Retrospective Identification of a Broad IgG Repertoire Differentiating Patients With S. aureus Skin and Soft Tissue Infections From Controls

Background: Although the relevance of humoral immunity for protection against S. aureus skin and soft tissue infections (SSTIs) has been suggested by several animal and human studies, the question of which human antibodies may be protective has so far impeded the development of a safe and effective vaccine. Because most adults have developed certain anti-S. aureus antibodies due to S. aureus colonization or infection, we hypothesized that the titers of antibodies to S. aureus in uninfected controls would differ from those in infected patients and would also differ in infected patients from the time of acute infection to a 40-day convalescent serum.Methods: To test these hypotheses, we measured human antibody levels against a panel of 134 unique antigens comprising the S. aureus surfome and secretome in subjects with active culture-confirmed S. aureus SSTIs (cases) and in controls with no infection, using a novel S. aureus protein microarray.Results: Most S. aureus SSTI patients (n = 60) and controls (n = 142) had antibodies to many of the tested S. aureus antigens. Univariate analysis showed statistically weak differences in the IgG levels to some antigens in the SSTI patient (case) sera compared with controls. Antibody levels to most tested antigens did not increase comparing acute with 40-day serum. Multiple logistic regression identified a rich subset of antigens that, by their antibody levels, together correctly differentiated all cases from all controls.Conclusions: Antibodies directed against S. aureus antigens were present both in patients with S. aureus SSTIs and in uninfected control patients. We found that SSTI patients and controls could be distinguished only based on differences in antibody levels to many staphylococcal surface and secreted antigens. Our results demonstrate that in the studied population, the levels of anti-S. aureus antibodies appear largely fixed, suggesting that there may be some level of unresponsiveness to natural infection

Hybrid control plane architecture for dynamic impairment-aware routingin transparent optical networks

We propose a hybrid control plane architecture, in which both RSVP-TE and OSPF-TE are extended to carry PLIs information and disseminate wavelength availability information, respectively, for impairment-aware routing in transparent optical networks. The results suggest that, hybrid approach provides good trade-off between control overhead and network performance

Impairment aware GMPLS-based control plane architectures to realize dynamically reconfigurable transparent optical networks

Standard GMPLS protocols used for dynamic establishment of lightpaths in transparent optical networks suffer from lack of physical layer impairments (PLIs) information, which makes it difficult to evaluate optical feasibility. In this paper, we compare two impairment aware (IA)-GMPLS architectures: signalling based-in which RSVP-TE is extended to carry PLIs and hybrid architecture-in which RSVP-TE and OSPF-TE are extended to carry PLIs and wavelength availability information, respectively. We show that it is sufficient to extend OSPF-TE to disseminate wavelength availability information, while RSVP-TE carries PLIs to validate the optical feasibility and to achieve trade-off between performance and control overhead

Impairment and regenerator aware lightpath setup using distributed reachability graphs

GMPLS-based transparent optical networks suffer from accumulation of physical layer impairments (PLIs) along the optical path and inefficient wavelength utilization due to wavelength continuity constraint. To increase the optical reach, resource utilization, and average call acceptance ratio, network operators resort to translucent optical networks in which a limited number of regenerators are placed at a selected set of nodes. In this scenario development of an optical control plane which is aware of PLIs, location and number of regenerators, is of paramount importance for on-demand lightpath provisioning. In this paper, we propose a novel three phase approachreachability graph construction, route computation on reachability graph, and signalingimpairment and regenerator aware routing and wavelength assignment (IRA-RWA). We also propose corresponding GMPLS protocol extensions. The simulation results suggest that our proposed approach together with LSP stitching signaling mechanism can be deployed in realworld translucent optical networks

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic feature

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiological parameters

It is unclear whether karyotype aberrations occurring in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel, have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC, n=64) and in a validation cohort (VC, n=84) of CLL with "normal" FISH. An abnormal karyotype was found in 21.5% and 35,7% of cases in the LC and VC, respectively, and was associated with lower immunophenotypic score (p=0.030 in the LC, 0.035 in the VC), advanced stage (p=0.040 in the VC) and need of treatment (p=0.002 in the LC, <0.0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In CLL patients with "normal" FISH, karyotypic aberrations by conventional cytogenetics using novel mitogens identify a subset of cases with adverse prognostic features

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters.

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features

Chromosome Aberrations by Conventional Karyotyping in Chronic Lymphocytic Leukemia Carrying No Aberration by Fluorescence in Situ Hybridization: Correlation with Prognostic Parameters and Clinical Features

Background. Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. Adverse prognostic parameters include stage, CD38 and/or ZAP70 expression, the unmutated configuration of the variable region of the Ig heavy chain gene (IGHV) and the presence of specific chromosome aberrations. Using fluorescence in situ hybridization (FISH) with probes detecting trisomy 12 and deletions at 13q14, 11q22–23/ATM and 17p13/p53, approximately 60–80% of the cases carry an abnormality. Patients without FISH aberrations ("normal" FISH) have a relatively favourable outcome. Improved mitotic stimulation using oligonucleotide (odn) and interleukin-2 (IL-2) can detect karyotype aberrations in chromosome regions not covered by the classical 4-probe panel. This study was designed to assess whether the presence of karyotypic aberrations in CLL patients with "normal" FISH may have a correlation with established clinical and prognostic parameters. Methods. Eighty-four patients with "normal" FISH results referred to our laboratory between 2007 and June 2011 were included in the present report. These patients represent consecutive CLL cases diagnosed and treated, according to the NCI criteria, at 4 GIMEMA CLL group centres between 2006 and 2011. Indications for treatment included advanced stage (Binet C) or disease progression. The Matutes immunophenotypic score was calculated giving 1 point to CD5+, CD23+, CD22weak+, sIg weak+ and FMC7- and only patients with a score ≥3 (i.e. typical CLL) were included. The coexpression of the CD38 and CD19 antigens and ZAP-70 was tested on fresh PB cells with a 20% cut-off for positivity. IGVH genes were amplified from genomic DNA and sequenced according to standard methods and the cut-off of 98% homology to the germline sequence was chosen to discriminate between mutated (<98% homology) and unmutated (≥98% homology) cases, as reported previously. FISH studies were performed using probes for the following regions 13q14, 12q13; 11q22/ATM; 17p13/TP53. Conventional cytogenetic analysis using immunostimulatory CpG-oligonucleotide DSP30 plus IL2 (2μmol/L TibMolBiol / IL2 100U/mL Stem Cell Technologies Inc) was performed on the same samples that had been used for FISH studies. At least 20 metaphases were karyotyped. Stage, time to first treatment (TTFT) were obtained by review of clinical records at each centre. Results. An abnormal karyotype was found in 30/84 cases (35,7%) with "normal" FISH. The chromosome aberrations affected regions not covered by the 4-probe panel used by FISH. Recurring aberrations were: interstitial deletions of 14q and of 7q in 5 and 3 cases, respectively; 14q32 translocations in 2 cases, balanced and unbalanced structural changes in 1 case each. A complex karyotype with 3 or more aberrations was found in 12 patients. The correlations between karyotype and clinicobiological parameters are shown in tables 1 and 2. View this table: [in this window] [in a new window] Table 1: Correlation between karyotype and salient clinicobiologic parameters View this table: [in this window] [in a new window] Table 2: Factors affectingTTFT in univariate snalysis At multivariate analysis, the following factors were independently predictive of shorter TTFT: advanced disease Binet stage (p=0.049, Hazard Ratio 2.39 [se: 1.06]), and abnormal karyotype (p<0.001, Hazard ratio 6.8 [se: 3.28]). IGHV mutations were not included in the TTFT analysis, because the data were not available for all patients. Conclusions. Conventional karyotyping using odn + IL-2 as mitogens is an effective method for the detection of chromosome aberrations in approximately 1/3 of patients with "normal" FISH on a conventional 4-probe panel. Recurrent aberrations include interstitial deletions at 14q and 7q. The current data show that, in CLL patients with "normal" FISH, conventional cytogenetic analysis using odn + IL-2 identifies a subset of cases with adverse clinical and prognostic features

Chromosome abnormalities additional to the Philadelphia chromosome at the diagnosis of chronic myelogenous leukemia: pathogenetic and prognostic implications

Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). In some cases, on the basis of the persistence of the ACAs in Ph-negative cells after response to imatinib, a secondary origin of the Ph chromosome has been demonstrated. In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs as a primary event, but not in those in whom it occurs as a secondary one