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Although major advancements have been made in the therapeutics for people with cystic fibrosis (PwCF), many still require the use of multiple medications to manage acute exacerbations of disease and maintain health. Iterative trial and error processes of pharmacotherapeutic management can be optimized by assessing and incorporating pharmacogenetics. For 82 PwCF, we reviewed 2 years of medication use and response history and interrogated metabolizer status for common pharmacogenes, revealing 3336 medication exposure events (MEEs) to 286 unique medications. As expected, the more frequent MEEs were those commonly used to treat cystic fibrosis (CF), such as antibiotics and respiratory medications. Antibiotics also comprised 56.7% of the undesirable drug responses. The impact of gene variants on drug responses was assessed using Pharmacogenomics Knowledgebase (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Thirty‐three (11.5%) medications have strong evidence of genetic influence on response as evidenced by gene‐based dosing guidelines. 110 (38.5%) unique medications had at least one association with a very important pharmacogene, whereas 143 (50%) were associated with at least one clinical or variant annotation. Over 97% of participants had at least one actionable genotype. Eleven (13.4%) patients with an actionable genotype, taking the impacted medication, had an undesirable drug response described in the CPIC guidelines that could potentially have been mitigated with a priori knowledge of the genotype. PwCF take many medications for disease management, with frequent dose changes to elicit a desired clinical effect. As CF care evolves, implementing pharmacogenetics testing can improve efficiency and safety of prescribing practices using precision selection and dosing at medication initiation.

Background: Social determinants of health (SDOH) and health-related social needs (HRSN) drive disparities in lung function, nutrition, and survival in People with Cystic Fibrosis (PwCF). Addressing HRSN can improve access to care, yet standardized screening and intervention methods remain underutilized. Objectives: The aim of this project was to develop, test, and refine a remote HRSN screening and intervention model across multiple cystic fibrosis (CF) centers. Design: A multicenter, prospective Quality Improvement (QI) initiative Methods: Four CF centers, serving both pediatric and adult populations, piloted an electronic HRSN screening tool and a remote social need intervention strategy. Developed collaboratively with CF clinicians and patient and family partners (PFPs), the tool assesses nine HRSN domains. Multidisciplinary teams, including PwCF, held regular meetings to tailor implementation to each site’s existing clinical workflow and staff structure. Over 1 year, each site conducted iterative Plan-Do-Study-Act (PDSA) cycles every 2 weeks to refine the screening process, sharing adaptations across centers. Results: All four CF centers successfully implemented the remote HRSN screening and intervention workflows, completing 26 iterative PDSA cycles to refine site-specific processes. Study site meetings were held with multidisciplinary attendance at 100% of meetings. The screening tool was integrated into pre-visit planning and telehealth workflows, allowing for social worker follow-up of identified needs. Multidisciplinary collaboration from all sites resulted in the generation of a comprehensive library of local and regional resources to support unmet needs identified during screening. Narrative patient testimonial highlighted the screening tool’s effectiveness in facilitating discussions about social needs and connecting individuals to available resources from the perspective of PwCF. Conclusion: Our study has shown that HRSN screening and intervention are feasible, adaptable and acceptable to PwCF. Next steps include gathering comprehensive data on screening and intervention rates, domains of unmet social needs across regions, and sustainability interventions. Expanding HRSN screening and intervention to other CF Centers can provide data to support public policy and advocacy initiatives for reducing health disparities driven by SDOH. Plain language summary Screening for and addressing social challenges in people with cystic fibrosis Social determinants of health (SDOH) are an individual’s personal circumstances that impact their overall health and well-being. SDOH can lead to health-related social needs (HRSN) that include limited access to healthy food, affordable housing, transportation, education, and access to health insurance. These factors have been shown to impact lung health, nutrition status, and survival in people with cystic fibrosis (CF). While the use of telehealth has increased access to care for many people with CF, it has also created some challenges in how we can help people get access to the social resources that they might need. The goal of our project is to test an HRSN screening tool and resource packet that can be used with telehealth in CF. We hope to increase identification of unmet needs and be able to provide remote interventions to connect people with resources and services that can help. Four different CF Programs tested a virtual HRSN screener and intervention packet. These teams meet regularly and work together to find the best way to use the screener and provide resources to patients who are in need, and patients and families at their center are helping to guide the process. Our goal is to improve access to care through picking up on areas of need and linking patients with resources without patients having to come into the clinic in-person. What we learn from this project can be used in other CF programs and can be used to develop resources for the national CF community.

We describe a human nasal epithelial (HNE) organoid model derived directly from patient samples that is well-differentiated and recapitulates the airway epithelium, including the expression of cilia, mucins, tight junctions, the cystic fibrosis transmembrane conductance regulator (CFTR), and ionocytes. This model requires few cells compared to airway epithelial monolayer cultures, with multiple outcome measurements depending on the application. A novel feature of the model is the predictive capacity of lumen formation, a marker of baseline CFTR function that correlates with short-circuit current activation of CFTR in monolayers and discriminates the cystic fibrosis (CF) phenotype from non-CF. Our HNE organoid model is amenable to automated measurements of forskolin-induced swelling (FIS), which distinguishes levels of CFTR activity. While the apical side is not easily accessible, RNA- and DNA-based therapies intended for systemic administration could be evaluated in vitro, or it could be used as an ex vivo biomarker of successful repair of a mutant gene. In conclusion, this highly differentiated airway epithelial model could serve as a surrogate biomarker to assess correction of the mutant gene in CF or other diseases, recapitulating the phenotypic and genotypic diversity of the population.

Background/Objectives: Adjuvant radiation for gynecologic malignancies often exposes organs at risk (OARs), such as the bone marrow, bowel, rectum, and bladder, to radiation, leading to toxicities that impact treatment tolerance and patient quality of life. Scanning proton beam therapy, particularly with Individual Field Simultaneous Optimization (IFSO), may offer dosimetric and biological advantages over volumetric modulated arc therapy (VMAT). This study evaluates the clinical impact of IFSO-based proton planning in post-operative gynecologic cancer patients. Materials and Methods: Fourteen patients receiving adjuvant proton therapy to 45 Gy in 25 fractions were retrospectively analyzed. Comparison VMAT plans were generated on the same datasets. Dose–volume metrics for key OARs and normal tissue complication probabilities (NTCPs) were compared using paired statistical tests. Robustness evaluations accounted for setup and range uncertainties. Results: Proton plans significantly reduced dose to bone marrow (V10Gy: 58% vs. 86%, p < 0.00001; V20Gy: 47% vs. 58%, p < 0.00001), small bowel (V20Gy: 21% vs. 56%, p < 0.00001), and femoral heads (left femoral head mean: 11Gy vs. 13Gy, p = 0.032; right femoral head mean: 11Gy vs. 13Gy, p = 0.022). NTCP modeling predicted significantly lower rates of bowel urgency (9.4% vs. 3.3%, p < 0.001) and hematologic toxicity (10.2% vs. 4.9%, p < 0.001) with proton therapy. Plans remained robust across uncertainty scenarios. Conclusions: IFSO-based scanning proton therapy provides clinically meaningful sparing of bone marrow and bowel, with the potential to reduce hematologic and gastrointestinal toxicities. These findings support its use in patients receiving adjuvant pelvic radiotherapy, particularly those undergoing extended field treatment or chemotherapy.

Atherosclerosis is a prevalent disease affecting millions of Americans. Despite our advances in diagnosis and treatment, atherosclerosis is the leading cause of death in America. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading noninvasive imaging modality for atherosclerotic disease. Atherosclerosis of the arterial wall of the human carotid, aortic, peripheral and coronary arteries have all been successfully evaluated. In addition, the power of magnetic resonance imaging to differentiate the major components of atherosclerotic plaque has been validated. The ability to image the vessel wall and risk stratify atherosclerotic plaque will create management decisions not previously faced, and has the potential to change the way atherosclerosis is treated.

We hypothesized that percutaneous intervention in the affected lower extremity artery would improve calf muscle perfusion and cellular metabolism in patients with claudication and peripheral artery disease (PAD) as measured by magnetic resonance imaging (MRI) and spectroscopy (MRS). Ten patients with symptomatic PAD (mean ± SD: age 57 ± 9 years; ankle–brachial index (ABI) 0.62 ± 0.17; seven males) were studied 2 months before and 10 months after lower extremity percutaneous intervention. Calf muscle phosphocreatine recovery time constant (PCr) in the revascularized leg was measured by 31P MRS immediately after symptom-limited exercise on a 1.5-T scanner. Calf muscle perfusion was measured using first-pass gadolinium-enhanced MRI at peak exercise. A 6-minute walk and treadmill test were performed. The PCr recovery time constant improved significantly following intervention (91 ± 33 s to 52 ± 34 s, p < 0.003). Rest ABI also improved (0.62 ± 0.17 to 0.93 ± 0.25, p < 0.003). There was no difference in MRI-measured tissue perfusion or exercise parameters, although the study was underpowered for these endpoints. In conclusion, in this pilot study, successful large vessel percutaneous intervention in patients with symptomatic claudication, results in improved ABI and calf muscle phosphocreatine recovery kinetics.

Meeting abstracts - A single PDF containing all abstracts in this supplement is available at http://www.biomedcentral.com/content/files/pdf/1532-429X-13-S1-full.pdf.EMPTY Objective We hypothesized that changes in atherosclerotic plaque composition with lipid lowering therapy could be measured in patients with peripheral arterial disease (PAD) using MRI of the superficial femoral artery (SFA). Table 1 Changes in plaque over time *ANOVA p<0.05 Conclusion LDL lowering therapy over 2 years decreases plaque lipids without a significant change in plaque area or other components as demonstrated by MRI.