Measurement of Natriuretic Peptides in Patients with Suspected Heart Failure to Prevent Overuse of Echocardiography - a Pilot Study.

BACKGROUND: European Society of Cardiology (ESC) guidelines recommend measuring natriuretic peptides (BNP or NT-proBNP) in patients with suspected heart failure (HF) as a first-line tool. HF should be ruled-out if concen-trations of NT-proBNP are below 300 ng/L and 125 ng/L for acute HF and chronic HF, respectively. METHODS: Patients with suspected HF referred for transthoracic echocardiography (TTE) were enrolled; NT-pro-BNP concentrations were obtained from medical charts (measurement < 48 hours) or prospectively measured on the day of TTE. RESULTS: Out of 109 patients, NT-proBNP was measured by the referring department before TTE in 40 patients (36.7%), and 37.5% of these patients had NT-proBNP concentration below the rule-out threshold. NT-proBNP was measured in additional 38 patients on the day of TTE. Overall, 38.5% of the patients had a NT-proBNP concentration below the threshold value. CONCLUSIONS: Natriuretic peptides are not routinely measured in patients with suspected HF; systematic measurement would reduce unnecessary TTE by at least 38.5%.

Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management.

Breast cancer (BC) is the first worldwide most frequent cancer in both sexes and the most commonly diagnosed in females. Although BC mortality has been thoroughly declining over the past decades, there are still considerable differences between women diagnosed with early BC and when metastatic BC is diagnosed. BC treatment choice is widely dependent on precise histological and molecular characterization. However, recurrence or distant metastasis still occurs even with the most recent efficient therapies. Thus, a better understanding of the different factors underlying tumor escape is mainly mandatory. Among the leading candidates is the continuous interplay between tumor cells and their microenvironment, where extracellular vesicles play a significant role. Among extracellular vesicles, smaller ones, also called exosomes, can carry biomolecules, such as lipids, proteins, and nucleic acids, and generate signal transmission through an intercellular transfer of their content. This mechanism allows tumor cells to recruit and modify the adjacent and systemic microenvironment to support further invasion and dissemination. By reciprocity, stromal cells can also use exosomes to profoundly modify tumor cell behavior. This review intends to cover the most recent literature on the role of extracellular vesicle production in normal and cancerous breast tissues. Specific attention is paid to the use of extracellular vesicles for early BC diagnosis, follow-up, and prognosis because exosomes are actually under the spotlight of researchers as a high-potential source of liquid biopsies. Extracellular vesicles in BC treatment as new targets for therapy or efficient nanovectors to drive drug delivery are also summarized.

[Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)]. / Caractéristiques immuno-analytiques du PSA et des biomarqueurs dérivés (PSA total, PSA libre et P2ProPSA).

Prostate-specific antigen (PSA) is the recommended tumor marker for individual screening and follow-up of prostate cancer. This paper reviews main structural and physiological data about prostate specific antigen isoforms: total PSA, free PSA, [-2]proPSA (also named p2PSA). It describes the pre-, per- and post-analytical conditions for these different parameters. It presents the interpretation of results and derived calculated indices (free/total PSA ratio, Prostate Health Index or PHI) for the management of prostate cancer (initial diagnosis and follow-up).

Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease.

The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta (Abeta) oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure long-term administration of CNTF in the brain, we used recombinant cells secreting CNTF encapsulated in alginate polymers. The implantation of these bioreactors in the brain of Abeta oligomer-infused mice led to a continuous secretion of recombinant CNTF and was associated with the robust improvement of cognitive performances. Most importantly, CNTF led to full recovery of cognitive functions associated with the stabilization of synaptic protein levels in the Tg2576 AD mouse model. In vitro as well as in vivo, CNTF activated a Janus kinase/signal transducer and activator of transcription-mediated survival pathway that prevented synaptic and neuronal degeneration. These preclinical studies suggest that CNTF and/or CNTF receptor-associated pathways may have AD-modifying activity through protection against progressive Abeta-related memory deficits. Our data also encourage additional exploration of ex vivo gene transfer for the prevention and/or treatment of AD.

Should kidney tubular markers be adjusted for urine creatinine? The example of urinary cystatin C.

BACKGROUND: Evaluation of specific urinary markers with respect to urine creatinine (uCreat) is common. However, as uCreat is a function of both glomerular filtration and tubular secretion, using uCreat for specific tubular markers, suggests that glomerular function is normal, and there is no tubular secretion. Thus, adjusting values of any tubular marker to uCreat, especially in patients with acute or even moderate chronic renal failure, can be misleading. METHODS: Using urine cystatin-C (uCST3) as a model tubular marker for following 120 kidney graft recipients daily, we evaluated the utility of either uCST3 alone or the uCST3/uCreat ratio to detect tubular damage. All positive kidney biopsies were always associated with a uCST3>0.18 mg/L. RESULTS: Using the uCST3/uCreat ratio, discrepancies regarding biopsy status were observed in nine patients (4 false positive, 5 false negative results). In two patients, variability of uCreat appeared to be the most important factor causing inconsistent uCST3/uCreat ratios. With a negative predictive value (NPV) of 85.7%, uCST3/uCreat can lead to errors in clinical interpretation. These errors can be avoided when estimates of tubular damage are based on uCST3 concentrations alone (NPV=100%). CONCLUSIONS: We recommend using the uCST3 value to evaluate the extent of renal tubular damage. Indeed, our conflicting results on uCST3/uCreat can be extended to every marker of tubular function. Evaluating a urine marker specific for renal tubular damage to a second urine marker that is itself strongly dependent upon glomerular or other renal or non-renal conditions, impairs its clinical relevance and may lead to incorrect interpretations. Correction with uCreat can be performed only in pure glomerulopathy, when specific markers of glomerular function are measured (i.e., urinary albumin). In all other cases of renal diseases, such correction is inappropriate and should be avoided. Clin Chem Lab Med 2009;47:1553-6.

[A primitive plasma cell leukemia with immunoglobulin (Ig) E]. / À propos d'un cas de leucémie plasmocytaire primitive à IgE.

We report here a case of primitive plasma cell leukemia with immunoglobulin (Ig) E. IgE myeloma is an exceptional variant of multiple myeloma, with a very poor prognosis. Its biological diagnosis requires specific analyzes in order to detect IgE gammopathy. Plasma cell leukemia (PCL) is also a very rare and very severe form of multiple myeloma. There are two variants: primitive PCL (pPCL) occurring de novo and secondary PCL (sPCL), evolution of a preexisting myeloma. Its diagnosis is essentially biological since it is defined by a blood plasmocytosis greater than 2 G/L or 20% of the leucocytes.

[Immunoanalytical characteristics of HE4 protein]. / Caractéristiques immunoanalytiques de la protéine HE4.

Besides structural and physiological data of HE4 protein, this paper points out the optimal conditions for sampling, assays and interpretation of results for the management of ovarian cancer.

Immunoanalytical characteristics of fecal calprotectin.

Besides structural and physiological data of calprotectin, this paper points out the optimal conditions for sampling, fecal assays and interpretation of results.

Type III cryoglobulinemia complicated by renal cortical necrosis.

Renal involvement is rare in patients with type III cryoglobulinemia. We report a case of renal cortical necrosis in a patient with type III cryoglobulinemia. Renal function improved partially after treatment with plasma exchange, steroids, and cyclophosphamide. Renal magnetic resonance imaging was a valuable tool in the evaluation of the extent of renal cortical necrosis and improvement in renal vascularization after treatment.

[Immunoanalytical characteristics of galectin-3]. / Caractéristiques immunoanalytiques de la galectine-3.

This paper points out the structural and physiological data of galectin-3, and emphasizes its role in cardiac fibrosis and heart failure pathophysiology. Then we summarize the optimal conditions for sampling, assays and we discuss the interpretation of results.

Critical role of cPLA2 in Aß oligomer-induced neurodegeneration and memory deficit.

Soluble beta-amyloid (Aß) oligomers are considered to putatively play a critical role in the early synapse loss and cognitive impairment observed in Alzheimer's disease. We previously demonstrated that Aß oligomers activate cytosolic phospholipase A(2) (cPLA(2)), which specifically releases arachidonic acid from membrane phospholipids. We here observed that cPLA(2) gene inactivation prevented the alterations of cognitive abilities and the reduction of hippocampal synaptic markers levels noticed upon a single intracerebroventricular injection of Aß oligomers in wild type mice. We further demonstrated that the Aß oligomer-induced sphingomyelinase activation was suppressed and that phosphorylation of Akt/protein kinase B (PKB) was preserved in neuronal cells isolated from cPLA(2)(-/-) mice. Interestingly, expression of the Aß precursor protein (APP) was reduced in hippocampus homogenates and neuronal cells from cPLA(2)(-/-) mice, but the relationship with the resistance of these mice to the Aß oligomer toxicity requires further investigation. These results therefore show that cPLA(2) plays a key role in the Aß oligomer-associated neurodegeneration, and as such represents a potential therapeutic target for the treatment of Alzheimer's disease.

The essential role of lipids in Alzheimer's disease.

In the absence of efficient diagnostic and therapeutic tools, Alzheimer's disease (AD) is a major public health concern due to longer life expectancy in the Western countries. Although the precise cause of AD is still unknown, soluble beta-amyloid (Abeta) oligomers are considered the proximate effectors of the synaptic injury and neuronal death occurring in the early stages of AD. Abeta oligomers may directly interact with the synaptic membrane, leading to impairment of synaptic functions and subsequent signalling pathways triggering neurodegeneration. Therefore, membrane structure and lipid status should be considered determinant factors in Abeta-oligomer-induced synaptic and cell injuries, and therefore AD progression. Numerous epidemiological studies have highlighted close relationships between AD incidence and dietary patterns. Among the nutritional factors involved, lipids significantly influence AD pathogenesis. It is likely that maintenance of adequate membrane lipid content could prevent the production of Abeta peptide as well as its deleterious effects upon its interaction with synaptic membrane, thereby protecting neurons from Abeta-induced neurodegeneration. As major constituents of neuronal lipids, n-3 polyunsaturated fatty acids are of particular interest in the prevention of AD valuable diet ingredients whose neuroprotective properties could be essential for designing preventive nutrition-based strategies. In this review, we discuss the functional relevance of neuronal membrane features with respect to susceptibility to Abeta oligomers and AD pathogenesis, as well as the prospective capacities of lipids to prevent or to delay the disease.