Aims Eight years ago, a paper‐based survey was administered during the World Pharma 2010 meeting, asking about the challenges of implementing pharmacogenetics (PGx) in clinical practice. The data collected at the time gave an idea about the progress of this implementation and what still needs to be done. Since then, although there have been major initiatives to push PGx forward, PGx clinical implementation may still be facing different challenges in different parts of the world. Our aim was therefore to distribute a follow‐up international survey in electronic format to elucidate an overview on the current stage of implementation, acceptance and challenges of PGx in academic institutions around the world. Methods This is an online anonymous LimeSurvey‐based study launched on 11 November 2018. Survey questions were adapted from the initially published manuscript in 2010. An extensive web search for worldwide scientists potentially involved in PGx research resulted in a total of 1973 names. Countries were grouped based on the Human Development Index. Results There were 204 respondents from 43 countries. Despite the wide availability of PGx tests, the consistently positive attitude towards their applications and advances in the field, progress of the clinical implementation of PGx still faces many challenges all around the globe. Conclusions Clinical implementation of PGx started over a decade ago but there is a gap in progress around the globe and discrepancies between the challenges reported by different countries, despite some challenges being universal. Further studies on ways to overcome these challenges are warranted.
TPS758 Background: KRAS mutations are identified in the majority of premalignant lesions that precede pancreatic ductal adenocarcinoma (PDAC). Arising during tumorigenesis, mutant KRAS (mKRAS) neoantigens are less susceptible to central tolerance mechanisms and serve as ideal vaccine targets. Indeed, targeting mKRAS neoantigens with vaccines has shown promising anti-tumor activity in the preclinical setting. For instance, our group previously demonstrated that a Listeria-based vaccine targeting mKRAS G12D combined with Treg-depleting agents can prevent the progression of early pancreatic intraepithelial neoplasia to overt PDAC in a mouse model (Keenan et al, 2014). Building upon this work, the current study aims to determine the safety and immunogenicity of a pooled synthetic long peptide (SLP) mKRAS vaccine in patients identified as high risk for developing PDAC based on family history and germline mutation testing. Methods: This is a single-arm, open-label phase I trial evaluating a pooled SLP mKRAS vaccine in patients at high risk of developing PDAC ( n = 20). The vaccine consists of poly-ICLC adjuvant admixed with SLPs corresponding to six common mKRAS subtypes: G12D, G12R, G12V, G12A, G12C, and G13D. A four-dose series of the mKRAS vaccine is administered on weeks 1, 3, 4, and 17. Following completion of the treatment phase, all patients have the option to continue annual follow-up visits until study closure. Eligible patients must have radiographic evidence of a premalignant pancreatic lesion and fall under at least one of the following three high-risk groups: 1) ≥ 2 familial pancreatic cancer relatives, 2) germline mutation carriers with ≥ 10% lifetime PDAC risk and 3) germline mutation carriers with ~5% lifetime PDAC risk. The co-primary endpoints of this study are safety and T cell response. Safety will be assessed by the frequency and grading of adverse events per NCI CTCAE v5.0. T cell response will be determined by the maximal percent change in IFNγ-producing mKRAS-specific T cell density within 16 weeks post-vaccination compared to baseline. Correlative studies will explore vaccine-associated changes in T cell quality (e.g., memory, exhaustion, poly-functionality, and activation) using mass cytometry analysis of peripheral blood samples. Patient accrual began in April 2022 and is currently ongoing. Clinical trial information: NCT05013216 .
Among patients with short bowel syndrome who commonly have kidney disease, kidney transplantation remains challenging. We describe the clinicopathologic course of a 59-year old man with short bowel syndrome secondary to Crohn’s disease who underwent a deceased donor kidney transplant that was complicated by recurrent acute kidney allograft injury due to volume depletion from diarrhea, ultimately requiring the placement of permanent intravenous access for daily volume expansion at home resulting in the recovery of allograft function. Teduglutide treatment at 1.8 years post-transplant led to a dramatic decrease in diarrhea. A literature review of similar cases yielded 18 patients who underwent 19 kidney transplants. Despite high rates of complications, at the time of last follow-up (median 2.1 years [0.04-7]), 94% of the patients were still alive and 89% had functioning allografts, with a median eGFR of 37.5 [14-122] ml/min/1.73m2. In conclusion, despite high rates of complications, kidney transplantation in patients with short bowel syndrome is associated with acceptable short- and midterm outcomes. Further, we report for the first time the effects of the glucagon-like peptide-2 analogue teduglutide for short bowel syndrome in a kidney transplant recipient.
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