Performance of the Labcor Dokimos Plus pericardial aortic prosthesis: a single-centre experience.

Objectives: In patients with a small aortic annulus, aortic valve replacement (AVR) is frequently associated with high residual pressure gradients. Supra-annular pericardial aortic prostheses are gaining popularity due to the increased effective orifice areas (EOA) and resulting lower gradients. This study reports the clinical and echocardiographic results following implantation of the new supra-annular pericardial aortic prosthesis Dokimos Plus (Labcor, Belo Horizonte, Brazil). Methods: Between October 2013 and July 2015, 137 patients (41% women, mean age: 74 years) underwent supra-annular AVR with or without concomitant procedures using the Dokimos Plus prosthesis in our department. Transthoracic echocardiography was performed pre- and postoperatively on all patients to assess haemodynamic parameters (gradients, acceleration time [AT], Doppler velocity indices [DVIs] and indexed EOA [EOAI]) and to detect paravalvular leakage (PVL). Data were collected retrospectively from our hospital databases. Methods: Patients were grouped by prosthesis size: Most patients received 23-mm (57.6%), followed by 21-mm (19%), 25-mm (15.4%) and 27-mm (8%) prostheses. The mean EOAI in all groups was 1.1 ± 0.26 cm 2 /m 2 . Pressure gradients were low in all groups (mean: 8.9 ± 4.4 mmHg; peak: 18.8 ± 6.8 mmHg); AT and DVI were in the normal range according to American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (mean AT 73.3 ± 29 ms; mean DVI 0.5 ± 0.2). One patient had severe PVL and one presented with central regurgitation, both requiring re-intervention. The mortality rate was 5.1% ( n = 7); none of the cases was associated with valve insufficiency. Conclusions: The Dokimos prosthesis showed a satisfactory overall performance, presenting low gradients and DVIs as well as high EOAI. Further investigations are needed to analyse the cases of regurgitation and monitor long-term performance.

Methylation-associated dysregulation of the suppressor of cytokine signaling-3 gene in multiple myeloma.

The family of suppressor of cytokine signaling (SOCS) proteins negatively regulates cytokine signaling in different cellular pathways including interleukin-6 (IL-6). Since IL-6 plays an essential role in regulating growth and survival of multiple myeloma (MM) cells, methylation-associated dysregulation of SOCS3 may contribute to the malignant phenotype of MM cells. We used methylation-specific PCR (MSP) to assess the methylation status of the SOCS3 CpG island in five MM cell lines and 70 patient samples. Additional bisulfite sequencing and RNA expression analysis using reverse transcriptase polymerase chain reaction was performed in two cell lines. We identified aberrant SOCS3 methylation in 3/5 MM cell lines. Methylation of SOCS3 in cell lines was associated with transcriptional downregulation. Treatment of OPM-2 cells, which carry a methylated SOCS3 gene, with the demethylating agent 5-aza-2'-deoxycytidine restored SOCS3 expression in association with partial demethylation. In patient samples with malignant plasma cell disorders, SOCS3 was methylated in 5/70 (7.1 %) cases, while there was no aberrant SOCS3 methylation in normal peripheral blood and non-malignant bone marrow cells. We found an association of SOCS3 methylation with extramedullary manifestations (p = 0.03), plasma cell leukemia (p = 0.003), elevated LDH (p = 0.001), increased creatinine ( p = 0.01) and remarkably shortened survival (6.9 vs. 56.1 months, HR 5.9, p = 0.0007). Our findings reveal a novel epigenetic event possibly implicated in the pathogenesis of MM and representing a potential prognostic biomarker. Epigenetic dysregulation of the SOCS3 gene may interfere with the cellular response to the complex cytokine network thus supporting survival and expansion of MM cells.