Citations

The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson’s disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

Opioid use disorder (OUD) is a cause of significant morbidity and mortality in the United States. Although efforts are being made to limit access to prescription opioids, the use of heroin and synthetic opioids as well as death due to opioid overdose has increased. Medication-assisted treatment (MAT) is the pairing of psychosocial intervention with a Food and Drug Administration (FDA)–approved medication (methadone, buprenorphine plus naltrexone) to treat OUD. MAT has resulted in reductions in overdose deaths, criminal activity, and infectious disease transmission. Access to MAT in rural areas is limited by shortages of addiction medicine-trained providers, lack of access to comprehensive addiction programs, transportation, and cost-related issues. Rural physicians express concern about lack of mentorship and drug diversion as reasons to avoid MAT. The prescribing of MAT with buprenorphine requires a Drug Enforcement Agency (DEA) waiver that can easily be obtained by Family Medicine providers. MAT can be incorporated into the outpatient practice, where patient follow-up rates and number needed to treat to effect change are similar to that of other chronic medical conditions. We describe a case of opioid overdose and a suggested protocol for the induction of MAT with buprenorphine/naloxone (Suboxone) for OUD in a rural family medicine outpatient practice. Treatment access is facilitated by utilizing the protocol, allowing office staff work to the extent allowed by their licensure, promoting teamwork and minimizing physician time commitment. We conclude that improved access to MAT can be accomplished in a rural family medicine outpatient clinic by staff that support and mentor one another through use of a MAT protocol.

11041 Background: Twitter (TW) is an essential tool in the medical community. Few studies have examined the use of TW by medical trainees. We aimed to assess its utilization among trainees in hematology-oncology related areas (HORAs). Methods: 576 training programs in HORAs were obtained. We contacted a potential pool of 3,142 trainees. A 50 item survey was distributed between 2/2019-5/2019, focusing on: demographics, professional use, attitudes toward TW, and patient interactions. Responses were analyzed using parametric descriptive statistics. Results: 442 responses (14% response rate) were received; 203 (46%) used a TW account for professional activities. See table for demographics. The most common reasons for using TW were: continuous education (73%), dissemination of information (62%), and networking (62%). > 80% of users have positive views on using TW for: promoting academic discussions (92%), trainees education (89%), and conference networking (83%). 50 (25%) have used TW for collaborations, with abstracts and papers being the most common (20%). Most agreed or strongly agreed that TW: is a useful education tool (89%), and might be useful for career advancement (85%). The most common challenges were: the value of TW content can be decreased by irrelevant content and biased sources (64%), not peer-reviewed (51%), and difficulty searching information (50%). 68% considered that programs should promote the engagement of trainees, but only 21% reported instruction in the use of TW. 83% agree or strongly agree that TW is useful for physicians and patient interactions, but 82% have concerns about legal repercussions. Conclusions: Almost half of trainees in HORAs use TW for professional activities. The most common uses are for education, dissemination of information and networking. Most trainees that use TW have positive views regarding education and academic collaborations. Use of Twitter may strengthen trainees’ education, provide mentorship opportunities, and promote career advancement. Challenges on TW use should continue to be addressed. [Table: see text]

e20029 Background: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary disorder with neuroendocrine cell proliferation with potential progression to lung neuroendocrine tumor (Lu-NET). Optimal diagnostic and treatment strategies have yet to be well defined. Herein, we aim to describe the Mayo Clinic experience with DIPNECH. Methods: A retrospective analysis was performed of patients diagnosed with DIPNECH within Mayo Clinic between January 2000-Febuary 2019. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, disease characteristics, time of diagnosis, surgery, and last follow up date were extracted. Extent of symptom burden, treatment approaches, disease progression, and disease-free survival (DFS) were evaluated by chart review. Results: A total of 59 patients were identified with a median age of 63(43-81) years. The cohort was predominantly female (93.2%) and non-smoking (76.3%). Most patients (86.4%) had symptomatic disease with chronic cough being the most common (71.2%) followed by exertional dyspnea (44.1%). Imaging typically showed bilateral lung nodules (93.2%) with mosaic attenuation noted 69.5% of the time. Surgical resection was frequently completed to confirm diagnosis (94.9%). Most patients received inhaled glucocorticoids combined with a beta agonist (79.7%). Oral steroid use was seen in 49.2% of patients whereas a somatostatin analog was used in 15.3% following the diagnosis of DIPNECH. These medical interventions led to symptom relief in 23.7% of the patients. The median follow up for all patients was 19.5 months. Progression of tumorlets was seen in 48.7% of patients with only 7(17.9%) patients progressing to a diagnosis of Lu-NET. The 3-year DFS was 90.5%. Conclusions: This is amongst the largest studies completed evaluating DIPNECH patients. DIPNECH remains a rare disease more commonly diagnosed in women in their early 60’s. DIPNECH appears to have an indolent course with obstructive symptoms being the most common finding. A minority of patients experienced symptom relief with therapy. Overall, DIPNECH appears to have a low risk of progressing to Lu-NET based on the observation of this study.

Objective: The objective of this study was to compare posttransplant outcomes in patients undergoing bridging locoregional therapy (LRT) with Y-90 transarterial radioembolization (TARE) based protocol compared with transarterial chemoembolization based protocol for hepatocellular carcinoma (HCC) prior liver transplantation (LT). Materials and Methods: Patients listed for LT with HCC within the Milan criteria at our center who had bridging LRT were treated according to transarterial chemoembolization (TACE) based protocol from May 2012 to April 2014 and a TARE based protocol from October 2014 to December 2017. Early posttransplant survival and tumor recurrence were compared between the groups. Tumor response to LRT, microvascular invasion (mVI), and the rate of delisting was also evaluated. Results: One hundred three patients who were listed for LT with HCC within the Milan criteria received LRT. LT was performed in 65 patients, 28 treated with TARE protocol and 37 on TACE protocol. There were no statistical differences in baseline pretransplant characteristics and tumor recurrence. There was a trend toward improved 3-year survival in the TARE group (92.9% vs. 75.7%; P=0.052). The mVI was seen in 1/28 (3.6%) explants in the TARE group compared with 10/37 (27%) in the TACE group (P=0.013). The TARE group also required fewer LRT treatments (1.46 vs. 2.43; P=0.001) despite no difference in time on the transplant list. Conclusions: Despite requiring fewer LRT treatments, there was significantly less mVI in the explants of patients treated with TARE protocol LRT as a bridge to LT as well as a trend toward improved 3-year survival. Therefore, TARE may be associated with improved tumor control and reduced post-LT recurrence.

We developed a novel model to study peripheral tolerance using mice expressing chicken ovalbumin under a rat insulin promoter. In contrast to previous RIP‐OVA mouse models, we induce autoimmune diabetes by activating the natural T cell repertoire; not by transfer of high affinity TCR T cells. Our treatment, DCXAb + OVA, employs adoptive transfer of dendritic cells (DC) pulsed with neoself antigen OVA and monoclonal therapeutic antibody (MTAb) B7‐DC XAb. This immunomodulatory MTAb crosslinks B7‐DC (PD‐L2) and activates DC. In our model, Tg mice develop severe hyperglycemia and loss of islet beta cells in 7 days. Adoptive transfer of IL‐6 KO DC, a cytokine involved in suppression of Treg, fails to cause diabetes. Also, nondiabetic splenocytes suppress proliferation of diabetogenic T cells, suggesting Treg are involved. DCXAb + OVA induces a specific break in tolerance that is beneficial when targeting tumors. In this light, splenocytes from diabetic mice specifically kill B16‐OVA targets but not B16. DCXAb treatment allows specific activation of the natural T cell repertoire and will help elucidate effectors important in autoimmunity and cancer therapy.

Abstract Abstract 880 Pulmonary marginal zone lymphoma is a distinct subgroup of B-cell non-Hodgkin's lymphomas originating from the bronchial-associated lymphoid tissue (BALT) and characterized by an indolent clinical course. Here we present the data of the IELSG-28 study of the International Extranodal Lymphoma Study Group (IELSG) on primary pulmonary lymphoma patients. Clinical records and histological material of 186 patients diagnosed with pulmonary marginal zone lymphoma from December 1986 to June 2009 were collected. The pathology was reviewed centrally and the diagnosis was confirmed in 180 (96%) patients. The median age at diagnosis was 62 (30 – 88). The majority of the patients (149/180) had localized disease at diagnosis with a good performance status (0–1) and low prognostic index (IPI 0–2). Eighty-one patients (45%) received local treatment, including surgery (74%) or radiotherapy (4%). Ninety-nine patients with advanced stage disease or incomplete surgical resection received an additional systemic treatment. Most of these patients (66; 66%) received an alkylating containing regimen, 22 (22%) patients were treated with an anthracycline containing regimen and 29 (29%) received the anti-CD20 monoclonal antibody in combination with chemotherapy. With a median follow up of 67 (range 1–256) months, 47/180 patients (26%) experienced disease progression. (median time to progression 30 months, range 0–109). Progression free survival analysis showed a trend in favour of patients treated with immuno-chemotherapy versus those receiving chemotherapy alone (HR 0.53–95%CI: 0.21, 1.33), while no difference in terms of OS and PFS was observed between patients receiving systemic anthracycline or alkylating containing regimens. In twenty five cases a specific PCR-assay was carried out for detecting the presence of Achromobacter (Alcaligenes) xylosoxidans. The presence of Achromobacter was detected in 50% of patients. Our results confirm that local therapy (surgery or radiotherapy) is the treatment of choice for patients with localized disease. Chemotherapy has to be considered in case of relapse, incomplete surgical excision or advanced disease. In this setting, alkylating containing regimens plus rituximab is the most effective option. Further studies are ongoing to confirm the relevance of infection/colonization with Achromobacter (Alcaligenes) xylosoxidans for pathogenesis of BALT lymphoma. Disclosures: No relevant conflicts of interest to declare.

AbstractGranular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA‐1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), −13q in 4 of 6, and −14 in 4 of 6. Next‐generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB‐1 (P > 0.05). GCA is a variant of IDH‐wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.

Health professions educators face multiple challenges, among them the need to adapt educational methods to new technologies. In the last decades, multiple new digital platforms have appeared in the learning arena, including massive open online courses and social-media-based education. The major critique of these novel methods is the lack of the ability to ascertain the origin, validity, and accountability of the knowledge that is created, shared, and acquired. Recently, a novel technology based on secured data storage and transmission, called blockchain, has emerged as a way to generate networks where validity, trust, and accountability can be created. Conceptually, blockchain is an open, public, distributed, and secure digital registry where information transactions are secured and have a clear origin, explicit pathways, and concrete value. Health professions education based on blockchain will potentially allow improved tracking of content and the individuals who create it, quantify educational impact on multiple generations of learners, and build a relative value of educational interventions. Furthermore, institutions adopting blockchain technology would be able to provide certification and credentialing of health care professionals with no intermediaries. There is potential for blockchain to significantly change the future of health professions education and radically transform how patients, professionals, educators, and learners interact around safe, valid, and accountable information.