only a reduced CMAP on day 8 was associated with higher 1-year mortality [35.6 vs 15.2 % (p < 0.001)]. This association remained significant after correction for weakness and other risk factors [OR 2.463 (95 % CI 1.113-5.452), p = 0.026]. Also among conscious/cooperative patients without weakness, reduced CMAP was independently associated with a higher likelihood of death occurring during 1 year [HR 2.818 (95 % CI 1.074-7.391), p = 0.035]. CONCLUSIONS: The diagnostic properties of electrophysiological screening vary over time. Abnormal CMAP documented early during critical illness carries information about longer-term outcome, which should be further investigated mechanistically.

Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis.

RATIONALE: Intensive care unit (ICU)-acquired weakness is a frequent complication of critical illness. It is unclear whether it is a marker or mediator of poor outcomes. OBJECTIVES: To determine acute outcomes, 1-year mortality, and costs of ICU-acquired weakness among long-stay (≥8 d) ICU patients and to assess the impact of recovery of weakness at ICU discharge. METHODS: Data were prospectively collected during a randomized controlled trial. Impact of weakness on outcomes and costs was analyzed with a one-to-one propensity-score-matching for baseline characteristics, illness severity, and risk factor exposure before assessment. Among weak patients, impact of persistent weakness at ICU discharge on risk of death after 1 year was examined with multivariable Cox proportional hazards analysis. MEASUREMENTS AND MAIN RESULTS: A total of 78.6% were admitted to the surgical ICU; 227 of 415 (55%) long-stay assessable ICU patients were weak; 122 weak patients were matched to 122 not-weak patients. As compared with matched not-weak patients, weak patients had a lower likelihood for live weaning from mechanical ventilation (hazard ratio [HR], 0.709 [0.549-0.888]; P = 0.009), live ICU (HR, 0.698 [0.553-0.861]; P = 0.008) and hospital discharge (HR, 0.680 [0.514-0.871]; P = 0.007). In-hospital costs per patient (+30.5%, +5,443 Euro per patient; P = 0.04) and 1-year mortality (30.6% vs. 17.2%; P = 0.015) were also higher. The 105 of 227 (46%) weak patients not matchable to not-weak patients had even worse prognosis and higher costs. The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge (P < 0.001). CONCLUSIONS: After careful matching the data suggest that ICU-acquired weakness worsens acute morbidity and increases healthcare-related costs and 1-year mortality. Persistence and severity of weakness at ICU discharge further increased 1-year mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial.

BACKGROUND: Patients who are critically ill can develop so-called intensive-care unit acquired weakness, which delays rehabilitation. Reduced muscle mass, quality, or both might have a role. The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered with ClinicalTrials.gov, number NCT00512122) showed that tolerating macronutrient deficit for 1 week in intensive-care units (late parenteral nutrition [PN]) accelerated recovery compared with early PN. The role of weakness was unclear. Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres. METHODS: In this prospectively planned subanalysis of the EPaNIC trial, weakness (MRC sum score) was assessed in 600 awake, cooperative patients. Skeletal muscle biopsies, harvested from 122 patients 8 days after randomisation and from 20 matched healthy controls, were studied for autophagy and atrophy. We determined the significance of differences with Mann-Whitney U, Median, Kruskal-Wallis, or χ(2) (exact) tests, as appropriate. FINDINGS: With late PN, 105 (34%) of 305 patients had weakness on first assessment (median day 9 post-randomisation) compared with 127 (43%) of 295 patients given early PN (absolute difference -9%, 95% CI -16 to -1; p=0·030). Weakness recovered faster with late PN than with early PN (p=0·021). Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls, similarly with early PN and late PN. The LC3 (microtubule-associated protein light chain 3) II to LC3I ratio, related to autophagosome formation, was higher in patients given late PN than early PN (p=0·026), reaching values almost double those in the healthy control group (p=0·0016), and coinciding with less ubiquitin staining (p=0·019). A higher LC3II to LC3I ratio was independently associated with less weakness (p=0·047). Expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants (p≤0·0006), but was unaffected by nutrition. INTERPRETATION: Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting, but allowed more efficient activation of autophagic quality control of myofibres and reduced weakness. FUNDING: UZ Leuven, Research Foundation-Flanders, the Flemish Government, and the European Research Council.

Interobserver agreement of Medical Research Council sum-score and handgrip strength in the intensive care unit.

INTRODUCTION: Muscle weakness often complicates critical illness and is associated with devastating short- and long-term consequences. For interventional studies, reliable measurements of muscle force in the intensive care unit (ICU) are needed. METHODS: To examine interobserver agreement, two observers independently measured Medical Research Council (MRC) sum-score (n = 75) and handgrip strength (n = 46) in a cross-sectional ICU sample. RESULTS: The intraclass correlation coefficient (ICC) for MRC sum-score was 0.95 (0.92-0.97). The kappa coefficient for identifying "significant weakness" (MRC sum-score <48, MRC subtotal upper limbs <24) and "severe weakness" (MRC sum-score <36) was 0.68 ± 0.09, 0.88 ± 0.07, and 0.93 ± 0.07, respectively. The ICC for left and right handgrip strength was 0.97 (0.94-0.98) and 0.93 (0.86-0.97), respectively. CONCLUSIONS: Interobserver agreement on MRC sum-score and handgrip strength in the ICU was very good. Agreement on "severe weakness" (MRC sum-score <36) was excellent and supports its use in interventional studies. Agreement on "significant weakness" (MRC sum-score <48) was good, but even better using the equivalent cut-off in the upper limbs. It remains to be determined whether this may serve as a substitute.