The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. PATIENTS AND METHODS: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. RESULTS: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). CONCLUSIONS: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.

Genetic analysis provides insights into species distribution and population structure in East Atlantic horse mackerel (Trachurus trachurus and T. capensis).

Two sister species of horse mackerel (Trachurus trachurus and T. capensis) are described that are intensively harvested in East Atlantic waters. To address long-standing uncertainties as to their respective geographical ranges, overlap and intraspecific population structure this study combined genetic (mitochondrial DNA and microsatellite) analysis and targeted sampling of the hitherto understudied West African coast. mtDNA revealed two reciprocally monophyletic clades corresponding to each species with interspecies nuclear differentiation supported by FST values. The T. trachurus clade was found across the north-east Atlantic down to Ghana but was absent from Angolan and South African samples. The T. capensis clade was found only in South Africa, Angola and a single Ghanaian individual. This pattern suggests that both species may overlap in the waters around Ghana. The potential for cryptic hybridization and/or indiscriminate harvesting of both species in the region is discussed. For T. capensis mtDNA supports high gene flow across the Benguela upwelling system, which fits with the species' ecology. The data add to evidence of a lack of significant genetic structure throughout the range of T. trachurus though the assumption of demographic panmixia is cautioned against. For both species, resolution of stock recruitment heterogeneity relevant to fishery management, as well as potential hybridization, will require more powerful genomic analyses.

A multi-gene dataset reveals a tropical New World origin and Early Miocene diversification of croakers (Perciformes: Sciaenidae).

Widely distributed groups of living animals, such as the predominantly marine fish family Sciaenidae, have always attracted the attention of biogeographers to document the origins and patterns of diversification in time and space. In this study, the historical biogeography of the global Sciaenidae is reconstructed within a molecular phylogenetic framework to investigate their origin and to test the hypotheses explaining the present-day biogeographic patterns. Our data matrix comprises six mitochondrial and nuclear genes in 93 globally sampled sciaenid species from 52 genera. Within the inferred phylogenetic tree of the Sciaenidae, we identify 15 main and well-supported lineages; some of which have not been recognized previously. Reconstruction of habitat preferences shows repeated habitat transitions between marine and euryhaline environments. This implies that sciaenids can easily adapt to some variations in salinity, possibly as the consequence of their nearshore habitats and migratory life history. Conversely, complete marine/euryhaline to freshwater transitions occurred only three times, in South America, North America and South Asia. Ancestral range reconstruction analysis concomitant with fossil evidence indicates that sciaenids first originated and diversified in the tropical America during the Oligocene to Early Miocene before undergoing two range expansions, to Eastern Atlantic and to the Indo-West Pacific where a maximum species richness is observed. The uncommon biogeographic pattern identified is discussed in relation to current knowledge on origin of gradients of marine biodiversity toward the center of origin hypothesis in the Indo-West Pacific.

Fibres found in the eye during and after phacoemulsification cataract surgery.

PURPOSE: Fibres are regularly found within the delivery cartridge (DC) and in the anterior chamber (AC) during phacoemulsification cataract surgery (PCS) and postoperatively. The purpose of this study was to identify their frequency and possible significance. SETTING: Dedicated ophthalmic day surgery. DESIGN: Prospective, consecutive, single-surgeon, cohort study. METHODS: In 639 eyes undergoing PCS, the presence of fibres was documented in or on both the DC and in the AC intraoperatively, and in the AC postoperatively. The intraoperative method of fibre removal was documented. Corrected distance visual acuity (CDVA) was recorded preoperatively, and at day 1, week 1, and week 4 postoperatively. The incidence of clinical cystoid macular oedema (CMO) and endophthalmitis in the retained fibre subcohort was compared with that of the non-fibre subcohort. RESULTS: A total of 5.2% of the operated eyes had a fibre or fibres in or on the DC, which in all cases was removed with forceps intraoperatively. A total of 14.6% of operated eyes had a fibre or fibres in the AC intraoperatively; these were removed by irrigation/aspiration. Postoperatively, five eyes (0.78%) had a fibre in the AC. There was no significant difference in postoperative CDVA between the fibre and non-fibre subcohorts (P=0.26), and no clinically significant CMO or endophthalmitis in either subcohort. CONCLUSIONS: Most fibres seen on the DC or in the eye are sterile and non-inflammatory. However, there have been reports of endophthalmitis attributed to retained fibres. In this study, there were no complications attributable to the fibres, but their removal may minimise any adverse potential.