Citations

AbstractBackgroundMultiple mononeuropathy is a rare presentation of primary (AL) amyloidosis and nerve biopsy is usually needed for diagnosis. Conventional imaging is useful to identify proximal nerve involvement but may be inadequate. We report a patient with multiple mononeuropathy whose presentation was suggestive of AL amyloid neuropathy and in whom repeated tissue biopsies were negative for amyloid (including two sensory nerves and one muscle).MethodsThe patient underwent magnetic resonance imaging (MRI) and whole body 18F‐florbetapir positron emission tomography (PET)/MRI.ResultsWhole body 18F‐florbetapir PET/MRI revealed abnormal low‐level florbetapir uptake in the right proximal tibial and peroneal nerves, which provided a target for a sciatic bifurcation fascicular nerve biopsy that was diagnostic of AL amyloidosis.Conclusions 18F‐florbetapir PET/MRI imaging is a promising diagnostic tool for patients with suspected peripheral nerve amyloidosis (including multiple mononeuropathy) in whom conventional imaging and nerve and muscle biopsies miss the pathology.

Abstract The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the adult critical care medicine core including complications of chemotherapy, acute-on-chronic liver failure, alcohol withdrawal syndrome, mechanical circulatory support, direct oral anticoagulants, upper gastrointestinal hemorrhage, and vasopressor selection.

AbstractBackgroundThe role of lymphadenectomy in adrenocortical carcinoma resection is controversial. Therefore, we conducted a population‐based study to assess the association between positive lymph nodes (LN) and survival.MethodsThe Surveillance, Epidemiology, and End Results set of cancer registries were utilized. The associations between positive lymph nodes and tumor size, grade and laterality were assessed. Cancer specific survival (CSS) trends and factors affecting survival were analyzed.ResultsA total of 2170 adult patients were identified; 60% underwent resection. Among those resected, LN were examined in 23% and were positive in 25% of patients with LN examined. Patients with positive LN tended to have smaller tumors compared to those with negative LN (12 ± 5 vs 15 ± 11 cm, p = 0.02). The rate of positive LN was higher in right ACC, p = 0.03. Median overall CSS was 21 months, with significant differences between resection (42 months) and no resection (4 months), p < 0.01. Median CSS did not change over time when comparing ACC patients who underwent surgery before 2000, 2000–2009, and 2010–2016. On multivariable analysis including resection group, advanced age, grades III and IV, regional and distant stage, in addition to positive LN were associated with worse survival, p < 0.05.ConclusionLymphadenectomy is infrequently performed during ACC resection, and when performed, regional LN involvement tends to be associated with worse survival. Neoplasm size and grade were not associated with LN involvement and therefore, do not inform lymphadenectomy need. Further studies are needed to assess the indications for, and value of lymphadenectomy in ACC.

AbstractAn 80-year-old man presented with new-onset pain in the shoulders and lower extremities and elevated serum inflammatory markers. A clinical diagnosis of polymyalgia rheumatica (PMR) was made, but there was a suboptimal response to glucocorticoid therapy, prompting further evaluation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed intense FDG uptake in the arteries of the bilateral lower extremities, head, and neck, but sparing the aorta, suggestive of an uncommon pattern of giant cell arteritis (GCA). There were also imaging signs consistent with PMR, including FDG uptake in the synovium of large joints. This case highlights the uncommon manifestation of GCA with lower extremity involvement and sparing of the aorta. The combination of FDG PET imaging features and elevated serum markers obviated the need for invasive biopsy. One might also conclude that standard FDG PET/CT imaging protocols covering orbits/vertex to thighs incompletely evaluate the extent of arterial distribution of GCA.

AbstractInfection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient‐ and surgeon‐dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9–54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5–149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR.

Abstract Background Currently acceptable management options for patients with adult papillary thyroid microcarcinoma (APTM) range from immediate surgery, either unilateral lobectomy or bilateral lobar resection, to active surveillance (AS). An alternative minimally invasive approach, originally employed for eliminating neck nodal metastases, may be ultrasound-guided percutaneous ethanol ablation (EA). Here we present our experience of definitively treating with EA 15 patients with APTM. Patients and Methods During 2010 through 2017, the 15 cT1aN0M0 patients selected for EA were aged 36 to 86 years (median, 45 years). Tumor volumes (n = 17), assessed by sonography, ranged from 25 to 375 mm3 (median, 109 mm3). Fourteen of 15 patients had 2 ethanol injections on successive days; total volume injected ranged from 0.45 to 1.80 cc (median, 1.1 cc). All ablated patients were followed with sonography and underwent recalculation of tumor volume and reassessment of tumor perfusion at each follow-up visit. Results The ablated patients have now been followed for 10 to 100 months (median, 64 months). There were no complications and no ablated patient developed postprocedure recurrent laryngeal nerve dysfunction. All 17 ablated tumors shrank (median 93%) and Doppler flow eliminated. Median tumor volume reduction in 9 identifiable avascular foci was 82% (range, 26%-93%). After EA, 8 tumors (47%) disappeared on sonography after a median of 10 months. During follow-up no new PTM foci and no nodal metastases have been identified. Conclusions Definitive treatment of APTM by EA is effective, safe, and inexpensive. Our results suggest that, for APTM patients who do not wish neck surgery and are uncomfortable with AS, EA represents a well-tolerated and minimally invasive outpatient management option.

Abstract Background: Early detection decreases patient mortality for many cancers, but prevailing paradigms focus on distinct screening modalities for each cancer type. A minimally invasive test that detects multiple tumor types could substantially reduce cancer mortality and improve screening efficiency. In preliminary studies, we showed that a targeted methylation cell-free DNA (cfDNA) test can detect cancer and determine the tissue of origin (TOO) of abnormally methylated cfDNA with high sensitivity and specificity; however, blood was collected at the time of diagnosis and results were not disclosed to inform care. The current study includes disclosure of results to the study investigator to understand the care pathways prompted by a “signal detected” test result, and the benefits, harms, and burdens associated with a multi-cancer detection test. Methods: PATHFINDER (NCT04241796) is a prospective, longitudinal, multi-center clinical study. Approximately 6,200 participants with varying levels of cancer risk will be enrolled at 5-10 clinical sites in the United States. Participants must be ≥50 years of age. If participants have at least 1 of the following–a smoking history of ≥100 cigarettes, a genetic cancer predisposition, or a history of invasive or hematologic malignancy with definitive treatment completed &gt;3 years prior to enrollment–they are eligible for the Elevated Risk Cohort (n = 4340); otherwise, they are eligible for the Non-Elevated Risk Cohort (n = 1860). Individuals being evaluated for cancer or who have a history of invasive or hematologic malignancy within 3 years of enrollment will be excluded. Blood drawn at study sites will be analyzed at GRAIL, Inc. (Menlo Park, CA). Participants and study investigators will be informed of the test results. Participants with “signal not detected” results will be advised to continue routine clinical care, including age- and risk-based cancer screening. Those with “signal detected” test results will be informed of the predicted origin and undergo diagnostic evaluation. The primary study objective is to determine the extent of diagnostic testing required to achieve diagnostic resolution following a “signal detected” test result, defined as the date when the study investigator determines to end diagnostic evaluation triggered by a “signal detected” test result. Health resource utilization, the number and types of tests and time required to reach this point, is the primary endpoint. Secondary objectives include evaluation of test performance (specificity, positive predictive value, and TOO accuracy), and assessment of participants' perceptions about the test and changes in anxiety and health-related quality of life. Exploratory aims include assessment of the number and types of invasive cancer diagnoses among participants with “signal not detected” test results and changes in attitude toward adherence to guideline-recommended screening. Citation Format: Lincoln Nadauld, Charles H. McDonnell III, Minetta C. Liu, Eric Klein, Tomasz M. Beer, Deborah Schrag, Andrew G. Hudnut, Richard Whittington, Bruce Taylor, Joanna Tierney, Catherine Marinac, Jafi Lipson, Margarita Lopatin, Karen C. Chung, Eric Fung, Anne-Renee Hartman, Geoffrey R. Oxnard. The PATHFINDER Study: Assessment of the implementation of an investigational multi-cancer early detection test into clinical practice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT291.

Abstract Background: The Circulating Cell-free Genome Atlas study (NCT02889978) is a multi-center, case-control, observational study with longitudinal follow-up (n=15,254; 56% cancer, 44% non-cancer) to support development of a cell-free DNA (cfDNA) multi-cancer early detection test. Previously, we reported that a targeted methylation assay detected and localized &gt;20 cancer types at &gt;99% specificity in individuals with cancer.1,2 Here, we report prediction of cancer (presence/absence) and tissue of origin (TOO) in individuals enrolled with clinical suspicion of cancer but without pathologic diagnosis or treatment at time of enrollment. Methods: Plasma cfDNA from blood samples collected prior to clinical diagnosis was subjected to targeted methylation sequencing. Samples were divided into a training set and an independent validation set to train and validate a machine learning classifier to assess cancer and predict TOO. Performance was assessed in a subset of participants enrolled with suspicion of cancer; subsequently, cancer was confirmed by evaluating a pathologic specimen. Results: Participants being evaluated for suspicion of cancer were classified as confirmed cancer (&gt;20 cancer types; n=164 in training, n=75 in validation) or confirmed non-cancer (n=49 training, n=15 validation). In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer (100% specificity). In the confirmed cancer group, cancer detection across all stages was 40.2% (66/164; 95% confidence interval [CI], 32.7-48.2%) in training and 46.7% (35/75; 95% CI, 35.1-58.6%) in validation. Excluding stage I renal cancers (where detection/tumor fraction is low in plasma and which comprised 20% of participants in this subset) detection across stages was 50.4% (66/131; 95% CI, 41.5-59.2%) and 59.3% (35/59; 95% CI, 45.7-71.9%), respectively. In stages II and above, detection was 70.7% (58/82; 95% CI, 59.6-80.3%) and 78.9% (30/38; 95% CI, 62.7-90.4%), respectively. For detected cancers, TOO was predicted in 93.9% (62/66) samples in training and 100% (35/35) in validation. Of those with a TOO call, accuracy was 85.5% (53/62; 95% CI, 74.2-93.1%) and 97.1% (34/35; 95% CI, 85.1-99.9%), respectively. Conclusion: A cfDNA multi-cancer detection test has shown the potential to predict cancer and TOO in individuals with suspicion of cancer ahead of histologic diagnosis with performance comparable to those with confirmed cancer at the time of blood collection. This was achieved with high specificity and TOO accuracy. The high specificity suggests that the false positive rate could be comparable in populations with average versus higher risk (suspicion) of cancer. These findings suggest that a cfDNA multi-cancer detection test could accelerate the diagnostic resolution of suspicion of cancer. References: 1. Oxnard GR, et al. ASCO Breakthrough Meeting 2019; Abstract 44. 2. Oxnard GR, et al. ESMO Annual Meeting 2019; Abstract 5639. Citation Format: David D. Thiel, Xiaoji Chen, Kathryn N. Kurtzman, Jessica Yecies, Tony Wu, Quan Zhang, Hai Liu, Nan Zhang, Eric T. Fung, Michael V. Seiden, Minetta C. Liu, Geoffrey R. Oxnard, Earl Hubbell, Alexander M. Aravanis, Anne-Renee Hartman, Eric A. Klein. Prediction of cancer and tissue of origin in individuals with suspicion of cancer using a cell-free DNA multi-cancer early detection test [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT021.

Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13–15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3–15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3–15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472–3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26–397) or orthopedic trauma controls ( n = 122; median = 13 pg/mL, IQR: 7–20), p < 0.001. Serum S100B levels were likewise higher in CT+ TBI subjects (median = 0.17 μg/L, IQR: 0.09–0.38) than in CT- TBI subjects (median = 0.10 μg/L, IQR: 0.06–0.18), p < 0.001. Receiver operating characteristic curves were generated for prediction of intracranial injury on admission CT scan; area under the curve (AUC) for GFAP was significantly higher than for S100B in the same cohort (GFAP AUC – 0.85, 95% confidence interval [CI] 0.83–0.87; S100B AUC – 0.67, 95% CI 0.64-0.70; p < 0.001). GFAP, measured on a point-of-care platform prototype assay, has high discriminative ability to predict intracranial abnormalities on CT scan in patients with TBI across the full injury spectrum of GCS 3–15 through 24 h post-injury. GFAP substantially outperforms S100B.