Faculty Bibliography

Traditionally, diets for kidney disease were low in potassium. This recommendation was based on outdated research and often wrong assumptions that do not reflect current evidence. In fact, studies conducted over the past decades show patients with CKD, including kidney failure, do not benefit from the restriction of plant foods relative to control. Generally, dietary potassium does not correlate with serum potassium, and we posit that this is due to the effects of fiber on colonic potassium absorption, the alkalinizing effect of fruits and vegetables on metabolic acidosis, and the bioavailability of dietary potassium in plant foods. Also, consumption of plant foods may provide pleiotropic benefits to patients with CKD. Emerging dietary recommendations for kidney health should be devoid of dietary potassium restrictions from plant foods so that patient-centered kidney recipes can be encouraged and promoted.

Background As tumor genomes are shaped by their interaction with the immune system, a phenomenon known as immunoediting, it is critical to understand how immunotherapies impact this process. Checkpoint inhibitors directly influence T cells responding to neoantigens, as such, these therapies drastically affect the genomes of surviving tumor clones. Similar to the concept of immune camouflage, where genomes of pathogens evolve in a way to avoid immune detection, we hypothesized that tumor clones surviving checkpoint inhibition therapy harbor mutations more prone to immune avoidance. Methods We analyzed a published cohort of Nivolumab-treated melanoma patients (n=41) for which tumor samples were collected from the same site prior ('Pre' samples) and during ('On' samples) Nivolumab therapy.1 The immunogenic and tolerance potential of mutations from the Pre and On samples were evaluated with the Ancer neoantigen screening platform,2 which includes the EpiMatrix algorithm to identify HLA class I and HLA class II neoepitopes and the JanusMatrix algorithm to evaluate neoepitopes for homology with the self genome. Prior work with JanusMatrix showed that neoantigens highly homologous to self might be inhibitory.3 Results Tumor samples collected during Nivolumab therapy demonstrated increased homology (self-like) scores from their matched pre-therapy samples (paired t test, p=0.0475). While this increase in homology with self was significant across the cohort, the effect was more pronounced in patients exhibiting complete (CR) or partial responses (PR), compared to patients with stable (SD) or progressive disease (PD). An ANOVA analysis confirmed that increase in homology after Nivolumab therapy was significantly greater in CR/PR patients, as opposed to SD or PD patients (p=0.0005). This observation was supported by Receiver Operating Characteristic (ROC) analysis discriminating CR/PR patients from SD/PD patients based on differences in homology with self between Pre and On treatment samples (AUC=0.7484, p=0.0313). A comparative ROC analysis employing baseline patient tumor mutation burden (TMB) yielded non-conclusive results (AUC= 0.5054, p=0.9613). Conclusions Our Ancer analysis highlights that Nivolumab therapy affects the tolerance profile of tumors in a manner that is consistent with the concepts of immunoediting and immune camouflaging. Interestingly, tumors in patients with favorable outcomes demonstrated the greatest increase in selflike neoepitopes. This observation suggests that collecting tumor biopsies shortly after the initiation of checkpoint inhibitor therapy and evaluating their tolerance profile may be employed as a prognostic biomarker. Furthermore, this approach highlights in silico tools may distinguish effector from tolerance inducing neoepitopes, a critical feature for designing novel neoantigen-based precision immunotherapies

RATIONALE & OBJECTIVE/UNASSIGNED:Adherence to recommended medical treatment is critical in chronic kidney disease (CKD) to prevent complications and progression to kidney failure. Overall adherence to treatment is low in CKD, and as few as 40% of patients with kidney failure receive any documented CKD-related care. The purpose of this study was to explore the experiences of patients with CKD and their adherence to CKD treatment plans, and the role their health care providers played in supporting their adherence. STUDY DESIGN/UNASSIGNED:One-on-one interviews were conducted in 2019-2020 using a semi-structured interview guide. Participants described experiences with adherence to treatment plans and what they did when experiencing difficulty. SETTING & PARTICIPANTS/UNASSIGNED:Participants were recruited from the Chronic Renal Insufficiency Cohort (CRIC) study. All CRIC participants were older than 21 years with CKD stages 2-4; this sample consisted of participants from the University of Pennsylvania CRIC site. ANALYTICAL APPROACH/UNASSIGNED:Interviews were recorded, transcribed, and coded using conventional content analysis. Data were organized into themes using NVivo 12. RESULTS/UNASSIGNED:. From analysis of factors relevant to treatment planning and adherence, following 4 major themes emerged: patient factors (multiple chronic conditions, motivation, outlook), provider factors (attentiveness, availability/accessibility, communication), treatment planning factors (lack of plan, proactive research, provider-focused treatment goals, and shared decision making), and treatment plan responses (disagreeing with treatment, perceived capability deficit, lack of information, and positive feedback). LIMITATIONS/UNASSIGNED:The sample was drawn from the CRIC study, which may not be representative of the general population with CKD. CONCLUSIONS/UNASSIGNED:These themes align with Behavioral Learning Theory, which includes concepts of internal antecedents (patient factors), external antecedents (provider factors), behavior (treatment planning factors), and consequences (treatment plan responses). In particular, the treatment plan responses point to innovative potential intervention approaches to support treatment adherence in CKD.

OBJECTIVE:F]NaF PET-MRI was used to study the acute joint response to exercise in OA knees, and compare relationships between regions of increased uptake after loading and structural OA progression two years later. METHODS:> 3) were identified and the presence of structural MRI features was noted. Five participants returned two years later to assess structural change on MRI. RESULTS:P < 0.001) that differed by bone region. CONCLUSION:There were regional differences in the acute bone metabolic response to exercise and areas of focally large changes in the metabolic bone response that might be representative of whole-joint dysfunction.

Human papillomavirus (HPV) is currently linked to almost 35,000 new cases of cancer in women and men each year in the United States. Gardasil-9 (Merck & Company), the only HPV vaccine now available in the United States, is nearly 100% effective at preventing precancers caused by oncogenic HPV types. In the United States, however, only about one half of adolescents are up to date with HPV vaccination. It is well known that health care clinicians' recommendations play a significant role in parents' decisions regarding HPV vaccination. A growing body of literature examines specific communication strategies for promoting uptake of the HPV vaccine. A comprehensive review of the evidence for each of these strategies is needed. The authors searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Complete databases for original articles with a defined clinician communication strategy and an outcome of HPV vaccine uptake or intention to vaccinate (PROSPERO registry no. CRD42020107602). In total, 46 studies were included. The authors identified two main strategies with strong evidence supporting their positive impact on vaccine uptake: strong recommendation and presumptive recommendation. Determinations about a causal relationship were limited by the small numbers of randomized controlled trials. There is also opportunity for more research to determine the effects of motivational interviewing and cancer-prevention messaging.

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.