PurposeThis study examined 46 articles in total, which yielded 5 recurring themes: perceived discrimination, language barriers, socioeconomic barriers, cultural barriers and educational/knowledge barriers. The two most dominant themes found were the inability to speak the country's primary language and belonging to a culture with different practices and values from the host country. The review provides vital insights into the numerous challenges that immigrants and refugees encounter as they navigate through the primary care systems of English-speaking (E-S) countries and potential solutions to overcome these barriers.Design/methodology/approachAccess to adequate healthcare plays a central part in ensuring the physical and mental wellbeing of society. However, vulnerable groups such as immigrants and refugees, face numerous challenges when utilizing these healthcare services. To shed further light on the barriers impacting healthcare quality, the authors’ team performed a scoping thematic review of the available literature on immigrant and refugees' experiences in primary healthcare systems across E-S countries. Articles were systematically reviewed while focusing on healthcare perceptions by immigrants, potential barriers and suggestions to improve the quality of primary care.FindingsThis work looked at qualitative and quantitative information, attempting to combine both paradigms to give a rich and robust platform with which to devise a further study through focus groups. Qualitative inquiry accounted for 28/46, or 61%, of studies, and quantitative inquiry made up 9/46, or 20%, while 9/46 or 20% combined both qualitative and qualitative. Emerging themes are -perceived ethnic discrimination faced by immigrants accessing primary care, language barriers, socioeconomic barriers, cultural barriers and educational barriers.Research limitations/implicationsMost medical journals rely on quantitative data to relate “results” and cases. The authors set out to change ways in which medical reports can be done. Most of the authors were solely trained in quantitative research; consequently, they had to learn to isolate themes and to use a narrative approach in the article.Practical implicationsResearch implications clearly indicated that using a qualitative (phenomenological) approach with quantitative data created a human and reachable discourse around patient comfort and the realities of immigrants and refugees to E-S countries. The use of this research opens medical practitioners (and patients) to a richer understanding within a usually difficult arena.Social implicationsBy understanding the qualitative nature of medical research, practitioners, students and mentors are able to bridge medical quantitivity to the human, widening doors to social science and medical collaboratory research.Originality/valueAs stated above, this work is important as it understands the human/patient element and de-emphasizes the medical obsession with quantifying the lives of patients through hard data. This is a unique collaboration that relies on the qualitative to pinpoint and define the difficulties of newcomers to E-S countries.

Background: Genetic instability and heterogeneity are fundamental to AML biology and pivotal to its prognosis. Acute myeloid leukaemia (AML) is most frequent in older adults (>60 years) and a significant majority are considered "treatment-naïve" given medical comorbidities, high-risk disease biology, and poor tolerance to chemotherapy. These patients receive low-intensity regimens, mostly hypomethylating agents due to impaired tolerance to induction chemotherapy, resulting in low overall survival. Thus, there is a critical need to develop targeted therapies capable of rapidly inducing a high rate of clinical response, with better tolerability and durable responses for these elderly AML patients. DNA damage response (DDR) is a specialized and highly orchestrated signalling cascade to maintain genetic stability and is closely linked to the cell cycle. The cell cycle checkpoints result in arrest and the resumption of cell cycle progression when DNA damage has been repaired. However, the DNA repair failure will direct cells towards cellular senescence or apoptosis. Hence, DDR and apoptosis are intricately related physiological processes. In AML, mutations in key regulators of gene expression and/or chromatin structure, such as p53, K-RAS, and isocitrate dehydrogenase 1 and 2 (IDH1/2) results in defective DDR. Defects in DDR are also age-related; therefore, resulting in an exponential increase in the incidence of cancer with age. The emerging treatment regimens for elderly AML are focusing on synergistic lethality using a combination of DDR inhibitors (PARP1) and/ or anti-apoptotic inhibitors (BCL2) in combination with low dose anthracycline and additional targeted therapies like (IDH2/DNTM etc.). However, the wider implication and influence of DDR genes either alone or in combination with anti-apoptotic genes remains uncharacterized in elderly AML. In this pilot study, we screened a large cohort of AML samples for mRNA expression for a series of DDR and apoptotic genes to investigate the age-related variation in expression of these molecules. We observed distinct differences in DDR and anti-apoptotic gene expression between elderly AML compared to paediatric patients. We anticipate, that these preliminary observations will pave the pathway for future comprehensive studies to expand the employment of synergistic lethality strategy for elderly AML patients. Methods: We employed RNA extracted from formalin-fixed paraffin-embedded (FFPE) diagnostic tissuesamples in 100 AML patients. Age defined the categorization of patients into three groups; a, <18 years (n=34); b,18-60 years (n=32) and c, >60 years (n=34). nCounter (NanoString Technologies) platform was used for the quantification of mRNA. Qlucore Omics Explorer software was employed with defined criteria (fold change >2.0; p<0.01 and q <0.05) for statistical analysis. Results:We noted that several DDR mediators (BRIP1, POLD1, XRCC4) are differentially up-regulated in the AML samples linked with elderly patient group, alongside anti-apoptotic genes (IDH2, IKBKB) when compared with samples from patient <18 years (Figure 1). Moreover, DDR effectors (BRCA1& ATM) were up-regulated in the elderly cohort relative to paediatric AML samples, suggesting potential targets for treating elderly AML (Figure2). Conclusions:This pilot study identifies several additional and novel DDR targets; which can be exploited to enhance chemotherapeutic efficacy in "treatment fit" as well as "treatment naïve" elderly AML patients. Besides, we also report numerous novel anti-apoptotic molecules up-regulated in elderly AML. Taken together the preliminary data, presented here, expand the repertoire for targeted therapy in elderly AML with a specific focus on synergistic lethality. Disclosures No relevant conflicts of interest to declare.

Background:Plasmablastic lymphoma (PBL), is a rare aggressive B-cell lymphoma that shares many overlapping characteristics with activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL) and multiple myeloma (MM). High expression ofWnt/β-cateninpathway molecules has been linked with several aspects of tumour biology in ABC-DLBCL and MM. In MMWnt/β-cateninplay critical role in chemoresistance, while high FOXP1 in ABC-DLBCL exert poor prognosis through up-regulation of theWnt/β-cateninsignalling pathway. There is strong evidence that enhanced crosstalk between the Wnt/β-catenin andRASpathways impact tumorigenesis and metastasis of cancerous stem cells in various cancers. In breast cancer; targeting theWnt/β-cateninand RAS pathways with small molecular inhibitors have shown effective results. The role of the Wnt/β-catenin signalling pathway and its corresponding linkage toRASsignalling molecules remained unknown in PBL. This pilot study provides preliminary data in relation to expressionof Wnt/β-cateninandRASpathways molecules in PBL in contrast to ABC-DLBCL. Method:FFPE RNA from diagnostic tissue samples in PBL patients (n=31) were compared with ABC-DLBCLs (n=18) patients for keyWnt/β-cateninandRASpathway molecules expression, utilizing nCounter (NanoString Technologies) platform. Qlucore Omics Explorer software was employed with defined criteria (fold change >2.0; p<0.01 and q <0.05) for statistical analysis. Gene Set Enrichment Analysis (GSEA) from 5 publicly available gene data sets was used to analyze the expression of other accompanying pathways. Result:We identified significant differential expression of mRNA related toWnt/β-cateninsignalling between ABC-DLBCL and PBL (Figure 1). Expression ofWnt/β-cateninsignalling inhibitors (CXXC4, SFRP2, and DKK1) were significantly higher among PBL compared to ABC-DLBCL (8.12-3.22 log fold difference). In divergence, molecules linked withWnt/β-cateninsignalling activation were elevated in PBL when compared to ABC-DLBCL (FZD3andWNT10B). The GESA analysis proved that the RAS pathway was significantly up-regulated in PBL patients compared to ABC-DLBCL. In particular, the expression of crucial RAS pathway genes such asNRAS, RAF1, SHC1, andSOS1was significantly up-regulated in PBL patients when compared to ABC-DLBCL patients (Figure 2). Conclusion:Our data suggest that the expression ofWnt/B-catenintarget genes and ligands are enhanced in PBL patients along with the up-regulation of theRASsignalling pathway molecules as compared to ABC-DLBCL. The heightened expression of crucialWnt/B-catenininhibitors does not down-regulate the Wnt/β-catenin signalling. We anticipate that the combined down-regulation of theWnt/ β-cateninandRASpathways by targeting its key members (RAF1, NRAS, FZD3) may serve to contain tumor progression in PBL, hence impacting prognosis. Disclosures Stewart: Gilead:Honoraria;Sandoz:Honoraria;Teva:Honoraria;Amgen:Honoraria;Celgene:Honoraria;Abbvie:Honoraria;Roche:Honoraria;Janssen:Honoraria;Novartis:Honoraria;AstraZeneca:Honoraria.

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