Clinical outcomes and predictors of success with Impella weaning in cardiogenic shock: a single-center experience.

Introduction: Cardiogenic shock (CS) is a severe syndrome with poor prognosis. Short-term mechanical circulatory support with Impella devices has emerged as an increasingly therapeutic option, unloading the failing left ventricle (LV) and improving hemodynamic status of affected patients. Impella devices should be used for the shortest time necessary to allow LV recovery because of time-dependent device-related adverse events. The weaning from Impella, however, is mostly performed in the absence of established guidelines, mainly based on the experience of the individual centres. Methods: The aim of this single center study was to retrospectively evaluate whether a multiparametrical assessment before and during Impella weaning could predict successful weaning. The primary study outcome was death occurring during Impella weaning and secondary endpoints included assessment of in-hospital outcomes. Results: Of a total of 45 patients (median age, 60 [51-66] years, 73% male) treated with an Impella device, 37 patients underwent impella weaning/removal and 9 patients (20%) died after the weaning. Non-survivors patients after impella weaning more commonly had a previous history of known heart failure (p = 0.054) and an implanted ICD-CRT (p = 0.01), and were more frequently treated with continuous renal replacement therapy (p = 0.02). In univariable logistic regression analysis, lactates variation (%) during the first 12-24 h of weaning, lactate value after 24 h of weaning, left ventricular ejection fraction (LVEF) at the beginning of weaning, and inotropic score after 24 h from weaning beginning were associated with death. Stepwise multivariable logistic regression identified LVEF at the beginning of weaning and lactates variation (%) in the first 12-24 h from weaning beginning as the most accurate predictors of death after weaning. The ROC analysis indicated 80% accuracy (95% confidence interval = 64%-96%) using the two variables in combination to predict death after weaning from Impella. Conclusions: This single-center experience on Impella weaning in CS showed that two easily accessible parameters as LVEF at the beginning of weaning and lactates variation (%) in the first 12-24 h from weaning begin were the most accurate predictors of death after weaning.

Expression of potassium channel isoforms mRNA in normal human adrenals and aldosterone-secreting adenomas.

Increased aldosterone secretion has been found in a mouse lacking the KCNE1 gene which codes for a regulatory protein of the KCNQ1 gene product, forming the channel for the outward rectifying delayed K+ current. Abnormalities in proteins regulating the K+ fluxes across membranes may be responsible for aldosterone-secreting adenomas (aldosteronomas) also because K+ channels are involved in cell growth. Normal and adenomatous adrenal samples and NCI-H295 cell line were used to: a) evaluate KCNE1 and KCNQ1 gene expression, b) sequence the full length cDNAs of KCNE1 and both KCNQ1 isoforms. These differently spliced KCNE1 and KCNQ1 mRNAs were expressed in adrenal tissue. In contrast, KCNQ1 isoform 2 mRNA was not expressed in kidney control tissues and NCl-H295 cell line. NCI-H295 cell line also had a significantly lower expression of KCNQ1 isoform 1 mRNA than normal adrenals and aldosteronomas. We did not find any somatic mutations in the coding sequences of both genes. This different expression pattern of KCNQ1 isoforms in NCI-H295 cell line with the lack of the mRNA for the dominant-negative KCNQ1 isoform 2 supports the involvement of voltage-gated K+ channel in cell proliferation.

Absence of somatic mutations in natriuretic peptide receptor type A gene in human aldosterone-secreting adenomas.

Somatic mutations of genes codifying for key regulatory proteins are the cause of different types of hormone-secreting adenomas. Natriuretic peptides (NP) are the strongest inhibitors of aldosterone secretion but aldosterone-secreting adenomas (aldosteronomas) are resistant to this inhibition and have reduced binding sites for NPs. The objective of this study was to sequence the entire coding region of the NP receptor type A (NPRA, codified by the Npr1 gene) to find loss-of-function somatic mutations. Total RNA was extracted from eight aldosteronomas and cDNA was synthesized. NPRA mRNA expression was evaluated by Northern blot analysis and compared with beta-actin mRNA as the housekeeping gene. Twelve primer couples were designed on the basis of the Npr1 gene organization to amplify, by PCR, all 22 coding exons of the gene. The two strands of amplified DNAs were purified and directly sequenced by automated capillary sequencer. NPRA mRNA expression did not differ among aldosteronomas. Npr1 open reading frame sequences obtained from eight aldosteronomas did not contain any mutation. The coding sequences of all 22 exons were identical in all samples and identical to published sequences. In the 3'-untranslated region (3'-UTR) a new length difference 3C/4C polymorphism was found at position 15 129 (three adenomas were 3C/4C and two were 3C/3C). Such a 3C/4C polymorphism was present in genomic DNA from 80 control subjects (25, 4C/4C; 40, 3C/4C; 15, 3C/3C). Mutations in the coding exons of the Npr1 gene do not appear to be a common cause of aldosteronomas. Moreover, the exons of Npr1 encoding for the translated portion of mRNA do not appear to be prone to polymorphisms. The polymorphism identified in the 3'-UTR might affect mRNA stability resulting in lower receptor synthesis, but it is not likely to confer a predisposition to the development of aldosteronomas.

[Historicity and the epistemological condition of psychoanalysis: filiation and orthopraxis]. / Historicité et situation épistémologique de la psychanalyse: filiation et ortho-praxis.

The very particular epistemological condition of psychoanalysis (that of a "psychology" closely tied to "metapsychology") is well evidenced in the genesis and historical development of this "new science"; so intrinsically tied to Freud's personality that it requires a personal and guaranteed transmission: a "filiation". Indeed, from this epistemological situation, as well as from the clinical character of psychoanalytical interpretation, was been the deontological necessity for a societal institution that attests to the orthodoxy of psychoanalytical praxis: an "ortho-praxis". This yields a body of problems specific to the scientific historiography of psychoanalysis, to the extent that the diversity of heuristic conditions of historians, whether psychoanalysts or non-psychoanalysts, although effective, does not always ensure a privilege or natural advantage. The epistemological analysis of such a body of problems--starting from the notions of "chronicle" and "history" in general--lead, nonetheless, to the exclusion of relativism and historiographic solipsism.