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PURPOSE: Hospital-acquired pressure injuries (HAPIs) have significant impacts on patient morbidity and mortality, with approximately 2.5 million patients treated for pressure-related injuries annually.1 This study aimed to describe the influence of a comprehensive wound care team on HAPIs over an 8-year period. DESIGN: Retrospective cohort study. SUBJECTS AND SETTING: All inpatients at an academic public hospital system with HAPIs during the study period from May 2012 to February 2020. METHODS: Data on wound stage, location, infection, medical device location if applicable, and risk factors were recorded from medical records. A 1-way analysis of variance was performed to assess for significance of mean number of cases, National Pressure Injury Advisory Panel (NPIAP) stage on initial presentation, and mean number of medical device-related wounds by year. RESULTS: A total of 957 cases were included. The median stage of pressure injury on assessment was 2, with the mean NPIAP stage declining from 2012 to 2020 (P = .003). Thirty-three percent of pressure injuries were attributed to medical devices, most commonly endotracheal tubing. The most common site of pressure injury was the sacrum (33.6%). CONCLUSION: Creation of a comprehensive wound care team within our academic public hospital system demonstrated a significant decline in device-related and pressure injury cases over the past 8 years. The wound care team focused on frequent assessment, education, and evidence-based treatment to lower these HAPI events.
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Úlcera por Presión , Hospitales Públicos , Humanos , Pacientes Internos , Grupo de Atención al Paciente , Úlcera por Presión/epidemiología , Úlcera por Presión/prevención & control , Estudios RetrospectivosRESUMEN
PURPOSE: Women undergoing postmastectomy breast reconstruction face many complex choices. A myriad of online patient education materials exist to assist in decision making. Understanding of these materials, termed health literacy, affects surgical decision making and outcomes. The National Institutes of Health recommends writing patient education materials at a sixth- to seventh-grade reading level. The primary goal of this study was to assess readability of online breast reconstruction materials. METHODS AND MATERIALS: Resources were collected from every academic hospital with a plastic surgery residency program, 97 in total. These data were compared with the top nonacademic Web sites ranked by search engine results, 14 in total. Materials were analyzed using 3 validated readability assessment scales: Coleman-Liau Index, SMOG (Simplified Measure of Gobbledygook) Readability Formula, and Flesch-Kincaid Grade Level. Average readability was analyzed, and results were compared using a 1-way analysis of variance to assess for significance between the different tools and a 2-sided t test to assess for significance between academic and nonacademic readability results. RESULTS: The mean readability scores across the academic programs were a Coleman-Liau Index of 13.38 (standard Deviation [SD] 2.81, 13th to 14th grade), Flesch-Kincaid Grade Level of 13.04 (SD = 3.9, 13th grade), and SMOG Readability of 13.64 (SD = 2.99, 13th to 14th grade). For the 14 nonacademic sites, results showed a Coleman-Liau Index of 11.93 (SD = 1.14, 12th grade), Flesch-Kincaid of 11.82 (SD = 2.33, 11th to 12th grade), and SMOG Readability of 10.91 (SD = 1.79, 11th grade). One-way analysis of variance demonstrated no significant differences in mean readability scores across the 3 readability tools used (academic F = 2.7804, P = 0.06; nonacademic F = 1.14, P = 0.33). Two-tailed t test results demonstrated that there was statistical significance between readability of the academic in comparison with nonacademic search engine results (t = 2.04, P = 0.04). CONCLUSIONS: Average readability across all Web sites were much higher than the recommended reading level, at a 13th to 14th grade reading level for academic institutions, and an 11th to 12th grade for nonacademic Web sites. Plastic surgeons may contribute to improving patient understanding and perioperative outcomes through revising patient education materials.
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Neoplasias de la Mama , Alfabetización en Salud , Mamoplastia , Comprensión , Femenino , Hospitales , Humanos , Internet , Mastectomía , Educación del Paciente como AsuntoRESUMEN
ABSTRACT: Modern breast surgery was first introduced in the United States in 1962 with the use of silicone gel-filled breast implants. Over the past 6 decades, development of breast implants has been challenged by a variety of influencers including aesthetic appeal in shape, texture, and material; challenges in managing outcomes such as contracture, disease, and rupture; and public perception of risks associated with implants. In 1992, silicone breast prostheses were banned by the US Food and Drug Administration with exception for use in breast reconstruction, congenital deformities, or to replace existing implants.The ban led to heightened concerns about implants and possible disease manifestations. Knowledge of the historical evolution of breast prostheses is useful for understanding the associated risks and outcomes unique to each breast implant era. This article aimed to explore characteristics of breast implants by generation, with implications for diagnosis and assistance to modern surgical planning for novice plastic surgeons.
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Implantación de Mama , Implantes de Mama , Mamoplastia , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Humanos , Mastectomía , Geles de Silicona/efectos adversos , Estados UnidosRESUMEN
BACKGROUND: Dog bite injuries cause significant preventable patient morbidity and health care expenditure in children. This study aimed to characterize the patient and healthcare burden related to pediatric dog bite injuries at a level 1 trauma center. METHODS: This is a retrospective review of 356 pediatric patients who presented to Virginia Commonwealth University Pediatric Emergency Department between July 2007 and August 2017 after sustaining dog bite injuries. Demographic information, injury details, management, outcomes, and financial information were analyzed. RESULTS: Most pediatric dog bite injuries afflicted male children (55.6%), ages 6 to 12 years (45.7%), by a household dog (36.2%). The most common offending breed was a pit bull or pit bull mix (53.0%). Infants and grade schoolers were more likely to sustain bites to the head/face (P = 0.001). Usual management consisted of primary repair (75.9%), whereas approximately 25% of the patients required advanced reconstructive techniques. Most patients healed uneventfully, but prolonged antibiotics, additional wound care, or procedures were necessary in 8.4% of the patients. Hospital charges per patient averaged US $8830.70 and tended to be higher in the younger age groups. Insurance status was statistically associated with use of conscious sedation, surgical consult placement, and surgical repair. CONCLUSIONS: Although most pediatric dog bite injuries in this study healed uneventfully from primary management in the emergency department, 25% required additional interventions. Furthermore, patient care for these injuries was associated with significant but potentially avoidable personal and financial burden to families. Our data reflect a need for safety education on animal care, behavior, and interaction.
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Mordeduras y Picaduras , Traumatismos Faciales , Animales , Mordeduras y Picaduras/epidemiología , Mordeduras y Picaduras/terapia , Niño , Preescolar , Perros , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Centros Traumatológicos , Virginia/epidemiologíaRESUMEN
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-γ induces HLA class II, HLA-DM, CD80, and CD40 expression on MCs, whereas MCs take up soluble and particulate antigens in an IFN-γ-independent manner. IFN-γ-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-γ 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.
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Presentación de Antígeno , Linfocitos T CD4-Positivos/inmunología , Mastocitos/inmunología , Presentación de Antígeno/inmunología , Células Presentadoras de Antígenos/inmunología , Antígenos Virales/inmunología , Transporte Biológico , Biomarcadores , Linfocitos T CD4-Positivos/metabolismo , Comunicación Celular , Células Cultivadas , Dinaminas , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Inmunofenotipificación , Interferón gamma/metabolismo , Mastocitos/metabolismo , Especificidad del Receptor de Antígeno de Linfocitos TRESUMEN
BACKGROUND: Pediatric dog bite injuries account for 1% of emergency department visits per year and represent an underrecognized and underreported public health problem. Reconstructive surgery is frequently utilized, and in the most extreme injuries, microvascular replantation may be considered. We sought to systematically review the available literature on microvascular replantation after facial dog bite injuries in children, with particular attention to perioperative morbidity and long-term follow-up. METHODS: We reviewed a case of microvascular replantation after a facial dog bite injury in a child from our own institution and conducted a systematic literature search to identify other similar reports. Clinical variables were collected from the reported cases, and descriptive statistics were calculated. A management algorithm was developed from the reviewed published experience. RESULTS: We report the youngest child to date in the literature to undergo replantation after a facial dog bite injury. Nineteen other cases were found involving children aged 18 months to 17 years, with follow-up ranging from 2 weeks to 28 years. Anastomosis techniques varied considerably and included both an artery and vein in only 9 (47%) of 19 cases. Venous congestion was nearly universal, and multimodal techniques were used until native venous outflow was reestablished. Blood transfusion was common, but intensive care unit utilization was not frequently reported. Long-term outcomes were excellent, with growth of the replanted part and recovery of function; however, minor revision procedures were common. CONCLUSIONS: Microvascular replantation following facial dog bite amputation injuries in the pediatric population is the ultimate step in the reconstructive ladder. Strong consideration should be given to microvascular exploration with involvement of large or whole segments of the lip, nose, or ear; however, parents should be counseled extensively regarding the known morbidity of replantation surgery. With meticulous surgical technique and careful postoperative care, replantation after facial dog bite amputation injuries may successfully achieve dramatic and lasting results for pediatric patients.
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Amputación Traumática/cirugía , Mordeduras y Picaduras/cirugía , Traumatismos Faciales/cirugía , Reimplantación/métodos , Adolescente , Algoritmos , Amputación Traumática/etiología , Animales , Mordeduras y Picaduras/complicaciones , Niño , Preescolar , Perros , Traumatismos Faciales/etiología , Femenino , Humanos , Masculino , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/cirugía , Cicatrización de HeridasRESUMEN
This was a pilot study to examine pre- and postoperative stress experienced by women who were undergoing autologous breast reconstruction and how stress might impact wound healing, specifically examining cytokines and other chemical mediators in the wound environment. A nonexperimental descriptive design over time was utilized. Participants were women who were undergoing autologous abdominal breast reconstruction for breast cancer (N = 20). Data were collected preoperatively and at 24, 48, 72, and 96 hr postsurgery. Complications were monitored intraoperatively and up to 30 days postsurgery. Psychological stress was measured with the 10-item Perceived Stress Scale (PSS), the Impact of Events Scale-Revised (IES-R), and a 100-mm Visual Analog Scale (VAS). Cytokines were assayed using the 27-plex kit with a Bio-Plex Plus. Although breast cancer is considered a stressor, in this sample of women, scores of the PSS, IES-R, and VAS showed that in fact these participants experienced low levels of psychological stress. All measured biochemical mediators in serum and wound fluid were detected and trends were identified. IL-1ra, IL-6, IL-8, G-CSF, IP-10, MCP-1, MIP-1ß, RANTES, and VEGF were present in the highest concentrations. Significant changes in levels of cytokines in wound fluid were observed in IL-1ß, IL-2, IL-5, IL-6, IL-8, IL-9, IL-10, IL-17, FGF-basic, G-CSF, MIP-1α, PDGF-bb, MIP-1ß, RANTES, and TNF-α. The remaining cytokine concentrations stayed stable over time. These findings suggest that although these women were not experiencing high levels of stress, meaningful cytokine patterns were detected.
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Mamoplastia/psicología , Percepción , Estrés Psicológico/psicología , Adulto , Anciano , Fenómenos Bioquímicos/fisiología , Quimiocinas/análisis , Quimiocinas/sangre , Citocinas/análisis , Citocinas/sangre , Drenaje , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/análisis , Péptidos y Proteínas de Señalización Intercelular/sangre , Mamoplastia/efectos adversos , Mamoplastia/métodos , Persona de Mediana Edad , Proyectos Piloto , Psicometría/instrumentación , Psicometría/métodos , Estrés Fisiológico/fisiología , Estrés Psicológico/complicaciones , Herida Quirúrgica/complicaciones , Encuestas y Cuestionarios , VirginiaRESUMEN
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.
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Complicaciones Posoperatorias/epidemiología , Colgajos Quirúrgicos/estadística & datos numéricos , Neoplasias Torácicas/cirugía , Pared Torácica/cirugía , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Mamoplastia/estadística & datos numéricos , Persona de Mediana Edad , Músculo Esquelético/cirugía , Estudios RetrospectivosRESUMEN
Vaporizing 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.
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Traumatismos por Explosión/etiología , Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Traumatismos de la Mano/etiología , Maxilar/lesiones , Traumatismos por Explosión/diagnóstico , Traumatismos de la Mano/diagnóstico , Humanos , Masculino , Adulto JovenRESUMEN
Utilizing inclusive terminology in patient education materials is an increasing area of focus in plastic surgery. Over 300,000 cases of breast cancer were diagnosed in 2020, affecting cisgender and gender diverse patients alike. Both cisgender and gender diverse patients may choose to undergo breast reconstruction. This study aims to assess the use of inclusive language in online patient education materials on reconstruction after breast cancer. Methods: Materials were collected from all academic hospitals with a plastic surgery integrated and/or independent residency program, 97 in total. Programs were further classified by the presence of a comprehensive gender program. Materials were analyzed for gender diverse terminology outlined by the National LGBTQIA+ Health Education Center. A chi-square test evaluated for statistical significance of inclusive terminology based on the presence or absence of a comprehensive gender program. Results: The majority (75%) of programs referenced cis women alone, with 25% referring to both men and women or using gender neutral terms such as "patients." Although most (85%) programs wrote in second person ("you"), 15% used she/her/hers pronouns alone, and no programs utilized gender diverse language outlined by the National LGBTQIA+ Health Education Center. The presence or absence of a comprehensive gender program was not predictive of the use of inclusive terminology (P = 0.32). Conclusions: This study found that only 25% of breast reconstruction materials contained inclusive gender terminology. Plastic surgeons should provide patient education materials with language that supports members of a gender diverse population to facilitate a safe, inclusive space and conversation.
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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.
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Quemaduras/etiología , Maltrato a los Niños/diagnóstico , Protección a la Infancia , Modelos Teóricos , Accidentes , Factores de Edad , Quemaduras/patología , Servicios de Protección Infantil , Preescolar , Hospitalización , Humanos , Lactante , Recién Nacido , Pediatría , Mejoramiento de la Calidad , Índice de Severidad de la Enfermedad , Trabajadores SocialesRESUMEN
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.
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Accidentes Domésticos/estadística & datos numéricos , Quemaduras/epidemiología , Incendios , Vidrio , Artículos Domésticos , Tacto , Unidades de Quemados , Quemaduras/diagnóstico , Quemaduras/terapia , Canadá , Niño , Preescolar , Combustibles Fósiles , Humanos , Lactante , Estudios Retrospectivos , Estados UnidosRESUMEN
OBJECTIVE: Neostigmine is one of the treatment options for colonic pseudo-obstruction in the medical patient. However, experience in using neostigmine for this indication in burn patients has not been reported in the literature. We will present a case of a woman who developed colonic pseudo-obstruction during her hospital stay. When conservative management failed, neostigmine was administered with no adverse effects and resolution of the pseudo-obstruction. We will review the literature regarding the pathophysiology and treatment options for acute colonic pseudo-obstruction in burn patients. METHODS: A 27-year-old woman with 35% total body surface area deep-partial and full-thickness flame burns. On hospital day 17, she developed a nonobstructive ileus. She failed conservative medical therapy. After consultation with colleagues in trauma surgery and a review of the literature (MeSH/PubMed/NLM), the decision was made to try neostigmine therapy rather than a surgical/procedural option such as colonoscopy. RESULTS: The patient was moved to the intensive care unit and 2 mg of neostigmine was administered intravenously over 4 minutes. After 30 minutes, all abdominal examination findings had returned to baseline. No significant adverse effects were noted, and she did not redevelop abdominal distension afterward. CONCLUSION: This case report provides an alternative treatment modality in which neostigmine was used successfully in a burn patient after conservative medical treatment had failed. The authors believe that neostigmine may be a viable alternative to decompressive colonoscopy in burn patients for whom mechanical obstruction is properly excluded.
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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.
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Benchmarking , Incendios , Cianuro de Hidrógeno/envenenamiento , Hidroxocobalamina/uso terapéutico , Lesión por Inhalación de Humo/tratamiento farmacológico , Complejo Vitamínico B/uso terapéutico , Adulto , Unidades de Quemados , Intoxicación por Monóxido de Carbono/complicaciones , Servicios Médicos de Urgencia , Femenino , Humanos , Embarazo , Complicaciones del Embarazo , Humo/efectos adversosRESUMEN
Uncommon wounds present unique challenges to plastic surgeons and other wound care providers in regard to their presentation, recognition, and ultimate treatment. This article presents an overview of diagnosis and actual case treatment of unusual wounds, a review of the literature, and case studies of interest. A systematic approach to diagnosis; careful review of history; and full understanding of topical, systemic, and surgical therapies is paramount to proper treatment recommendations, appropriate patient management, and successful wound-healing outcomes. The ability to identify and treat wounds caused by an unusual etiology or presentation is an important skill.
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Heridas y Lesiones/diagnóstico , Heridas y Lesiones/terapia , Desbridamiento , Humanos , Cicatrización de Heridas , Heridas y Lesiones/cirugíaRESUMEN
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 Fc epsilonRI. Prior to mast cell activation, mRNA only for TNF-alpha was detected, while after activation mRNA for IL-5, IL-6, IL-13, TNF-alpha, 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-alpha; 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-alpha, 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.
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Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Endopeptidasas/fisiología , Mastocitos/inmunología , Mastocitos/metabolismo , Piel/inmunología , Piel/metabolismo , Anticuerpos Monoclonales/farmacología , Catepsina G , Catepsinas/fisiología , Degranulación de la Célula/inmunología , Células Cultivadas , Quimasas , Citocinas/genética , Citocinas/metabolismo , Humanos , Interleucina-4/análisis , Interleucina-4/genética , Mastocitos/enzimología , Inhibidores de Proteasas/farmacología , ARN Mensajero/análisis , Receptores de IgE/inmunología , Serina Endopeptidasas/fisiología , Piel/citología , Regulación hacia Arriba/inmunologíaRESUMEN
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 MC(T) phenotype from rhIL-4-mediated apoptosis, because neutralization of IL-6 renders these mast cells sensitive. In contrast, mast cells of the MC(TC) phenotype from skin and lung were resistant to IL-4-mediated apoptosis, even after neutralization of endogenous IL-6. MC(TC) cells were CD124(low), whereas those of the MC(T) cells were CD124(high). These observations extend the phenotypic differences between MC(T) and MC(TC) types of human mast cells to include different functional responses to IL-4.