Diehl, Nancy N.

BACKGROUNDAndrogenic alopecia (AGA) is a common hair loss disorder. Studies have demonstrated successful treatment with platelet-rich plasma (PRP) in men, but studies in women are few.OBJECTIVETo evaluate PRP in the treatment of AGA in women, compared with topical minoxidil.MATERIALS AND METHODSTwenty women with AGA received topical minoxidil for 12 weeks and injectable PRP for 12 weeks in a randomized crossover design with an 8-week washout between treatments. Standardized TrichoScan analysis and quality-of-life questionnaires were assessed at baseline and 12-week follow-up for each treatment.RESULTSAfter PRP, significant increases from baseline to Week 12 in TrichoScan analysis hair count (p= .002) and vellus hair density (p= .009) occurred. However, minoxidil resulted in significant increases in hair count (p< .001), vellus hair density (p= .03), terminal hair density (p= .004), and cumulative thickness (p= .004). Several quality of life responses improved from baseline to Week 12 after PRP treatment, whereas no improvements were noted after minoxidil.CONCLUSIONPlatelet-rich plasma is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil. However, the improved quality of life responses after PRP, but not minoxidil, suggest a potential overall greater degree of satisfaction with PRP.LEVELS OF EVIDENCEI.CLINICAL TRIAL REGISTRATIONNCT03488108.

AbstractChronic traumatic encephalopathy is a debilitating neurodegenerative disorder associated with repetitive traumatic brain injuries often sustained through prior contact sport participation. The frequency of this disorder in a diverse population, including amateur athletes, is unknown. Primary historical obituary and yearbook records were queried for 2566 autopsy cases in the Mayo Clinic Tissue Registry resulting in identification of 300 former athletes and 450 non‐athletes. In these cases, neocortical tissue was screened for tau pathology with immunohistochemistry, including pathology consistent with chronic traumatic encephalopathy, blinded to exposure or demographic information. Using research infrastructure of the Rochester Epidemiology Project, a comprehensive and established medical records‐linkage system of care providers in southern Minnesota and western Wisconsin, medical diagnostic billing codes pertaining to head trauma, dementia, movement disorders, substance abuse disorders and psychiatric disorders were recorded for cases and controls in a blinded manner. A total of 42 individuals had pathology consistent with, or features of, chronic traumatic encephalopathy. It was more frequent in athletes compared to non‐athletes (27 cases versus 15 cases) and was largely observed in men (except for one woman). For contact sports, American football had the highest frequency of chronic traumatic encephalopathy pathology (15% of cases) and an odds ratio of 2.62 (P‐value = 0.005). Cases with chronic traumatic encephalopathy pathology had higher frequencies of antemortem clinical features of dementia, psychosis, movement disorders and alcohol abuse compared to cases without chronic traumatic encephalopathy pathology. Understanding the frequency of chronic traumatic encephalopathy pathology in a large autopsy cohort with diverse exposure backgrounds provides a baseline for future prospective studies assessing the epidemiology and public health impact of chronic traumatic encephalopathy and sports‐related repetitive head trauma.

Abstract Introduction: An inverse association between alcohol consumption and risk of renal cell carcinoma (RCC) is well reported in the literature. Despite this, no investigators have explored the potential for effect modification of this association by genetic variations in enzymes that metabolize alcohol. Motivated by this, we conducted a pilot investigation of the role of genetic variation in the alcohol dehydrogenase genes (ADH) as an effect modifier of the association of alcohol and RCC risk. Methods: We analyzed data on 121 RCC cases and 121 controls. Cases were prospectively collected as part of our Renal Registry in the Department of Urology. Controls were recruited through the Family Medicine and frequency matched to cases on age, gender and state of residence. We collected detailed risk factor data (self-report questionnaire) as well as a DNA sample on cases and controls. We utilized Sequenome analysis to determine presence of published SNPs in the ADH gene cluster (ADH1-7). We employed logistic regression with interaction terms as well as stratified analyses to evaluate effect modification by genetic variants in the ADH gene cluster on the association of alcohol consumption and RCC risk. Results: Compared to non-drinkers, those that consumed alcohol above the median experienced a lowering in RCC risk (OR=0.80; 95% CI 0.5 to 1.43). We observed evidence of interactions with 6 SNPs in the ADH gene (p-values from 0.05-0.2). As an example, in stratified analysis, the inverse association strengthened in those without the minor allele present at rs1154454 in ADH7 (OR=0.56; 95% CI 0.3 to 1.0; p=0.08) while evidence of an increased in RCC risk was noted among those with the minor allele (OR=2.14; 95CI 0.8 – 5.7; p=0.1). Adjustment for age and gender did not alter our results. Conclusion: Our pilot data suggest that specific variants in the ADH gene cluster may modify the reported protective effect of alcohol consumption on RCC risk. Given the possible implications for improving our understanding of the biology of this association and informing prevention, future investigations that analyze a larger sample size and examine additional variants are warranted. Citation Format: Alexander Scott Parker, Nancy Diehl, Michelle L. Arnold, Shauna Rivera, Ashley Cannon, Kaitlynn Custer, Bradley Leibovich. Alcohol consumption, genetic variation in alcohol dehydrogenase genes, and risk of clear cell renal cell carcinoma. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A62.

e20599 Background: The anti-PD-1 antibodies nivolumab and pembrolizumab have demonstrated improved overall survival (OS) and progression free survival (PFS) in a subset of patients with metastatic or locally advanced lung cancer (LC). To date, no blood biomarkers have been identified to predict clinical outcome to anti-PD-1 agents. Methods: A retrospective analysis of 52 patients with advanced LC and treated with anti-PD-1 antibodies in a single institution was performed. White blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute neutrophil to absolute lymphocyte count ratio (ANC/ALC), absolute eosinophil count (AEC), and platelet counts at baseline before start of anti-PD-1 antibody were assessed. Kaplan–Meier and Cox regression analysis were done. Results: 48 patients were treated with nivolumab (92.3%) and 4 patients with pembrolizumab (7.7%). Median follow up was 13.6 months and median OS was 26 months. Higher baseline ANC and ANC/ALC ratio significantly correlated with worse clinical outcomes. Patients with baseline ANC > 6060/mm3 had a significantly increased risk of death [hazard ratio (HR) = 2.46; 95% CI 1.12–5.42, P = 0.025] and of progression on anti-PD-1 antibody [HR = 2.41; 95% CI 1.25–4.64, P = 0.009] compared with patients with ANC ≤6060/mm3. Similarly, patients with baseline ANC/ALC ratio ≥ 4.59 had a significantly increased risk of death [HR = 2.41; 95% CI 1.11–5.24, P = 0.027] and of progression on anti-PD-1 antibody [HR = 2.08; 95% CI 1.10–3.95, P = 0.027] compared with patients with ANC/ALC < 4.59. One year survival rate in patients who had ANC < 3390/mm3, ANC 3390-6060/mm3 and ANC > 6060/mm3 were 86.5%, 76.9% and 48.1% respectively. Conclusions: Increased baseline ANC and ANC/ALC were associated with poor PFS and OS in LC patients treated with anti-PD-1 antibodies. Although these findings need to be validated in a large sample size, our data suggested that baseline ANC and ANC/ALC ratio might help the risk stratification and assist treatment strategies. The potential predictive value of peripheral blood biomarkers for clinical outcomes to anti-PD-1 antibody should be further investigated in a prospective study.

Objective Bone marrow aspiration and concentration (BMAC) is becoming a more common regenerative therapy for musculoskeletal pathology. In our current pilot study, we studied patients with mild-to-moderate bilateral knee osteoarthritis, compared pain at 12-month follow-up between BMAC-injected and saline-injected knees, and examined cartilage appearance measured by magnetic resonance imaging (MRI) T2 quantitative mapping. Design Twenty-five patients with mild-to-moderate bilateral osteoarthritic knee pain were randomized to receive BMAC into one knee and saline placebo into the other. Bone marrow was aspirated from the iliac crests, concentrated in an automated centrifuge, combined with platelet-poor plasma for knee injection, and compared with saline injection into the contralateral knee. Primary outcome measures were T2 MRI cartilage mapping at 6-month and Visual Analog Scale and Osteoarthritis Research Society International Intermittent and Constant Osteoarthritis Pain scores and radiographs at 12-month follow-up. Results Constant, intermittent, and overall knee pain remained significantly decreased from baseline at 12-month follow-up (all P ⩽ 0.01), with no apparent difference between BMAC- and saline-treated knees (all P ⩾ 0.54). A similar significant increase from baseline to 12-month follow-up regarding quality of life was observed for both BMAC- and saline-treated knees (all P ⩽ 0.04). T2 quantitative MRI mapping showed no significant changes as a result of treatment. Conclusions BMAC is safe to perform and relieves pain from knee arthritis but showed no superiority to saline injection at 12-month follow-up. MRI cartilage sequences failed to show regenerative benefit with single BMAC injection. The mechanisms of action that led to pain relief remain unclear and warrant further studies.