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LBA8501 Background: Plasma cfDNA genomic analysis is used widely for the care of advanced lung cancer, but its suitability for early stage lung cancer detection is not well established. CCGA (NCT02889978) is a prospective, multi-center, observational study launched for the development of a noninvasive assay for cancer detection. Methods: Blood was prospectively collected (N = 1627) from 749 controls (no cancer diagnosis) and 878 participants (pts) with newly-diagnosed untreated cancer in this preplanned substudy, including 127 pts with lung cancer. Three prototype sequencing assays were performed: paired cfDNA and white blood cell (WBC) targeted sequencing (507 genes, 60,000X) for single nucleotide variants/indels; paired cfDNA and WBC whole genome sequencing (WGS) for copy number variation (30X); and cfDNA whole genome bisulfite sequencing (WGBS) for methylation (30X). For each assay, a classification model using 10-fold cross-validation was developed for all pts with cancer, then evaluated in the pts with lung cancer; sensitivity was estimated at 95% specificity. Results: We evaluated pts with lung cancer (127) and a subset of controls (580) with similar ages (mean±SD yrs: 67±9, 60±13), 85% and 43% were ever-smokers, and 46% and 22% were men, respectively. Of 3055 nonsynonymous mutations detected across 122 evaluable pts with lung cancer, > 50% were detected in WBC consistent with clonal hematopoiesis (CH). Accounting for CH, sensitivity in 63 stage I-IIIA pts evaluable across all 3 assays was 48% (35-61, targeted), 54% (41-67, WGS), and 56% (43-68, WGBS); in 54 stage IIIB-IV pts it was 85% (73-93, targeted), 91% (80-97, WGS), and 93% (82-98, WGBS) . Similar sensitivities were observed across histological subtypes (adenocarcinoma, squamous cell, small cell). Comparison to tumor WGS and multi-assay classification will be reported. Conclusions: Early stage lung cancers are detectable in cfDNA using a genome-wide sequencing approach. For lung cancer detection using targeted assays, CH must be accounted for to minimize false positives. Assay optimization is ongoing to allow further clinical development in the intended use population. Clinical trial information: NCT02889978.

AbstractBackgroundClinical diagnostic criteria for PD rely on rest tremor, bradykinesia, and rigidity. These features are non‐specific and neuropathological confirmation remains the gold standard for diagnosis. This study presents data on clinical certainty ratings in autopsy‐proven PD.MethodsSubjects were assessed annually by a movement disorders specialist and assigned to a clinical certainty group for PD based on multiple clinical features before autopsy. The three groups considered for analysis are as follows: Group I 0–49% certainty, Group II 50‐89% certainty, and Group III 90–100% certainty. All subjects were autopsied and had a standardized neuropathological assessment.Results275 subjects were assigned a PD certainty at their last visit before death. Group I had 80 subjects, Group II 56 subjects, and Group III 139 subjects. The clinical features recorded in Group I, II, and III, were as follows: rest tremor, bradykinesia, rigidity, postural instability, asymmetric onset, persistent asymmetry, current response to dopaminergic treatment, motor fluctuations, and dyskinesia. Rigidity, postural instability, asymmetric onset, current response to dopaminergic treatment, motor fluctuation, and dyskinesia were more likely to be present in the group which was rated with higher certainty. The final diagnosis of PD was confirmed by neuropathological assessment in 85% of the patients in Group III as compared to 30% in Group II and 5% in Group I.ConclusionsHigh certainty (90–100%) had strong positive predictive value (85%) for autopsy‐proven PD as compared to either lower certainty groups (0–49% and 50–89%) which had lower predictive value (5% and 30% respectively).

BACKGROUND After histopathological confirmation of a biopsy sample, cutaneous squamous cell carcinoma (cSCC) is often treated surgically; yet, residual tumor within the excision sample is not always found. The prevalence of residual cSCC after shave biopsy in solid organ transplant recipients (SOTRs) is unknown. OBJECTIVE Determine the prevalence of residual cSCC after shave biopsy in SOTRs. METHODS A retrospective case-controlled review was performed from a single center. Data were collected for 117 SOTRs and 117 age-matched nonimmunosuppressed controls diagnosed with shave biopsy–proven cSCC who underwent subsequent wide local excision from January 2004 to December 2016. Multivariable conditional logistic regression was used to determine variables associated with residual tumor in the combined population. Univariate logistic regression was used to investigate if transplant-related variables were associated with residual tumor in the SOTR group. RESULTS Of the 117 SOTRs, 57 (48.7%) had residual tumor within the excisional specimen. Of the 117 controls, 31 (26.5%) had residual tumor within the excisional specimen. Solid organ transplant recipients have 2.59 times greater odds of having residual cSCC after shave biopsy (95% confidence interval: 1.29–5.22, p = .0076). CONCLUSION Solid organ transplant recipients have a higher prevalence of residual cSCC after shave biopsy when compared with nonimmunosuppressed controls and should be prioritized for margin-controlled surgery.

AbstractIntroductionDepression and neuropsychiatric disorders in individuals with essential tremor (ET) are not well characterized in the literature.MethodsWe compared 104 ET subjects with 481 non‐ET controls involved in the Arizona Study of Aging and Neurodegenerative Disorders. An analysis of baseline depression scales and neuropsychiatric inventory (NPI) was done between the two groups. Additionally, comparisons were made within the ET group based on tremor severity, duration of tremor, and age of onset.ResultsThere were no significant differences between the ET and non‐ET groups. There were no significant differences in the ET group above and below the median tremor duration. Additionally, no differences were found in the ET group based on objective measures of tremor severity, age of onset, or those with subjectively distressing tremor compared with those without.ConclusionThere were no significant differences in depressive symptoms between ET and non‐ET groups. Furthermore, no correlation was found between depressive symptoms in ET groups based on tremor severity, duration, or age of onset.

Introduction: This study set out to clarify the differential acute cognitive impact of lorazepam based on varying genetic risk for Alzheimer disease. Methods: Fifty-seven cognitively unimpaired individuals aged 51 to 88, genotyped according to apolipoprotein E (APOE) and translocase of outer mitochondrial membrane (40 homolog) poly-T lengths, completed cognitive testing before, 2.5 and 5 hours after receiving a 1 mg dose of lorazepam. Results: Post-lorazepam, there were significant (P<0.05) declines from baseline in memory, psychomotor processing speed, and executive function. At 2.5 hours, the magnitude of this lorazepam-induced cognitive change was significantly greater in the APOE3/4 group than in the APOE3/3 group for tests of working memory and visuospatial memory/executive function. At 5 hours postchallenge, verbal memory and working memory deficits persisted in the APOE3/4 group compared with the APOE3/3 group. At 5 hours after lorazepam challenge, as compared with the very long/very long group, the short/short group performed slightly worse on a test of working memory (P<0.05), but no other differences were observed among translocase of the outer mitochondrial membrane 40 homolog poly-T variant groups. Discussion: The lorazepam challenge may be unmasking presymptomatic cognitive dysfunction associated with APOE4 carriage.

AbstractBackgroundThorn injuries are common in the desert Southwest; however, the frequency and microbiology of thorn-associated infections have not been systematically described. Most information comes from case reports describing infections from atypical or environmental microorganisms. Our aim was to summarize the spectrum of thorn-associated infections.MethodsWe conducted a retrospective review of electronic health records for patients presenting to our institution from January 1, 2005 to December 31, 2014 for treatment of thorn-associated injuries and then focused on the patients with cultures.ResultsOf 2758 records reviewed, 1327 patients had thorn-associated injuries; however, only 58 (4.4%) had cultures. Of these patients, 37 (64%) had positive findings; 5 had polymicrobial infection. The most commonly identified organisms were Staphylococcus aureus (n = 22, 59.0%) and coagulase-negative Staphylococcus species (n = 8, 21.6%). Other pathogens included Nocardia species (n = 3, 8.1%), Streptococcus species (n = 2, 5.4%), Gram-negative bacteria (n = 2, 5.4%), Aspergillus species (n = 2, 5.4%), Paecilomyces lilacinus (n = 1, 2.7%), and Candida species (n = 1, 2.7%). There were no infections caused by Pantoea agglomerans, Sporothrix schenckii, or Coccidioides spp.ConclusionsIn contrast to most published case reports, we found that typical cutaneous microorganisms, such as Staphylococcus species, caused the majority of culture-positive, thorn-related infections.

AbstractBackgroundSurvivors of childhood non‐Hodgkin lymphoma (NHL) are at increased risk for chronic health conditions. The objective of this study was to characterize health conditions, neurocognitive function, and physical performance among a clinically evaluated cohort of 200 childhood NHL survivors.MethodChronic health and neurocognitive conditions were graded as per a modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and impaired physical function defined as performance < 10th percentile of normative data. Multivariable regression was used to investigate associations between sociodemographic characteristics, therapeutic exposures, and outcomes.ResultsSurvivors were a median age of 10 years (range 1–19) at diagnosis and 34 years (range 20–58) at evaluation. Eighty‐eight (44%) received radiation, 46 (23%) cranial radiation, and 69 (35%) high‐dose methotrexate. Most prevalent CTCAE Grades 3–4 (severe life‐threatening) conditions were obesity (35%), hypertension (9%), and impairment of executive function (13%), attention (9%), and memory (4%). Many had impaired strength (48%), flexibility (39%), muscular endurance (36%), and mobility (36%). Demographic and treatment‐related factors were associated with the development of individual chronic diseases and functional deficits.ConclusionsClinical evaluation identified a high prevalence of chronic health conditions, neurocognitive deficits, and performance limitations in childhood NHL survivors.

Abstract Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness‐based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness‐based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6‐week mindfulness‐based resilience training ( MBRT ) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty‐one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health‐related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant ( P <.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality‐of‐life mental component ( P =.006) and positive affect ( P =.02) also improved at follow‐up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well‐being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.

Background.Sarcoma is a rare malignancy, and more recent management algorithms emphasize a multidisciplinary approach and limb salvage, which has resulted in an increase in overall survival and limb preservation. However, limb salvage has resulted in a higher rate of wound complications.Objective.To compare the complications between immediate and delayed (>three weeks) reconstruction in the multidisciplinary limb salvage sarcoma patient population.Methods.A ten-year retrospective review of patients who underwent sarcoma resection was performed. The outcome of interest was wound complication in the postoperative period based on timing of reconstruction. We defined infection as any infection requiring intravenous antibiotics, partial flap failure as any flap requiring a debridement or revision, hematoma/seroma as any hematoma/seroma requiring drainage, and wound dehiscence as a wound that was not completely intact by three weeks postoperatively.Results.70 (17 delayed, 53 immediate) patients who underwent sarcoma resection and reconstruction met the inclusion criteria. Delayed reconstruction significantly increased the incidence of postoperative wound infection and wound dehiscence. There was no difference in partial or total flap loss, hematoma, or seroma between the two groups.Discussion and Conclusion.Immediate reconstruction results in decreased wound complications may reduce the morbidity associated with multidisciplinary treatment in the limb salvage sarcoma patient.