Restrictions in the T-cell repertoire of chronic lymphocytic leukemia: high-throughput immunoprofiling supports selection by shared antigenic elements.

Immunoglobulin (IG) gene repertoire restrictions strongly support antigen selection in the pathogenesis of chronic lymphocytic leukemia (CLL). Given the emerging multifarious interactions between CLL and bystander T cells, we sought to determine whether antigen(s) are also selecting T cells in CLL. We performed a large-scale, next-generation sequencing (NGS) study of the T-cell repertoire, focusing on major stereotyped subsets representing CLL subgroups with undisputed antigenic drive, but also included patients carrying non-subset IG rearrangements to seek for T-cell immunogenetic signatures ubiquitous in CLL. Considering the inherent limitations of NGS, we deployed bioinformatics algorithms for qualitative curation of T-cell receptor rearrangements, and included multiple types of controls. Overall, we document the clonal architecture of the T-cell repertoire in CLL. These T-cell clones persist and further expand overtime, and can be shared by different patients, most especially patients belonging to the same stereotyped subset. Notably, these shared clonotypes appear to be disease-specific, as they are found in neither public databases nor healthy controls. Altogether, these findings indicate that antigen drive likely underlies T-cell expansions in CLL and may be acting in a CLL subset-specific context. Whether these are the same antigens interacting with the malignant clone or tumor-derived antigens remains to be elucidated.

Two dimensional wavelet energy analysis on a beat to beat basis: application to Atrial Fibrillation.

Atrial Fibrillation (AF) is a condition in which heart rhythm is not associated with normal sinoatrial (SA) node pacemaker but it derives from different areas on the atrium, often from the area of Pulmonary veins (PVs) A way to eliminate the influence of PVs in the inducement of AF is the PVs isolation surgery. In this study, an effort is made towards investigating the morphology and dynamics of P-waves, when the potentially arrhythmogenic tissue in PVs is involved or isolated via ablation. For this reason, 20 patients who were subjected to PVs isolation were studied, via vectrorcardiography recordings obtained before and after the ablation. Wavelet energies for five frequency bands were analyzed, using a two dimensional representation. The proposed technique was applied for the analysis of wavelet energies in consecutive beats, and their correlation with the RR interval. Features for the evaluation of those plots were extracted, such as the axes of a fitted to the plot ellipse and the center of the mass. The statistical analysis demonstrated significant differences between the groups, which imply the modification of the atrial substrate concerning electrical conduction toward to a more stable condition.

Interferon alpha-2a and combined chemotherapy as first line treatment in SCLC patients: a randomized trial.

BACKGROUND: Interferons (IFNs) are known to act synergistically with antineoplastic agents when applied to SCLC cell cultures. This study was conducted in order to detect the clinical benefits, if any, of the addition of IFN-alpha in the induction chemotherapy (CT) of SCLC patients. PATIENTS AND METHODS: Ninety previously untreated patients with SCLC were randomly assigned to receive either CT alone (arm A) or CT plus IFN alpha-2a in a dose of 3 MU/m2 twice weekly (arm B). CT for both arms consisted of carboplatin 420 mg/m2, etoposide 200 mg/m2 and ifosfamide 3.5 g/m2 or epirubicin 80 mg/m2 every 28 days for a total of eight cycles. Responding patients received primary site and prophylactic cranial irradiation and then had maintenance CT with cyclophosphamide 100 mg/m2/day for 20 days every month. Patients in arm B received IFN throughout these treatments. RESULTS: Eighty-one patients were evaluable for response, 39 in arm A and 42 in arm B. Both arms were comparable in terms of age, performance status and extent of disease. Overall response rates were not significantly different between the two arms (90% vs. 86%), although complete response rate was higher in arm B (38% vs. 28%). More importantly, Kaplan-Meier analysis disclosed a clear survival benefit in the arm receiving IFN-alpha (P < 0.05). For limited disease the difference was even more significant (P < 0.0067), while for extensive disease no significant difference was found (P < 0.35). Fever, fatigue and anorexia were more frequent in arm B (P < 0.001), as also leukopenia (P < 0.01). CONCLUSION: The addition of IFN-alpha to induction CT appears to confer a survival benefit to SCLC patients but optimal dosing schedule has yet to be defined.

Decision support for insulin regime prescription based on a neural-network approach.

Insulin regime prescription is performed by medical personnel based on a number of patient related factors such as age, activity, type of current medication, desirable control, whether the patient belongs to a special category, for example whether he has fever or has undergone surgery, etc. No general rules apply so that each expert adopts his/her own rules for insulin regime specification based on his/her experience, intuition and expertise. This is why there is very little in medical literature concerning this issue. This paper describes a system supporting the decision making of medical personnel with respect to the specification of insulin regimes, based on a neural network methodology. In particular, an adaptive version of the backpropagation algorithm is used for the system training. This algorithm dramatically reduces training time and guarantees the monotonically decreasing nature of the error function. The training set consisted of one hundred and eight training vectors. The system offers support with respect to diabetes management by insulin regime prescription. The choice of the factors participating in the decision making of the system described in this paper, is based on an extensive interviewing of a number of diabetologists in leading diabetological centres in Greece.