Splenic Embolization Decreases Infectious Complications and Resource Utilization Compared to Splenectomy in Severely Injured Patients

Introduction. Increasing use of main coil angioembolization for splenic injury has raised concerns of increased complication rates and resource utilization compared to splenectomy. This study examined complication rates for severely injured patients undergoing splenectomy versus main coil angioembolization. Methods. Demographic data (age, sex, and race), Injury Severity Score (ISS), and splenic injury grade were collected prospectively on all patients admitted to the intensive care unit with blunt splenic injury treated with splenectomy or main coil angioembolization. Outcome measures (transfusion requirements, mechanical ventilation use and duration, mortality, intensive care unit and hospital length of stay, infection rate, and systemic inflammatory response syndrome or SIRS score) were reviewed daily. Results. Of 116 patients reviewed, 65 underwent splenectomy and 51 underwent main coil angioembolization. Groups were comparable for age, sex, race, and mechanism of injury. Splenectomized patients had a higher ISS (41 vs 31) and splenic injury grade (3.7 vs 3.2). The main coil angioembolization group had a lower transfusion requirement, hospital length of stay, incidence of mechanical ventilation, nosocomial infection rate, and SIRS score. Overall, mortality and ventilator days were lower but not statistically significant. Conclusions. Severely injured patients treated with splenectomy had significantly higher infection rates and resource utilization compared to those treated with main coil angioembolization

Utility of esophageal gastroduodenoscopy at the time of percutaneous endoscopic gastrostomy in trauma patients

<p>Abstract</p> <p>Background</p> <p>The utility of esophagogastroduodenoscopy (EGD) performed at the time of percutaneous endoscopic gastrostomy (PEG) is unclear. We examined whether EGD at time of PEG yielded clinically useful information important in patient care. We also reviewed the outcome and complication rates of EGD-PEG performed by trauma surgeons.</p> <p>Methods</p> <p>Retrospective review of all trauma patients undergoing EGD with PEG at a level I trauma center from 1/01–6/03.</p> <p>Results</p> <p>210 patients underwent combined EGD with PEG by the trauma team. A total of 37% of patients had unsuspected upper gastrointestinal lesions seen on EGD. Of these, 35% had traumatic brain injury, 10% suffered multisystem injury, and 47% had spinal cord injury. These included 15 esophageal, 61 gastric, and six duodenal lesions, mucosal or hemorrhagic findings on EGD. This finding led to a change in therapy in 90% of patients; either resumption/continuation of H₂-blockers or conversion to proton-pump inhibitors. One patient suffered an upper gastrointestinal bleed while on H2-blocker. It was treated endoscopically. Complication rates were low. There were no iatrogenic visceral perforations seen. Three PEGs were inadvertently removed by the patient (1.5%); one was replaced with a Foley, one replaced endoscopically, and one patient underwent gastric repair and open jejunostomy tube. One PEG leak was repaired during exploration for unrelated hemorrhage. Six patients had significant site infections (3%); four treated with local drainage and antibiotics, one requiring operative debridement and later closure, and one with antibiotics alone.</p> <p>Conclusion</p> <p>EGD at the time of PEG <b>may add </b>clinically useful data in the management of trauma patients. Only one patient treated with acid suppression therapy for EGD diagnosed lesions suffered delayed gastrointestinal bleeding. Trauma surgeons can perform EGD and PEG with acceptable outcomes and complication rates.</p

Percutaneous Endoscopic Gastrostomy in the Super-Morbidly Obese Patient

INTRODUCTION: Obesity is reaching epidemic proportions in the United States, and as patients at the extremes of morbid obesity come under the care of surgeons, routine procedures may become increasingly complex in the face of greater body mass. We prospectively evaluated the success rate of percutaneous endoscopic gastrostomy (PEG) placement in a group of morbidly obese patients outside the current classification systems used to stratify obesity. METHODS: Patients with a body mass index (BMI) greater than 60 kg/m2 who presented for PEG over a one year period were prospectively enrolled. Each patient underwent attempted PEG placement using the pull method by a single surgeon. Outcome variables included: successful PEG, wound infection, tube dislodgement, or bleeding. RESULTS: Six patients with BMI \u3e 60 kg/m2 presented for PEG. All patients were in a surgical critical care unit maintained on mechanical ventilation. All underwent successful PEG placement with standard techniques and sustained no post-procedural complications. CONCLUSION: In the hands of an experienced surgical endoscopist, percutaneous endoscopic gastrostomy can be safely performed in patients at the extremes of morbid obesity. Future studies are warranted to validate the results of our small series

Hybrid selection for sequencing pathogen genomes from clinical samples

We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of human and Plasmodium falciparum malaria parasite DNA as well as clinical samples from infected patients, we demonstrate an average of approximately 40-fold enrichment of parasite DNA after hybrid selection. This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla

Response of high-risk MDS to azacitidine and lenalidomide is impacted by baseline and acquired mutations in a cluster of three inositide-specific genes

Specific myeloid-related and inositide-specific gene mutations can be linked to myelodysplastic syndromes (MDS) pathogenesis and therapy. Here, 44 higher-risk MDS patients were treated with azacitidine and lenalidomide and mutations analyses were performed at baseline and during the therapy. Results were then correlated to clinical outcome, overall survival (OS), leukemia-free-survival (LFS) and response to therapy. Collectively, 34/44 patients were considered evaluable for response, with an overall response rate of 76.25% (26/34 cases): 17 patients showed a durable response, 9 patients early lost response and 8 patients never responded. The most frequently mutated genes were ASXL1, TET2, RUNX1, and SRSF2. All patients early losing response, as well as cases never responding, acquired the same 3 point mutations during therapy, affecting respectively PIK3CD (D133E), AKT3 (D280G), and PLCG2 (Q548R) genes, that regulate cell proliferation and differentiation. Moreover, Kaplan–Meier analyses revealed that this mutated cluster was significantly associated with a shorter OS, LFS, and duration of response. All in all, a common mutated cluster affecting 3 inositide-specific genes is significantly associated with loss of response to azacitidine and lenalidomide therapy in higher risk MDS. Further studies are warranted to confirm these data and to further analyze the functional role of this 3-gene cluster

Outcomes of polytrauma patients with diabetes mellitus.

BACKGROUND: The impact of diabetes mellitus in patients with multiple system injuries remains obscure. This study was designed to increase knowledge of outcomes of polytrauma in patients who have diabetes mellitus. METHODS: Data from the Trauma Audit and Research Network was used to identify patients who had suffered polytrauma during 2003 to 2011. These patients were filtered to those with known outcomes, then separated into those with diabetes, those known to have other co-morbidities but not diabetes and those known not to have any co-morbidities or diabetes. The data were analyzed to establish if patients with diabetes had differing outcomes associated with their diabetes versus the other groups. RESULTS: In total, 222 patients had diabetes, 2,558 had no past medical co-morbidities (PMC), 2,709 had PMC but no diabetes. The diabetic group of patients was found to be older than the other groups (P <0.05). A higher mortality rate was found in the diabetic group compared to the non-PMC group (32.4% versus 12.9%), P <0.05). Rates of many complications including renal failure, myocardial infarction, acute respiratory distress syndrome, pulmonary embolism and deep vein thrombosis were all found to be higher in the diabetic group. CONCLUSIONS: Close monitoring of diabetic patients may result in improved outcomes. Tighter glycemic control and earlier intervention for complications may reduce mortality and morbidity

Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations

Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2–5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma

Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission

A Major Determinant of Cyclophilin Dependence and Cyclosporine Susceptibility of Hepatitis C Virus Identified by a Genetic Approach

Since the advent of genome-wide small interfering RNA screening, large numbers of cellular cofactors important for viral infection have been discovered at a rapid pace, but the viral targets and the mechanism of action for many of these cofactors remain undefined. One such cofactor is cyclophilin A (CyPA), upon which hepatitis C virus (HCV) replication critically depends. Here we report a new genetic selection scheme that identified a major viral determinant of HCV's dependence on CyPA and susceptibility to cyclosporine A. We selected mutant viruses that were able to infect CyPA-knockdown cells which were refractory to infection by wild-type HCV produced in cell culture. Five independent selections revealed related mutations in a single dipeptide motif (D316 and Y317) located in a proline-rich region of NS5A domain II, which has been implicated in CyPA binding. Engineering the mutations into wild-type HCV fully recapitulated the CyPA-independent and CsA-resistant phenotype and four putative proline substrates of CyPA were mapped to the vicinity of the DY motif. Circular dichroism analysis of wild-type and mutant NS5A peptides indicated that the D316E/Y317N mutations (DEYN) induced a conformational change at a major CyPA-binding site. Furthermore, nuclear magnetic resonance experiments suggested that NS5A with DEYN mutations adopts a more extended, functional conformation in the putative CyPA substrate site in domain II. Finally, the importance of this major CsA-sensitivity determinant was confirmed in additional genotypes (GT) other than GT 2a. This study describes a new genetic approach to identifying viral targets of cellular cofactors and identifies a major regulator of HCV's susceptibility to CsA and its derivatives that are currently in clinical trials

European Atlas of Natural Radiation

Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose. This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations. This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity; • be informed about the levels of natural radioactivity caused by different sources; • have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor; • and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.JRC.G.10-Knowledge for Nuclear Security and Safet