High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.     

Levosimendan vs. intra-aortic balloon pump in high-risk cardiac surgery

The purpose of our study was to compare the efficiency of levosimendan and preventive intra-aortic balloon pump in high-risk cardiac patients (left ventricular ejection fraction <35%) operated under cardiopulmonary bypass. In 20 patients, intra-aortic balloon pump was started 16-18 h before surgery; another 20 had a levosimendan infusion starting after induction of anesthesia with an initial bolus of 12 μg·kg(-1) for 10 min, followed by 0.1 μg·kg(-1)·min(-1) for 24 h. Postoperative complications, hemodynamics, and markers of cardiac damage were analyzed. In the levosimendan group, cardiac index was significantly higher 5 min after cardiopulmonary bypass, at the end of the operation, 2 and 4 h after perfusion, compared to the intra-aortic balloon pump group. The level of troponin I in the levosimendan group was significantly lower at 6 h after the operation. Intensive care unit stay was significantly shorter in the levosimendan group. It was concluded that the use of levosimendan in high-risk cardiac patients is as effective as intra-aortic balloon pump, in terms of maintaining stable hemodynamic during and after operations under cardiopulmonary bypass. The lower level of troponin I at 6 h postoperatively suggests cardioprotective properties of levosimendan, but requires further investigation.     

Neurodevelopmental outcome in high-risk preterm infants treated with inhaled nitric oxide

Inhaled nitric oxide (iNO) is used to treat preterm infants with hypoxaemic respiratory failure. In this study we describe the long-term survival and neurodevelopmental status of high-risk preterm infants enrolled into a randomized controlled trial of iNO therapy. Information regarding long-term outcome was available for all 25 children enrolled in the original trial who survived until discharge from hospital. Formal, blinded, developmental assessment and neurological examinations were performed in 21 out of 22 children still alive at 30 mo of age, corrected for prematurity. No significant differences were found in long-term mortality (12/20 vs 8/22, RR 1.65, 95% CI 0.87-3.3), neurodevelopmental delay (4/7 vs 9/14, RR 0.89, 95% CI 0.37-1.75), severe neurodisability (0/7 vs 5/14, p = 0.12) or cerebral palsy (0/7 vs 2/14, p = 0.53) between iNO-treated and control infants. CONCLUSION: In this study there was no evidence of a significant effect on either survival or long-term neurodevelopmental status in infants treated with iNO.