tbuckley/cabot-search huggingface dataset:
Expert-Level Diagnosis of Nonpigmented Skin Cancer by Combined Convolutional Neural Networks
Authors: Philipp Tschandl, Cliff Rosendahl, Bengu Nisa Akay, Giuseppe Argenziano, Andreas Blum, Ralph P. Braun, Horacio Cabo, Jean-Yves Gourhant, Jürgen Kreusch, Aimilios Lallas, Jan Lapins, Ashfaq Marghoob, Scott Menzies, Nina Maria Neuber, John Paoli, Harold S. Rabinovitz, Christoph Rinner, Alon Scope, H. Peter Soyer, Christoph Sinz, Luc Thomas, Iris Zalaudek, Harald Kittler
Journal: JAMA Dermatology (2018)

Convolutional neural networks (CNNs) achieve expert-level accuracy in the diagnosis of pigmented melanocytic lesions. However, the most common types of skin cancer are nonpigmented and nonmelanocytic, and are more difficult to diagnose.To compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience.A CNN-based classification model was trained on 7895 dermoscopic and 5829 close-up images of lesions excised at a primary skin cancer clinic between January 1, 2008, and July 13, 2017, for a combined evaluation of both imaging methods. The combined CNN (cCNN) was tested on a set of 2072 unknown cases and compared with results from 95 human raters who were medical personnel, including 62 board-certified dermatologists, with different experience in dermoscopy.The proportions of correct specific diagnoses and the accuracy to differentiate between benign and malignant lesions measured as an area under the receiver operating characteristic curve served as main outcome measures.Among 95 human raters (51.6% female; mean age, 43.4 years; 95% CI, 41.0-45.7 years), the participants were divided into 3 groups (according to years of experience with dermoscopy): beginner raters (<3 years), intermediate raters (3-10 years), or expert raters (>10 years). The area under the receiver operating characteristic curve of the trained cCNN was higher than human ratings (0.742; 95% CI, 0.729-0.755 vs 0.695; 95% CI, 0.676-0.713; P < .001). The specificity was fixed at the mean level of human raters (51.3%), and therefore the sensitivity of the cCNN (80.5%; 95% CI, 79.0%-82.1%) was higher than that of human raters (77.6%; 95% CI, 74.7%-80.5%). The cCNN achieved a higher percentage of correct specific diagnoses compared with human raters (37.6%; 95% CI, 36.6%-38.4% vs 33.5%; 95% CI, 31.5%-35.6%; P = .001) but not compared with experts (37.3%; 95% CI, 35.7%-38.8% vs 40.0%; 95% CI, 37.0%-43.0%; P = .18).Neural networks are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting.
Improving communication about prognosis on an academic inpatient solid tumor oncology consult service.
Authors: Chrystal Ann Landry, Alaina J Kessler, Aarti Sonia Bhardwaj, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2018)

46 Background: As the number of patients living with cancer increases, a growing proportion of hospital inpatients will have an advanced cancer diagnosis. Data suggests that an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of less than 6 months. As hospitalists more frequently become the primary team taking care of admitted cancer patients, communication between a patient's oncologic care team and inpatient primary providers is crucial. We sought to implement and assess the impact of improved oncology consult documentation of patient prognosis on outcomes of advanced cancer patients admitted to our hospitalist medicine teaching services. Methods: We implemented an EMR-based oncology consult note template which required documentation of prognosis, potential future treatment options (if available), and advance care planning. We reviewed all patients with stage IV solid tumors admitted to the hospitalist teaching service for 8 weeks prior and 8 weeks post-template implementation for comparison. We utilized descriptive statistics and chi-squared testing as appropriate for analysis. Results: We evaluated 51 patients in the pre- and 36 patients in the post-intervention groups. Post-intervention, there was an improvement in documentation of prognosis (29.4% vs. 52.8%, p = 0.03), advanced care planning (37.2% vs. 83.3%, p &lt; 0.0001), and in number of palliative care consults (58.8% vs. 83.3%, p = 0.02). On average, goals of care conversations occurred 2 days earlier in the post-intervention group (11 vs 9 days). Similarly, there was a decrease in inpatient chemotherapy administration (3 cases vs. 0), unit codes (2 vs. 0) and in-hospital death (23.5% vs. 11.1%). Conclusions: Creation of an oncology consult note template which incorporates current oncologic prognostic information improved documentation of prognosis and advance care planning as well as outcomes for advanced solid tumor oncology patients and enhanced inter-service communication. Based on these results, continued and targeted interventions are planned to further improve interservice communication.
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Stephen J. Schuster, Michael R. Bishop, Constantine S. Tam, Edmund K. Waller, Peter Borchmann, Joseph P. McGuirk, Ulrich Jäger, Samantha Jaglowski, Charalambos Andreadis, Jason R. Westin, Isabelle Fleury, Veronika Bachanova, S. Ronan Foley, P. Joy Ho, Stephan Mielke, John M. Magenau, Harald Holte, Serafino Pantano, Lida B. Pacaud, Rakesh Awasthi, Jufen Chu, Özlem Anak, Gilles Salles, Richard T. Maziarz
Journal: New England Journal of Medicine (2018)

Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee.A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found.In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel. (Funded by Novartis; JULIET ClinicalTrials.gov number, NCT02445248 .).
Early discussion of patients’ values by oncology nurses.
Authors: Andrew S. Epstein, Kimberly Chow, Kelley Anderson, Molly Okpako, Camila Bernal, Danielle R. Romano, Anjali Varma Desai, Virginia M. Klimek, Robin Rawlins-Duell, Jessica Goldberg, Dana Kramer, Judith Eve Nelson
Journal: Journal of Clinical Oncology (2018)

3 Background: Optimal advance care planning allows patients to articulate their values as an affirmation of personhood and a touchstone for medical decision-making. Ideally, it occurs when patients are well enough to express themselves thoughtfully, with opportunities for iteration as the clinical situation unfolds. We piloted a novel program of systematic, oncology nurse-led values discussions with patients soon after diagnosis, testing feasibility, and acceptability in high-volume clinics in a dedicated cancer center. Methods: Within an institutional initiative integrating primary and specialist palliative care from diagnosis for all cancer patients regardless of stage or prognosis, specialists trained oncology nurses (90 minutes) to use specific questions ( re living well, hopes, fears, sources of strength, abilities essential for acceptable quality of life) and an empathic communication framework to discuss health-related values with newly-diagnosed patients over two consecutive clinic visits. Nurses summarized discussions on a template for patient verification, oncologist review, and EMR documentation. Documentation was re-reviewed with the patient quarterly (sooner on patient or clinician request). Feasibility and acceptability were evaluated in three clinics for patients with hematologic or gastrointestinal (GI) cancers. Results: Oncology nurses conducted a total of 83 discussions (part 1=38, part 2=29, template review=16) with 15 and 23 newly-diagnosed hematologic and GI cancer patients, respectively. No patient declined participation. Discussions averaged 8 minutes; summaries were reviewed in 4 minutes, and all were verified by patients. Clinic workflow and volume (about 20 patients/clinic day) were maintained. Of 12 patients, all reported feeling comfortable with the process, 92% considered it helpful, 92% would recommend it to others. In structured interviews, patients, families, and clinicians strongly endorsed this process. Conclusions: Early, nurse-led discussions of patient values are feasible and acceptable in high-volume outpatient oncology clinics. Next steps include optimization of EMR accessibility, scalability, and evaluation of impact on other patient-focused and utilization outcomes.
Alkaline Phosphatase Controls Lineage Switching of Mesenchymal Stem Cells by Regulating the LRP6/GSK3β Complex in Hypophosphatasia
Authors: Wenjia Liu, Liqiang Zhang, Kun Xuan, Chenghu Hu, Liya Li, Yongjie Zhang, Fang Jin, Yan Jin
Journal: Theranostics (2018)

Lineage differentiation of bone marrow mesenchymal stem cells (BMMSCs) is the key to bone-fat reciprocity in bone marrow. To date, the regulators of BMMSC lineage switching have all been identified to be transcription factors, and researchers have not determined whether other genes control this process. This study aims to reveal a previously unknown role of tissue-nonspecific alkaline phosphatase (TNSALP) in controlling BMMSC lineage selection.
Association of Phenotypic Characteristics and UV Radiation Exposure With Risk of Melanoma on Different Body Sites
Authors: Reza Ghiasvand, Trude E. Robsahm, Adele C. Green, Corina S. Rueegg, Elisabete Weiderpass, Eiliv Lund, Marit B. Veierød
Journal: JAMA Dermatology (2018)

Two pathways have been hypothesized for the development of cutaneous melanoma: one typically affects the head and neck, a site with chronic sun damage, and the other affects the trunk, which is less exposed to the sun. However, the possible cause of limb melanomas is less studied under this hypothesis.
Tumor Lysate‐Loaded Lipid Hybrid Nanovaccine Collaborated with an Immune Checkpoint Antagonist for Combination Immunotherapy
Authors: Xiaomeng Hu, Tingting Wu, Xianya Qin, Yan Qi, Qi Qiao, Conglian Yang, Zhiping Zhang
Journal: Advanced Healthcare Materials (2018)

Abstract Cancer vaccines have shown great potential for treating different types of cancer. However, the application of vaccination still presents two major challenges. One is efficiency of antigen delivery, and the other is dealing with immune tolerance accompanied with tumor development. Lipid zinc phosphate hybrid nanoparticles (LZnP NPs) with a unique material structure can realize efficient delivery of antigens to dendritic cells (DCs) and also serve as an adjuvant to promote immune responses. Herein, ZnP NPs are introduced to load toll‐like receptor 4 agonist (monophosphoryl lipid A) and B16F10 melanoma cell‐derived tumor lysate (TLS) for vaccination. To regulate immune tolerance, the immune checkpoint antagonist, d ‐peptide antagonist ( D PPA‐1), is involved in treatment. TLS‐loaded LZnP nanovaccine can efficiently prime DCs and induce cytotoxic T lymphocytes response. The explored combination treatment further exhibits the anticipated tumor inhibition on therapeutic and prophylactic melanoma models with extended survival time. It demonstrates the possibility to combine TLS‐loaded LZnP nanovaccine with D PPA‐1 against melanoma and provides support to optimize the combination treatment based on nanovaccine and immune checkpoint therapy.
Long‐term effects upon rituximab treatment of acquired angioedema due to C1‐inhibitor deficiency
Authors: Marcel Levi, Danny Cohn, Sacha Zeerleder, Magdalena Dziadzio, Hilary Longhurst
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 17678: The Change in Gut Microbiota-Dependent Trimethylamine N-oxide Between Acute and Chronic Phase Related to the Progression of Coronary Plaque Complexity in Patients With Acute Myocardial Infarction
Authors: Hidefumi Nakahashi, Yasushi Matsuzawa, Toshiaki Ebina, Kiyoshi Hibi, Noriaki Iwahashi, Nobuhiko Maejima, Masaaki Konishi, Yuichirou Kimura, Naoki Nakayama, Masami Kosuge, Kazuo Kimura, Kouichi Tamura
Journal: Circulation (2017)

Introduction: Gut microbiota are shown to participate in the formation of a pro-atherogenic compound called trimethylamine-N-oxide (TMAO). TMAO levels were shown to directly influence the propensit...
Abstract 17718: Assessment of Different Force Time Interval (FTI) Requirements in Different Segments of Pulmonary Veins by High Output Pacing Module
Authors: Nway L Ko Ko, Tughral J Khan, Usman R Siddiqui
Journal: Circulation (2017)

Introduction: Pulmonary vein isolation (PVI) has been proven to be efficacious for ablation of paroxysmal atrial fibrillation. Several advances have been made in PVI techniques to lower the rate of recurrences while ensuring the accuracy and adequacy of lesion formation. In addition to using optimal contact force as per the TOCCATA trial, it was shown in another multicenter trial (EFFICAS I) that using a minimal “Force Time Interval” (FTI) of 400gs for all segments of the pulmonary veins (PV) further improves the ablation outcomes with less gaps and gap reconnections evident with invasive re-evaluation of PVI at 3 months. Hypothesis: We assessed the hypothesis that, in contrast to EFFICAS I, the different segments of PV require different contact force parameters, particularly FTI. Methods: By using the high output pacing module (10 mA at 2 ms) during the PVI of 13 patients, the values of FTI were collected. The digital records of 458 lesions were correlated with catheter position in each of the 4 anatomic...
A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105
Authors: Alexander Drilon, Siqing Fu, Manish R. Patel, Marwan Fakih, Ding Wang, Anthony J. Olszanski, Daniel Morgensztern, Stephen V. Liu, Byoung Chul Cho, Lyudmila Bazhenova, Cristina P. Rodriguez, Robert C. Doebele, Antoinette Wozniak, Karen L. Reckamp, Tara Seery, Petros Nikolinakos, Zheyi Hu, Jennifer W. Oliver, Denise Trone, Katherine McArthur, Rupal Patel, Pratik S. Multani, Myung-Ju Ahn
Journal: Cancer Discovery (2018)

Abstract RET fusions are oncogenic drivers of various tumors, including non–small cell lung cancers (NSCLC). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase II dose of 275 mg fed daily was identified. The most common treatment-related adverse events were fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash (18%), and nonmaculopapular rash (17%). In the phase Ib cohort of RET inhibitor–naïve patients with RET fusion–positive NSCLCs, the objective response rate (ORR) was 19% (95% CI, 8%–38%, n = 6/31). Interestingly, the ORR varied significantly by the gene fusion partner (P &amp;lt; 0.001, Fisher exact test): 0% (95% CI, 0%–17%, n = 0/20) with KIF5B (the most common upstream partner for RET fusion–positive NSCLC), and 67% (95% CI, 30%–93%, n = 6/9) with non-KIF5B partners. The median duration of response in all RET fusion–positive NSCLCs was not reached (range, 5 to 18+ months). Significance: Although KIF5B–RET is the most common RET fusion in NSCLCs, RET inhibition with RXDX-105 resulted in responses only in non–KIF5B–RET-containing cancers. Novel approaches to targeting KIF5B–RET-containing tumors are needed, along with a deeper understanding of the biology that underlies the differential responses observed. This article is highlighted in the In This Issue feature, p. 305
Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: a multi-center study
Authors: Hamzah Abu-Sbeih, Faisal S. Ali, Dana Alsaadi, Joseph Jennings, Wenyi Luo, Zimu Gong, David M. Richards, Aline Charabaty, Yinghong Wang
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immune-mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitors (ICIs) treatment, which is efficacious for advanced malignancies. Steroids and infliximab are commonly used to treat it. These agents induce systemic immunosuppression, with its associated morbidity. We assessed clinical outcomes of vedolizumab as an alternative treatment for IMDC. <h3>Methods</h3> We analyzed a retrospective case series of adults who had IMDC refractory to steroids and/or infliximab and received vedolizumab from 12/2016 through 04/2018. <h3>Results</h3> Twenty-eight patients were included. The median time from ICI therapy to IMDC onset was 10 weeks. Fifteen patients (54%) had grade 2 and 13 (46%) had grade 3 or 4 IMDC. Mucosal ulceration was present in 8 patients (29%), and nonulcerative inflammation was present in 13 (46%). All patients had features of active histologic inflammation; 14 (50%) had features of chronicity, and 10 (36%) had features of microscopic colitis concurrently. The mean duration of steroid therapy was 96 days (standard deviation 74 days). Nine patients received infliximab in addition to steroids and their IMDC was refractory to it. Among these, the duration of steroid use was 131 days compared with 85 days in patients who did not receive infliximab. Likewise, patients who failed infliximab before vedolizumab had a clinical success rate of 67% compared to 95% for patients that did not receive infliximab. The median number of vedolizumab infusions was 3 (interquartile range 1–4). The mean duration of follow-up was 15 months. Twenty-four patients (86%) achieved and sustained clinical remission. Repeat endoscopic evaluation was performed in 17 patients. Endoscopic remission was attained in 7 (54%) of the 13 patients who had abnormal endoscopic findings initially; 5/17 patients (29%) reached histologic remission as well. <h3>Conclusions</h3> Vedolizumab can be appropriate for the treatment of steroid-refractory IMDC, with favorable outcomes and a good safety profile.
Peripheral blood biomarkers of early immune reconstitution in newly diagnosed multiple myeloma
Authors: Moritz Binder, S. Vincent Rajkumar, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Angela Dispenzieri, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven R. Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, Shaji K. Kumar
Journal: American Journal of Hematology (2018)

Abstract Peripheral blood biomarkers of tumor microenvironment and immune surveillance are independent prognostic factors in multiple myeloma. The timing and prognostic impact of immune reconstitution has been studied after autologous hematopoietic stem cell transplantation, less is known about its significance in newly diagnosed multiple myeloma. We studied absolute lymphocyte (ALC) and absolute monocyte (AMC) counts at the time of treatment initiation and 1 month thereafter in 771 newly diagnosed patients. Two hundred and thirty‐four patients (31%) had evidence of immune dysregulation at baseline (abnormal biomarkers). Eighty‐seven of these patients (37%) recovered normal biomarkers at 1 month (early immune reconstitution). The absence of immune dysregulation at baseline (compared to the presence thereof) was associated with better overall survival (HR 0.77, 95% CI 0.61‐0.97, P = 0.025, n = 771). The absence of immune dysregulation at 1 month (compared to the persistence or development thereof) was associated with better overall survival (HR 0.63, 95% CI 0.50‐0.80, P &lt; 0.001, n = 771). Early immune reconstitution (compared to the persistence or development of immune dysregulation) was associated with better overall survival (HR 0.62, 95% CI 0.43‐0.92, P = 0.016, n = 771). Cytogenetic high‐risk disease was negatively, and treatment with immunomodulators positively, associated with early immune reconstitution. The presence or development of immune dysregulation in newly diagnosed multiple myeloma is an independent risk factor. The favorable impact of early immune reconstitution suggests immune dysregulation to be a potentially modifiable risk factor that may be exploited for therapeutic benefit.
Dutch hospital’s manufacture of drug for rare condition was legal, says inspectorate
Authors: Tony Sheldon
Journal: BMJ (2018)

A five month investigation by Dutch health inspectors into a leading university hospital’s cost price production of orphan drug chenodeoxycholic acid (CDCA) has concluded that such “small scale” preparation is legal.

But, it has halted the Amsterdam University Medical Center’s current production of the primary bile acid used to treat the rare hereditary metabolic disorder cerebrotendinous xanthomatosis on safety grounds. Tests carried out on behalf of the Dutch Healthcare Inspectorate showed that the raw materials used in the drug’s production had potentially dangerous levels of unknown impurities.

The hospital has welcomed the principle that their action is legal, although Leadiant Biosciences, which has a 10 year market exclusivity on the drug from …
Up to 7 Years of Follow-up of Single-Agent Ibrutinib in the Phase 1b/2 PCYC-1102 Trial of First Line and Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Authors: John C. Byrd, Richard R. Furman, Steven Coutre, Ian W. Flinn, Jan A. Burger, Kristie A. Blum, Jeff Sharman, William G. Wierda, Weiqiang Zhao, Nyla A. Heerema, Ying Luan, Emily A. Liu, James P. Dean, Susan M. O'Brien
Journal: Blood (2018)