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Ashraf S.,University of Southampton | Nitschke K.,Albert Ludwigs University of Freiburg | Warshow U.M.,Derriford Hospital | Brooks C.R.,University of Southampton | And 8 more authors.
Hepatology | Year: 2013

CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing infection. Human leukocyte antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection of infected cells, and tapasin is an important component of the peptide loading complex for HLA class I. We sought to determine if tapasin polymorphisms affected the outcome of HCV infection. Patients with resolved or chronic HCV infection were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin gene. In a European, but not a US, Caucasian population, the tapasin G allele was significantly associated with the outcome of HCV infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals (P=0.02, odds ratio [OR]=1.90 95% confidence interval [CI]=1.11-3.23). This was more marked at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was protective (P<0.03). Individuals with an HLA-B allele with an aspartate at residue 114 and the tapasin G allele were more likely to spontaneously resolve HCV infection (P<0.00003, OR=3.2 95% CI=1.6-6.6). Additionally, individuals with chronic HCV and the combination of an HLA-B allele with an aspartate at residue 114 and the tapasin G allele also had stronger CD8+ T-cell responses (P=0.02, OR=2.58, 95% CI-1.05-6.5). Conclusion: Tapasin alleles contribute to the outcome of HCV infection by synergizing with polymorphisms at HLA-B in a population-specific manner. This polymorphism may be relevant for peptide vaccination strategies against HCV infection. (Hepatology 2013;53:881-889). © 2013 by the American Association for the Study of Liver Diseases.


Florescu D.F.,Infectious Diseases Division | Mindru C.,Infectious Diseases Division | Fey P.D.,University of Nebraska Medical Center | Kalil A.C.,Infectious Diseases Division
Clinical Infectious Diseases | Year: 2012

Background. Experience with intravenous and aerosolized forms of colistin for the treatment of ventilator-associated pneumonia (VAP) in patients without cystic fibrosis is limited. We aimed to assess the safety and efficacy of colistin for the treatment of VAP. Methods. We searched MEDLINE and Cochrane Database of Systematic Reviews for studies comparing colistin vs other antibiotics for treatment of VAP in patients without cystic fibrosis. QUOROM guidelines were followed, the I 2 method was used for heterogeneity, and a random-effects model for odds ratio (OR) estimates. Results. Six controlled studies met the inclusion criteria. Clinical response did not differ significantly between colistin and control groups (OR, 1.14; 95% confidence interval [CI],. 74-1.77; P =. 56; I 2 = 0%). The efficacy of colistin was independent of study design (prospective OR, 0.89 [95% CI,. 48-1.66; P =. 71; I 2 = 0%]; retrospective OR, 1.45 [95% CI,. 79-2.68; P =. 23; I 2 = 0%]); randomized trials OR, 0.86 [95% CI,. 43-1.74; P =. 68; I 2 = 0%]). There was no indication of a significant change in clinical response after controlling for concomitant antibiotic treatment (intercept, 0.121; slope, 0.0315; P =. 95). Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI,. 50-1.67; P =. 78; I 2 = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI,. 59-2.20; P =. 69; I 2 = 0%). Fourteen single-arm studies have been analyzed, and the results were in concordance with the findings of the controlled studies.Conclusions.Our results suggest that colistin may be as safe and as efficacious as standard antibiotics for the treatment of VAP. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.


SALT LAKE CITY and GAITHERSBURG, Md., Oct. 27, 2016 (GLOBE NEWSWIRE) -- A first-of-its-kind study of 900,000 hospital admissions from an integrated health system has yielded insights into shifts in the epidemiology of multi-drug resistant organisms (MDROs) in the community. New research, funded by OpGen (NASDAQ:OPGN) and conducted by Intermountain Healthcare and Enterprise Analysis Corporation (EAC) found that Methicillin Resistant Staphylococcus aureus (MRSA), Clostridium difficile (C. difficile) and ESBL harboring Gram-negative rods were the most common organisms treated by the Intermountain Healthcare system over an eight-year period between January 1, 2008 and December 31, 2015. The study examined data from Intermountain Healthcare over an eight-year period to characterize the trends occurring in C. difficile and MDROs. The abstracted electronic data was pulled from patients seen at Intermountain’s 22 hospitals and affiliated clinics who had clinical cultures positive for antibiotic resistant Gram-positive or Gram-negative bacteria and/or laboratory tests positive for toxigenic C. difficile. The researchers discovered that resistant organisms were found in 1.4 percent of the 900,000 hospital admissions during the study period with most originating from the ambulatory setting. Researchers found that a 222% increase was observed in the prevalence of C. difficile as well as a 322% increase in ESBL positive organisms. The good news is that the prevalence of MRSA decreased by 32%. The study measured both the prevalence of infections, as well as impacts on patient care. Economic data are still being analyzed and will be revealed in a future presentation. Results from the study were presented on Thursday, Oct. 27 at 12:30 p.m. CDT in the Poster Hall at IDWeek in New Orleans by Bert Lopansri, M.D., lead author of the study at Intermountain Medical Center, the flagship hospital of Intermountain Healthcare. “For the last 10 to 15 years, the number of antibiotic-resistant bacteria continues to increase. We wanted to turn on the lights and look at all the different types of antibiotic-resistant bacteria that have been highlighted as serious and urgent threats by the Centers for Disease Control to see what the landscape looks like in our system,” said Dr. Lopansri, Chief of the Infectious Diseases Division at Intermountain Medical Center. “Although MRSA still poses the greatest challenge, the rise in ESBLs is a major concern and mirrors findings reported at other centers in the U.S.,” added Dr. Lopansri. “One concern with ESBLs is that the most common antibiotic used to treat them are carbapenems, known as ‘last-resort’ antibiotics.” “Our support for a study of this magnitude provides a benchmark to hospitals and health systems on what could be lurking in their facilities as we seek to validate the health and economic impact of our rapid MDRO products and services to improve infection control,” said Evan Jones, Chairman and CEO of OpGen. “The next step in this collaboration will revolve around leveraging our technologies to guide rapid clinical decisions with a goal of reducing the spread of these infections and improving health outcomes.” In addition to presenting these study results, Dr. Lopansri will be hosting a discussion of the study and its results at the Learning Lounge. The discussion is titled, “Antibiotic resistant bacteria in our Integrated Healthcare Network: are new diagnostic tests needed?” and will take place on Saturday, October 29, 2016 from 1:15 p.m. to 1:45 p.m. CDT at booth #1300. About Intermountain Healthcare Intermountain Healthcare is a Utah-based, not-for-profit system of 22 hospitals, 185 clinics, a Medical Group with about 1,500 employed physicians and advanced practitioners, a health plans group called SelectHealth, and other health services. With a mission of helping people live the healthiest lives possible®, Intermountain is widely recognized as a leader in transforming healthcare through high quality and sustainable costs. About OpGen OpGen, Inc. is harnessing the power of informatics and genomic analysis to provide complete solutions for patient, hospital and network-wide infection prevention and treatment. Learn more at www.opgen.com and follow OpGen on Twitter and LinkedIn.


A first-of-its-kind study of 900,000 hospital admissions from an integrated health system has yielded insights into shifts in the epidemiology of multi-drug resistant organisms (MDROs) in the community. New research, funded by OpGen (NASDAQ: OPGN) and conducted by Intermountain Healthcare and Enterprise Analysis Corporation (EAC), found that Methicillin Resistant Staphylococcus aureus (MRSA), Clostridium difficile (C. difficile) and ESBL harboring Gram-negative rods were the most common organisms treated by the Intermountain Healthcare system over an eight-year period between January 1, 2008 and December 31, 2015. The study examined data from Intermountain Healthcare over an eight-year period to characterize the trends occurring in C. difficile and MDROs. The abstracted electronic data was pulled from patients seen at Intermountain's 22 hospitals and affiliated clinics who had clinical cultures positive for antibiotic resistant Gram-positive or Gram-negative bacteria and/or laboratory tests positive for toxigenic C. difficile. The researchers discovered that resistant organisms were found in 1.4 percent of the 900,000 hospital admissions during the study period with most originating from the ambulatory setting. Researchers found that a 222% increase was observed in the prevalence of C. difficile as well as a 322% increase in ESBL positive organisms. The good news is that the prevalence of MRSA decreased by 32%. The study measured both the prevalence of infections, as well as impacts on patient care. Economic data are still being analyzed and will be revealed in a future presentation. Results from the study were presented on Thursday, Oct. 27, at 1:30 p.m., EDT, in the Poster Hall at IDWeek in New Orleans by Bert Lopansri, M.D., lead author of the study at Intermountain Medical Center, the flagship hospital of Intermountain Healthcare. "For the last 10 to 15 years, the number of antibiotic-resistant bacteria continues to increase. We wanted to turn on the lights and look at all the different types of antibiotic-resistant bacteria that have been highlighted as serious and urgent threats by the Centers for Disease Control to see what the landscape looks like in our system," said Dr. Lopansri, Chief of the Infectious Diseases Division at Intermountain Medical Center. "Although MRSA still poses the greatest challenge, the rise in ESBLs is a major concern and mirrors findings reported at other centers in the U.S. One concern with ESBLs is that the most common antibiotic used to treat them are carbapenems, known as 'last-resort' antibiotics." "Our support for a study of this magnitude provides a benchmark to hospitals and health systems on what could be lurking in their facilities as we seek to validate the health and economic impact of our rapid MDRO products and services to improve infection control," said Evan Jones, Chairman and CEO of OpGen. "The next step in this collaboration will revolve around leveraging our technologies to guide rapid clinical decisions with a goal of reducing the spread of these infections and improving health outcomes." In addition to presenting these study results, Dr. Lopansri will be hosting a discussion of the study and its results at the Learning Lounge. The discussion is titled, "Antibiotic resistant bacteria in our Integrated Healthcare Network: are new diagnostic tests needed?" and will take place on Saturday, October 29, 2016, from 2:15 p.m. to 2:45 p.m., EDT, at booth #1300. Intermountain Healthcare is a Utah-based, not-for-profit system of 22 hospitals, 185 clinics, a Medical Group with about 1,500 employed physicians and advanced practitioners, a health plans group called SelectHealth, and other health services. With a mission of helping people live the healthiest lives possible, Intermountain is widely recognized as a leader in transforming healthcare through high quality and sustainable costs. OpGen, Inc. is harnessing the power of informatics and genomic analysis to provide complete solutions for patient, hospital and network-wide infection prevention and treatment. Learn more at http://www. and follow OpGen on Twitter and LinkedIn.


SALT LAKE CITY and GAITHERSBURG, Md., Oct. 27, 2016 (GLOBE NEWSWIRE) -- A first-of-its-kind study of 900,000 hospital admissions from an integrated health system has yielded insights into shifts in the epidemiology of multi-drug resistant organisms (MDROs) in the community. New research, funded by OpGen (NASDAQ:OPGN) and conducted by Intermountain Healthcare and Enterprise Analysis Corporation (EAC) found that Methicillin Resistant Staphylococcus aureus (MRSA), Clostridium difficile (C. difficile) and ESBL harboring Gram-negative rods were the most common organisms treated by the Intermountain Healthcare system over an eight-year period between January 1, 2008 and December 31, 2015. The study examined data from Intermountain Healthcare over an eight-year period to characterize the trends occurring in C. difficile and MDROs. The abstracted electronic data was pulled from patients seen at Intermountain’s 22 hospitals and affiliated clinics who had clinical cultures positive for antibiotic resistant Gram-positive or Gram-negative bacteria and/or laboratory tests positive for toxigenic C. difficile. The researchers discovered that resistant organisms were found in 1.4 percent of the 900,000 hospital admissions during the study period with most originating from the ambulatory setting. Researchers found that a 222% increase was observed in the prevalence of C. difficile as well as a 322% increase in ESBL positive organisms. The good news is that the prevalence of MRSA decreased by 32%. The study measured both the prevalence of infections, as well as impacts on patient care. Economic data are still being analyzed and will be revealed in a future presentation. Results from the study were presented on Thursday, Oct. 27 at 12:30 p.m. CDT in the Poster Hall at IDWeek in New Orleans by Bert Lopansri, M.D., lead author of the study at Intermountain Medical Center, the flagship hospital of Intermountain Healthcare. “For the last 10 to 15 years, the number of antibiotic-resistant bacteria continues to increase. We wanted to turn on the lights and look at all the different types of antibiotic-resistant bacteria that have been highlighted as serious and urgent threats by the Centers for Disease Control to see what the landscape looks like in our system,” said Dr. Lopansri, Chief of the Infectious Diseases Division at Intermountain Medical Center. “Although MRSA still poses the greatest challenge, the rise in ESBLs is a major concern and mirrors findings reported at other centers in the U.S.,” added Dr. Lopansri. “One concern with ESBLs is that the most common antibiotic used to treat them are carbapenems, known as ‘last-resort’ antibiotics.” “Our support for a study of this magnitude provides a benchmark to hospitals and health systems on what could be lurking in their facilities as we seek to validate the health and economic impact of our rapid MDRO products and services to improve infection control,” said Evan Jones, Chairman and CEO of OpGen. “The next step in this collaboration will revolve around leveraging our technologies to guide rapid clinical decisions with a goal of reducing the spread of these infections and improving health outcomes.” In addition to presenting these study results, Dr. Lopansri will be hosting a discussion of the study and its results at the Learning Lounge. The discussion is titled, “Antibiotic resistant bacteria in our Integrated Healthcare Network: are new diagnostic tests needed?” and will take place on Saturday, October 29, 2016 from 1:15 p.m. to 1:45 p.m. CDT at booth #1300. About Intermountain Healthcare Intermountain Healthcare is a Utah-based, not-for-profit system of 22 hospitals, 185 clinics, a Medical Group with about 1,500 employed physicians and advanced practitioners, a health plans group called SelectHealth, and other health services. With a mission of helping people live the healthiest lives possible®, Intermountain is widely recognized as a leader in transforming healthcare through high quality and sustainable costs. About OpGen OpGen, Inc. is harnessing the power of informatics and genomic analysis to provide complete solutions for patient, hospital and network-wide infection prevention and treatment. Learn more at www.opgen.com and follow OpGen on Twitter and LinkedIn.


SALT LAKE CITY and GAITHERSBURG, Md., Oct. 27, 2016 (GLOBE NEWSWIRE) -- A first-of-its-kind study of 900,000 hospital admissions from an integrated health system has yielded insights into shifts in the epidemiology of multi-drug resistant organisms (MDROs) in the community. New research, funded by OpGen (NASDAQ:OPGN) and conducted by Intermountain Healthcare and Enterprise Analysis Corporation (EAC) found that Methicillin Resistant Staphylococcus aureus (MRSA), Clostridium difficile (C. difficile) and ESBL harboring Gram-negative rods were the most common organisms treated by the Intermountain Healthcare system over an eight-year period between January 1, 2008 and December 31, 2015. The study examined data from Intermountain Healthcare over an eight-year period to characterize the trends occurring in C. difficile and MDROs. The abstracted electronic data was pulled from patients seen at Intermountain’s 22 hospitals and affiliated clinics who had clinical cultures positive for antibiotic resistant Gram-positive or Gram-negative bacteria and/or laboratory tests positive for toxigenic C. difficile. The researchers discovered that resistant organisms were found in 1.4 percent of the 900,000 hospital admissions during the study period with most originating from the ambulatory setting. Researchers found that a 222% increase was observed in the prevalence of C. difficile as well as a 322% increase in ESBL positive organisms. The good news is that the prevalence of MRSA decreased by 32%. The study measured both the prevalence of infections, as well as impacts on patient care. Economic data are still being analyzed and will be revealed in a future presentation. Results from the study were presented on Thursday, Oct. 27 at 12:30 p.m. CDT in the Poster Hall at IDWeek in New Orleans by Bert Lopansri, M.D., lead author of the study at Intermountain Medical Center, the flagship hospital of Intermountain Healthcare. “For the last 10 to 15 years, the number of antibiotic-resistant bacteria continues to increase. We wanted to turn on the lights and look at all the different types of antibiotic-resistant bacteria that have been highlighted as serious and urgent threats by the Centers for Disease Control to see what the landscape looks like in our system,” said Dr. Lopansri, Chief of the Infectious Diseases Division at Intermountain Medical Center. “Although MRSA still poses the greatest challenge, the rise in ESBLs is a major concern and mirrors findings reported at other centers in the U.S.,” added Dr. Lopansri. “One concern with ESBLs is that the most common antibiotic used to treat them are carbapenems, known as ‘last-resort’ antibiotics.” “Our support for a study of this magnitude provides a benchmark to hospitals and health systems on what could be lurking in their facilities as we seek to validate the health and economic impact of our rapid MDRO products and services to improve infection control,” said Evan Jones, Chairman and CEO of OpGen. “The next step in this collaboration will revolve around leveraging our technologies to guide rapid clinical decisions with a goal of reducing the spread of these infections and improving health outcomes.” In addition to presenting these study results, Dr. Lopansri will be hosting a discussion of the study and its results at the Learning Lounge. The discussion is titled, “Antibiotic resistant bacteria in our Integrated Healthcare Network: are new diagnostic tests needed?” and will take place on Saturday, October 29, 2016 from 1:15 p.m. to 1:45 p.m. CDT at booth #1300. About Intermountain Healthcare Intermountain Healthcare is a Utah-based, not-for-profit system of 22 hospitals, 185 clinics, a Medical Group with about 1,500 employed physicians and advanced practitioners, a health plans group called SelectHealth, and other health services. With a mission of helping people live the healthiest lives possible®, Intermountain is widely recognized as a leader in transforming healthcare through high quality and sustainable costs. About OpGen OpGen, Inc. is harnessing the power of informatics and genomic analysis to provide complete solutions for patient, hospital and network-wide infection prevention and treatment. Learn more at www.opgen.com and follow OpGen on Twitter and LinkedIn.


Castellanos-Gonzalez A.,Infectious Diseases Division | Cabada M.M.,Infectious Diseases Division | Nichols J.,Infectious Diseases Division | Gomez G.,University of Texas Medical Branch | White Jr. A.C.,Infectious Diseases Division
Infection and Immunity | Year: 2013

The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of hostparasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. © 2013, American Society for Microbiology.


A first-of-its-kind study of 900,000 hospital admissions from an integrated health system has yielded insights into shifts in the epidemiology of multi-drug resistant organisms (MDROs) in the community. New research, funded by OpGen (NASDAQ: OPGN) and conducted by Intermountain Healthcare and Enterprise Analysis Corporation (EAC), found that Methicillin Resistant Staphylococcus aureus (MRSA), Clostridium difficile (C. difficile) and ESBL harboring Gram-negative rods were the most common organisms treated by the Intermountain Healthcare system over an eight-year period between January 1, 2008 and December 31, 2015. The study examined data from Intermountain Healthcare over an eight-year period to characterize the trends occurring in C. difficile and MDROs. The abstracted electronic data was pulled from patients seen at Intermountain's 22 hospitals and affiliated clinics who had clinical cultures positive for antibiotic resistant Gram-positive or Gram-negative bacteria and/or laboratory tests positive for toxigenic C. difficile. The researchers discovered that resistant organisms were found in 1.4 percent of the 900,000 hospital admissions during the study period with most originating from the ambulatory setting. Additionally, researchers found that a 222% increase was observed in the prevalence of C. difficile as well as a 322% increase in ESBL positive organisms. The good news is that the prevalence of MRSA decreased by 32%. The study measured both the prevalence of infections, as well as impacts on patient care. Economic data are still being analyzed and will be revealed in a future presentation. Results from the study were presented in the Poster Hall at IDWeek 2016 in New Orleans by Bert Lopansri, M.D., lead author of the study at Intermountain Medical Center, the flagship hospital of Intermountain Healthcare. • Of the 900,000 hospital admissions during the study period, 12,905 (1.4%) were from patients positive for an MDRO and/or C. difficile. • While MRSA continues to be the most common MDRO, rates have declined. • MRSA, ESBL and CRE forms of E. coli were less frequently acquired in the hospital while VRE, multi-drug resistant Pseudomonas, and other CRE's were more frequently encountered in a healthcare setting. • 70% of all MDROs and C. difficile cases originated from an ambulatory setting. • While all-cause, in hospital mortality was relatively low (7%), significantly more patients with MDRO require continued medical care in some capacity. "For the last 10 to 15 years, the number of antibiotic-resistant bacteria continues to increase. We wanted to turn on the lights and look at all the different types of antibiotic-resistant bacteria that have been highlighted as serious and urgent threats by the Centers for Disease Control to see what the landscape looks like in our system," said Dr. Lopansri, Chief of the Infectious Diseases Division at Intermountain Medical Center. "Although MRSA still poses the greatest challenge, the rise in ESBLs is a major concern and mirrors findings reported at other centers in the U.S. One concern with ESBLs is that the most common antibiotic used to treat them are carbapenems, known as 'last-resort' antibiotics." "Our support for a study of this magnitude provides a benchmark to hospitals and health systems on what could be lurking in their facilities as we seek to validate the health and economic impact of our rapid MDRO products and services to improve infection control," said Evan Jones, Chairman and CEO of OpGen. "The next step in this collaboration will revolve around leveraging our technologies to guide rapid clinical decisions with a goal of reducing the spread of these infections and improving health outcomes."


Florescu D.F.,Infectious Diseases Division | Florescu D.F.,85400 Nebraska Medical Center | Kwon J.Y.,Infectious Diseases Division | Dumitru I.,University of Nebraska Medical Center
Cardiology in Review | Year: 2013

Adenovirus infections have been associated with significant morbidity and mortality in immunocompromised hosts. The clinical significance of adenovirus disease in heart transplantation is not well-defined; in particular, the significance of adenovirus identification in myocardium remains unclear. Although severe adenovirus disease has been described in heart transplant recipients, adenovirus infections seem to be more frequently associated with increased risk of adverse cardiac events, such as rejection, ventricular dysfunction, coronary vasculopathy, need for retransplantation, and graft loss because of death. Cidofovir is currently considered the standard of treatment for adenovirus disease not responding to reduction of immunosuppression. © 2012 Lippincott Williams & Wilkins.

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