Presence Of Iss Research Articles

The Impact of Socioeconomic Risk Factors on the Survival Outcomes of Patients with Newly Diagnosed Multiple Myeloma

Introduction: Several patient and disease biology characteristics that impact overall survival (OS) outcomes of patients with newly diagnosed multiple myeloma (NDMM) have been well described. However, several prior population-based registry studies in the US such as SEER and NCDB databases have demonstrated the negative prognostic impact of socio-economic (SE) factors such as low median household income based on US national census bureau data for zip code of residence as well as absence of marital support on the OS of NDMM patients. Whether such SE factors are independent of established host and disease biology related factors remains unknown due to the absence of detailed patient-level data in population-based cancer registries. Thus, we evaluated whether such SE factors independently affected the OS of NDMM patients in our institution when accounting for patient and disease biology related factors. Methods: We analyzed a retrospective cohort of consecutive NDMM patients seen at the Mayo Clinic from January 2005 to December 2015. Median household income for each patient's area of residence was estimated by matching their home zip code at diagnosis with data available through the US National Census Bureau. Median household income < $63,000 for a zip code were used to classify patients as having low income based on the National Cancer Database classification of the bottom three quartiles. Absence of marital support was considered in patients divorced, single or widowed at the time of diagnosis. Survival estimates were calculated using the Kaplan-Meier method. Patient and disease biology related factors taken into consideration included age, FISH cytogenetics, ISS stage and LDH levels. Survival estimates were compared between groups using the log-rank test. Multivariable adjusted proportional hazards regression models were fit for the association between known prognostic factors and OS. Results: A total of 2,621 MM patients were analyzed from the Mayo Clinic cohort of which 60% were male and the median age was 64 (22 - 96) years with 14% being 75 years of age or older. In this cohort, 541 (33%) patients had ISS 3 disease and 370 (22%) had high risk cytogenetics by FISH. The median OS based on estimated average household income was 65 months for the group of patients with low household income (N = 32%) and 80 months for the remainder (P = 0.001) (Fig 1A). The median OS based on marital support was 59 months for those without marital support at diagnosis (N = 21%) versus 76 months for remainder (P = 0.003) (Fig 1B). However, in a multivariable analysis that included the aforementioned SE factors and patient and disease biology characteristics , only age of 75 years or older (p < 0.001), the presence of high-risk FISH cytogenetics (p < 0.001), presence of ISS 3 disease (p < 0.001) and elevated LDH (p = 0.005) retained independent statistical significance in predicting for worse OS. Lower household income (p = 0.264) and absence of marital support (p = 0.054) were not independent predictors of worse OS. Conclusions: With the caveat of patient selection bias in a tertiary academic center, SE factors such as estimated average household income and marital support at diagnosis do not appear to impact OS of NDMM patients when considered in the context of traditional host and disease biology risk factors. These findings are in contrast to those suggested by population based registry studies; nevertheless, similar patient-level assessments should be considered in patient cohorts from non-tertiary medical centers as these results may likely be different. Disclosures Dispenzieri: Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Lacy:Celgene: Research Funding. Kapoor:Amgen: Research Funding; Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding. Russell:Imanis: Equity Ownership. Gertz:Medscape: Consultancy, Speakers Bureau; Research to Practice: Consultancy; Springer Publishing: Patents & Royalties; Ionis/Akcea: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Whole-genome analysis of extraintestinal Escherichia coli sequence type 73 from a single hospital over a 2 year period identified different circulating clonal groups.

Sequence type (ST)73 has emerged as one of the most frequently isolated extraintestinal pathogenic Escherichia coli. To examine the localized diversity of ST73 clonal groups, including their mobile genetic element profile, we sequenced the genomes of 16 multiple-drug resistant ST73 isolates from patients with urinary tract infection from a single hospital in Sydney, Australia, between 2009 and 2011. Genome sequences were used to generate a SNP-based phylogenetic tree to determine the relationship of these isolates in a global context with ST73 sequences (n=210) from public databases. There was no evidence of a dominant outbreak strain of ST73 in patients from this hospital, rather we identified at least eight separate groups, several of which reoccurred, over a 2 year period. The inferred phylogeny of all ST73 strains (n=226) including the ST73 clone D i2 reference genome shows high bootstrap support and clusters into four major groups that correlate with serotype. The Sydney ST73 strains carry a wide variety of virulence-associated genes, but the presence of iss, pic and several iron-acquisition operons was notable.

Virulence Genes and Antibiotic Resistance Of Escherichia coli Isolates From Dead-In Shell Chicken Embryos

A study on isolated Escherichia coli from dead in shell chicken embryos was aimed to detect the incidence of three virulence genes and the antibiotic resistance pattern of isolated samples. Eighty dead in shell chicken embryos were obtained from three different Balady hatcheries in Kafr El Sheikh Governorate, Egypt were subjected to microbiological analysis for detection of Escherichia coli infection. The percentage of positive samples were 7.5%. According to sensitivity test Gentamycin was the most proper antibiotics with the highest efficiency against the isolated Escherichia coli in vitro. The isolates of Escherichia coli obtained by detective enriched and plating were screaned for PCR using pho-A gene as a general marker for Escherichia coli and the presence of 3 virulence-associated genes, including iss , tsh and eae A by direct PCR on the enrichment broth lysate, results revealed that all isolates had the pho A, tsh and iss virulence genes , meanwhile, eae A virulence gene was not detected in any isolate . It is concluded that the presence of iss and tsh genes increase the virulence of E. coli and the usage of antibacterial agent must be used under control and according to sensitivity test.

A study on the presence of some potential virulence genes and quinolone resistance in avian pathogenic Escherichia coli isolated from chickens in Northeast of Iran

Background: Avian pathogenic Escherichia coli (APEC), which is the causative agent of colibacillosis, harbors several putative virulence genes. An important trait of APEC for both poultry and public health is antibiotic resistance. Objectives: In the present study, some potential virulence genes of APECs isolated from Northeast of Iran and their resistance to the quinolones antibiotics were studied. Methods: The conventional polymerase chain reaction (PCR) was used to determine the presence of four virulence genes, including iss, cvi, iuc, and tsh, in 52 isolates of E. coli from avian colibacillosis and 11 isolates from feces of apparently healthy chicken. Disk diffusion method was used to also determine the resistance of all the isolates against nalidixic acid, norofloxacin, ciprofloxacin, and enrofloxacin. Results: The presence of iss and tsh virulence genes in isolates from diseased chickens was significantly higher than isolates from healthy chickens. There was no significant difference between APEC and fecal E. coli when it comes to quinolone resistance. However, cvi and iuc genes were significantly higher in susceptible isolates of E. coli from healthy chickens. Conclusions: iss and tsh genes are more prevalent in APEC isolates than in fecal isolates. There is no association between lack of virulence and resistance to quinolones in E. coli isolates from diseased chickens.

Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

BACKGROUNDHigh dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old).Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT.AIMSThe goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM).METHODSWe reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression.RESULTS106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%).Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03).Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007).CONCLUSIONSThe lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. DisclosuresOcio:Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Role of Previous Thalidomide Administration on Final Outcome for 72 Patients with Relapsed Multiple Myeloma (MM) Treated with Bortezomib–Based Therapy

New drugs such as thalidomide, bortezomib and lenalidomide have expanded the therapeutic options for MM while improving outcome in both young and elderly patients. However, the best novel agents sequence in the therapeutic strategy for MM is still not definitely delineated as relapsed MM right after first line thalidomide therapy seems to be more resistant jeopardizing final outcome as per overall survival while still making questionable when to administer it, either at the beginning or later during the course of the disease. We analyzed 72 relapsed MM patients who were enrolled in two salvage study protocols which included bortezomib, dexamethasone and chemotherapy (Offidani et al, ASH 2007 and EHA 2008) and who had been treated with thalidomide first (18 patients) or subsequently (30 patients) or not treated at all with thalidomide (24 patients). We compared these three groups of patients in terms of response rate, post-relapse PFS and post-relapse OS with the aim to assess the role of previous administration of thalidomide on final outcome in this patient population. Median age for the 72 patients was 65 years (range 31–82); ISS stage 2–3 assessed in 51% of patients and unfavourable cytogenetics in 42%. Thirty four patients had been rescued in first relapse, 19 in second and 19 in third or subsequent relapse. Median disease history was 34 months (range 8–173). Forty four patients relapsed after high-dose therapy and autologous stem cell transplantation. The 48 patients were previously treated with thalidomide a median time of 8 months (range 4–48 months). VGPR or better response rate in the groups of patients treated with thalidomide in first line, second or subsequent line or never treated with thalidomide were 44%, 42% (p=0.795) and 79% (p=0.003; p=0.002), respectively.. Multivariate stepwise regression analysis selected only previous thalidomide treatment (OR=1.9; 95%CI=1.5–2.4; p=0.024) as factors affecting response whereas age, previous therapy lines, previous remission duration, previous transplant, previous disease history, sCRP, ISS stage and cytogenetics were not significantly associated to response. In the same groups post-relapse PFS was 9 months, 14 months (p=0.308) and not reached (p=0.018; p=0.055) while post-relapse 2 years OS was 51%, 50% (p=0.564) and 72% (p=0.074; p=0.135). Cox regression analysis showed that the presence of ISS 2–3 (p=0.010), previous thalidomide administration (p=0.052), and response < VGPR (p<0.0001) translated in significantly poorer post-relapse PFS and OS. Stepwise Cox regression analysis selected only response < VGPR as factor significantly associated to poor post-relapse OS (2yrs OS 26% vs 83%; p<0.0001; HR=7.0 95CI=2.6–18.9). In the group of 48 patients previously treated with thalidomide, time on thalidomide (cut-offs 4, 8, 12, 24 months) did not affect post-relapse PFS and OS. These data suggest that, even in relapse, response to salvage therapy is the most powerful predictor of PFS and OS. Unfortunately, previous thalidomide administration, particularly as front-line therapy, apart from time on treatment, significantly decreases VGPR and consequently post-relapse PFS. This lead to a final outcome in terms of OS not different, if worse, in those patients previously treated vs those never treated with thalidomide. These and other data (Barlogie et al NEJM 2006, Palumbo et al, JCO 2008), strongly questioned the use of front-line thalidomide as the best therapeutic strategy for patients with MM since alternatives are now possible.