HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice.

Aging increases the risk of age-related diseases, imposing substantial healthcare and personal costs. Targeting fundamental aging mechanisms pharmacologically can promote healthy aging and reduce this disease susceptibility. In this work, we employed transcriptome-based drug screening to identify compounds emulating transcriptional signatures of long-lived genetic interventions. We discovered compound 60 (Cmpd60), a selective histone deacetylase 1 and 2 (HDAC1/2) inhibitor, mimicking diverse longevity interventions. In extensive molecular, phenotypic, and bioinformatic assessments using various cell and aged mouse models, we found Cmpd60 treatment to improve age-related phenotypes in multiple organs. Cmpd60 reduces renal epithelial-mesenchymal transition and fibrosis in kidney, diminishes dementia-related gene expression in brain, and enhances cardiac contractility and relaxation for the heart. In sum, our two-week HDAC1/2 inhibitor treatment in aged mice establishes a multi-tissue, healthy aging intervention in mammals, holding promise for therapeutic translation to promote healthy aging in humans.

A comparison of rat models that best mimic immune-driven preeclampsia in humans.

Preeclampsia (PE), a hypertensive pregnancy disorder, can originate from varied etiology. Placenta malperfusion has long been considered the primary cause of PE. However, we and others have showed that this disorder can also result from heightened inflammation at the maternal-fetal interface. To advance our understanding of this understudied PE subtype, it is important to establish validated rodent models to study the pathophysiology and test therapies. We evaluated three previously described approaches to induce inflammation-mediated PE-like features in pregnant rats: 1) Tumor necrosis factor-α (TNF-α) infusion via osmotic pump from gestational day (GD) 14-19 at 50ng/day/animal; 2) Polyinosinic:polycytidylic acid (Poly I:C) intraperitoneal (IP) injections from GD 10-18 (alternate days) at 10mg/kg/day/animal; and, 3) Lipopolysaccharide (LPS) IP injections from GD 13-18 at 20ug-70ug/kg/day per animal. Maternal blood pressure was measured by tail-cuff. Upon sacrifice, fetal and placenta weights were recorded. Placenta histomorphology was assessed using H&E sections. Placenta inflammation was determined by quantifying TNF-α levels and inflammatory gene expression. Placenta metabolic and mitochondrial health were determined by measuring mitochondrial respiration rates and placenta NAD+/NADH content. Of the three rodent models tested, we found that Poly I:C and LPS decreased both fetal weight and survival; and correlated with a reduction in region specific placenta growth. As the least effective model characterized, TNF-α treatment resulted in a subtle decrease in fetal/placenta weight and placenta mitochondrial respiration. Only the LPS model was able to induce maternal hypertension and exhibited pronounced placenta metabolic and mitochondrial dysfunction, common features of PE. Thus, the rat LPS model was most effective for recapitulating features observed in cases of human inflammatory PE. Future mechanistic and/or therapeutic intervention studies focuses on this distinct PE patient population may benefit from the employment of this rodent model of PE.

Radiation induces long-term muscle fibrosis and promotes a fibrotic phenotype in fibro-adipogenic progenitors.

BACKGROUND: Radiation-induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation-induced muscle pathology has not previously been explored. METHODS: Four-week-old Male CBA or C57Bl/6J mice received a single dose (16 Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non-IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56 days post-IR (long-term IR response). Changes in skeletal muscle morphology, myofibre composition, muscle niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, and metabolism and changes in progenitor cell fate where assessed. RESULTS: Juvenile radiation exposure resulted in smaller myofibre cross-sectional area, particularly in type I and IIA myofibres (P < 0.05) and reduced the proportion of type I myofibres (P < 0.05). Skeletal muscle fibrosis (P < 0.05) was evident at 56 days post-IR. The IR-limb had fewer endothelial cells (P < 0.05) and fibro-adipogenic progenitors (FAPs) (P < 0.05) at 56 days post-IR. Fewer muscle satellite (stem) cells were detected at 3 and 56 days in the IR-limb (P < 0.05). IR induced FAP senescence (P < 0.05), increased their fibrogenic differentiation (P < 0.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (P < 0.05) and fusion (P < 0.05). CONCLUSIONS: Our study suggests that following juvenile radiation exposure, FAPs contribute to long-term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP-targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.

Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging.

OBJECTIVE: The epidermal barrier is renewed by the activation, proliferation, and differentiation of keratinocyte stem cells after injury and aging impedes this repair process through undefined mechanisms. We previously identified a gene signature of metabolic dysfunction in aged murine epidermis, but the precise regulators of epidermal repair and age-related growth defects are not well established. Aged mouse models as well as mice with conditional epidermal loss of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were used to explore the cellular pathways which control skin repair after injury and stress. METHODS: Aged mice or those with epidermal Pgc-1α deletion (epiPgc-1α KO) and young or Pgc1afl/fl controls were subjected to wound injury, UVB exposure or the inflammatory agent TPA. In vivo and ex vivo analyses of wound closure, skin structure, cell growth and stem cell differentiation were used to understand changes in epidermal re-growth and repair resulting from aging or Pgc-1α loss. RESULTS: Aging impairs epidermal re-growth during wound healing and results in lower expression of Pgc-1α. Mice with conditional deletion of epidermal Pgc-1α exhibit greater inflammation- and UVB-induced cell differentiation, reduced proliferation, and slower wound healing. epiPgc-1α KO mice also displayed reduced keratinocyte NAD+ levels, shorter telomeres, and greater poly ADP-ribosylation, resulting in enhanced stress-stimulated p53 and p21 signaling. When NAD+ was reduced by Pgc-1α loss or pharmacologic inhibition of NAD+ synthesis, there was reduced stress-induced proliferation, increased differentiation, and protection against DNA damage via enhanced epidermal shedding. Similarly, aged mice exhibit disrupted epidermal NAD+ homeostasis and enhanced p53 activation, resulting in p21 growth arrest after wounding. NAD+ precursor treatment restores epidermal growth from old skin to that of young. CONCLUSIONS: Our studies identify a novel role for epidermal Pgc-1α in controlling epidermal repair via its regulation of cellular NAD+ and downstream effects on p53-driven growth arrest. We also establish that parallel mechanisms are evident in aged epidermis, showing that NAD+ signaling is an important controller of physiologic skin repair and that dysfunction of this pathway contributes to age-related wound repair defects.

Proteomics characterization of mitochondrial-derived vesicles under oxidative stress.

Mitochondria share attributes of vesicular transport with their bacterial ancestors given their ability to form mitochondrial-derived vesicles (MDVs). MDVs are involved in mitochondrial quality control and their formation is enhanced with stress and may, therefore, play a potential role in mitochondrial-cellular communication. However, MDV proteomic cargo has remained mostly undefined. In this study, we strategically used an in vitro MDV budding/reconstitution assay on cardiac mitochondria, followed by graded oxidative stress, to identify and characterize the MDV proteome. Our results confirmed previously identified cardiac MDV markers, while also revealing a complete map of the MDV proteome, paving the way to a better understanding of the role of MDVs. The oxidative stress vulnerability of proteins directed the cargo loading of MDVs, which was enhanced by antimycin A (Ant-A). Among OXPHOS complexes, complexes III and V were found to be Ant-A-sensitive. Proteins from metabolic pathways such as the TCA cycle and fatty acid metabolism, along with Fe-S cluster, antioxidant response proteins, and autophagy were also found to be Ant-A sensitive. Intriguingly, proteins containing hyper-reactive cysteine residues, metabolic redox switches, including professional redox enzymes and those that mediate iron metabolism, were found to be components of MDV cargo with Ant-A sensitivity. Last, we revealed a possible contribution of MDVs to the formation of extracellular vesicles, which may indicate mitochondrial stress. In conclusion, our study provides an MDV proteomics signature that delineates MDV cargo selectivity and hints at the potential for MDVs and their novel protein cargo to serve as vital biomarkers during mitochondrial stress and related pathologies.

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.

Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD+) synthesis, consistent with a potential role for the essential cofactor NAD+ in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD+ and are involved in pleiotropic events, including inflammation. In the mdx mouse model of DMD, we observed significant reductions in muscle NAD+ levels, concurrent increases in PARP activity, and reduced expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ biosynthesis. Replenishing NAD+ stores with dietary nicotinamide riboside supplementation improved muscle function and heart pathology in mdx and mdx/Utr-/- mice and reversed pathology in Caenorhabditis elegans models of DMD. The effects of NAD+ repletion in mdx mice relied on the improvement in mitochondrial function and structural protein expression (α-dystrobrevin and δ-sarcoglycan) and on the reductions in general poly(ADP)-ribosylation, inflammation, and fibrosis. In combination, these studies suggest that the replenishment of NAD+ may benefit patients with muscular dystrophies or other neuromuscular degenerative conditions characterized by the PARP/NNMT gene expression signatures.

Protein acetylation in metabolism - metabolites and cofactors.

Reversible acetylation was initially described as an epigenetic mechanism regulating DNA accessibility. Since then, this process has emerged as a controller of histone and nonhistone acetylation that integrates key physiological processes such as metabolism, circadian rhythm and cell cycle, along with gene regulation in various organisms. The widespread and reversible nature of acetylation also revitalized interest in the mechanisms that regulate lysine acetyltransferases (KATs) and deacetylases (KDACs) in health and disease. Changes in protein or histone acetylation are especially relevant for many common diseases including obesity, diabetes mellitus, neurodegenerative diseases and cancer, as well as for some rare diseases such as mitochondrial diseases and lipodystrophies. In this Review, we examine the role of reversible acetylation in metabolic control and how changes in levels of metabolites or cofactors, including nicotinamide adenine dinucleotide, nicotinamide, coenzyme A, acetyl coenzyme A, zinc and butyrate and/or ß-hydroxybutyrate, directly alter KAT or KDAC activity to link energy status to adaptive cellular and organismal homeostasis.

Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice.

UNLABELLED: With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD(+) ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD(+) repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD(+) biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic ß-oxidation and mitochondrial complex content and activity. The cell-autonomous beneficial component of NR treatment was revealed in liver-specific Sirt1 knockout mice (Sirt1(hep-/-) ), whereas apolipoprotein E-deficient mice (Apoe(-/-) ) challenged with a high-fat high-cholesterol diet affirmed the use of NR in other independent models of NAFLD. CONCLUSION: Our data warrant the future evaluation of NAD(+) boosting strategies to manage the development or progression of NAFLD.

NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus.

NAD(+) has emerged as a vital cofactor that can rewire metabolism, activate sirtuins, and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD(+) metabolism revived interest in NAD(+)-boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD(+) metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.

SUMOylation-dependent LRH-1/PROX1 interaction promotes atherosclerosis by decreasing hepatic reverse cholesterol transport.

Reverse cholesterol transport (RCT) is an antiatherogenic process in which excessive cholesterol from peripheral tissues is transported to the liver and finally excreted from the body via the bile. The nuclear receptor liver receptor homolog 1 (LRH-1) drives expression of genes regulating RCT, and its activity can be modified by different posttranslational modifications. Here, we show that atherosclerosis-prone mice carrying a mutation that abolishes SUMOylation of LRH-1 on K289R develop less aortic plaques than control littermates when exposed to a high-cholesterol diet. The mechanism underlying this atheroprotection involves an increase in RCT and its associated hepatic genes and is secondary to a compromised interaction of LRH-1 K289R with the corepressor prospero homeobox protein 1 (PROX1). Our study reveals that the SUMOylation status of a single nuclear receptor lysine residue can impact the development of a complex metabolic disease such as atherosclerosis.

Clinical and dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high mortality rate. Diagnosis is often delayed. OBJECTIVES: To characterize the dermoscopic features of MCC. METHODS: Clinical and dermoscopic images of 12 biopsy-proven MCCs were analysed in a retrospective manner, with existing dermoscopic criteria being scored independently by three dermatologists. RESULTS: The four most frequent clinical features were cherry red colour, shiny surface, sharp circumscription and nodular morphology. Significant dermoscopic features included linear irregular and polymorphous vessels, poorly focused vessels, milky pink areas, white areas, structureless areas and architectural disorder. Pigmented structures were absent from all lesions. CONCLUSIONS: The dermoscopic features described herein help the clinician to distinguish MCC from other benign and malignant red nodules. Increasing recognition of the presenting features will facilitate earlier diagnosis of MCC and reduced mortality.

Neuroendocrine carcinoma of the ethmoid sinuses treated with radiotherapy alone.

OBJECTIVE: We present the first report of a case of neuroendocrine carcinoma of the paranasal sinuses treated successfully with radiotherapy alone. METHOD: A case report and literature review are presented. RESULTS: Fewer than 50 cases of paranasal sinus neuroendocrine carcinoma have been reported. We present an 82-year-old man referred with recurrent epistaxis. He was investigated by biopsy, computed tomography and magnetic resonance imaging, and was found to have a rare neuroendocrine carcinoma. He declined any surgery or chemotherapy but consented to radiotherapy. Thirty months later, he remained clinically free from cancer. CONCLUSION: There is no consensus for the management of paranasal sinus neuroendocrine carcinoma. Most cases are treated with surgery with or without chemoradiotherapy. This case shows that radiotherapy alone may be a viable treatment option for some cases.

Dermoscopy of scalp tumours: a multi-centre study conducted by the international dermoscopy society.

BACKGROUND: Little is known about the dermoscopic features of scalp tumours. Objective To determine the dermoscopic features of scalp tumours. METHODS: Retrospective analysis of dermoscopic images of histopathologically diagnosed scalp tumours from International Dermoscopy Society members. RESULTS: A total of 323 tumours of the scalp from 315 patients (mean age: 52 years; range 3-88 years) were analysed. Scalp nevi were significantly associated with young age (<30 years) and exhibited a globular or network pattern with central or perifollicular hypopigmentation. Melanoma and non-melanoma skin cancer were associated with male gender, androgenetic alopecia, age >65 years and sun damage. Atypical network and regression were predictive for thin (≤1 mm) melanomas, whereas advanced melanomas (tumour thickness > 1 mm) revealed blue white veil, unspecific patterns and irregular black blotches or dots. CONCLUSIONS: The data collected provide a new knowledge regarding the clinical and dermoscopy features of pigmented scalp tumours.

Increased neutrophil adenosine a3 receptor expression is associated with hemorrhagic shock and injury severity in trauma patients.

Hypertonic saline (HS) has been investigated as an immune modulator following hemorrhagic shock and sepsis. The polymorphonuclear neutrophil (PMN) response to HS is regulated by the release of ATP, which is converted to adenosine and activates adenosine receptors. Binding to A3 adenosine receptors promotes PMN activation, and inhibition of A3 receptors improves the efficacy of HS resuscitation. A3 receptor expression of PMNs has not been previously evaluated in injured patients. Whole blood was obtained from 10 healthy volunteers and 60 injured patients within 2 h of injury. Inclusion criteria were blunt or penetrating injury with evidence of hypovolemic shock (systolic blood pressure [SBP] ≤90 mmHg and base deficit ≥6 mEq/L or need for blood transfusion) or evidence of severe traumatic brain injury including initial Glasgow Coma Scale score of 8 or less or evidence of traumatic brain injury on head computed tomography scan (head Abbreviated Injury Score ≥3) or intubation in the field or emergency department. A3 receptor expression was assessed by flow cytometry. Polymorphonuclear neutrophils were also exposed to fMLP or HS (20-40 mM) in vitro. Clinical data were collected including admission physiology, injury severity (Injury Severity Score [ISS]), development of multiple organ failure, and survival. In normal volunteers, less than 1% of PMNs expressed A3 receptors on the cell surface. A3 receptor expression was significantly higher in injured patients, and the level of expression correlated with the severity of injury (ISS ≥25: A3 positive PMN 36.6% vs. ISS <25: 16.2%; P = 0.019) and degree of hypovolemic shock (SBP ≤90 mmHg: A3 positive PMN 43.8% vs. SBP>90 mmHg: 20.6%; P = 0.008). Stimulation with fMLP or HS increased A3 expression in normal volunteers, but only in patients with ISS of less than 25 or without hypovolemic shock. A3 receptor expression on the surface of PMNs is upregulated by injury, and increased expression levels are associated with greater injury severity and hypovolemic shock. Hypertonic saline increases A3 expression of PMNs from healthy volunteers and less severely injured patients.

Biofilms in chronic rhinosinusitis: systematic review and suggestions for future research.

BACKGROUND: A biofilm is a community of micro-organisms encased within a self-produced, extracellular, polymeric substance. The role of biofilms as a major pathological aetiology in chronic rhinosinusitis would help explain the clinical manifestation of the disease. OBJECTIVES: To examine the current evidence, and to discuss possible future research directions, in relation to biofilms and chronic rhinosinusitis. STUDY DESIGN: Systematic literature review. EVALUATION METHOD: Two assessors independently undertook critical appraisal of the studies identified by the literature search. Significant findings were incorporated into this review. The primary outcome assessed was the presence of biofilm in human mucosal biopsy samples taken from patients with chronic rhinosinusitis, and from healthy controls. RESULTS: We identified 11 studies examining biofilm formation in human mucosal biopsy samples taken from patients with chronic rhinosinusitis. CONCLUSION: It is unlikely that biofilms occur in every case of chronic rhinosinusitis; consequently, the significance of 'biofilm detection' in some series should be considered carefully. Several authors have argued strongly for the use of confocal scanning laser microscopy with fluorescent in situ hybridisation probes as the 'gold standard' for biofilm imaging. This imaging modality should be combined with further investigation of the microbiology of chronic rhinosinusitis, and of the efficacy of traditional culture techniques used for pathogen identification.

Timing of intubation and ventilator-associated pneumonia following injury.

HYPOTHESIS: In an emergency medical system with established rapid-sequence intubation protocols, prehospital (PH) intubation of patients with trauma is not associated with a higher rate of ventilator-associated pneumonia (VAP) than emergency department (ED) intubation. DESIGN: Retrospective observational cohort. SETTING: Level I trauma center. PATIENTS: Adult patients with trauma intubated in a PH or an ED setting from July 1, 2007, through July 31, 2008. MAIN OUTCOME MEASURES: Diagnosis of VAP by means of bronchoscopic alveolar lavage or clinical assessment when bronchoscopic alveolar lavage was impossible. Secondary outcomes included time to VAP, length of hospitalization, and in-hospital mortality. RESULTS: Of 572 patients, 412 (72.0%) underwent PH intubation. The ED group was older than the PH group (mean ages, 46.4 vs 39.1 years; P < .001) and had a higher incidence of blunt injury (142 [88.8%] vs 322 [78.2%]; P = .002). The mean (SD) lowest recorded ED systolic blood pressure was lower in the ED group (102.8 [1.9] vs 111.4 [1.2] mm Hg; P < .001), despite similar mean injury severity scores in both groups (27.2 [0.7] vs 27.0 [1.1]; P = .94). There was no difference in the mean rate of VAP (30 [18.8%] vs 71 [17.2%]; P = .66) or mean time to diagnosis (8.1 [1.2] vs 7.8 [1.0] days; P = .89). Logistic regression analysis identified history of drug abuse, lowest recorded ED systolic blood pressure, and injury severity score as 3 independent factors predictive of VAP. CONCLUSIONS: Prehospital intubation of patients with trauma is not associated with higher risk of VAP. Further investigation of intubation factors and the incidence and timing of aspiration is required to identify potentially modifiable factors to prevent VAP.

Multivariate predictors of failure after flap coverage of pressure ulcers.

BACKGROUND: Pressure ulcers are estimated to be present in more than one-third of patients with spinal cord injury. The rate of recurrence after flap surgery over last 50 years has ranged between 3 and 82 percent, with no trend toward improvement. This study seeks to identify and evaluate patient and operative characteristics associated with flap dehiscence and ulcer recurrence. METHODS: A retrospective chart review of all patients who underwent pressure ulcer flap coverage between 1993 and 2008 was performed. Thirty-one demographic and operative variables were collected. Multivariate logistic regression with generalized estimating equation was used to evaluate the effect of significant variables. The primary outcome was recurrence of pressure ulcer at the operative site. Secondary outcomes included flap line dehiscence and the need for operative revision. RESULTS: There were 88 recurrences of pressure ulcers after flap surgery (39 percent) of 227 operations performed on 135 patients. Thirty-six flaps (16 percent) had dehiscences necessitating return to the operating room. Hemoglobin A1c less than 6 percent and previous same-site flap failure were associated with both dehiscence and recurrence (odds ratios, 2.15 and 3.84; and odds ratios, 6.51 and 3.27). Younger age and albumin less than 3.5 were associated with early flap failure (odds ratios, 5.95 and 2.45). Ischial wound location correlated with late recurrence (odds ratio, 4.01). Patients with multiple risk factors had operative success rates that approached zero. CONCLUSIONS: Confirmation of adequate nutritional status and strict preoperative management of blood glucose may improve operative success rates. The authors propose that operative management should be approached with trepidation, if at all, in young patients with recurrent ischial ulcers.

Sodium azide-associated laryngospasm after air bag deployment.

The advent and incorporation of the air bag into motor vehicles has resulted in the mitigation of many head and truncal injuries in motor vehicle collisions. However, air bag deployment is not risk free. We present a case of sodium azide-induced laryngospasm after air bag deployment. An unrestrained male driver was in a moderate-speed motor vehicle collision with air bag deployment. Medics found him awake, gasping for air with stridorous respirations and guarding his neck. The patient had no external signs of trauma and was presumed to have tracheal injury. The patient was greeted by the Anesthesiology service, which intubated him using glidescope-assisted laryngoscopy. The patient was admitted for overnight observation and treatment of alkaline ocular injury and laryngospasm. Although air bags represent an important advance in automobile safety, their use is not without risk. Bruising and tracheal rupture secondary to air bag deployment have been reported in out-of-position occupants. Additionally, alkaline by-products from the combustion of sodium azide in air bags have been implicated in ocular injury and facial burns. Laryngospasm after sodium azide exposure presents another diagnostic challenge for providers. Therefore, it is incumbent to maintain vigilance in the physical examination and diagnosis of occult injuries after air bag deployment.

Prevention of blood staining of endoscope tip during Functional Endoscopic Sinus Surgery: sleeve technique.

Optimisation of the endoscopic view during FESS may require correction of a deviated septum. The resulting incision leads to bleeding which could obscure the view of the endoscope. Repeated cleaning of the endoscope intraoperatively is time consuming and traumatisation of the lining of the nasal mucosa may lead to formation of adhesions post operatively. We discuss the use a segment of suction tubing that can act as a conduit or sleeve for the passage of the endoscope into the nasal cavity. This protects the endoscope tip from the bleeding area.

The incidence of post-discharge surgical site infection in the injured patient.

BACKGROUND: Approximately 50% of surgical site infections (SSI) after elective surgery occur after discharge. Adequate surveillance for these infections requires a mechanism for post-discharge follow up. The incidence of SSI after injury is as high as 30%. As post-discharge follow up in the trauma population is difficult, we set out to ascertain the incidence of post-discharge SSI in a cohort of high-risk trauma patients. METHODS: Patients (n = 268) enrolled in a randomized controlled trial of leukoreduced versus regular blood transfusions were evaluated either in person or by structured telephone survey 28 days after admission regarding the presence of SSI. Inclusion criteria were age >17 years and blood transfusion within 24 hours of injury. RESULTS: Among the 268 patients, 39 (15%) developed a SSI. There were 27 SSI identified in hospital and 13 identified in the post-discharge period after a median length of stay of 17 days (one patient had more than one SSI). Although the 13 patients who developed a SSI in the post-discharge period comprised only 7% (13 of 194) of the cohort that had at least one operative procedure and survived to discharge, these patients represented 33% (13 of 39) of all patients who developed a SSI. CONCLUSION: Despite their prolonged length of stay compared with elective surgical patients, a significant proportion of SSI after injury occurs after discharge. These data support the need for a post-discharge surveillance system in either clinical trials or for quality assurance.