P) for stage 2 (green), systolic pulmonary artery pressure (SPAP) for stage 3 (purple) and right atrial pressure (RAP) for stage 4 (yellow). The cake chart shows the distribution of the different stage in the whole cohort. (Bottom) Survival Analyses According to Stage of Cardiac Damage after Transcatheter Aortic Valve Replacement using Invasive Criteria. Kaplan-Meier plots comparing overall (left) and cardiovascular (right) 4-year survival showing with the more advancing stage a higher mortality rate. ModraDoc006 is a novel oral formulation of docetaxel. The clearance of intravenous docetaxel is higher in medically castrated prostate cancer patients as compared to patients with other types of solid tumours. Oral docetaxel requires co-administration ritonavir (r), which might further impact the pharmacokinetics (PK). We now compare the PK of docetaxel and ritonavir between patients with Hormone Sensitive Prostate Cancer (HSPC), metastatic Castration-Resistant Prostate Cancer (mCRPC) and other metastatic solid tumours, treated on the same dose and weekly schedule of ModraDoc006/r. The docetaxel and ritonavir PK were compared between four patient groups from three clinical phase I trials, including eight male and eight female patients with different types of solid tumours (study 1), seven patients with HSPC (study 2) and five patients with mCRPC (study 3). All patients were treated with ModraDoc006 30mg and ritonavir 100mg in the morning, followed by ModraDoc006 20mg and ritonavir 100mg in the evening (Mowas significantly lower in prostate cancer patients as compared to patients with other types of solid tumours, treated on ModraDoc006/r 30-20/100-100. An increase of the ritonavir dose increased the docetaxel exposure in mCRPC patients. Therefore, a different RP2D of ModraDoc006/r is pursued in castrated prostate cancer patients as compared to patients with other types of solid tumours. Study 1 ClinicalTrials.gov Identifier NCT01173913, date of registration August 2, 2010. https://www.selleckchem.com/products/BIBF1120.html Study 2 ClinicalTrials.gov Identifier NCT03066154, date of registration February 28, 2017. Study 3 ClinicalTrials.gov Identifier NCT03136640, date of registration May 2, 2017. Study 1 ClinicalTrials.gov Identifier NCT01173913, date of registration August 2, 2010. Study 2 ClinicalTrials.gov Identifier NCT03066154, date of registration February 28, 2017. Study 3 ClinicalTrials.gov Identifier NCT03136640, date of registration May 2, 2017.Gastrointestinal cancers are one of the most common types of cancer that have high annual mortality; therefore, identification and introduction of safe drugs in the control and prevention of these cancers are of particular importance. Metformin, a lipophilic biguanide, is the most commonly prescribed agent for type 2 diabetes management. In addition to its great effects on lowering the blood glucose concentrations, the anti-cancer properties of this drug have been reported in many types of cancers such as gastrointestinal cancers. Hence the effects of this agent as a safe drug on the reduction of gastrointestinal cancer risk and suppression of these types of cancers have been studied in different clinical trials. Furthermore, the proposed mechanisms of metformin in preventing the growth of these cancers have been investigated in several studies. In this review, we discuss recent advances in elucidating the molecular mechanisms that are relevant for metformin use in gastrointestinal cancer treatment. To analyze the evolution of type 3 neovascularization in eyes with age-related macular degeneration during anti-vascular endothelial growth factor (VEGF) treatment using optical coherence tomography angiography (OCTA) analysis. Forty-one treatment-naïve eyes (37 patients) with type 3 neovascularization were retrospectively included in the study. The growth and morphological changes in the type 3 lesions, which were recorded using OCTA, were compared across time. The high-flow signal of the lesion on OCTA was significantly increased at the sub-retinal pigment epithelium (RPE) and the choriocapillaris during anti-VEGF treatment. The detection rate of the flow signal in the sub-RPE increased from 50.0% at baseline and 51.2% at 12 months to 65.9% at 24 months (P = 0.013). The flow signal extending into the choriocapillaris was detected in 0% of the eyes at baseline, 9.8% of the eyes at 12 months, and 17.1% of the eyes at 24 months (P = 0.018). The presence of subretinal drusenoid deposits (SDD) was significantly more frequent in the group with extension into the choriocapillaris (100%) than in the group without (61.8%, P = 0.036). For the four eyes with extension into the choroid, the morphological feature of the lesion on en face OCTA evolved into a tangled vascular network, similar to type 1 neovascularization. OCTA analysis revealed that type 3 neovascularization gradually extended downward toward the sub-RPE and choroid during anti-VEGF treatment. The extension of the lesion into the choriocapillaris, suggesting retinal-choroidal anastomosis, was significantly more frequent in eyes with SDD. OCTA analysis revealed that type 3 neovascularization gradually extended downward toward the sub-RPE and choroid during anti-VEGF treatment. The extension of the lesion into the choriocapillaris, suggesting retinal-choroidal anastomosis, was significantly more frequent in eyes with SDD. To evaluate the prevalence and visual outcomes of macular Bruch membrane (BM) defects in patients treated with anti-vascular endothelial growth factors (VEGF) for choroidal neovascularization secondary to pathological myopia (mCNV). Single-center retrospective observational case series of 68 eyes from 62 patients with mCNV treated with one anti-VEGF injection followed by a pro re nata (1 + PRN) regimen. A minimum follow-up of 6 months was defined. Chorioretinal atrophy was assessed by fundus examination, fluorescein angiography, and SD-OCT. Median follow-up was 28.5 (range 6-89) months with a median number of 5 anti-VEGF injections. At baseline, 27.9% of eyes had macular BM defects increasing to 36.8% during follow-up (p<0.001). Eyes without macular BM defects at the baseline had higher BCVA at the last observation than patients with BM defects (p=0.003). An increase of 5 or more ETDRS letters was more frequent in eyes without BM defects (p=0.001). At the end of follow-up, mCNV-related macular atrophy was present in 44.