Bentall procedure: quarter century of clinical experiences of a single surgeon

BACKGROUND: We retrospectively analyzed 25 years of experiences with the button Bentall procedure in patients with aortic root pathologies. Even though this procedure has become widespread, there are only a few very long term follow-ups available in the clinical literature, especially regarding single surgeon results. METHODS: Between 1988 and 2013, a total of 147 patients underwent the Bentall procedure by the same surgeon. Among them there were 62 patients with Marfan syndrome. At the time of the surgery the mean age was 46.5 +/- 17.6 years. The impact of surgical experience on long-term survival was evaluated using a cumulative sum analysis chart. RESULTS: The Kaplan-Meier estimated overall survival rates for the 147 patients were 91.8 +/- 2.3 %, 84.3 +/- 3.1 %, 76.3 +/- 4.9 % and 59.5 +/- 10.7 % at 1,5,10 and 20 years, respectively. Multivariate Cox regression analysis identified EuroSCORE II over 3 % (OR 4.245, 95 % CI, 1.739-10.364, p = 0.002), acute indication (OR 2.942, 95 % CI, 1.158-7.480, p = 0.023), use of deep hypothermic circulatory arrest (OR 3.267, 95 % CI, 1.283-8.323, p = 0.013), chronic kidney disease (OR 6.865, 95 % CI, 1.339-35.189, p = 0.021) and early complication (OR 3.134, 95 % CI, 1.246-7.883, p = 0.015) as significant risk factors for the late overall death. The survival rate for freedom from early complication was 94.3 +/- 2.2 %, 88.0 +/- 3.3 %, 82.9 +/- 4.7 % and 69.2 +/- 8.4 % at 1,5,10 and 20 years. The main pathological findings of the aortic wall were cystic medial degeneration in 75 %, fibrosis in 6 %, atherosclerosis in 13 % and no pathological alteration in 6 % of the samples. The overall survival rate was significantly lower in patients operated in first 15 years compared to patients operated in the last decade (log-rank p = 0.011). CONCLUSION: According to our long-term follow-up the Bentall operation provides an appropriate functional result by resolving the lesions of the ascending aorta. Based on our results, 25-30 operations done is necessary to gain such a level of confidence and experince to aquire better results on long-term survival. In addition, we discussed that there were no co-morbidities affecting on the survival of Marfan patients and prophylactic aortic root replacement ensures a longer survival among patients with Marfan syndrome

Az enyhe kognitív deficitben szenvedők differenciálása az egészséges idős populációtól neuropszichológiai tesztek segítségével

OBJECTIVE: Paired Associates Learning (PAL) test assesses brain functions in those brain regions affected earliest by Alzheimer's dementia. The aim of the present study was to assess the usability of our implementation of the PAL test for screening mild cognitive impairment. METHODOLOGY: Based on Petersen criteria, 14 out of the 63 subjects were diagnosed with mild cognitive impairment. Visuospatial learning was assessed by our implementation of PAL test. The ability of the PAL test to differentiate between study groups was compared to the Addenbrook Cognitive Examination (ACE) and to the Mini Mental State Examination (MMSE). Linear logistic regression was used for statistical analysis, and the results are presented as Receiver Operating Characteristics (ROC) curves. All analyses were performed by SAS 9.2. RESULTS: All the results of neuropsychological tests differed significantly between the study groups. However, considerable difference could be detected between the tests regarding specificity and sensitivity. The PAL test reached the sensitivity of the ACE, while its specificity was slightly under the ACE. DISCUSSION: The PAL test developed in the framework of the present study is found to be able to differentiate between MCI and healthy controls. It outperformed the MMSE in terms of sensitivity and specificity, while it needs comparable time to perform. Its sensitivity, the important parameter for screening, is comparable to ACE, while it needs significantly shorter time and less assistance

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours