Local Tissue Injury Research Articles

Endoscopic Tattooing Site Presenting as Colonic Pseudotumor

Purpose: Endoscopic tattooing is performed to facilitate identification of gastrointestinal lesions at follow-up endoscopy or surgery. We present a rare complication of endoscopic tattooing presenting as inflammatory pseudotumor. Case: A 62-year-old male presented with painless hematochezia and acute blood loss anemia. The patient had undergone colonoscopy with polypectomy 2 days prior to admission. During polypectomy, piecemeal resection of a large 2-cm sessile serrated adenoma was performed in the ascending colon. Proximal and distal ends of the polypectomy site were tattooed by injecting a sterile suspension of highly purified carbon particles (SPOT ink). A repeat colonoscopy was performed after admission for likely post-polypectomy bleed. A large amount of fresh blood was seen throughout the colon. Recent polypectomy site was identified in the ascending colon with ulceration and an adherent clot. The clot was dislodged and a visible vessel with active bleeding was seen. Hemostasis was achieved by injecting 1:10,000 diluted epinephrine and placing three endoclips on the bleeding lesion. Incidentally, a second large ulcer (1.5 x 1.0 cm in size) with heaped-up margins and surrounding induration was noted just proximal to the polypectomy site. This was the area of recent endoscopic tattooing with blue-black discoloration of the colonic mucosa and the ulcer crater. Conclusion: Endoscopic tattooing is an effective technique to mark gastrointestinal lesions by submucosal dye injection. It is a safe procedure; however, rare complications (focal peritonitis, abscess formation, infected hematomas, perforation) have been reported. Tattooing agents may elicit inflammation, thrombosis, and fibroblast proliferation resulting in fat necrosis and ulceration at the injection site. It is important for endoscopists to be aware of the potential localized tissue injury induced by endoscopic tattooing because it can mimic malignancy.

Tumour necrosis factor in infectious disease

TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease.

The role of cytokines in the pathogenesis of systemic lupus erythematosus – from bench to bedside

The pathogenesis of systemic lupus erythematosus (SLE) entails a complex interaction between the different arms of the immune system. While autoantibodies production and immune complex deposition are cornered as hallmark features of SLE, there is growing evidence to propose the pathogenic role of cytokines in this disease. Examples of these cytokines include BLys, interleukin-6, interleukin-17, interleukin-18, type I interferons and tumour necrosis factor alpha. These cytokines all assume pivotal functions to orchestrate the differentiation, maturation and activation of various cell types, which would mediate local inflammatory process and tissue injury. The knowledge on these cytokines not only fosters our understanding of the disease, but also provides insights in devising biomarkers and targeted therapies. In this review, we focus on cytokines which have substantial pathogenic significance and also highlight the possible clinical applications of these cytokines.

Local Toxicity from Local Anesthetic Polymeric Microparticles

Local tissue injury from sustained-release formulations for local anesthetics can be severe. There is considerable variability in reporting of that injury. We investigated the influence of the intrinsic myotoxicity of the encapsulated local anesthetic (lidocaine, low; bupivacaine, high) on tissue reaction in rats. Cytotoxicity from a range of lidocaine and bupivacaine concentrations was measured in C2C12 myotubes over 6 days. Rats were given sciatic nerve blocks with 4 microparticulate formulations of lidocaine and bupivacaine: 10% (w/w) lidocaine poly(lactic-co-glycolic) acid (PLGA), 10% (w/w) bupivacaine PLGA, 50% (w/w) lidocaine PLGA, and 50% (w/w) bupivacaine PLGA. Effectiveness of nerve blockade was assessed by a modified hotplate test and weightbearing measurements. Myotoxicity was scored in histologic sections of injection sites. Bupivacaine and lidocaine release kinetics from the particles were measured. Median sensory blockade duration for 50% (w/w) lidocaine was 255 (90-540) minutes versus 840 (277-1215) minutes for 50% (w/w) bupivacaine (P = 0.056). All microparticulate formulations resulted in myotoxicity. The choice of local anesthetic did not influence the severity of myotoxicity. Median myotoxicity scores for 50% (w/w) lidocaine compared with 50% (w/w) bupivacaine at 4 days were 3.4 (2.1-4.2) vs 3.3 (2.9-3.5) (P = 0.44) and at 14 days 1.9 (1.8-2.4) vs 1.7 (1.3-1.9) (P = 0.23), respectively. Lidocaine and bupivacaine PLGA microspheres resulted in similar degrees of myotoxicity, irrespective of drug loading. Intrinsic myotoxicity did not predict tissue injury from sustained release of these anesthetics. Caution is warranted in the use of such devices near muscle and nerve.

Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice

Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with increased expression of proinflammatory cytokines. Two of these cytokines, interleukin-1β (IL-1β) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (NLR) family. These NLRs form an inflammasome that is activated by pathogens and signals released through local tissue injury or death. NLR family pyrin domain containing 3 (Nlrp3) and NLR family CARD domain containing protein 4 (Nlrc4) have been studied minimally for their role in the development of ALD. Using mice with gene targeted deletions for Nlrp3 (Nlrp3−/−) and Nlrc4 (Nlrc4−/−), we analyzed the response to chronic alcohol consumption. We found that Nlrp3−/− mice have more severe liver injury with higher plasma alanine aminotransferase (ALT) levels, increased activation of IL-18, and reduced activation of IL-1B. In contrast, the Nlrc4−/− mice had similar alcohol-induced liver injury compared to C57BL/6J (B6) mice but had greatly reduced activation of IL-1β. This suggests that Nlrp3 and Nlrc4 inflammasomes activate IL-1β and IL-18 via caspase-1 in a differential manner. We conclude that the Nlrp3 inflammasome is protective during alcohol-induced liver injury.

Application of the self-made 10％ sodium chloride solution pad ice packs in early local soft tissue injury patients

Objective To explore the effect of self-made 10％ sodium chloride solution pad ice packs on the patients with local soft tissue injury in early time.Methods Totals of 62 cases with lower limb soft tissue injury were selected and randomly divided into experimental group ( n =32 ) that received the cold compress treatment by homemade 10％ sodium chloride solution pad ice packs,and control group( n =30) that received the cold compress treatment by water pad ice packs.Then,0,0.5,1.5,2 h later,the internal temperature,the temperature between the body surface and ice bag,hardness,the surface of contact surface size,and patients' satisfaction of two groups were observed.Results In the experimental group,the initial temperature of 10％sodium chloride solution pad ice packs was ( - 18.38 ±0.81 ) ℃,temperature between ice bag and body surface was 18℃ during cold compress,half an hour later,the temperature of inside ice bag was ( -9.73 ± 0.54)℃.After one hour in the room,the second cold compress,internal temperature was ( - 2.55 ± 1.66) ℃ and the temperature between ice bag and the surface was about 22 ℃,the end of ice internal temperature was (8.5 ±1.81 )℃.Hardness of first and secondary cold compress was small,the area size of skin contact with ice was about 72％.In the control goup,for the water cotton pad ice bags were so hardness that early thermometers were not inserted and temperature can not accurate measured.And the area of skin contact with ice was 29％.Significant differences were found in the contact area between two groups in different time (t =49.32,49.32,49.32,39.64,respectively; P ＜ 0.05 ).There was no significant difference in the pain degree of patients between two groups,while after 48 h cold compress,pain rating index and the swelling score of experimental group was significantly lower than that of control group(x2 =0.017,P ＜0.05).Patients' satisfaction of experimental group was significantly higher than that of control group ( x2 =4.4,P ＜ 0.05 ).Condusions Appling the selfmade 10％ sodium chloride solution pad ice packs,for the temperature between ice bag and the surface was higher than the skin freezing temperature( -5 ℃ ) and below the basal body temperature,which can reach the objective with no cause frostbite,it has large contact area,easy fixing and shaping,and good for patients with local soft tissue injury in early stage. Key words: Soft tissue injury; Cold compress; 10％ sodium chloride solution

A new zebrafish bone crush injury model

SummaryWhile mammals have a limited capacity to repair bone fractures, zebrafish can completely regenerate amputated bony fin rays. Fin regeneration in teleosts has been studied after partial amputation of the caudal fin, which is not ideal to model human bone fractures because it involves substantial tissue removal, rather than local tissue injury. In this work, we have established a bone crush injury model in zebrafish adult caudal fin, which consists of the precise crush of bony rays with no tissue amputation. Comparing these two injury models, we show that the initial stages of injury response are the same regarding the activation of wound healing molecular markers. However, in the crush assay the expression of the blastema marker msxb appears later than during regeneration after amputation. Following the same trend, bone cells deposition and expression of genes involved in skeletogenesis are also delayed. We further show that bone and blood vessel patterning is also affected. Moreover, analysis of osteopontin and Tenascin-C reveals that they are expressed at later stages in crushed tissue, suggesting that in this case bone repair is prolonged for longer than in the case of regeneration after amputation. Due to the nature of the trauma inflicted, the crush injury model seems more similar to fracture bone repair in mammals than bony ray amputation. Therefore, the new model that we present here may help to identify the key processes that regulate bone fracture and contribute to improve bone repair in humans.

Protective role of R-spondin3 in mesenteric ischemia/reperfusion induced tissue injury (54.11)

Abstract Ischemia reperfusion (I/R) injury represents a leading cause of morbidity and mortality. R-spondins, acknowledged as ligands of Wnt pathways, demonstrate their physiological role as mitogens, morphogens, stem cell factors, and wound healing agents in various development and disease models. We asked whether these proteins could prevent inflammation-associated tissue damage in ischemic disorders. C57BL/6J mice were pretreated with vehicle or R-spondin3 (R-spo3) before inducing mesenteric I/R for 30/180 min. At the end of reperfusion, intestinal tissues were harvested for different experimental analysis. Treatment with R-spo3 significantly decreased local intestinal injury. mRNA and protein analyses revealed that this effect was achieved through the modulation of the expression of pro-inflammatory cytokines (IL-6, TNFα and COX2) and deposition of IgM and complement. The decreased levels of IgM on tissues correlated with the reduced vascular leakage in the intestine of R-spo3 treated mice. Further we determined the effect of R-spo3 on endothelial barrier function in vitro using HUVECs and FITC-dextran (500kDa). R-spo3 pretreated groups showed significant reduction in histamine-enhanced FITC-dextran permeability of endothelial monolayer. Our results demonstrate that R-spo3 mitigates I/R-induced local tissue injury by preventing vascular leakage and decreasing the local inflammatory response. These findings confer the protective effects of R-spondin3 in I/R-related tissue damage.

Platelet-associated CD40/CD154 mediates remote tissue damage after mesenteric ischemia/reperfusion injury (54.1)

Abstract Several innate and adaptive immune cell types participate in ischemia/reperfusion induced tissue injury. Amongst them, platelets have received little attention as contributors in the process of tissue damage after ischemia reperfusion (I/R) injury. It is currently unknown whether platelets participate through the immunologically important molecules including, CD40 and when activated, CD154 (CD40L), in the pathogenesis of I/R injury. We hypothesized that constitutive expression of CD40 and activation-induced expression of CD154 on platelets mediate local mesenteric and remote lung tissue damage after I/R injury. Wild type (WT; C57BL/6J), CD40 and CD154 deficient mice underwent mesenteric ischemia for 30 minutes followed by reperfusion for 3 hours. WT mice subjected to mesenteric I/R injury displayed both local intestinal and remote lung damage. In contrast, there was significantly less intestinal damage and no remote lung injury in CD40 and CD154 deficient mice when compared to WT mice. Platelet-depleted WT mice transfused with platelets from CD40 or CD154 deficient mice failed to reconstitute remote lung damage. In contrast, when CD40 or CD154 deficient mice were transfused with WT platelets lung tissue damage was re-established. Together, these findings suggest that multiple mechanisms are involved in local and remote tissue injury and also identify platelet-expressed CD40 and/or CD154 as mediators of remote tissue damage.

Activated Pericytes and the Inhibition of Renal Vascular Stability

The hallmark feature of CKD and its progression to end stage is the presence and severity of interstitial fibrosis.1,2 This long-recognized association is the prime driving force of research to understand the nature of renal scarification. Much of the research in this area can be grouped into one of two broad categories: efforts geared toward understanding the biochemical and pathophysiological factors that govern the degree of progression and efforts aimed at defining the cellular and molecular elements that comprise renal scars. With regard to the former, it is clear that a profibrotic environment is promoted by activity from a variety of factors with activity driving the production of extracellular matrix (ECM). Of these, TGFβ and other profibrotic cytokines have been widely studied, and these are enhanced by local tissue injury, epithelial cell cycle arrest, cell differentiation status, or hypoxia.1,3

Platelet-Associated CD40/CD154 Mediates Remote Tissue Damage after Mesenteric Ischemia/Reperfusion Injury

Several innate and adaptive immune cell types participate in ischemia/reperfusion induced tissue injury. Amongst them, platelets have received little attention as contributors in the process of tissue damage after ischemia reperfusion (I/R) injury. It is currently unknown whether platelets participate through the immunologically important molecules including, CD40 and when activated, CD154 (CD40L), in the pathogenesis of I/R injury. We hypothesized that constitutive expression of CD40 and activation-induced expression of CD154 on platelets mediate local mesenteric and remote lung tissue damage after I/R injury. Wild type (WT; C57BL/6J), CD40 and CD154 deficient mice underwent mesenteric ischemia for 30 minutes followed by reperfusion for 3 hours. WT mice subjected to mesenteric I/R injury displayed both local intestinal and remote lung damage. In contrast, there was significantly less intestinal damage and no remote lung injury in CD40 and CD154 deficient mice when compared to WT mice. Platelet-depleted WT mice transfused with platelets from CD40 or CD154 deficient mice failed to reconstitute remote lung damage. In contrast, when CD40 or CD154 deficient mice were transfused with WT platelets lung tissue damage was re-established. Together, these findings suggest that multiple mechanisms are involved in local and remote tissue injury and also identify platelet-expressed CD40 and/or CD154 as mediators of remote tissue damage.

Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats

BackgroundSmall intestinal ischemia-reperfusion (IIR) injury may lead to severe local and remote tissue injury, especially acute lung injury (ALI). Mast cell activation plays an important role in IIR injury. It is unknown whether IIR mediates lung injury via mast cell activation. MethodsAdult SD rats were randomized into sham operated group (S), sole IIR group (IIR) in which rats were subjected to 75min of superior mesenteric artery occlusion followed by 4h reperfusion, or IIR being respectively treated with the mast cell stabilizer Cromolyn Sodium (IIR+CS group), with the tryptase antagonist Protamine (IIR+P group), with the histamine receptor antagonist Ketotifen (IIR+K group), or with the mast cell degranulator Compound 48/80 (IIR+CP group). The above agents were, respectively, administrated intravenously 5min before reperfusion. At the end of experiment, lung tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7(MCP7). Pulmonary mast cell number and levels of histamine, TNF-α and IL-8 were quantified. ResultsIIR resulted in lung injury evidenced as significant increases in lung histological scores (P<0.05 IIR vs. S), accompanied with concomitant increases of mast cell counts and elevations in TNF-α and IL-8 concentrations and reductions in histamine levels (all P<0.05 IIR vs. S). IIR also increased lung tissue tryptase and MCP7 protein expressions (all P<0.05, IIR vs. S). Cromolyn Sodium, Ketotifen and Protamine significantly reduced whilst Compound 48/80 aggravated IIR mediated ALI and the above biochemical changes (P<0.05). ConclusionsMast cells activation play a critical role in IIR mediated ALI.

Pulmonary embolism with acute pancreatitis: A case report and literature review

Acute pancreatitis is an inflammatory disease characterized by local tissue injury which can trigger a systemic inflammatory response. So vascular complications of pancreatitis are a major cause of morbidity and mortality. Pulmonary embolism in acute pancreatitis has been reported to be very rare. We reported a case of pulmonary embolism with acute pancreatitis. A 38-year-old woman broke out upper abdomen pain without definite inducement. She had no nausea and vomiting, fever, dyspnea, cough and expectoration, chest pain. The patient had been diagnosed with acute pancreatitis in local hospital. The patient was treated with antibiotics and proton pump inhibitors, and the abdomen pain was alleviated slightly. But the patient came forth cough and expectoration with a little blood, progressive dyspnea. A computed tomographic scan of the abdomen revealed pancreatitis. Subsequent computer tomography angiography of chest revealed pulmonary embolism (both down pulmonary arteries, left pulmonary artery and branch of right pulmonary artery). Dyspnea of the patient got well with thrombolytic treatment and anticoagulation therapy. Pulmonary embolism is a rare but potentially lethal complication of pancreatitis. Familiarity with this complication will aid in its early diagnosis, therapy and prevent pulmonary embolism, a rare but catastrophic phenomenon.

Mesenchymal stem cells as all-round supporters in a normal and neoplastic microenvironment

Mesenchymal stem cells (MSC) represent a heterogeneous population exhibiting stem cell-like properties which are distributed almost ubiquitously among perivascular niches of various human tissues and organs. Organismal requirements such as tissue damage determine interdisciplinary functions of resident MSC including self-renewal, migration and differentiation, whereby MSC support local tissue repair, angiogenesis and concomitant immunomodulation. However, growth of tumor cells and invasion also causes local tissue damage and injury which subsequently activates repair mechanisms and consequently, attracts MSC. Thereby, MSC exhibit a tissue-specific functional biodiversity which is mediated by direct cell-to-cell communication via adhesion molecule signaling and by a tightly regulated exchange of a multifactorial panel of cytokines, exosomes, and micro RNAs. Such interactions determine either tumor-promoting or tumor-inhibitory support by MSC. Moreover, fusion with necrotic/apoptotic tumor cell bodies contributes to re-program MSC into an aberrant phenotype also suggesting that tumor tissue in general represents different types of neoplastic cell populations including tumor-associated stem cell-like cells. The present work summarizes some functional characteristics and biodiversity of MSC and highlights certain controversial interactions with normal and tumorigenic cell populations, including associated modulations within the MSC microenvironment.

Duration and Local Toxicity of Sciatic Nerve Blockade With Coinjected Site 1 Sodium-Channel Blockers and Quaternary Lidocaine Derivatives

Quaternary lidocaine derivatives (QLDs) have recently received much attention because of their potential application in prolonged or sensory-selective local anesthesia. However, associated tissue toxicity is an impeding factor that makes QLDs unfavorable for clinical use. Based on the proposed intracellular site of action, we hypothesized that nerve blocks obtained from lower concentrations of QLDs would be enhanced by the coapplication of extracellularly acting site 1 sodium-channel blocker, resulting in prolonged block duration but with minimal tissue toxicity. Quaternary lidocaine derivatives (QX-314 or QX-222), site 1 sodium-channel blockers (tetrodotoxin [30 μM] or saxitoxin [12.5 μM]), or both were injected in the vicinity of the sciatic nerve. Thermal nociceptive block was assessed using a modified hot plate test; motor block by a weight-bearing test. Tissue from the site of injection was harvested for histological assessment. Coapplication of 25 mM QX-314 or 100 mM QX-222 with site 1 sodium-channel blockers produced an 8- to 10- fold increase in the duration of nerve blocks (P < 0.05), compared with QLDs or site 1 blockers alone. Quaternary lidocaine derivatives elicited severe myotoxicity; this was not exacerbated by coinjection of the site 1 sodium-channel blockers. Coadministration of site 1 sodium-channel blockers and QLDs greatly prolongs the duration of peripheral nerve block without enhancing local tissue injury, but minimal myotoxicity still persists. It is not clear that the risks of QLDs are outweighed by the benefits in providing prolonged nerve blockade.

Abstract 18240: Wnt Signaling Negatively Regulates the Proliferation of Adult Cardiac Progenitor Cells

Recent studies have demonstrated the existence of endogenous cardiac stem/progenitor cells capable of regenerating damaged myocardium following myocardial infarction (MI). Cardiac side population (CSP) cells are cardiac precursors found in the adult myocardium, which are able to differentiate into functional cardiomyocytes both in vitro and in vivo, following MI. In response to local tissue injury, CSP cells are maintained through a process of self-renewal. The molecular signals that control the self-renewal of adult progenitor cells in the heart remain unclear. Canonical Wnt signaling pathway has been implicated in the regulation of tumor progression, development and regeneration in various tissues. The goal of this study was to determine the effects of Wnt signaling pathway on the homeostasis of adult CSP cells under normal and disease conditions. Results: In contrast to previous work in embryonic or early post-natal cardiac stem cells, we reveal that Wnt signaling negatively regulates adult CSP progenitor cell proliferation, both in vitro and in vivo through suppression of cell cycle progression. Furthermore, we demonstrate that Wnt signaling exerts its anti-proliferative effect through the activation of insulin-like growth factor binding protein 3 (IGFBP3). Administration of recombinant Wnt3a protein in the infarct/border zone of mouse hearts, following MI decreases the amount of cardiac CSP cells and impairs the endogenous cardiac regenerative capacity, as evidenced by the decreased number of BrdU positive cardiomyocytes. Reduction of cardiac regenerative capacity mediates adverse effects on post-MI remodeling and performance. Conclusion: Our data demonstrate that Wnt signaling represents an effective negative regulator of adult cardiac progenitor cell proliferation, under physiologic conditions and post-MI. Inhibition of Wnt signaling may be considered as an approach to promote cardiac regeneration following ischemic injury.

The untold truth about “bath salt” highs: A case series demonstrating local tissue injury

The epidemic of injecting cathinone derivatives, marketed as "bath salts", by intravenous drug users among inner city Dubliners led to an associated rise in soft tissue complications. The spectrum of the cases encountered, ranging from self-limiting cellulitis to extensive abscess formation, at a single institution is described.

Ventilator-associated pneumonia in burn patients: a cause or consequence of critical illness?

Infectious complications are a constant threat to thermally injured patients during hospitalizations and are a predominant cause of death. Most of the infections that develop in burn patients are nosocomial and of a pulmonary etiology. The bacteria that cause ventilator associated pneumonia (VAP) take advantage of the fact that uniquely among intensive care unit patients endotracheal intubation allows them a ‘free’ passage to the sterile lower airways; however, the combination of severe thermal injury (systemic immunosuppression) and inhalation injury (local immunosuppression and tissue injury) create an ideal environment for development of VAP. Thus, strategies directed at preventing and treating VAP in burn patients must address not only rapid extubation and VAP prevention bundles known to work in other intensive care unit populations, but therapies directed to more rapid wound healing and restoration of pulmonary patency.

From neutrophil extracellular traps release to thrombosis: an overshooting host‐defense mechanism?

Innate immunity and blood coagulation are evolutionary entangled in an intricate network of molecular and cellular interactions, thus forming an integral part of the host‐defense system [1]. Polymorphonuclear cells, in particular neutrophils, are essential for the primary innate immune response against local and systemic infections or tissue injury [2], but are also major cellular mediators supporting inflammation–coagulation interactions [3]. Upon inflammation, multiple chemotactic stimuli (cytokines, chemokines, etc.) are released to promote neutrophil activation, extravazation and migration towards the infectious foci.

Pressure Immobilization Bandages Not Indicated in the Pre-hospital Management of North American Snakebites

To the Editor, We would like to express our concern regarding the “2010 American Heart Association and American Red Cross Guidelines for First Aid” [1] which was published in the October 2010 issue of the journal Circulation. While overall the guidelines are well written and evidence-based, we strongly disagree with the recommendations regarding pre-hospital management of snakebite victims. Specifically, the guidelines recommending the application of a pressure immobilization bandage for both neurotoxic and non-neurotoxic American snakes. The authors cite a study by Bush and colleagues, which demonstrated that pressure immobilization is associated with delayed mortality in a porcine model of rattlesnake envenomation [2]. However, tissue injury and necrosis, rather than mortality, is the primary toxicity associated with North American rattlesnake envenomations. The application of a pressure immobilization bandage may exacerbate local tissue injury and, as demonstrated in Dr. Bush’s study, may increase intracompartmental pressure, creating a surgical emergency when one did not otherwise exist. It should be noted that the very paper the guidelines cite in support of this intervention concludes “on the basis of our findings, we cannot recommend pressure immobilization widely for viper envenomation” [2]. Based on the absence of evidence for improved outcome following application of pressure immobilization devices in patients with pit viper bites and the potential risk of increased tissue injury, we advise against the use of such devices. We ask that all medical toxicologists and other experts in management of snake envenomation continue to educate and advise pre-hospital providers against the use of pressure immobilization devices in North American snakebite victims.