BackgroundThe effects of neuromuscular electrical stimulation (NMES) in critically ill patients after cardiothoracic surgery are unknown. The objectives were to investigate whether NMES prevents loss of muscle layer thickness (MLT) and strength and to observe the time variation of MLT and strength from preoperative day to hospital discharge.MethodsIn this randomized controlled trial, 54 critically ill patients were randomized into four strata based on the SAPS II score. Patients were blinded to the intervention. In the intervention group, quadriceps muscles were electrically stimulated bilaterally from the first postoperative day until ICU discharge for a maximum of 14 days. In the control group, the electrodes were applied, but no electricity was delivered. The primary outcomes were MLT measured by ultrasonography and muscle strength evaluated with the Medical Research Council (MRC) scale. The secondary functional outcomes were average mobility level, FIM score, Timed Up and Go Test and SF-12 health survey. Additional variables of interest were grip strength and the relation between fluid balance and MLT. Linear mixed models were used to assess the effect of NMES on MLT, MRC score and grip strength.ResultsNMES had no significant effect on MLT. Patients in the NMES group regained muscle strength 4.5 times faster than patients in the control group. During the first three postoperative days, there was a positive correlation between change in MLT and cumulative fluid balance (r = 0.43, P = 0.01). At hospital discharge, all patients regained preoperative levels of muscle strength, but not of MLT. Patients did not regain their preoperative levels of average mobility (P = 0.04) and FIM score (P = 0.02) at hospital discharge, independent of group allocation.ConclusionsNMES had no effect on MLT, but was associated with a higher rate in regaining muscle strength during the ICU stay. Regression of intramuscular edema during the ICU stay interfered with measurement of changes in MLT. At hospital discharge patients had regained preoperative levels of muscle strength, but still showed residual functional disability and decreased MLT compared to pre-ICU levels in both groups.Trial registrationClinicaltrials.gov identifier NCT02391103. Registered on 7 March 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1199-3) contains supplementary material, which is available to authorized users.

The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector expressing a melanocyte differentiation antigen resulted in T cell-dependent long-term control of melanomas. Using single-cell RNA-seq analysis, we demonstrate that viral vector-mediated transduction reprogrammed and activated a Cxcl13-expressing FSC subset that show a pronounced immunostimulatory signature and increased expression of the inflammatory cytokine IL-33. Ablation of Il33 gene expression in Cxcl13-Cre-positive FSCs reduces the functionality of intratumoral T cells and unleashes tumor growth. Thus, reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment by locally sustaining the activity of tumor-specific T cells.

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Summary: Soft tissue defect reconstruction at joint regions is a challenging problem due to the sparse excessive tissue and late complication of constrigent scar formation. Priorly irradiated tissue, often the case in sarcoma patients, is especially problematic. The keystone design perforator island flap is safe and reliable. We now present a new keystone flap design, which is particularly suitable for the reconstruction of large soft tissue defects at joint regions. It provides a cutaneous component without the need for a skin graft and therefore minimizes the risk of contracture. Donor site morbidity is negligible. Furthermore, it offers a favorable aesthetic result compared to other flaps, eg, a muscular flap. We propose a new keystone flap design as an extension of Behan's classification, the Keystone flap type IIIb.

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