Multi-stage open surgical and endovascular treatment of progressive aortic degeneration in a patient with Marfan syndrome.

Aortic interventions in patients with underlying connective tissues disorders present a unique challenge. The inevitable degeneration of the native aorta can lead to the need for multiple staged interventions with significant risk of complications associated with reoperative aortic procedures. We present a challenging case of progressive aortic degeneration in a patient with Marfan syndrome treated with multi-staged open surgical and endovascular procedures.

Mechanisms of Chromium-Induced Toxicity.

Chromium is a pervasive environmental contaminant that is of great importance because of its toxicity. Hexavalent chromium is a classified group 1 carcinogen with multiple complex mechanisms by which it triggers cancer development. Increased levels of oxidative stress, chromosome breaks, and DNA-adduct formation are some of the major mechanisms by which C(VI) causes cellular damage. Trivalent chromium is another species of chromium that is described as a non-essential metal, and is used in nutritional supplementation. Evidence on nutritional benefit is conflicting which could suggest that humans absorb enough Cr(III) from diet alone, and that extra supplementation is not necessary. This review highlights the differences between Cr(VI) and Cr(III) from a chemical and toxicological perspective, describes short-comings in nutritional research of Cr(III), and explains the multiple mechanisms by which Cr(VI) is involved in the process of carcinogenesis.

Metals and Mechanisms of Carcinogenesis.

Metal exposure is pervasive and not limited to sporadic poisoning events or toxic waste sites. Hundreds of millions of people around the globe are affected by chronic metal exposure, which is associated with serious health concerns, including cancer, as demonstrated in a variety of studies at the molecular, systemic, and epidemiologic levels. Metal-induced toxicity and carcinogenicity are sophisticated and complex in nature. This review provides a broad context and holistic view of currently available studies on the mechanisms of metal-induced carcinogenesis. Specifically, we focus on the five most prevalent carcinogenic metals, arsenic, nickel, cadmium, chromium, and beryllium, and their potential to drive carcinogenesis in humans. A comprehensive understanding of the mechanisms behind the development of metal-induced cancer can provide valuable insights for therapeutic intervention involving molecular targets in metal-induced carcinogenesis.

Role of miR-31 and SATB2 in arsenic-induced malignant BEAS-2B cell transformation.

Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.

Malignant human cell transformation of Marcellus Shale gas drilling flow back water.

The rapid development of high-volume horizontal hydraulic fracturing for mining natural gas from shale has posed potential impacts on human health and biodiversity. The produced flow back waters after hydraulic stimulation are known to carry high levels of saline and total dissolved solids. To understand the toxicity and potential carcinogenic effects of these wastewaters, flow back waters from five Marcellus hydraulic fracturing oil and gas wells were analyzed. The physicochemical nature of these samples was analyzed by inductively coupled plasma mass spectrometry and scanning electron microscopy/energy dispersive X-ray spectroscopy. A cytotoxicity study using colony formation as the endpoint was carried out to define the LC50 values of test samples using human bronchial epithelial cells (BEAS-2B). The BEAS-2B cell transformation assay was employed to assess the carcinogenic potential of the samples. Barium and strontium were among the most abundant metals in these samples and the same metals were found to be elevated in BEAS-2B cells after long-term treatment. BEAS-2B cells treated for 6weeks with flow back waters produced colony formation in soft agar that was concentration dependent. In addition, flow back water-transformed BEAS-2B cells show better migration capability when compared to control cells. This study provides information needed to assess the potential health impact of post-hydraulic fracturing flow back waters from Marcellus Shale natural gas mining.

Management and outcomes of traumatic hemothorax in children.

BACKGROUND: Adult guidelines for the management of traumatic hemothorax are well established; however, there have been no similar studies conducted in the pediatric population. The purpose of our study was to assess the management and outcomes of children with traumatic hemothorax. MATERIALS AND METHODS: Following Institutional Review Board approval, we conducted a retrospective cross-sectional study of all trauma patients diagnosed with a hemothorax at a Level-1 pediatric trauma center from 2007 to 2012. RESULTS: Forty-six children with hemothorax were identified, 23 from blunt mechanism and 23 from penetrating mechanism. The majority of children injured by penetrating mechanisms were treated with tube thoracostomy while the majority of blunt injury patients were observed (91.3% vs. 30.4% tube thoracostomy, penetrating vs. blunt, P = 0.00002). Among patients suffering from blunt mechanism, children who were managed with chest tubes had a greater volume of hemothorax than those who were observed. All children who were observed underwent serial chest radiographs demonstrating no progression and required no delayed procedures. Children with a hemothorax identified only by computed tomography, after negative plain radiograph, did not require intervention. No child developed a delayed empyema or fibrothorax. CONCLUSION: The data suggest that a small-volume hemothorax resulting from blunt mechanism may be safely observed without mandatory tube thoracostomy and with overall low complication rates.

Oxidative stress alters global histone modification and DNA methylation.

The JmjC domain-containing histone demethylases can remove histone lysine methylation and thereby regulate gene expression. The JmjC domain uses iron Fe(II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl lysine. We hypothesize that reactive oxygen species will oxidize Fe(II) to Fe(III), thereby attenuating the activity of JmjC domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3h) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3h exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; preincubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2',7'-dichlorofluorescein, GSH/GSSG ratio, and protein carbonyl content. A cell-free system indicated that H2O2 inhibited histone demethylase activity where increased Fe(II) rescued this inhibition. TET protein showed a decreased activity under oxidative stress. Cells exposed to a low-dose and long-term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short-term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters the epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.

Enteral nutrition in neonatal and pediatric extracorporeal life support: a survey of current practice.

PURPOSE: The purpose of this study was to characterize enteral (EN) nutrition practices in neonatal and pediatric patients receiving extracorporeal life support (ECLS). METHODS: A Web-based survey was administered to program directors and coordinators of Extracorporeal Life Support Organization centers providing neonatal and pediatric ECLS. The survey assessed patient and clinical factors relating to the administration of EN. RESULTS: A total of 122 responses (122/521, 23.4%) from 96 institutions (96/187; 51.3%) were received. One hundred fifteen provided neonatal or pediatric ECLS, and 84.2% reported utilizing EN during ECLS. 55% and 71% of respondents provide EN 'often' or 'always' for venoarterial and venovenous ECLS, respectively. EN was reported as given 'often' or 'always' by 24% with increased vasopressor support, 53% with "stable" vasopressor support, and 60% with weaning of vasopressor support. Favorable diagnosis for providing EN includes respiratory distress syndrome, pneumonia, asthma, trauma/post-operative, pulmonary hemorrhage, and infectious cardiomyopathy. Vasopressor requirement and underlying diagnosis were the primary or secondary determinant of whether to provide EN 81% and 72% of the time. 38% reported an established protocol for providing EN. CONCLUSION: EN support is common but not uniform among neonatal and pediatric patients receiving ECLS. ECLS mode, vasopressor status, and underlying diagnosis play an important role in the decision to provide EN.

Management of Traumatic Wounds and a Novel Approach to Delivering Wound Care in Children.

Significance: The costs and morbidity of pediatric traumatic wounds are not well known. The literature lacks a comprehensive review of the volume, management, and outcomes of children sustaining soft tissue injury. We briefly review the existing literature for traumatic wounds such as open fractures and burns. Such injuries require dedicated wound care and we propose a novel approach for more efficient and more effective delivery of dedicated pediatric wound care. Recent Advances: New pediatric literature is emerging regarding the long-term effects of wound care pain in traumatic injuries-especially burns. A variety of wound dressings and alternative management techniques exist and are geared toward reducing wound care pain. Our institution utilizes a unique model to provide adequate sedation and pain control through a dedicated pediatric wound care unit. We believe that this model reduces the cost of wound care by decreasing emergency department and operating room visits as well as hospital length of stay. Critical Issues: First, medical costs related to pediatric traumatic wound care are not insignificant. The need for adequate pain control and sedation in children with complex wounds is traditionally managed with operating room intervention. Afterward, added costs can be from a hospital stay for ongoing acute wound management. Second, morbidities of complex traumatic wounds are shown to be related to the acute wound care received. Future Directions: Further guidelines are needed to determine the most effective and efficient care of complex traumatic soft tissue injuries in the pediatric population.

Pectus carinatum.

PURPOSE OF REVIEW: Pectus carinatum has been termed the undertreated chest wall deformity. Recent advances in patient evaluation and management, including the development of nonoperative bracing protocols, have improved the care of children with this condition. RECENT FINDINGS: Recent evidence confirms that children with pectus carinatum have a disturbed body image and a reduced quality of life. Treatment has been shown to improve the psychosocial outcome of these patients. SUMMARY: Patients with pectus carinatum are at risk for a disturbed body image and reduced quality of life. Until recently, treatment required surgical reconstruction. A growing body of literature, however, now supports the use of orthotic bracing as a nonoperative alternative in select patients. This article reviews the current literature and describes the evaluation and management of children with pectus carinatum deformity.

The use of a lightly preserved cadaver and full thickness pig skin to teach technical skills on the surgery clerkship--a response to the economic pressures facing academic medicine today.

BACKGROUND: In response to declining instruction in technical skills, the authors instituted a novel method to teach basic procedural skills to medical students beginning the surgery clerkship. METHODS: Sixty-three medical students participated in a skills training laboratory. The first part of the laboratory taught basic suturing skills, and the second involved a cadaver with pig skin grafted to different anatomic locations. Clinical scenarios were simulated, and students performed essential procedural skills. RESULTS: Students learned most of their suturing skills in the laboratory skills sessions, compared with the emergency room or the operating room (P = .01). Students reported that the laboratory allowed them greater opportunity to participate in the emergency room and operating room. Students also felt that the suture laboratory contributed greatly to their skills in wound closure. Finally, 90% of students had never received instruction on suturing, and only 12% had performed any procedural skills before beginning the surgery rotation. CONCLUSIONS: The laboratory described is an effective way of insuring that necessary technical skills are imparted during the surgery rotation.