According to the multistep route of genetic alterations in the colorectal adenoma-carcinoma sequence, the complex K-ras/p53 mutation is one of the first alterations to occur and represent an important genetic event in colorectal cancer (CRC). An evaluation of the mutation spectra in K-ras and p53 gene was effected in 167 Tunisian patients with sporadic CRC to determine whether our populations have similar pattern of genetic alteration as in Maghrebin's population. Mutation patterns of codon 12-13 of K-ras and exon 5-8 of p53 were analyzed by immunohistochemistry and PCR-SSCP and confirmed by sequencing. Mutations in the K-ras gene were detected in 31.13 % and affect the women more than the men (p = 0.008). Immunostaining showed that expression of p21 ras was correlated with the advanced age (p = 0.004), whereas loss of signal was associated with mucinous histotype (p = 0.003). Kaplan-Meier survival curve found that patients with the K-ras mutation had a shorter survival compared with patients without mutation (p = 0.005). Alteration in p53 was seen in 17.4 % of patients and affects three hot spot codons such as 175, 245, and 248. Overexpression of p53 was seen in 34.1 % and correlated with tumor node metastasis (TNM) advanced stage (p = 0.037) and mucinous histotype (p = 0.001). A high concordance between p53 expression and alteration (p<0.005) was shown. Concomitant mutations in K-ras and p53 gene were detected in only 4 % of tumors. K-ras and p53 undergo separate pathways in colorectal tumorogenesis. Interestingly, mutations in the K-ras gene might be considered a valuable prognostic factor correlated to poor outcome. p53 gene alterations were rather low in our set, and methylation pattern of p53 is required to elucidate the molecular basis of this protein in CRC.

<b><i>Background:</i></b> Pulmonary artery (PA) pulsatility index (PAPi), calculated as (PA systolic pressure – PA diastolic pressure)/right atrial pressure, emerged as a novel predictor of right ventricular failure in patients with acute inferior myocardial infarction, advanced heart failure, and severe pulmonary hypertension. However, the prognostic utility of PAPi in transcatheter mitral valve repair (TMVR) using the MitraClip® system has never been tested. <b><i>Objective:</i></b> To assess the prognostic impact of PAPi in patients with severe functional mitral regurgitation (MR) and chronic heart failure (CHF) undergoing TMVR. <b><i>Methods:</i></b> Consecutive patients with severe functional MR (grade 3+ or 4+) and CHF who underwent successful TMVR (MR ≤2+ at discharge) were enrolled and divided into 3 groups according to PAPi (A: low PAPi ≤2.2; B: intermediate PAPi 2.21–3.99; C: high PAPi ≥4.0). The primary endpoint was a composite of all-cause mortality and rehospitalization due to CHF during a mean follow-up period of 16 ± 4 months. The impact of PAPi on prognosis was assessed by a receiver-operating characteristic (ROC) analysis and a multivariable Cox proportional hazard regression analysis investigating independent predictors for outcome. <b><i>Results:</i></b> 78 patients (A: <i>n</i> = 27, B: <i>n</i> = 28, C: <i>n</i> = 23) at high operative risk (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation] 18.8 vs. 21.5 vs. 20.6%; nonsignificant) were enrolled. Mean PAPi was 1.6 ± 0.41 vs. 2.9 ± 0.53 vs. 6.8 ± 3.5; <i>p</i> &#x3c; 0.001). Patients with low PAPi showed significantly higher rates of early rehospitalization for heart failure at the 30-day follow-up (14.9 vs. 7.1 vs. 4.3%; <i>p</i> = 0.04). In the long term, a significantly lower event-free survival for the combined primary endpoint was observed in the low PAPi group (44.4 vs. 25.0 vs. 20.3%; log-rank <i>p</i> = 0.016). ROC curve analysis revealed that optimal sensitivity and specificity were achieved using a PAPi cutoff of 2.46 (sensitivity 83%, specificity 78.3%, area under the curve 0.82 [0.64–0.99]; <i>p</i> = 0.01). In Cox regression analysis, PAPi ≤2.46 was an independent predictor for the combined primary endpoint (hazard ratio 2.85; 95% confidence interval 1.15–7.04; <i>p</i> = 0.023). <b><i>Conclusions:</i></b> PAPi is strongly associated with clinical outcome among patients with CHF and functional MR undergoing TMVR. A PAPi value ≤2.46 predicts a worse prognosis independent of other important clinical, echocardiographic, and hemodynamic factors. Therefore, PAPi may serve as a new parameter to improve patient selection for TMVR.

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Background and aim: In the last decades, mitral valve repair techniques evolved towards a respect rather than resect procedure. This is an overview of our single-center experience in mitral valve repair by comparing the conventional (Group 1) and the minimally invasive (Group 2) approach. Methods: Between January 2004 and March 2018, we analysed 609 patients who received isolated mitral valve repair.The sternotomy approach was used in 462 patients (75.9%), the mini-thoracotomy in 147 (24.1%).Specifically, there were 77 (12.6%) isolated annular implantations, 53.7% triangular/quandrangular resections, 32.7% implantations of Gore-Tex chords, 12.5% edge-to-edge techniques.The Gore-Tex chords implantation was more frequently used in patients of Group 2 than in Group 1 (48.3% versus 27.7%,p-value 0.001).In addition to our series, we performed 28 NeoChord procedures. Results: The trend of mitral valve repair in sternotomy approach or mini-thoracotomy is represented in Figure 1 along with the use of PTFE chords or French correction.Overall In-hospital mortality was 0.3% (2 patients), post-operative MACCE occurred in 1 patient. In 2 patients was necessary perioperative reoperation due to repair failure. Follow-up time was of 62.57 ± 36 months.Follow up death was 5.2%. Conclusions: The evolution of mitral valve repair techniques during the last years have increased simultaneously with the minimally invasive approach. Among the different techniques of repair,the chords implantation is becoming one of the most used and the era of French correction is slowly disappearing.The observed results of our series highlight this trend and come out in favour of the minimally invasive approach.