A stable aneurysm sac after endovascular aneurysm repair as a predictor for mortality: An in-depth analysis.

OBJECTIVE: The aim of the present study was to compare the long-term survival of patients with a stable aneurysm sac vs those with aneurysm sac regression after endovascular aneurysm repair (EVAR) and to identify the independent risk factors for aneurysm sac regression and mortality after EVAR. METHODS: We reviewed all the patients who had undergone EVAR from 2005 to 2018 with computed tomography angiography available at 1 year of follow-up. Aneurysm sac regression was defined as a diameter decrease of >10%. We used multivariable regression to identify the independent risk factors for sac regression. Kaplan-Meier analysis and Cox regression were performed to test the differences in 5-year mortality between a stable sac diameter and sac regression. RESULTS: The inclusion criteria were met by 325 patients, with 185 in the sac regression group and 140 in the stable sac group. Multivariable logistic regression analysis showed that treatment of a ruptured aneurysm was an independent risk factor for aneurysm sac regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.96). Age (HR, 1.05; 95% CI, 1.01-1.09), ischemic heart disease (HR, 1.94; 95% CI, 1.13-3.31), neck thrombus (HR, 2.72; 95% CI, 1.07-6.95), and a type II endoleak (HR, 19.21; 95% CI, 7.32-50.40) were independent risk factors for a stable aneurysm sac diameter. Multivariable Cox regression showed a significantly increased risk of mortality for patients with a stable aneurysm sac after EVAR (odds ratio, 2.25; 95% CI, 1.36-3.72). No significant differences were found in cause of death between the two groups. CONCLUSIONS: A stable aneurysm sac after EVAR was associated with increased mortality. Age, ischemic heart disease, neck thrombus, and a type II endoleak were independent risk factors for a stable aneurysm sac. However, a well-founded explanation for this finding is still lacking. Future research should focus on aggressive treatment of type II endoleaks and inflammatory processes as potential pathophysiologic mechanisms.

[A pulsatile mass on the forehead after a fall]. / Een bult op de slaap na een val.

A 84-year-old man presented with a pulsatile mass on the forehead 2 weeks after blunt head injury. Doppler ultrasonography showed a yin-yang sign. The man was diagnosed with a pseudoaneurysm of the left superficial temporal artery.

Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma.

BACKGROUND: The O 6 -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors. RESULTS: The combination of veliparib and RT inhibited colony formation in the majority of PDCLs tested. The PDCL, RN1 showed significantly reduced levels of the homologous repair protein, Mre11 and a heightened response to PARP inhibition measured by increased apoptosis and decreased colony formation. The oral administration of veliparib (12.5 mg/kg, twice daily for 5 days in a 28-day treatment cycle) in combination with whole brain RT (4 Gy) induced apoptosis (Tunel staining) and decreased cell proliferation (Ki67 staining) in a PDX of MGMT unmethylated GBM. Significantly longer survival times of the PDX treated with the combination treatment were recorded compared to RT only or veliparib only. CONCLUSIONS: Our results demonstrate preclinical efficacy of targeting PARP at multiple levels and provide a new approach for the treatment of MGMT unmethylated GBM.

CDK4/6 Inhibitor PD0332991 in Glioblastoma Treatment: Does It Have a Future?

Glioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer. Common alterations in the cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway in glioblastoma make PD0332991 also an interesting drug for the treatment of glioblastoma. Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies. Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.