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Introduction Botulinum neurotoxin type-A (BoNTA) is licensed for the treatment of chronic migraine (CM), but it has been tested off-label as a therapeutic choice in other primary headaches (PHs). We aimed to provide a systematic review and expert opinion on BoNTA use in PHs, beyond CM.Areas covered After providing an overview on PHs and mechanism of BoNTA action, we report the results of a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, of BoNTA therapeutic trials in PHs beyond CM. Studies and results were reviewed and discussed, and levels of evidence were graded. We also collected data on relevant ongoing trials.Expert opinion Although there are contradictory findings on PHs other than CM, BoNTA may represent a therapeutic option for patients who do not respond to conventional prophylactic treatments. Based on limited available evidence, BoNTA may be considered in refractory tension-type headache, trigeminal autonomic cephalalgias, primary stabbing headache, nummular headache, hypnic headache, and new daily persistent headache, after the primary nature of cephalalgia has been documented and other drugs have failed. Experienced physicians in BoNTA treatment are required to guide the therapeutic protocol for each patient to optimize good and safe outcomes.

To assess the impact of post-thawing embryo culture on frozen embryo transfer (FET) outcomes.

A retrospective cohort study including 678 consecutive FET cycles performed between the years 2004 and 2017 was conducted. Patients older than 45 years old were excluded. FET cycles were stratified as follows (1) two-day (2d) embryos thawed and cultured to three-day (3d) versus 3d embryos thawed and transferred; (2) 2d or 3d embryos thawed and cultured to blastocysts versus blastocysts thawed and transferred. A

-value <.05 was considered statistically significant.

Maternal age, BMI, smoking, and basal FSH of the 2d and 3d cultured embryo group (

 = 110) and the 3d non-cultured embryo group (

 = 189) were comparable. Endometrium preparation protocols and the achieved endometrial thickness did not differ between groups. Pregnancy rate, implantation rate, clinical pregnancy, live birth rate, abortions, multiple pregnancies, perinatal outcomes, and birth weight were comparable.The 2d and 3d embryos cultured to blastocyst (

 = 41) compared to non-cultured blastocyst (

 = 338) showed that the non-cultured blastocyst patients had higher smoking rates and longer follicular phase. Endometrial thickness was comparable. The 2d and 3d embryos cultured to blastocyst stage had higher multiple pregnancies rate compared to the blastocyst non-cultured group, whereas pregnancy rate, implantation rate, live birth rate, miscarriages, perinatal outcomes, and birth weight were comparable.

We could not demonstrate that the post-thaw culture had a significant impact on the outcome of FET cycles.

We could not demonstrate that the post-thaw culture had a significant impact on the outcome of FET cycles.Central Nervous System (CNS) tumors are the most common pediatric solid tumor and development neuro psychomotor (DNPM) therapy can contribute to the rehabilitation of these children. This paper describes the development of a DNPM multidimensional assessment grid for children with CNS tumor (DNPM-CNS grid).The development process included 4 phases (P1) literature review and grid development (Version 1.0), (P2) two rounds consultations with experts (Version 1.1 and 2.0), (P3) field testing, (P4) final revision (Version 3.0).(P1) The DNPM-CNS grid was developed based on previous tools and manuals and on clinical experience with this patient population. (P2) A total of 52 questionnaires were filled in by experts about relevance of assessment areas, pertinence, comprehensibility and feasibility of the grid. Average scores ranged from 7.6 to 10. (P3) At case level, good inter-rater agreement scores (78%) and limited non-evaluability rates (18%) emerged. At item level, 27% of items reached high disagreement and 26% high not-evaluability rates. Epacadostat concentration The qualitative assessment was judged clinically useful for planning the neuro-oncology rehabilitation treatment and a good feasibility of the DNPM-CNS grid emerged both for preschool and school-age children. (P4) The final version of the grid consists of 8 assessment areas with 133 items.The DNPM-CNS grid is a comprehensive tool that can guide the overall DNPM assessment in a limited amount of time. It can be used as a screening tool to customize more specific assessments. Further research is needed to better characterize grid psychometric properties.Supplemental data for this article is available online at https//doi.org/10.1080/08880018.2021.1948648 .Introduction Genomic instability resulting from DNA damage repair (DDR) deficiencies is a hallmark of cancer and offers treatment opportunities. Homologous recombination DDR defect is a result of multiple critical gene mutations, including BRCA1/2. Targeting DNA DDR defects in pancreatic cancer (PC) is emerging as a potential treatment strategy with current focus on BRCA mutations.Areas covered Challenges in treating patients with PC are explained. We review DDR defects as a treatment target in PC, specifically, germline BRCA mutation and sensitivity to platinum compounds and exploiting the strategy of synthetic lethality using poly (ADP-ribose) polymerase (PARP) inhibition. Literature review was undertaken through PubMed, Google Scholar, and Clinicaltrials.gov website.Expert opinion DDR defects are promising targets for novel therapies in PC. Early application of such strategy is in patient subgroup with BRCA germline mutation, which is seen in only 5-7% of the PC population. The oral PARP inhibitor olaparib in the maintenance setting represents the first targeted therapy in metastatic PC based on a phase 3 study. There is a very modest benefit for patients with PC using PARP inhibitors. Future work must improve our understanding of mechanisms of sensitivity and resistance to PARP inhibitors in PC and enhance the molecular selection of patients for such therapy.

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