Telemedicine Improves Performance of a Two-Incision Lower Leg Fasciotomy by Combat Medics:A Randomized Controlled Trial

Introduction:The primary aim of this randomized controlled trial was to assess if a head-mounted display (HMD) providing telemedicine support improves performance of a two-incision lower leg fasciotomy by a NATO special operations combat medic (combat medic).Materials and Methods:Thirty-six combat medics were randomized into two groups: One group performed a two-incision lower leg fasciotomy with the assistance of an HMD, while the control group completed the procedure without guidance. A Mann-Whitney U test was used to determine the possible differences in release of compartments and performance scores, as assessed by a supervising medical specialist. A Fisher's exact test was used to compare the proportions of collateral damage between groups. An independent-samples t-test was used to interpret total procedure times. The usability and technical factors involving HMD utilization were also assessed.Results:Combat medics in the HMD group released the anterior compartment (P <= .001) and deep posterior compartment (P = .008) significantly better. There was significantly more iatrogenic muscle (P <= .001) and venous damage (P <= .001) in the control group. The overall performance of combat medics in the HMD group was significantly better than that of the control group (P < .001). Combat medics in the control group were significantly faster (P = .012). The combat medics were very satisfied with the HMD. The HMD showed no major technical errors.Conclusions:This randomized controlled trial shows that a HMD providing telemedicine support leads to significantly better performance of a two-incision lower leg fasciotomy by a combat medic with less iatrogenic muscle and venous damage

Telemedicine Improves Performance of a Two-Incision Lower Leg Fasciotomy by Combat Medics:A Randomized Controlled Trial

Introduction:The primary aim of this randomized controlled trial was to assess if a head-mounted display (HMD) providing telemedicine support improves performance of a two-incision lower leg fasciotomy by a NATO special operations combat medic (combat medic).Materials and Methods:Thirty-six combat medics were randomized into two groups: One group performed a two-incision lower leg fasciotomy with the assistance of an HMD, while the control group completed the procedure without guidance. A Mann-Whitney U test was used to determine the possible differences in release of compartments and performance scores, as assessed by a supervising medical specialist. A Fisher's exact test was used to compare the proportions of collateral damage between groups. An independent-samples t-test was used to interpret total procedure times. The usability and technical factors involving HMD utilization were also assessed.Results:Combat medics in the HMD group released the anterior compartment (P <= .001) and deep posterior compartment (P = .008) significantly better. There was significantly more iatrogenic muscle (P <= .001) and venous damage (P <= .001) in the control group. The overall performance of combat medics in the HMD group was significantly better than that of the control group (P < .001). Combat medics in the control group were significantly faster (P = .012). The combat medics were very satisfied with the HMD. The HMD showed no major technical errors.Conclusions:This randomized controlled trial shows that a HMD providing telemedicine support leads to significantly better performance of a two-incision lower leg fasciotomy by a combat medic with less iatrogenic muscle and venous damage

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addresse

Large-Scale Profiling of Signaling Pathways Reveals a Distinct Demarcation between Normal and Extended Liver Resection

Despite numerous studies addressing normal liver regeneration, we still lack comprehensive understanding of the biological processes underlying failed liver regeneration. Therefore, we analyzed the activity of 271 intracellular signaling pathways (ISPs) by genome wide profiling of differentially expressed RNAs in murine liver tissue biopsies after normal hepatectomy (nHx; 68% of liver removed) and extended hepatectomy (eHx; 86% of liver removed). Comprehensive, genome-wide transcriptome profiling using RNAseq was performed in liver tissue obtained from mice (sham, nHx, and eHx) harvested 1, 8, 16, 32, and 48 h after operation (n = 3 per group) and the OncoFinder toolkit was used for an unsupervised, unbiased identification of intracellular signaling pathways (ISP) activity. We observed that the normal regenerative process requires a transient activation and silencing of approximately two dozen of ISPs. After nHx, the Akt Pathway represented with 13 branches, the Chromatin Pathway and the DDR Pathways dominated. After eHx, the ATM main pathway and two of its branches (Cell Survival; G2_M Checkpoint Arrest) dominated, as well as the Hypoxia Pathways. Further, 14 ISPs demonstrated a strong inverse regulation, with the Hedgehog and the Brca1 Main Pathways as chief activators after nHx, and the ATM Pathway(G2_M Checkpoint Arrest) as the dominating constraining response after eHx

Proteolytic Activity Present in House-Dust-Mite Extracts Degrades ENA-78/CXCL5 and Reduces Neutrophil Migration

Background. Bronchial smooth muscle cells (BSMC) are a major source of proinflammatory and proangiogenic cytokines and chemokines, including VEGF and CXC-chemokines. CXC-chemokines act primarily on neutrophils, mediating their recruitment to and activation at the site of inflammation. In humans, house-dust mite (HDM) allergens can cause asthmatic exacerbations and trigger an inflammatory response through protease-dependent mechanisms. Objective. We investigated the effect HDM extract on the release of pro-angiogenic and proinflammatory cytokines from BSMC. Methods. Human primary BSMC were stimulated with HDM extract in the absence or presence of fetal calf serum (FCS). Twenty angiogenic cytokines were detected by a specific antibody array and modified protein levels were confirmed by ELISA. Neutrophil migration was measured using a 96-well Boyden chamber. Results. ENA-78/CXCL5 protein levels in conditioned medium of BSMC stimulated with HDM extract were significantly reduced (n=10, P<0.05) but restored in the presence of 5% FCS. HDM extracts did not affect ENA-78/CXCL5 mRNA levels. Recombinant ENA-78/CXCL5 was degraded after incubation with HDM extracts (n=7, P<0.05) but restored after the addition of the serine protease AEBSF. Neutrophil migration towards recombinant ENA-78/CXCL5 was also reduced in the presence of HDM extract. Conclusion. HDM proteases degrade ENA-78/CXCL5. Thus exposure to HDM allergens may alter ENA-78/CXCL5 levels in the lungs and may affect angiogenesis and the inflammatory response in the airways of asthma patients

Exploration of the Transcriptional Landscape of ALPPS Reveals the Pathways of Accelerated Liver Regeneration

Background and Aims: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy), a novel 2-staged hepatectomy, dramatically accelerates liver regeneration and thus enables extensive liver tumor resection. The signaling networks underlying the ALPPS-induced accelerated regeneration process are largely unknown. Methods: We performed transcriptome profiling (TP) of liver tissue obtained from a mouse model of ALPPS, standard hepatectomy (68% model), and additional control surgeries (sham, PVL and Tx). We also performed TP using human liver biopsies (n = 5) taken from the occluded lobe and the future liver remnant (FLR) during the first step of ALPPS surgery (4–5 h apart). We used Oncofinder computational tools, which covers 378 ISPs, for unsupervised, unbiased quantification of ISP activity. Results: Gene expression cluster analysis revealed an ALPPS specific signature: the IGF1R Signaling Pathway (Cell survival), the ILK Pathway (Induced cell proliferation), and the IL-10 Pathway (Stability determination) were significantly enriched, whereas the activity of the Interferon Pathway (Transcription) was reduced (p < 0.05). Further, the PAK- and ILK-associated ISPs were activated at an earlier time point, reflecting significant acceleration of liver regeneration (p < 0.001). These pathways, which were also recovered in human liver biopsies, control cell growth and proliferation, inflammatory response, and hypoxia-related processes. Conclusions: ALPPS is not a straightforward addition of portal vein ligation (PVL) plus transection—it is more. The early stages of normal and accelerated liver regeneration are clearly discernible by a significantly increased and earlier activation of a small number of signaling pathways. Compounds mimicking these responses may help to improve the ALPPS method and further reduce the hospitalization time of the patient