Journal articles: '629.3.023:027'

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Hoffman, Kate, Amy Kalkbrenner, Veronica Vieira, and Julie Daniels. "E-027." Epidemiology 23 (September 2012): 1. http://dx.doi.org/10.1097/01.ede.0000416627.59605.be.

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Wilkinson, Paul, Melvyn Hillsdon, Andy Jones, Emma Coombes, Pippa Griew, and Shakoor Hajat. "O-027." Epidemiology 23 (September 2012): 1. http://dx.doi.org/10.1097/01.ede.0000416685.81582.94.

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Aung, Ther, T. Pradeep, S. Narayanswami, Andy Grieshop, Jill Baumgartner, Conor Reynolds, Grishma Jain, Karthik Sethuraman, Michael Brauer, and Julian Marshall. "S-027." Epidemiology 23 (September 2012): 1. http://dx.doi.org/10.1097/01.ede.0000416881.89288.7c.

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Iavarone, Ivano, Paola Pisani, Milena Maule, Fabrizio Bianchi, Marco De Santis, Pietro Comba, and Roberta Pirastu. "P-027." Epidemiology 23 (September 2012): 1. http://dx.doi.org/10.1097/01.ede.0000417038.68684.08.

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Rameshkumar, R., K. Praveen, P. Satheesh, P. Jain, R. Bhowmick, and R. Soundravally. "Abstract PD-027." Pediatric Critical Care Medicine 19 (June 2018): 37. http://dx.doi.org/10.1097/01.pcc.0000537429.89653.34.

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Forbes, L., L. Cooper, R. Barton, and L. Pritchard. "Abstract P-027." Pediatric Critical Care Medicine 19 (June 2018): 56. http://dx.doi.org/10.1097/01.pcc.0000537484.24906.54.

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Zhi, Xiao, and Tingbo Liang. "Effect of ARK5 on the anti-tumour activity of OSI-027 via regulation of epithelial-mesenchymal transition in pancreatic cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e15758-e15758. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15758.

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e15758 Background: Pancreatic cancer (PC) is one of the most common lethal malignancies,OSI-027, a selective inhibitor of mTOR, has anti-tumour activity in PC and is currently in phase II clinical trials. According to the results of our previous study, OSI-027 sensitivity varies across pancreatic cancer cell lines; however, the underlying mechanisms are unclear. Methods: In this study,We sought to investigate the regulatory mechanisms underlying OSI-027 resistance in PC under both in vitro and in vivo conditions. Results: We demonstrated that in PC, sensitivity to OSI-027 was negatively correlated with ARK5 expression, and ARK5 knockdown could enhance OSI-027 sensitivity. Further, the mechanistic experiments showed that ARK5 inhibition could reverse EMT induced by OSI-027. Suppression of EMT by Twist siRNA could sensitize pancreatic cancer cells to OSI-027, but the combination of Twist siRNA and ARK5 siRNA did not enhance the anti-tumour effect of OSI-027. Moreover, under hypoxia-induced EMT, the cancer cells were less sensitive to OSI-027, but ARK5 siRNA could block the EMT process. The in vivo experiments showed that the combination of ARK5 and Twist siRNAs could enhance the anti-tumour effect of OSI-027 and restrain OSI-027-induced EMT. Conclusions: The results indicate that ARK5 plays a role in the resistance of pancreatic cancer cells to OSI-027 by regulating EMT and lay the groundwork for future clinical studies.

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Cassir, Nadim, Jean-Christophe Delarozière, Gregory Dubourg, Marion Delord, Jean-Christophe Lagier, Phillipe Brouqui, Florence Fenollar, Didier Raoult, and Pierre Edouard Fournier. "A Regional Outbreak of Clostridium difficile PCR-Ribotype 027 Infections in Southeastern France from a Single Long-Term Care Facility." Infection Control & Hospital Epidemiology 37, no. 11 (August 3, 2016): 1337–41. http://dx.doi.org/10.1017/ice.2016.164.

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OBJECTIVETo describe and analyze a large outbreak of Clostridium difficile 027 (CD-027) infections.METHODSConfirmed CD-027 cases were defined as CD infection plus real-time polymerase chain reaction assay (PCR) positive for CD-027. Clinical and microbiological data on patients with CD-027 infection were collected from January 2013 to December 2015 in the Provence-Alpes-Côte-d’Azur region (southeastern France).RESULTSIn total, 19 healthcare facilities reported 144 CD-027 infections (112 confirmed and 32 probable CD-027 infections) during a 22-month period outbreak. Although the incidence rate per 10,000 bed days was lower in long-term care facilities (LTCFs) than in acute care facilities (0.05 vs 0.14; P<.001), cases occurred mainly in LTCFs, one of which was the probable source of this outbreak. After centralization of CD testing, the rate of confirmed CD-027 cases from LTCFs or residential-care homes increased significantly (69% vs 92%; P<.001). Regarding confirmed CD-027 patients, the sex ratio and the median age were 0.53 and 84.2 years, respectively. The 30-day crude mortality rate was 31%. Most patients (96%) had received antibiotics within 3 months prior to the CD colitis diagnosis. During the study period, the rate of patients with CD-027 (compared with all patients tested in the point-of-care laboratories) decreased significantly (P=.03).CONCLUSIONSA large CD-027 outbreak occurred in southeastern France as a consequence of an initial cluster of cases in a single LTCF. Successful interventions included rapid isolation and testing of residents with potentially infectious diarrhea and cohorting of case patients in a specialized infectious diseases ward to optimize management.Infect Control Hosp Epidemiol 2016;1–5

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Stabler, Richard A., Lisa F. Dawson, Leslie T. H. Phua, and Brendan W. Wren. "Comparative analysis of BI/NAP1/027 hypervirulent strains reveals novel toxin B-encoding gene (tcdB) sequences." Journal of Medical Microbiology 57, no. 6 (June 1, 2008): 771–75. http://dx.doi.org/10.1099/jmm.0.47743-0.

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The reported incidence and mortality of Clostridium difficile-associated disease has increased significantly, which in part is likely to be due to the emergence of a new, highly virulent strain in North America and Europe. This epidemic strain, referred to as BI/NAP1/027, has increased virulence, attributed to overexpression of the two toxin-encoding genes, tcdA and tcdB, which may be due to truncation of the negative regulator (tcdC) by a 1 bp deletion. In a previous study of whole-genome comparisons using microarray analysis of 75 C. difficile isolates, it was noted that the 20 027 strains, which formed a hypervirulent clade, possessed a unique hybridization pattern for the 7 toxin B microarray reporters. This unique pattern was conserved in all of these 027 strains. The pattern was different for the 55 non-027 strains tested. These data, along with the knowledge that 027 strains are toxinotype III (i.e. possess a complete tcdB gene of comparable size to toxin reference strain VPI 10463), suggest that the sequence of the N-terminal binding domain of toxin B must be divergent from C. difficile strain 630 (and the other 55 strains tested). Additionally, these 027 strains had comparable hybridization patterns across the whole microarray, as well as for tcdB. Therefore, it was suggested that they share a similar, novel N-terminal binding domain. The aim of this study was to ascertain the sequence variation in tcdB from eight characterized BI/NAP1/027 strains. The study confirmed significant sequence variation of tcdB from the sequenced strain 630 and slight variation in tcdB among the eight 027 strains. These results suggest that toxin B from 027 strains may have a different binding capacity compared with its less-virulent counterparts and may, in addition to the mutated tcdC regulator, be responsible for the increased virulence of 027 strains.

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Sritharan, Meera, and Yashwant R. Mahida. "T2060 Disease Severity Due to 027 and Non-027 Strains of Clostridium difficile." Gastroenterology 136, no. 5 (May 2009): A—630. http://dx.doi.org/10.1016/s0016-5085(09)62906-1.

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Gupta, Mamta, Andrea Wahner Hendrickson, Jing Jing Han, Mary Stenson, Linda Wellik, Sharon Barr, Scott H. Kaufmann, and Thomas E. Witzig. "Dual Inhibition of mTORC1/mTORC2 Induces Apoptosis of Mantle Cell Lymphoma by Preventing Rictor Mediated AKTS473 Phosphorylation by Potentiating AKT2-PHLPP1 Association." Blood 116, no. 21 (November 19, 2010): 772. http://dx.doi.org/10.1182/blood.v116.21.772.772.

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Abstract Abstract 772 The mammalian target of rapamycin (mTOR) plays a crucial role in proliferative and anti-apoptotic signals in various lymphomas. The mTORC1 inhibitors, such as the rapamycin analogs temsirolimus and everolimus, have achieved a 38% overall response rate in heavily pretreated mantle cell lymphoma (MCL); however, most responses are partial, and many patients are resistant. One mechanism for resistance to mTORC1 inhibitors is that mTORC2 remains unaffected (Blood 2009 Oct 1; 114 (14): 2926–2935). We hypothesize that combined mTORC1/mTORC2 inhibition will be more effective in MCL. We tested the dual mTORC1/mTORC2 inhibitor OSI-027 (OSI Pharmaceuticals) on MCL cell lines and patient samples that were demonstrated to have a high amount of mTORC2 (Rictor and its target p-AKTS473) and mTORC1 (Raptor and its targets pS6 and p4E-BP1) targets. Dual inhibition through OSI-027 inhibited pAKTSer473, a direct target of mTORC2 without any obvious effect on AKTTh308 in these cells. On the other hand, the mTORC1 inhibitor rapamycin had no effect on pAKTSer473. Interestingly, both drugs effectively suppressed phosphorylation of S6; only OSI-027 decreased phosphorylation of 4E-BP1Th37/46. We next assessed the effect of OSI-027 on MCL proliferation and apoptosis and showed that dual inhibition of mTORC1/mTORC2 through OSI-027 caused growth arrest and apoptosis in a dose-dependent manner in both MCL patient cells treated ex vivo and established MCL cell lines; however, we did not see any significant effect of rapamycin on apoptosis. Recent studies have shown that AKT has direct effects on some members of the apoptosis pathway such as forkhead transcription factors (FOXO), caspase 9, and BAD. OSI-027 treatment significantly inhibited p-FOXO3AT32 with some inhibitory effect on pBADS136. These data suggest that FOXO3A is an important target of AKT through which OSI-027 is exerting its apoptotic effects. There are several potential mechanisms whereby OSI-027 prevents AKTS473 phosphorylation: 1) deactivation of kinases upstream of AKT; 2) activation of phosphatases down-stream of AKT. OSI-027 treatment of MCL cells produced no change in phosphorylated PI3K p85/p55 or PDK1 protein. These data eliminate the possibility of involvement of the PI3K pathway in OSI-027 mediated AKT dephosphorylation. We did find that OSI-027 mediated deactivation of AKTS473 is, at least in part, phosphatase dependent. The PH domain leucine-rich repeat protein phosphatase (PHLPP) family of phosphatases have been shown to directly dephosphorylate and inactivate AKTS473. To determine if AKT and PHLPP1 or PHLPP2 are associated in MCL cells, we immunoprecipitated AKT from MCL cells and probed for association with endogenous PHLPP1 and PHLPP2. All the MCL lines do express endogenous PHLPP1 and PHLPP2; however, they are not complexed to AKT. Further studies using the AKT isoforms AKT1 and AKT2 found AKT2 to be associated with PHLPP1; there was no association of AKT1 or AKT2 to PHLPP2. To investigate if OSI-027 enhanced the AKT2-PHLPP1 interaction, we repeated the co-immunoprecipitation assay in the OSI-027 treated MCL cell lines and demonstrated that OSI-027 increased the interaction of AKT2-PHLPP1. Further we showed that OSI-027 exposure did not alter the expression level of PHLPP1 and PHLPP2 proteins. In summary the dual inhibition of mTORC1/mTORC2 by OSI-027 in MCL is more effective than mTORC1 inhibition by rapamycin. We present the mechanism that OSI-027 induces apoptosis in MCL cell lines by inhibition of Rictor-AKT-FOXO3A signaling, and this is mediated in part by activation of the phosphatase PHLPP1. These findings indicate that simultaneously targeting mTORC1 and mTORC2 may be effective in patients with MCL. Disclosures: Barr: OSI Pharmaceuticals: Employment.

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Robinson, Catherine D., Jennifer M. Auchtung, James Collins, and Robert A. Britton. "Epidemic Clostridium difficile Strains Demonstrate Increased Competitive Fitness Compared to Nonepidemic Isolates." Infection and Immunity 82, no. 7 (April 14, 2014): 2815–25. http://dx.doi.org/10.1128/iai.01524-14.

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ABSTRACTClostridium difficileinfection is the most common cause of severe cases of antibiotic-associated diarrhea (AAD) and is a significant health burden. Recent increases in the rate ofC. difficileinfection have paralleled the emergence of a specific phylogenetic clade ofC. difficilestrains (ribotype 027; North American pulsed-field electrophoresis 1 [NAP1]; restriction endonuclease analysis [REA] group BI). Initial reports indicated that ribotype 027 strains were associated with increased morbidity and mortality and might be hypervirulent. Although subsequent work has raised some doubt as to whether ribotype 027 strains are hypervirulent, the strains are considered epidemic isolates that have caused severe outbreaks across the globe. We hypothesized that one factor that could lead to the increased prevalence of ribotype 027 strains would be if these strains had increased competitive fitness compared to strains of other ribotypes. We developed a moderate-throughputin vitromodel ofC. difficileinfection and used it to test competition between four ribotype 027 clinical isolates and clinical isolates of four other ribotypes (001, 002, 014, and 053). We found that ribotype 027 strains outcompeted the strains of other ribotypes. A similar competitive advantage was observed when two ribotype pairs were competed in a mouse model ofC. difficileinfection. Based upon these results, we conclude that one possible mechanism through which ribotype 027 strains have caused outbreaks worldwide is their increased ability to compete in the presence of a complex microbiota.

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Evans, J. "027 Rehabilitation for dysexecutive symptoms." Journal of Neurology, Neurosurgery & Psychiatry 81, no. 10 (September 24, 2010): e11-e12. http://dx.doi.org/10.1136/jnnp.2010.217554.27.

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van der Kooi, T. I. I., M. Koningstein, A. Lindemans, D. W. Notermans, E. Kuijper, R. van den Berg, H. Boshuizen, P. M. G. Filius, and S. van den Hof. "Antibiotic use and other risk factors at hospital level for outbreaks with Clostridium difficile PCR ribotype 027." Journal of Medical Microbiology 57, no. 6 (June 1, 2008): 709–16. http://dx.doi.org/10.1099/jmm.0.47711-0.

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The first Dutch outbreak due to Clostridium difficile ribotype 027 was observed in mid-2005; by the end of that year, eight hospitals were affected. To study the relationship between hospital-wide antibiotic use and the incidence of 027-linked C. difficile-associated disease (CDAD) three study groups were made: group A, all eight hospitals with an 027-associated epidemic; group B, five of a total of six hospitals with occasional 027 cases, without an increase in CDAD; and group C, ten randomly selected hospitals with no reported 027 epidemics or isolated 027 cases. Quarterly data on CDAD incidences, hygiene measures and the use of fluoroquinolones, second- and third-generation cephalosporins, extended-spectrum penicillins, penicillins with beta-lactamase inhibitors, carbapenems, lincomycins and macrolides were collected for 2004 and 2005, and divided into pre-epidemic and epidemic periods. Using a multilevel Poisson regression analysis, CDAD incidence was linked to antibiotic use in the previous quarter and to certain hygiene measures. In the pre-epidemic period, the total use of the studied antibiotics was comparable between affected and unaffected hospitals. Higher use of second-generation cephalosporins, macrolides and all of the studied antibiotics were independently associated with a small increase in CDAD incidence [relative risk (95 % confidence interval): 1.14 per increase of 100 defined daily doses per 10 000 bed days (1.06–1.23), 1.10 (1.01–1.19) and 1.02 (1.01–1.03), respectively]. However the effect was too small to predict which hospitals might be more prone to 027-associated outbreaks.

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Silva, Sandra Y., Brigid M. Wilson, Sarah N. Redmond, and Curtis J. Donskey. "Inpatient fluoroquinolone use in Veterans’ Affairs hospitals is a predictor of Clostridioides difficile infection due to fluoroquinolone-resistant ribotype 027 strains." Infection Control & Hospital Epidemiology 42, no. 1 (September 23, 2020): 57–62. http://dx.doi.org/10.1017/ice.2020.383.

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AbstractBackground:Reduction in the use of fluoroquinolone antibiotics has been associated with reductions in Clostridioides difficile infections (CDIs) due to fluoroquinolone-resistant strains.Objective:To determine whether facility-level fluoroquinolone use predicts healthcare facility-associated (HCFA) CDI due to fluoroquinolone-resistant 027 strains.Methods:Using a nationwide cohort of hospitalized patients in the Veterans’ Affairs Healthcare System, we identified hospitals that categorized >80% of CDI cases as positive or negative for the 027 strain for at least one-quarter of fiscal years 2011–2018. Within these facilities, we used visual summaries and multilevel logistic regression models to assess the association between facility-level fluoroquinolone use and rates of HCFA-CDI due to 027 strains, controlling for time and facility complexity level, and adjusting for correlated outcomes within facilities.Results:Between 2011 and 2018, 55 hospitals met criteria for reporting 027 results, including a total of 5,091 HCFA-CDI cases, with 1,017 infections (20.0%) due to 027 strains. Across these facilities, the use of fluoroquinolones decreased by 52% from 2011 to 2018, with concurrent reductions in the overall HCFA-CDI rate and the proportion of HCFA-CDI cases due to the 027 strain of 13% and 55%, respectively. A multilevel logistic model demonstrated a significant effect of facility-level fluoroquinolone use on the proportion of infections in the facility due to the 027 strain, most noticeably in low-complexity facilities.Conclusions:Our findings provide support for interventions to reduce use of fluroquinolones as a control measure for CDI, particularly in settings where fluoroquinolone use is high and fluoroquinolone-resistant strains are common causes of infection.

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Birgand, Gabriel, Katiuska Miliani, Anne Carbonne, and Pascal Astagneau. "Is High Consumption of Antibiotics Associated with Clostridium difficile Polymerase Chain Reaction–Ribotype 027 Infections in France?" Infection Control & Hospital Epidemiology 31, no. 3 (March 2010): 302–5. http://dx.doi.org/10.1086/650758.

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We compared antibiotic consumption between hospitals affected by a strain of Clostridium difficile designated as polymerase chain reaction–ribotype 027 (CD-027) and those unaffected during an outbreak in northern France. The mean consumption of several β-lactams, amikacin, and fluoroquinolones was high in affected hospitals (P<.05). However, only levofloxacin and imipenem remained associated with emerging CD-027 in the multivariate analysis, suggesting that those antibiotics should be better targeted by prevention campaigns.

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Denève, Cécile, Sylvie Bouttier, Bruno Dupuy, Frédéric Barbut, Anne Collignon, and Claire Janoir. "Effects of Subinhibitory Concentrations of Antibiotics on Colonization Factor Expression by Moxifloxacin-Susceptible and Moxifloxacin-Resistant Clostridium difficile Strains." Antimicrobial Agents and Chemotherapy 53, no. 12 (October 5, 2009): 5155–62. http://dx.doi.org/10.1128/aac.00532-09.

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ABSTRACT Recent outbreaks of Clostridium difficile infection have been related to the emergence of the NAP1/027 epidemic strain. This strain demonstrates increased virulence and resistance to the C-8-methoxyfluoroquinolones gatifloxacin and moxifloxacin. These antibiotics have been implicated as major C. difficile infection-inducing agents. We investigated by real-time reverse transcription-PCR the impact of subinhibitory concentrations of ampicillin, clindamycin, ofloxacin, and moxifloxacin on the expression of genes encoding three colonization factors, the protease Cwp84, the high-molecular-weight S-layer protein, and the fibronectin-binding protein Fbp68. We have previously shown in six non-NAP1/027 moxifloxacin-susceptible strains that the presence of ampicillin or clindamycin induced an upregulation of these genes, whereas the presence of fluoroquinolones did not. The objective of this study was to analyze the expression of these genes under the same conditions in four NAP1/027 strains, one moxifloxacin susceptible and three moxifloxacin resistant. Two in vitro-selected moxifloxacin-resistant mutants were also analyzed. Moxifloxacin resistance was associated with the Thr82→Ile substitution in GyrA in all but one of the moxifloxacin-resistant strains. The expression of cwp84 and slpA was strongly increased after culture with ampicillin or clindamycin in NAP1/027 strains. Interestingly, after culture with fluoroquinolones, the expression of cwp84 and slpA was only increased in four moxifloxacin-resistant strains, including the NAP1/027 strains and one of the in vitro-selected mutants. The overexpression of cwp84 was correlated with increased production of the protease Cwp84. The historical NAP1/027 moxifloxacin-susceptible strain and its mutant appear to be differently regulated by fluoroquinolones. Overall, fluoroquinolones appear to favor the expression of some colonization factor-encoding genes in resistant C. difficile strains. The fluoroquinolone resistance of the NAP1/027 epidemic strains could be considered an ecological advantage. This could also increase their colonization fitness and promote the infection.

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Dubreuil, L. "Clostridium difficile : de O’Toole à 027." Antibiotiques 9, no. 4 (December 2007): 268–73. http://dx.doi.org/10.1016/s1294-5501(07)73925-0.

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Drudy, Denise, Lorraine Kyne, Rebecca O’Mahony, and Séamus Fanning. "gyrAMutations in Fluoroquinolone-resistantClostridium difficilePCR-027." Emerging Infectious Diseases 13, no. 3 (March 2007): 504–5. http://dx.doi.org/10.3201/eid1303.060771.

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M, Brennan, Tyagi A, and Leach JP. "WED 027 Acute neurology in glasgow." Journal of Neurology, Neurosurgery & Psychiatry 89, no. 10 (September 13, 2018): A4.4—A4. http://dx.doi.org/10.1136/jnnp-2018-abn.16.

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Provision of acute liaison in-patient neurology reduces demand on neurology out patient services, reduces unnecessary investigations and use of medical beds by patients waiting on in-patient neurology review and allows speedier access to necessary neurological services for those with a neurological illness.The pressure on acute neurology beds at QEUH Glasgow is immense and there is considerable delay in patients waiting for admission to the ward. An audit of the acute on call service in mid 2015 showed a 100% increase in the number of phone calls received by the on call registrar when compared to a similar audit in 2008. The number of requests for ward visiting to review medical inpatients at the Queen Elizabeth University hospital increased by more than 100% over the previous year.In June 2016 an Acute Neurology rota was introduced whereby a Consultant Neurologist supervised and delivered patient care for the acute neurology wards, referrals from medical wards and acute receiving, as well as twice a week acute neurology clinics. This has led to a significantly improved care for patients referred with neurological problems as perceived by trainees, consultants and referring medical physicians, as evident on a survey carried out in 2017.

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Krutova, Marcela, Jana Matejkova, and Otakar Nyc. "C. difficile ribotype 027 or 176?" Folia Microbiologica 59, no. 6 (June 27, 2014): 523–26. http://dx.doi.org/10.1007/s12223-014-0323-5.

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Quarterman, C., M. Davies, HL Smart, N. Taggart, and S. Sarkar. "PTH-027 Anaesthesia-led Propofol Sedation For Complex Endoscopy: Climbing Higher: Abstract PTH-027 Table 1." Gut 63, Suppl 1 (June 2014): A220.1—A220. http://dx.doi.org/10.1136/gutjnl-2014-307263.473.

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Bhattacharyya, R., F. Chedgy, K. Kandiah, S. Tholoor, and P. Bhandari. "OC-027 Buried barrett’s dysplasia: rfa is not the only culprit: Abstract OC-027 Table 1." Gut 64, Suppl 1 (June 2015): A14.1—A14. http://dx.doi.org/10.1136/gutjnl-2015-309861.27.

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Gupta, Mamta, Andrea E. Wahner Hendrickson, Seong Seok Yun, Jing Jing Han, Paula A. Schneider, Brian D. Koh, Mary J. Stenson, et al. "Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies." Blood 119, no. 2 (January 12, 2012): 476–87. http://dx.doi.org/10.1182/blood-2011-04-346601.

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Abstract The mammalian target of rapamycin (mTOR) plays crucial roles in proliferative and antiapoptotic signaling in lymphoid malignancies. Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-lived. In the present study we compared the effects of rapamycin with the dual mTORC1/mTORC2 inhibitor OSI-027 in cell lines and clinical samples representing divers lymphoid malignancies. In contrast to rapamycin, OSI-027 markedly diminished proliferation and induced apoptosis in a variety of lymphoid cell lines and clinical samples, including specimens of B-cell acute lymphocytic leukemia (ALL), mantle cell lymphoma, marginal zone lymphoma and Sezary syndrome. Additional analysis demonstrated that OSI-027–induced apoptosis depended on transcriptional activation of the PUMA and BIM genes. Overexpression of Bcl-2, which neutralizes Puma and Bim, or loss of procaspase 9 diminished OSI-027–induced apoptosis in vitro. Moreover, OSI-027 inhibited phosphorylation of mTORC1 and mTORC2 substrates, up-regulated Puma, and induced regressions in Jeko xenografts. Collectively, these results not only identify a pathway that is critical for the cytotoxicity of dual mTORC1/mTORC2 inhibitors, but also suggest that simultaneously targeting mTORC1 and mTORC2 might be an effective anti-lymphoma strategy in vivo.

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Oñate-Gutiérrez, José Millán, Janier Segura, Adriana Correa, Erika Cantor, and María Virginia Villegas. "Infección por Clostridium difficile: descripción de las cepas NAP1/027 y de otros serotipos en un centro de alta complejidad de Cali, Colombia, 2012-2015." Biomédica 39 (May 1, 2019): 63–70. http://dx.doi.org/10.7705/biomedica.v39i2.3950.

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Introducción. Clostridium difficile ocasiona infecciones hospitalarias que resultan en altas tasas de morbilidad y mortalidad. La cepa NAP1/027 se ha asociado con una mayor producción de toxinas y con una mayor gravedad, lo que aumenta la carga de la enfermedad.Objetivo. Describir la epidemiología de las infecciones asociadas con C. difficile y las características de la cepa NAP1/027.Materiales y métodos. Se hizo un estudio observacional basado en la revisión de las historias clínicas de los pacientes con muestras de heces positivas para C. difficile identificadas mediante la prueba Xpert™ entre el 2012 y el 2015 en un hospital de alta complejidad. La gravedad de la enfermedad se evaluó con el índice ATLAS.Resultados. Se incluyeron 42 casos de pacientes infectados, 9 de los cuales fueron positivos para la cepa NAP1/027. El uso de antibióticos antes de la infección durante más de siete días fue más frecuente en los casos de pacientes con muestras negativas para NAP1/027. En la mitad de los pacientes, la duración de la diarrea fue mayor de cinco días y no hubo diferencias según el tipo de cepa (p>0,05). Los casos de pacientes positivos para la cepa NAP1/027 se caracterizaron por presentar deposiciones fétidas y sanguinolentas. La gravedad de la infección fue similar entre los grupos.Conclusión. Se comprobó la circulación de la cepa NAP1/027, pero su presencia no supuso diferencias clínicas significativas con respecto a otras cepas, lo cual podría deberse al limitado número de pacientes en este estudio. Sin embargo, su presencia debe alertar a los médicos y a las instituciones de salud, dada su frecuente asociación con la gravedad de la infección y la mortalidad.

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Redmond, Sarah N., Sandra Y. Silva, Brigid M. Wilson, Jennifer L. Cadnum, and Curtis J. Donskey. "Impact of Reduced Fluoroquinolone Use on Clostridioides difficile Infections Resulting From the Fluoroquinolone-Resistant Ribotype 027 Strain in a Veterans Affairs Medical Center." Pathogens and Immunity 4, no. 2 (October 1, 2019): 251. http://dx.doi.org/10.20411/pai.v4i2.327.

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Background: Fluoroquinolone restriction has been proposed as a control measure for Clostridioides difficile infection (CDI) outbreaks associated with fluoroquinolone-resistant ribotype 027 strains. However, relatively few reports of fluoroquinolone restriction interventions have evaluated the impact on C. difficile strain types and fluoroquinolone resistance.Methods: In a hospital and affiliated long-term care facility (LTCF), antimicrobial stewardship and environmental cleaning interventions were implemented between 2009 and 2018, and C. difficile isolates during this period (~20 per year) were ribotyped and tested for fluoroquinolone resistance by moxifloxacin minimum inhibitory concentrations (MICs). Pearson’s correlation coefficient was used to assess the association between use of fluoroquinolones and the percentage of CDI cases due to the 027 strain over time.Results: Between 2009 and 2018, prescribing of fluoroquinolones to inpatients decreased by 43%, coinciding with significant reductions in the healthcare-associated CDI rates in the hospital and LTCF and a decline in the percentage of C. difficile isolates that were ribotype 027 from 70% to 10%. Ninety-five percent of ribotype 027 and 6% of non-027 isolates were moxifloxacin resistant. Hospital fluoroquinolone use was strongly correlated with the incidence of hospital-associated CDI (r = 0.79, 95% confidence interval, 0.31-0.95), but LTCF fluoroquinolone use was not correlated with LTCF-associated CDI (r = 0.29, 95% confidence interval, -0.43-0.77). During the study period, there were statistically significant downward trends in the use of penicillins, intravenous vancomycin, carbapenems, and clindamycin.Conclusion: Our results provide support for fluoroquinolone restriction as a control measure for CDI outbreaks due to fluoroquinolone-resistant 027 strains, but also highlight the need for randomized trials as factors such as reduction in other antibiotic classes and improved cleaning may also impact CDI rates.

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Kociolek, Larry K., and Dale N. Gerding. "Clinical Utility of Laboratory Detection of Clostridium difficile Strain BI/NAP1/027." Journal of Clinical Microbiology 54, no. 1 (October 28, 2015): 19–24. http://dx.doi.org/10.1128/jcm.02340-15.

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Clostridium difficilestrain BI/NAP1/027 is associated with increasedC. difficileinfection (CDI) rates and severity, and the efficacy of some CDI therapies may be strain dependent. Although culturedC. difficileisolates can be reliably subtyped by various methods, the long turnaround times, high cost, and limited availability of strain typing preclude their routine use. Nucleic acid amplification tests identify BI/NAP1/027 rapidly from stool, but the emergence of closely related strains compromises test specificity. Although detection of epidemiologically significant pathogens is generally useful for infection control programs, specific data supporting use of rapid detection of BI/NAP1/027 as an infection control tool are still awaited.

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Hendrickson, Andrea E. Wahner, Mamta Gupta, Seongseok Yun, Jennifer C. Shing, Paula A. Schneider, Kevin L. Peterson, Judith E. Karp, Sharon Barr, Thomas E. Witzig, and Scott H. Kaufmann. "OSI-027, a Dual TORC1/TORC2 Inhibitor, Induces Bim- and Puma-Mediated Apoptosis In Lymphoid Malignancy." Blood 116, no. 21 (November 19, 2010): 970. http://dx.doi.org/10.1182/blood.v116.21.970.970.

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Abstract Abstract 970 The mammalian target of rapamycin, mTOR, is a highly conserved serine/threonine kinase known to play a role in regulating mRNA translation, cell cycle progression, cell proliferation and apoptosis. As a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, mTOR is a component of two distinct complexes, TORC1 and TORC2. While TORC1 facilitates cell cycle progression from G1 into S phase by phosphorylating p70S6 kinase and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), TORC2 catalyzes the activating phosphorylation of Akt on Ser473, providing a feedback loop for further activation of mTOR. Phase II trials have shown activity of the TORC1-selective inhibitor rapamycin and its analogs in a wide range of lymphoma subtypes. The purpose of this study was to evaluate the anti-proliferative and pro-apoptotic effects of the dual TORC1/TORC2 inhibitor OSI-027 in human neoplastic lymphoid cells in vitro. MTS assays demonstrated that OSI-027 inhibited proliferation in a wide range of lymphoid lines, including SeAx (Sezary syndrome), DoHH2 (large cell lymphoma), RL (follicular lymphoma) and Jurkat (T cell ALL), as well as clinical lymphoma and T cell ALL samples, with IC50 values ranging from 0.078 to 10 μM. Propidium iodide staining followed by flow cytometry for subdiploid cells revealed induction of apoptosis within 48 h of treatment with OSI-027 (but not rapamycin) in SeAx, DoHH2, and Jurkat cells. Examination of Jurkat variants with alterations in key proteins involved in the death receptor versus mitochondrial pathway revealed diminished apoptotic responses to OSI-027 when Bcl-2 was overexpressed or caspase 9 was silenced, indicating involvement of the mitochondrial pathway. Immunoblotting for Bcl-2 family members revealed upregulation of Bim and Puma after a 48-hour exposure to OSI-027 but not rapamycin. This upregulation was also seen at the mRNA level, with a 12- to 20-fold increase in Puma mRNA and 4- to 12-fold induction of Bim mRNA. Small interfering RNA (siRNA)-mediated knockdown of Bim and Puma significantly diminished the apoptotic response to OSI-027. Because the Foxo3a transcription factor has been implicated in Bim and Puma expression and is known to be activated when Akt is inhibited, we next examined whether Bim and Puma induction was Foxo3a-dependent. Luciferase reporter assays showed that OSI-027 activated the full-length Puma and Bim promoters and that this activation was diminished when the Foxo3a binding sites were deleted or mutated. In addition, OSI-027 induced nuclear translocation of Foxo3a, while Foxo3a siRNA diminished OSI-027-induced apoptosis in Jurkat cells. Collectively, these results indicate that OSI-027 inhibits proliferation and induces apoptosis in a wide range of neoplastic lymphoid cells through a process that involves Foxo3a-mediated upregulation of Bim and Puma. These results also suggest that dual inhibition of TORC1 and TORC2 may be an effective treatment strategy in lymphoid malignancy. Disclosures: Barr: OSI Pharmaceuticals: Employment. Witzig:Novartis and Celgene: Patents & Royalties, Research Funding, Served on advisory boards with Novartis and Celgene – both uncompensated with compensation to Mayo Clinic.

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Labbé, Annie-Claude, Louise Poirier, Duncan MacCannell, Thomas Louie, Michel Savoie, Claire Béliveau, Michel Laverdière, and Jacques Pépin. "Clostridium difficile Infections in a Canadian Tertiary Care Hospital before and during a Regional Epidemic Associated with the BI/NAP1/027 Strain." Antimicrobial Agents and Chemotherapy 52, no. 9 (June 23, 2008): 3180–87. http://dx.doi.org/10.1128/aac.00146-08.

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ABSTRACT Since 2002, an epidemic of Clostridium difficile infections has occurred in southern Quebec, Canada. At Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada, the incidence of C. difficile infections increased from 11/1,000 admissions (1999 to 2002) to 27/1,000 admissions (2003 to 2005). We compared the exposures and outcomes for patients infected with strains with different ribopatterns isolated before (n = 55) and during (n = 175) the epidemic, as well as the in vitro activities of antibiotics against those isolates. During the preepidemic period, 46 isolates (84%) were of ribotype 001, 1 was of ribotype 027, and 8 were of other ribopattern types. During the epidemic period, ribotype 027 strains accounted for 140 (80%) isolates; 26 (15%) were of ribotype 001, and 7 were of other ribopattern types. Ribotype 027 strains were highly resistant to fluoroquinolones (FQs) but were susceptible to clindamycin. A pattern of prior specific antibiotic exposure that selected for antibiotic-resistant ribotype C. difficile infections was observed for FQs (ribotype 027) and clindamycin (ribotype 001). The rate of mortality was higher among older patients, those with a high Charlson comorbidity index, and those with longer previous hospitalizations. By multivariate analysis, patients infected with ribotype 027 were twice as likely to die within 30 days of diagnosis than patients infected with other ribotypes (adjusted odds ratio, 2.06; 95% confidence interval, 1.00 to 4.22). The observations from this study support the notion that continued selective antibiotic pressure resulted in the superimposition of the hypertoxigenic ribotype 027 clone on top of the prior dominant ribotype 001 clone in a setting of preexisting high endemicity, thus leading to the high rates of morbidity and mortality seen in the Quebec outbreak. Stringent antibiotic stewardship measures, combined with aggressive infection control, are required to curtail the epidemic of C. difficile infections.

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Morfin-Otero, Rayo, Elvira Garza-Gonzalez, Sara A. Aguirre-Diaz, Rodrigo Escobedo-Sanchez, Sergio Esparza-Ahumada, Hector R. Perez-Gomez, Santiago Petersen-Morfin, Esteban Gonzalez-Diaz, Adrian Martinez-Melendez, and Eduardo Rodriguez-Noriega. "Clostridium difficile outbreak caused by NAP1/BI/027 strain and non-027 strains in a Mexican hospital." Brazilian Journal of Infectious Diseases 20, no. 1 (January 2016): 8–13. http://dx.doi.org/10.1016/j.bjid.2015.09.008.

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Falcone, M., G. Tiseo, F. Iraci, G. Raponi, P. Goldoni, D. Delle Rose, I. Santino, et al. "Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes." Clinical Microbiology and Infection 25, no. 4 (April 2019): 474–80. http://dx.doi.org/10.1016/j.cmi.2018.06.020.

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Ingebretsen, A., G. Hansen, C. Harmanus, and E. J. Kuijper. "First confirmed cases of Clostridium difficile PCR ribotype 027 in Norway." Eurosurveillance 13, no. 2 (January 10, 2008): 9–10. http://dx.doi.org/10.2807/ese.13.02.08011-en.

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Since 2003, the emergence and distribution of a hypervirulent strain of Clostridium difficile PCR ribotype 027 has been described in North America, Japan and several European countries [1-6]. In December 2007, C. difficile PCR ribotype 027 was found in two cases of C. difficile-associated disease treated in a hospital in Oslo, Norway.

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Knetsch, Cornelis W., Marjolein P. M. Hensgens, Céline Harmanus, Madelon W. van der Bijl, Paul H. M. Savelkoul, Ed J. Kuijper, Jeroen Corver, and Hans C. van Leeuwen. "Genetic markers for Clostridium difficile lineages linked to hypervirulence." Microbiology 157, no. 11 (November 1, 2011): 3113–23. http://dx.doi.org/10.1099/mic.0.051953-0.

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Rapid identification of hypervirulent Clostridium difficile strains is essential for preventing their spread. Recent completion of several full-length C. difficile genomes provided an excellent opportunity to identify potentially unique genes that characterize hypervirulent strains. Based on sequence comparisons between C. difficile strains we describe two gene insertions into the genome of hypervirulent PCR ribotypes 078 and 027. Analysis of these regions, of 1.7 and 4.2 kb, respectively, revealed that they contain several interesting ORFs. The 078 region is inserted intergenically and introduces an enzyme that is involved in the biosynthesis of several antibiotics. The 027 insert disrupts the thymidylate synthetase (thyX) gene and replaces it with an equivalent, catalytically more efficient, thyA gene. Both gene insertions were used to develop ribotype-specific PCRs, which were validated by screening a large strain collection consisting of 68 different PCR ribotypes supplemented with diverse 078 and 027 strains derived from different geographical locations and individual outbreaks. The genetic markers were stably present in the hypervirulent PCR ribotypes 078 and 027, but were also found in several other PCR ribotypes. Comparative analysis of amplified fragment length polymorphisms, PCR ribotype banding patterns and toxin profiles showed that all PCR ribotypes sharing the same insert from phylogenetically coherent clusters. The identified loci are unique to these clusters, to which the hypervirulent ribotypes 078 and 027 belong. This provides valuable information on strains belonging to two distinct lineages within C. difficile that are highly related to hypervirulent strains.

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Ma, Yan, David H. Byrne, Jing Chen, and Amanda Byrne. "027 MULTIPLICATION OF ROSE SPECIES IN VITRO." HortScience 29, no. 5 (May 1994): 431d—431. http://dx.doi.org/10.21273/hortsci.29.5.431d.

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Several rose species (Rosa rugosa, R. wichuraiana, R. setigera, R. laevigata, R. banksiae, R. roxburghii, R. odorata and hybrids) were employed to establish the appropriate nutrient media for shoot multiplication and root initiation of cultured shoots and to describe a procedure for the successful transfer to soil of plants obtained in vitro. Cultured shoot tips and lateral buds from different genotypes proliferated multiple shoots on a basal medium (MS salt, vitamins, glycine, sucrose and agar) supplemented with 0mg/l to 6mg/l 6-benzylamino purine (BA) and 0mg/l to 0.5 mg/l naphthalene acetic acid (NAA). Most rose species cultured in a modified MS medium supplemented with 2mg/l BA showed good growth and shoot proliferation. The buds nearest the apex exhibited the slowest rate of bud development. Root development was enhanced and shoot development inhibited by lowering the concentration of MS salts to quarter- and half-strength. With difficult-to-root species, rooting was improved by supplementing the media with auxin or giving them 3-7days of dark treatment.

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Janse, F. E., C. W. M. Van Veelen, P. C. Van Rijen, A. C. Van Huffelen, A. Jennekens-Schinkel, and O. Van Nieuwenhuizen. "027 Hemispherectomy for intractable epilepsy of childhood." European Journal of Paediatric Neurology 3, no. 6 (January 1999): A34—A35. http://dx.doi.org/10.1016/s1090-3798(99)91075-9.

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36

Flaux, L., M. Margaryan, Y. Montcho, A. Robine, and P. Clermidi. "SFCP P-027 - Abcès hépatique néonatal iatrogène." Archives de Pédiatrie 21, no. 5 (May 2014): 483. http://dx.doi.org/10.1016/s0929-693x(14)71743-9.

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37

Zouboulis, CC, D. Djawari, W. Kirch, W. Keitel, F. Ochsendorf, and CE Orfanos. "P 027 Adamantiades-Behçet's disease in Germany." La Revue de Médecine Interne 14 (January 1993): 66s. http://dx.doi.org/10.1016/s0248-8663(05)82329-x.

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Mader, S. "IS-027 Family Needs In The Nicu." Archives of Disease in Childhood 99, Suppl 2 (October 2014): A10.1—A10. http://dx.doi.org/10.1136/archdischild-2014-307384.27.

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39

García, C. Moreno, H. Serrano Gil, L. Ruiz Laza, and F. Monje Gil. "P.027 Esthesioneuroblastoma. Report of three cases." Journal of Cranio-Maxillofacial Surgery 34 (September 2006): 139. http://dx.doi.org/10.1016/s1010-5182(06)60536-2.

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40

Zaki, S., M. El Mansy, and M. El Shazly. "PP-027 Bacteriological studies of Pityriasis alba." International Journal of Infectious Diseases 14 (July 2010): S32—S33. http://dx.doi.org/10.1016/s1201-9712(10)60095-1.

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Kuijper, Ed J., Renate J. van den Berg, Sylvia Debast, Caroline E. Visser, Dick Veenendaal, Annet Troelstra, Tjallie van der Kooi, Susan van den Hof, and Daan W. Notermans. "Clostridium difficileRibotype 027, Toxinotype III, the Netherlands." Emerging Infectious Diseases 12, no. 5 (May 2006): 827–30. http://dx.doi.org/10.3201/eid1205.051350.

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42

Gnanasekaran, Gunadayalan, and Wilson Arisdason. "(027) Proposal to amend Recommendation 8A .4." TAXON 69, no. 6 (December 2020): 1380. http://dx.doi.org/10.1002/tax.12376.

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43

Frederiksen, S., and B. Tarby. "OHP-027 Educational Model For IT Systems." European Journal of Hospital Pharmacy 20, Suppl 1 (March 2013): A145.2—A145. http://dx.doi.org/10.1136/ejhpharm-2013-000276.401.

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44

Rodríguez-Villodres, Ángel, Julia Praena, María Reyes Vidal-Acuña, and Javier Aznar. "Enfermedad recurrente por Clostridium difficile ribotipo 027." Enfermedades Infecciosas y Microbiología Clínica 34, no. 7 (August 2016): 461–62. http://dx.doi.org/10.1016/j.eimc.2015.10.004.

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45

Volkwein, Axel, Werner Gerber, Johannes Klette, and Georg Spescha. "Review of Approval of Flexible Rockfall Protection Systems According to ETAG 027." Geosciences 9, no. 1 (January 18, 2019): 49. http://dx.doi.org/10.3390/geosciences9010049.

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In 2009, the European Guideline for Flexible Rockfall Protection Kits European Technical Approval Guideline 027 (ETAG 027) became valid. The aim of the guideline was to approve and certify steel barriers available on the market according to a common standard. In 2018, ETAG 027 was replaced by a so-called European Assessment Document (EAD). This contribution summarizes results and experiences that were obtained through the type testing, approval and assessment procedures of 66 protection systems evaluated between 2009 and 2018. Apart from the common main task of the barriers to stop falling blocks successfully, the different test conditions and constructions of barriers result in different performance characteristics. Some of these characteristics follow certain trends, whereas others show a wide range without any trend. In such a case, this contribution helps to classify a single system compared to the others.

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Lim, Sharon, Joseph Cherian, Kassoum Nacro, Yun Shan Chew, Meng Ling Choong, Jun Ding Li, Samantha Guo, et al. "Dual Specific Inhibitors Of The BCR-ABL and MNK Kinases As Potential Therapeutics For Blast Crisis Chronic Myeloid Leukemia." Blood 122, no. 21 (November 15, 2013): 2702. http://dx.doi.org/10.1182/blood.v122.21.2702.2702.

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Abstract Pharmacologic inhibition of BCR-ABL by tyrosine kinase inhibitors (TKI) provides effective therapy for chronic phase but not blast crisis (BC) CML. The inability of TKIs to control BC CML is due to the reactivation of BCR-ABL through TKI resistance-conferring mutations, as well as the activation of alternative oncogenic pathways that mediate acquired leukemia stem cell (LSC) function and differentiation block in leukemic progenitors. Accordingly, the development of effective BC therapeutics will require reversing multiple contributors to the BC phenotype, and indicates that targeting BCR-ABL alone will not be sufficient to control BC CML. Indeed, despite the ability of third-generation TKIs to effectively inhibit the majority of clinically-relevant BCR-ABL kinase domain mutations, most patients with BC treated with these agents continue to relapse despite initial responses. Because our recent work has highlighted the importance of the MNK kinase-eIF4E axis in b-catenin-associated BC self-renewal (Lim et al., PNAS18;110(25):E2298-307, 2013), we set out to develop compounds capable of targeting BCR-ABL, TKI-resistant BCR-ABL mutants, as well as the MNK kinases simultaneously. Here, we report the discovery and characterization of two lead compounds ETC-219 and ETC-027 that inhibit clinically relevant BCR-ABL isoforms (E255K, T315I) as well as the MNK1/2 kinases at nanomolar potency (Table 1).Table 1In vitro kinase assays for ETC-219 and ETC-027.Compound IDIC50 MNK1 (µM)IC50 MNK2 (µM)IC50 ABL (µM)IC50 ABL (T315I) (µM)IC50 ABL (E255K) (µM)ETC-2190.2540.0150.0140.0130.148ETC-0275.0150.0240.2140.0913.19 Using a panel of 104 kinases, we showed that ETC-219 and ETC-027 inhibited 90% of the activity of 15 and 12 kinases respectively when tested at 1uM. ETC-219 and ETC-027 interact with only 27 and 20 of off-target kinases respectively, and offer significant selectivity over kinases outside of the MNK and BCR-ABL families. ETC-219 and ETC-027 have favorable pharmacokinetic properties, and include the following ADME characteristics (Table 2).Table 2ADME characteristics of ETC-219 and ETC-027.ETC-219ETC-027ParametersUnitIVPOIVPODosemg/kg1050550C0ng/ml21241714Cmaxng/ml12122490Tmaxh12T1/2h22.21.82.1CLL/h/kg39.72.83.5VzL/kg8.831.37.410.8VssL/kg7.25.8AUC0-t(last)ng.h/ml32905128179514337AUC0-infng.h/ml33025133179814349Extrapolated area for AUC0-inf%0.37000.11000.16000.0800F%3180 Regarding targeting of BCR-ABL-dependent cellular proliferation and survival, we found that ETC-219 and ETC-027 exhibited potent anti-proliferative activity against a panel of BC CML cell lines (K562, BV-173, EM-2, KCL-22, JURL-MK1), as well as Ba/F3-BCR-ABL cells containing the T315I mutation. In an in vivo xenograft model, employing K562-eIF4E cell lines in NOD-SCID mice, we found that both compounds inhibited tumor growth in a dose-dependent manner, and a dose-dependent decrease in eIF4E phosphorylation in tumor explants were also observed. Tumor regression was observed at 100 mg/kg for ETC-219. Importantly, mice given ETC-219 and ETC-027 at 100 mg/kg and 200 mg/kg doses did not exhibit significant toxicity. With respect to MNK-eIF4E-b-catenin axis inhibition, ETC-219 and ETC-027 inhibited eIF4E phosphorylation at IC50s of 0.186 nM and 0.28 nM respectively in HeLa cells. In parallel, both compounds inhibited Wnt/b-catenin reporter activity in BC CML cell lines, as well as the expression of a panel of Wnt-regulated genes. Using the serial replating assay as a readout for LSC function and self-renewal capacity, we found that ETC-219 and ETC-027 were effective at 1nM at preventing serial replating using primary CD34+ cells from patients in BC. Furthermore, ETC-219 and ETC-027 inhibited the serial replating efficacy of BC cells from patients with clinical resistance to the third generation TKI, ponatinib. Conclusion Our results demonstrate that: i) small molecule compounds with favorable ADME properties can be developed to potently and specifically inhibit the BCR-ABL and MNK kinases simultaneously; ii) Dual specific MNK and BCR-ABL inhibitors are effective at abrogating BCR-ABL-driven growth and proliferation, as well as the MNK-eIF4E-dependent self-renewal function of BC LSCs. We conclude that dual specific BCR-ABL and MNK inhibitors may warrant testing in patients with BC CML. Disclosures: Chuah: Novartis: Honoraria; BMS: Honoraria.

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47

Weiss, Bettina, Niels Kleinkauf, Tim Eckmanns, Matthias an der Heiden, Matthias Neumann, Harald Michels, and Andreas Jansen. "Risk Factors Related to a Hospital-Associated Cluster of Clostridium difficile PCR Ribotype 027 Infections in Germany During 2007." Infection Control & Hospital Epidemiology 30, no. 3 (March 2009): 282–84. http://dx.doi.org/10.1086/594367.

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In 2007, Clostridium difficile polymerase chain reaction (PCR) ribotype 027 emerged in Germany. We conducted a hospital-based case-control study to identify specific risk factors for infection with this strain. Logistic regression analysis involving 15 case patients and 31 control patients revealed that exposure to fluoroquinolones (matched odds ratio, 36.2; P < .01) or cephalosporins (matched odds ratio, 19.1; P < .01) was independently related to C. difficile PCR ribotype 027 infection.

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48

Tickler, Isabella A., Richard V. Goering, Joseph D. Whitmore, Ashley N. W. Lynn, David H. Persing, and Fred C. Tenover. "Strain Types and Antimicrobial Resistance Patterns of Clostridium difficile Isolates from the United States, 2011 to 2013." Antimicrobial Agents and Chemotherapy 58, no. 7 (April 21, 2014): 4214–18. http://dx.doi.org/10.1128/aac.02775-13.

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ABSTRACTWe determined the PCR ribotypes and antimicrobial susceptibility patterns of 508 toxigenicClostridium difficileisolates collected between 2011 and 2013 from 32 U.S. hospitals. Of the 29 PCR ribotypes identified, the 027 strain type was the most common (28.1%), although the rates varied by geographic region. Ribotype 014/020 isolates appear to be emerging. Clindamycin and moxifloxacin resistances (36.8% and 35.8%, respectively) were the most frequent resistance phenotypes observed. Reduced susceptibility to vancomycin was observed in 39.1% of 027 isolates.

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Sinha, A., B. Hudson, J. M. Farrant, J. Linehan, and B. Colleypriest. "PTU-027 Prophylaxis of Post ERCP Pancreatitis in the UK. have the Esge Created Consensus?: Abstract PTU-027 Table." Gut 62, Suppl 1 (June 2013): A53.1—A53. http://dx.doi.org/10.1136/gutjnl-2013-304907.119.

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REIGADAS, E., L. ALCALÁ, M. MARÍN, A. MARTÍN, C. IGLESIAS, and E. BOUZA. "Role of binary toxin in the outcome ofClostridium difficileinfection in a non-027 ribotype setting." Epidemiology and Infection 144, no. 2 (June 29, 2015): 268–73. http://dx.doi.org/10.1017/s095026881500148x.

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SUMMARYBinary toxin (BT) has been associated with strains causing more severeClostridium difficileinfection (CDI), such as ribotype 027. Data on the outcome of patients having BT present in ribotypes other than 027 are scarce. Our objective was to investigate the association between BT isolates and outcome of CDI in a non-027 ribotype setting. We prospectively included CDI episodes (January–June 2013 and March–June 2014) from symptomatic patients aged >2 years. Epidemiological and clinical data were recorded. BT genes were detected using multiplex PCR. During the study period, we identified 326 episodes of CDI, of which 319 were available for molecular analysis. Of these, 54 (16·9%) were caused byC. difficilestrains with BT. Most (90·7%) isolates with BT were ribotype 078/126. CDI patients with BT-positive strains did not differ from those with BT-negative strains in terms of recurrence (13·0%vs. 15·5%,P= 0·835), treatment failure (0·0%vs. 2·3%,P= 0·594), overall mortality (11·1%vs. 9·1%,P= 0·612), or CDI-related mortality (0·0%vs. 1·9%,P= 0·612). Multivariate regression revealed no association between BT and poor outcome. In conclusion, in a non-027 setting, we found that most BT isolates were 078/126 and were not associated with poor outcome.

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Journal articles on the topic '629.3.023:027'

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