Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia

The relationship between chronic lymphocytic leukaemia (CLL) and qualitative/quantitative gammaglobulin abnormalities is well established. Nevertheless, in order to better understand this kind of connection, we examined 1505 patients with CLL and divided them into four subgroups on the basis of immunoglobulin (Ig) aberrations at diagnosis. A total of 73 (4·8%), 149 (10%), 200 (13·2%) and 1083 (72%) patients were identified with IgM monoclonal gammopathy (IgM/CLL), IgG monoclonal gammopathy (IgG/CLL), hypogammaglobulinaemia (hypo-γ) and normal Ig levels (γ-normal) respectively. IgM paraprotein was significantly associated with a more advanced Binet/Rai stage and del(17p)/TP53 mutation, while IgG abnormalities correlated with a higher occurrence of trisomy 12. Patients with any type of Ig abnormality had shorter treatment-free survival (TFS) but no significant impact affecting overall survival (OS) compared to those with normal Ig levels.     

“Baby Heart Project”: The Italian Project for Accreditation and Quality Management in Pediatric Cardiology and Cardiac Surgery

Optimization of the relationship between the supply and the demand for medical services should ideally be taken into consideration for the planning within each national Health System. Although government national health organizations embrace this policy specifically, the contribution of expert committees (under the scientific societies’ guarantee in any specific medical field) should be advocated for their capability to collect and analyze the data reported by the various national institutions. In addition, these committees have the competence to analyze the need for the resources necessary to the operation of these centers. The field of pediatric cardiology and cardiac surgery may represent a model of clinical governance of particular interest with regard to programming and to a definition of the quality standards that may be extended to highly specialized institutions and ideally to the entire Health System. The “Baby Heart Project,” which represents a model of governance and clinical quality in the field of pediatric cardiology and cardiac surgery, was born from the spontaneous aggregation of a committee of experts, supported by duly appointed Italian Scientific Societies and guided by a national agency for accreditation. The ultimate aim is to standardize both procedures and results for future planning within the national Health System.     

A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells

OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.     

Unshielded magnetocardiography: Repeatability and reproducibility of automatically estimated ventricular repolarization parameters in 204 healthy subjects

Background

Magnetocardiographic mapping (MCG) provides quantitative assessment of the magnetic field (MF) induced by cardiac ionic currents, is more sensitive to tangential currents, and measures vortex currents undetectable by ECG, with higher reported sensitivity of MCG ventricular repolarization (VR) parameters for earlier detection of acute myocardial ischemia. Aims of this study were to validate the feasibility of in‐hospital unshielded MCG and to assess repeatability and reproducibility of quantitative VR parameters, considering also possible gender‐ and age‐related variability.

Methods

MCG of 204 healthy subjects [114 males—mean age 43.4 ± 17.3 and 90 females—mean age 40.2 ± 15.7] was retrospectively analyzed, with a patented proprietary software automatically estimating twelve VR parameters derived from the analysis of the dynamics of the T‐wave MF extrema (five parameters) and from the inverse solution with the effective magnetic dipole model giving the effective magnetic vector components (seven parameters). MCG repeatability was calculated as coefficient of variation (CV) ±standard error of the mean (SEM). Reproducibility was assessed as intraclass correlation coefficient (ICC).

Results

The repeatability of all MCG parameters was 16 ± 1.2 (%) (average CV ± SEM). Optimal (ICC > 0.7) reproducibility was found for 11/12 parameters (mean values) and in 8/12 parameters (single values). No significant gender‐related difference was observed; six parameters showed a strong/moderate correlation with age.

Conclusion

Reliable MCG can be performed into an unshielded hospital ambulatory, with repeatability and reproducibility of quantitative assessment of VR adequate for clinical purposes. Wider clinical use is foreseen with the development of multichannel optical magnetometry.

     

Diagnostic yield of CT-guided lung biopsies: how can we limit negative sampling?

Objectives:To investigate whether lesion imaging features may condition the outcome of CT-guided lung biopsy (CTLB) and to develop a scoring system of biopsy outcome prediction.Methods:This is a single center retrospective study on 319 CTLBs that were performed in 319 patients (167 males/152 females, mean age 68 ± 12.2). Uni- and multivariate analysis were performed aiming to assess the imaging features that are likely to be correlated to a negative biopsy outcome and patients were stratified in groups accordingly.Results:Technical success was 100%. 78% of the biopsies (250/319) led to a concrete histology report (218 malignant/32 benign). The remaining lesions led to concrete histology at a second attempt that occurred on a later time. Multivariate analysis revealed increased risk of inconclusive result for nodules with low fludeoxyglucose uptake [odds ration (OR) = 2.64, 95% confidence interval (CI) 1.4–4.97; p = 0.003], for nodules with diameter smaller than 18 mm (OR = 2.03, 95% CI 1.14–3.62; p = 0.017) and for nodules that are located in one of the lung bases (OR = 1.96, 95% CI 1.06–3.62; p = 0.033). Three different groups of patients were identified accordingly with low (<30%), medium (30–50%) and high (>50%) probability of obtaining an inconclusive biopsy sample.Conclusion:This study confirms that percutaneous CT-guided biopsy in nodules that are either small in diameter or present low positron emission tomography-fludeoxyglucose uptake or are in one of the lung bases may lead to inconclusive histology. This information should be factored when planning percutaneous biopsies of such nodules in terms of patient informed consent and biopsy strategy.Advances in knowledge:Inconclusive histology after lung biopsy may be subject to factors irrelevant to technical success. Lung biopsy histology outcomes may be predicted and avoided after adequate planning.     

Activated innate immunity and the involvement of CX3CR1-fractalkine in promoting hematuria in patients with IgA nephropathy

A hallmark of immunoglobulin A nephropathy (IgAN) is episodes of gross hematuria coinciding with mucosal infections that can represent the disease-triggering event. Here we performed a whole genomic screen of IgAN patients during gross hematuria to clarify the link between mucosal antigens and glomerular hematuria. Modulated genes showed a clear involvement of the intracellular interferon signaling, antigen-presenting pathway, and the immunoproteasome. The mRNA and protein level of the chemokine receptor characterizing cytotoxic effector lymphocytes, CX3CR1, was upregulated. In vitro antigenic stimulation of peripheral blood mononuclear cells from IgAN patients, healthy blood donors, and other nephropathies with microscopic hematuria showed that only in IgAN patients was CX3CR1 enhanced in a dose-dependent manner. A significantly higher amount of glomerular and urinary fractalkine, the only ligand of CX3CR1, was also found in IgAN patients with recurrent episodes of gross hematuria compared with other patients with microscopic or no hematuria. This suggests a predisposition for cytotoxic cell extravasation only in patients with recurrent gross hematuria. Thus, we found a defect in antigen handling in peripheral blood mononuclear cells of IgAN patients with a specific increase of CX3CR1. This constitutive upregulation of glomerular and urinary fractalkine suggests an involvement of the CX3CR1-fractalkine axis in the exacerbation of gross hematuria.