Andrea L. Pozez

Cytokine Production by Skin-Derived Mast Cells: Endogenous Proteases Are Responsible for Degradation of Cytokines

The current study characterizes the cytokine protein (ELISA) and mRNA (gene array and RT-PCR) profiles of skin-derived mast cells cultured under serum-free conditions when activated by cross-linking of FcεRI. Prior to mast cell activation, mRNA only for TNF-α was detected, while after activation mRNA for IL-5, IL-6, IL-13, TNF-α, and GM-CSF substantially increased, and for IL-4 it minimally increased. However, at the protein level certain recombinant cytokines, as measured by ELISAs, were degraded by proteases released by these skin-derived mast cells. IL-6 and IL-13 were most susceptible, followed by IL-5 and TNF-α; GM-CSF was completely resistant. These observations also held for the endogenous cytokines produced by activated mast cells. By using protease inhibitors, chymase and cathepsin G, not tryptase, were identified in the mast cell releasates as the likely culprits that digest these cytokines. Their cytokine-degrading capabilities were confirmed with purified chymase and cathepsin G. Soy bean trypsin inhibitor, when added to mast cell releasates, prevented the degradation of exogenously added cytokines and, when added to mast cells prior to their activation, prevented degradation of susceptible endogenous cytokines without affecting either degranulation or GM-CSF production. Consequently, substantial levels of IL-5, IL-6, IL-13, TNF-α, and GM-CSF were detected 24–48 h after mast cells had been activated, while none were detected 15 min after activation, by which time preformed granule mediators had been released. IL-4 was not detected at any time point. Thus, unless cytokines are protected from degradation by endogenous proteases, cytokine production by human mast cells with chymase and cathepsin G cells may be grossly underestimated.

Neutralizing Endogenous IL-6 Renders Mast Cells of the MCT Type from Lung, but Not the MCTC Type from Skin and Lung, Susceptible to Human Recombinant IL-4-Induced Apoptosis

Human cord blood-derived mast cells undergo apoptosis upon exposure to recombinant human (rh)IL-4 and become resistant to rhIL-4-induced apoptosis when cultured in the presence of rhIL-6. The current study extends these effects of rhIL-4 to different populations of human mast cells, namely fetal liver-derived mast cells, lung-derived mast cells, and skin-derived mast cells. Endogenous production of IL-6 appears to protect fetal liver-derived mast cells and those of the MCT phenotype from rhIL-4-mediated apoptosis, because neutralization of IL-6 renders these mast cells sensitive. In contrast, mast cells of the MCTC phenotype from skin and lung were resistant to IL-4-mediated apoptosis, even after neutralization of endogenous IL-6. MCTC cells were CD124low, whereas those of the MCT cells were CD124high. These observations extend the phenotypic differences between MCT and MCTC types of human mast cells to include different functional responses to IL-4.

Smoke inhalation injury in a pregnant patient: a literature review of the evidence and current best practices in the setting of a classic case.

For smoke inhalation injury of a pregnant woman, one must treat two patients and be aware of the potential effects of carbon monoxide (CO) and cyanide (CN) poisoning on both the mother and the fetus. In a pregnant woman, the size and age of the fetus and the degree of poisoning allow for tremendous variability in the toxicity of CO and CN and their respective treatment options. The authors will review a case of a 32-year-old woman who was at 37 weeks of gestation and admitted to the Evans-Haynes Burn Center after a house fire and received hydroxocobalamin (Cyanokit) for suspected CN poisoning. In addition, a review of the literature, current guidelines, and treatment options of inhalation injury during pregnancy will be discussed. The authors will focus only on the toxic components of smoke inhalation injury rather than the mechanical components from heat and particulate damage. Literature review clearly identifies that the treatment of pregnant women with inhalation injury remains a controversial subject. The use of hydroxocobalamin (Cyanokit) as a treatment modality for potential CN poisoning in a pregnant patient has not been reported in the literature. Animal studies have shown that combined CO and CN poisoning are more lethal than either one alone and at lower concentrations. Due to the synergistic effects of CO and CN, and because these two toxins concentrate at even higher levels in the fetus than the mother, the authors will clarify the urgent seriousness of prompt administration of hydroxocobalamin in a pregnant patient with suspected smoke inhalation injury. This case review details the treatment of a 32-year-old woman who was at 36 weeks of gestation on admission to the Evans-Haynes Burn Center. The authors will report her injuries and the course of treatment. Although burned and presenting with concomitant smoke inhalation injury, both the woman and her child fared well with no significant complications due to the smoke inhalation at 6 months of follow-up. Smoke inhaled from modern structural fires potentially contains both CN and CO gases. This makes the prompt recognition of this injury and selection of appropriate therapy an emergent priority. In October 2010, the Food and Drug Administration approved hydroxocobalamin for use in pregnant patients in the acute setting when CN toxicity is suspected. Because CO and CN have additive effects when both are present in the body, the prompt administration of hydroxocobalamin not only eliminates the effects of CN but also potentially attenuates its synergistic effects on CO. It is only through a better understanding of the details of smoke inhalation injury, the current treatment options, and the considerations regarding their use that new research and strong guidelines can be developed to better serve our patients.

Human mast cells present antigen to autologous CD4+ T Cells

&NA; Figure. No caption available. Background: Mast cells (MCs), the primary effector cell of the atopic response, participate in immune defense at host/environment interfaces, yet the mechanisms by which they interact with CD4+ T cells has been controversial. Objective: We used in situ–matured primary human MCs and matched CD4+ T cells to diligently assess the ability of MCs to act as antigen‐presenting cells. Methods: We examined mature human skin‐derived MCs using flow cytometry for expression of antigen‐presenting molecules, for their ability to stimulate CD4+ T cells to express CD25 and proliferate when exposed to superantigen or to cytomegalovirus (CMV) antigen using matched T cells and MCs from CMV‐seropositive or CMV‐seronegative donors, and for antigen uptake. Subcellular localization of antigen, HLA molecules, and tryptase was analyzed by using structured illumination microscopy. Results: Our data show that IFN‐&ggr; induces HLA class II, HLA‐DM, CD80, and CD40 expression on MCs, whereas MCs take up soluble and particulate antigens in an IFN‐&ggr;–independent manner. IFN‐&ggr;–primed MCs guide activation of T cells by Staphylococcus aureus superantigen and, when preincubated with CMV antigens, induce a recall CD4+ TH1 proliferation response only in CMV‐seropositive donors. MCs co‐opt their secretory granules for antigen processing and presentation. Consequently, MC degranulation increases surface delivery of HLA class II/peptide, further enhancing stimulation of T‐cell proliferation. Conclusions: IFN‐&ggr; primes human MCs to activate T cells through superantigen and to present CMV antigen to TH1 cells, co‐opting MC secretory granules for antigen processing and presentation and creating a feed‐forward loop of T‐cell–MC cross‐activation.

Blast Injuries Caused by Vape Devices: 2 Case Reports

AbstractVaporizing devices have become a popular alternative to conventional nicotine products. They are thought to be safer as they produce aerosolized nicotine powered by a lithium ion battery. Many people have used these electronic devices as a tool to quit smoking; however, the batteries can be unstable and explode.We present 2 case reports where explosions of electronic vapor devices caused significant injuries. The first patient sustained a combustion injury to the maxilla resulting in bone and anterior maxillary tooth loss requiring reconstruction. The second patient had a severe blast injury to the hand which ultimately resulted in loss of a digit. Toxicology was consulted due to concerns for systemic absorption of metals in the soft tissue of the hand. Cobalt and manganese were initially elevated but decreased after surgical debridement. The patient did not have any systemic symptoms.Currently, there is no federal regulation of electronic cigarettes or vape devices in the United States. With the increasing use of these devices and no standard regulations, we anticipate more blast injuries occurring in the future. Medical providers will need to be able to be prepared to manage the devastating clinical injuries that ensue.

A Multicenter Study of Preventable Contact Burns From Glass Fronted Gas Fireplaces

Glass fronted gas fireplaces (GFGFs) have exterior surfaces that can reach extremely high temperatures. Burn injuries from contact with the glass front can be severe with long-term sequelae. The Consumer Product Safety Commission reported that these injuries are uncommon, whereas single-center studies indicate a much higher frequency. The purpose of this multi-institutional study was to determine the magnitude and severity of GFGF injuries in North America. Seventeen burn centers elected to participate in this retrospective chart review. Chart review identified 402 children ⩽10 years of age who sustained contact burns from contact with GFGF, who were seen or admitted to the study hospitals from January 2006 to December 2010. Demographic, burn, treatment, and financial data were collected. The mean age of the study group was 16.8 ± 13.3 months. The majority suffered burns to their hands (396, 98.5%), with burns to the face being the second, much less common site (14, 3.5%). Two hundred and sixty-nine required rehabilitation therapy (66.9%). The number of GFGF injuries reported was 20 times greater than the approximately 30 injuries estimated by the Consumer Product Safety Commission’s 10-year review. For the affected children, these injuries are painful, often costly and occasionally can lead to long-term sequelae. Given that less than a quarter of burn centers contributed data, the injury numbers reported herein support a need for broader safety guidelines for gas fireplaces in order to have a significant impact on future injuries.

A Model to Improve Detection of Nonaccidental Pediatric Burns

Context Pediatric burn patients warrant thorough evaluation because a sizeable proportion of pediatric burns are nonaccidental. Design A multidisciplinary method involving an internal child protection team (CPT) was developed and used to identify suspected nonaccidental pediatric burns in all pediatric burn patients 5 years of age or younger who were evaluated by the CPT and social workers at our institution over a 55-month period. Results We identified 343 cases for review that fit our age criteria, 6 of which we identified as cases of suspected abuse or neglect. On average, these patients were younger, suffered greater total body surface area burns (TBSA), and required a longer length of stay in the hospital than the total population. We have not had readmissions for repeat nonaccidental pediatric burn injuries in this group of patients since this model was implemented. Conclusions Our multidisciplinary method might provide a more consistent and reliable method for identifying cases of suspected abuse.

The Use of Vasopressors in Pedicled Flaps for Chest Wall Reconstruction

Introduction The effect of vasopressors on flaps remains controversial in the literature. Often, surgeons avoid vasopressors with the thought that vasoconstriction reduces flap perfusion resulting in flap loss. Methods A retrospective review was performed on patients who required chest wall reconstruction from 1998 to 2013. Patients were identified through the use of Current Procedural Terminology codes. The data collected included demographics, indications for surgery, prior debridement, preoperative albumin levels, and perioperative vasopressor use. Outcomes measures included flap survival, flap complications, reoperation rates, intensive care unit length of stay, and mortality. Results Of the 1220 patient records reviewed, 88 had chest reconstruction by a plastic surgeon. Twenty-one patient records were excluded due to incomplete data. One patient experienced complete flap loss; these data were excluded from statistical analysis. Fifty patients received perioperative vasopressors whereas 15 did not. There was no significant difference in flap survival or loss between groups who received perioperative vasopressors and those who did not receive vasopressors. Age, intensive care unit length of stay, flap complications, and reoperation rates were significantly higher in those with partial flap survival. Conclusions Perioperative vasopressor use does not adversely affect the outcome of pedicled flaps for chest wall reconstruction. Further research is warranted to review the effects of vasopressor dose and type on pedicled flaps.