tbuckley/cabot-search huggingface dataset:
Drug Rash after Tripolidine
Authors: A. Bigham
Journal: BMJ (1964)

these during a 24-hour period, and her headache improved, but the same day severe pain began in both ankles and feet, and the next day she was unable to walk.On admission she was normotensive, and febrile (99.5'F.; 37.5' C.).Apart from a soft pansystolic apical murmur, abnormal signs were confined to the legs.No pulses could be felt below the femorals, and there was a sudden temperature drop at both mid-calves.The distal parts of both feet were pale, ischaemic, and very painful.The ischaemia was attributed to intolerance to ergotamine with presumed underlying oblitera- tive arterial disease.The legs were exposed and kept cool, and tolazoline, 25 mg.thrice daily, given by mouth.For two days there was little change, but on the third day both feet were warm, red, and oedematous, and later all pulses became readily palpable.The feet remained painful for several days, but there was no gangrene and the patient was eventually discharged home free from signs and symptoms in the legs.There was no evidence of obliterative arterial disease or renal disease.The flocculation tests were weakly positive and the sedimentation rate 62 mm. at one hour falling to 32, but there was no increase of gammaglobulin on serum electro- phoresis and no other evidence of an under- lying collagen disease.
ACTR-34. SINGLE AGENT ONC201 IN PREVIOUSLY-TREATED, PROGRESSIVE ADULT H3 K27M-MUTANT GLIOMA
Authors: Isabel Arrillaga-Romany, Sylvia Kurz, Ashley Sumrall, Nicholas Butowski, Rebecca Harrison, John DeGroot, Andrew Chi, Erik Sulman, Nicole Shonka, Yoshie Umemura, Yazmin Odia, Minesh Mehta, Fabio Iwamoto, P Leia Nghiemphu, Timothy Cloughesy, Rohinton Tarapore, Krystal Merdinger, Wolfgang Oster, Joshua Allen, Tracy Batchelor, Andrew Lassman, Patrick Wen
Journal: Neuro-Oncology (2019)

Abstract H3 K27M-mutant gliomas often manifest as midline gliomas, have a dismal prognosis, and have no established or effective treatments at recurrence. ONC201 is the first clinical bitopic DRD2 antagonist/ClpP agonist and is under evaluation in Phase II trials for gliomas and other cancers. We previously reported in vitro studies suggesting dysregulated dopamine receptor expression and enhanced ONC201 sensitivity among H3 K27M-mutant gliomas. Following these observations, adults with midline H3 K27M-mutant glioma patients were enrolled to a dedicated Phase II clinical trial (NCT03295396), a multi-arm Phase II trial (NCT0252569), and expanded access protocols under the Sponsor’s IND. An integrated radiographic analysis with an objective response rate primary endpoint in patients who received ONC201 monotherapy with confirmed H3 K27M-mutant glioma (not primarily in the pons or spinal cord and without leptomeningeal spread) that was progressive and measurable disease by RANO criteria, &gt;90 days from completion of prior radiation, and had KPS &gt;60. As of December 15, 2018, 15 patients have received single agent ONC201 who meet these criteria (n=9 NCT03295396; n=5 NCT0252569; n=1 expanded access). ONC201 was orally administered at 625 mg weekly, except for one patient dosed once every 3 weeks. As midline gliomas can exhibit a mixture of contrast-enhancing and non-contrast-enhancing disease, objective response was assessed by blinded independent central review using RANO-HGG and RANO-LGG criteria for each patient. Best response to date by RANO-HGG criteria is at least 27%: 1 CR, 3 PR, 7 SD, and 4 PD; by RANO-LGG is at least 36%: 1 CR, 1 PR, 3 minor response (MR), 4 SD, 5 PD, 1 unevaluable. By RANO-HGG, median onset of response is 2.6 months (range 1.3–3.4); median duration of response has not been reached with a median follow-up of 7.7 months (range 1.8–29.8). Updated radiographic response, pharmacodynamics, safety, and other clinical outcomes will be reported.
Translational status of biomedical Mg devices in China
Authors: Yu Sun, Hongliu Wu, Wenhui Wang, Rui Zan, Hongzhou Peng, Shaoxiang Zhang, Xiaonong Zhang
Journal: Bioactive Materials (2019)

Magnesium (Mg) and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time. There are already three kinds of biodegradable Mg implants which are approved by Conformite Europeene (CE) or Korea Food and Drug Administration (KFDA), but not China Food and Drug Administration (CFDA, now it is National Medical Products Administration, NMPA). As we know, Chinese researchers, surgeons, and entrepreneurs have tried a lot to research and develop biodegradable Mg implants which might become other new approved implants for clinical applications. So in this review, we present the representative Mg implants of three categories, orthopedic implants, surgical implants, and intervention implants and provide an overview of current achievement in China from academic publications and Chinese patents. We would like to provide a systematic way to translate Mg and its alloy implants from experiment designs to clinical products.
Resistome analyses of sputum from COPD and healthy subjects reveals bacterial load-related prevalence of target genes
Authors: Mohammadali Yavari Ramsheh, Koirobi Haldar, Mona Bafadhel, Leena George, Robert C Free, Catherine John, Nicola F Reeve, Loems Ziegler-Heitbrock, Ivo Gut, Dave Singh, Vijay Mistry, Martin D Tobin, Marco R Oggioni, Chris Brightling, Michael R Barer
Journal: Thorax (2019)

Background Antibiotic resistance is a major global threat. We hypothesised that the chronic obstructive pulmonary disease (COPD) airway is a reservoir of antimicrobial resistance genes (ARGs) that associate with microbiome-specific COPD subgroups. Objective To determine the resistance gene profiles in respiratory samples from COPD patients and healthy volunteers. Methods Quantitative PCR targeting 279 specific ARGs was used to profile the resistomes in sputum from subjects with COPD at stable, exacerbation and recovery visits (n=55; COPD-BEAT study), healthy controls with (n=7) or without (n=22) exposure to antibiotics in the preceding 12 months (EXCEED study) and in bronchial brush samples from COPD (n=8) and healthy controls (n=7) (EvA study). Results ARG mean (SEM) prevalence was greater in stable COPD samples (35.2 (1.6)) than in healthy controls (27.6 (1.7); p=0.004) and correlated with total bacterial abundance (r 2 =0.23; p&lt;0.001). Prevalence of ARG positive signals in individuals was not related to COPD symptoms, lung function or their changes at exacerbation. In the COPD subgroups designated High γProteobacteria and High Firmicutes, ARG prevalence was not different at stable state but significantly declined from stable through exacerbation to recovery in the former (p=0.011) without changes in total bacterial abundance. The ARG patterns were similar in COPD versus health, COPD microbiome-subgroups and between sputum and bronchoscopic samples independent of antibiotic exposure in the last 12 months. Conclusions ARGs are highly prevalent in sputum, broadly in proportion to bacterial abundance in both healthy and COPD subjects. Thus, COPD appears to be an ARG reservoir due to high levels of bacterial colonisation.
Increased Early Mortality after Fludarabine and Melphalan Conditioning with Peripheral Blood Grafts in Haploidentical SCT with Post-Transplant Cyclophosphamide
Authors: Luke Eastburg, David A. Russler-Germain, Ramzi Abboud, Peter Westervelt, John F. DiPersio, Michael W. Becker, Neha Kumar, Omar S. Aljitawi, Jeffrey R. Andolina, Thomas J Fountaine, Jane L. Liesveld, Eric Huselton
Journal: Blood (2019)
Whole-Genome CRISPR Screen Reveals the Mechanism of Relapse in Patient-Derived Cells Representing High-Risk Paediatric ALL
Authors: Katarzyna Szoltysek, Helen Blair, Sirintra Nakjang, Ricky Tirtakusuma, Mankaran Singh, Ryan Nelson, Hesta McNeill, Catherine Dodd, Melanie Beckett, Lynsey McKenzie, Edward Law, Josef Vormoor, Deepali Pal, Olaf Heidenreich
Journal: Blood (2019)
Preclinical Activity of the MPS1 Inhibitor S81694 in Acute Lymphoblastic Leukemia (ALL)
Authors: Anna Kaci, Emilie Adiceam, Melanie Dupont, Marine Garrido, Jeannig Berrou, Hanane Djamai, Andre Baruchel, Mike Burbridge, Claude Gardin, Herve Dombret, Thorsten Braun
Journal: Blood (2019)
Predictive Factors of the Development of Leukemia in Patients with Transient Abnormal Myelopoiesis and Down Syndrome: The Jccg Study JPLSG TAM-10
Authors: Genki Yamato, Hideki Muramatsu, Tomoyuki Watanabe, Takao Deguchi, Shotaro Iwamoto, Daisuke Hasegawa, Kiminori Terui, Takahiro Ueda, Tomoko Yokosuka, Tsutomu Toki, Shiro Tanaka, Ryu Yanagisawa, Katsuyoshi Koh, Akiko M Saito, Keizo Horibe, Yasuhide Hayashi, Souichi Adachi, Shuki Mizutani, Takashi Taga, Etsuro Ito, Kenichiro Watanabe
Journal: Blood (2019)
TMOD-06. MODELLING ADULT AND PAEDIATRIC GLIOBLASTOMA MULTIFORME (GBM) USING A GENE SCREEN-BASED APPROACH IN MICE AND HUMAN IPSC-DERIVED CEREBRAL ORGANOIDS
Authors: Francesco Antonica, Francesca Garilli, Maria Del Mar Gardeazabal Bataller, Lucia Santomaso, Luca Tiberi
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma multiforme (GBM) represent the most devastating form of high-grade glioma (HGG) affecting adults and children. Despite a multi-therapeutic approach consisting in surgery, radio- and chemo-therapy the prognosis remains poor. Several models such as xenograft, animal models and recently organoids, have been developed in order to investigate the physiopathology of GBM. Although several mouse models (where either gain- or loss-of function of genes/pathway found altered in patients induce tumour formation) have been generated many aspects of how the tumour is formed, evolves, infiltrates and recurs after treatments remain unclear. Another challenge is the creation of proper GBM models showing intratumor heterogeneity found in the patient tumour but missing in the animal model generated so far. To overcome the lack of that human tumour characteristic, we decided to generate new model of GBM using a gene screen-based approach in mice. Firstly, we analysed the genes found amplified or mutated in GBM patients; secondly, we over-expressed the candidate genes (combination of multiple genes found to be mutated or amplified in specific GBM patients) in the subventricular zone (SVZ) of P2 mouse brain. Thirdly, we analysed the formation of tumour after 2 months. We over-expressed roughly 50 combinations in newborn mice and found that only 3 successfully led to the formation of lesions positive for proliferation and brain tumour marker (i.e. GFAP). We are currently characterising the tumours by DNA methylation analysis and RNA-seq (for further confirmation of the cancer subtype and intratumor heterogeneity) or investigating the cell of origin of the tumour. Moreover, we are testing the tumorigenicity of specific in GBM-amplified/mutated gene combinations in hiPSC-derived cerebal organoids. Our data suggest that a gene screen-based approach can be used for quickly and easily assaying the tumorigenicity of genes found amplified/mutated in GBM patients as well as the biology behind such complex process.
LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells
Authors: Zunling Li, Mi Deng, Fangfang Huang, Changzhu Jin, Shuang Sun, Heyu Chen, Xiaoye Liu, Licai He, Ali H. Sadek, Cheng Cheng Zhang
Journal: Cellular and Molecular Immunology (2019)
HTLV-1 Dysregulates IL-6 and IL-10-JAK/STAT Signaling and Induces Leukemia/Lymphoma of Mature CD4+ T Cells with Regulatory T-Cell-like Signatures
Authors: Yusuke Higuchi, Jun-ichirou Yasunaga, Yu Mitagami, Koichi Ohshima, Masao Matsuoka
Journal: Blood (2019)
VH CDR3-Focused Somatic Hypermutation in CLL IGHV-IGHD-IGHJ Gene Rearrangements with 100% IGHV Germline Identity
Authors: Katerina Gemenetzi, Andreas Agathangelidis, Fotis Psomopoulos, Kostas Pasentsis, Evdoxia Koravou, Michail Iskas, Niki Stavroyianni, Achilles Anagnostopoulos, Raphael Sandaltzopoulos, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Journal: Blood (2019)
Evaluating Isatuximab Interference with Monoclonal Protein Detection By Immuno-Capture and Liquid Chromatography Coupled to High Resolution Mass Spectrometry in the Pivotal Phase 3 Multiple Myeloma Trial, Icaria-MM
Authors: Greg Finn, Sandrine Macé, Frank Campana, Solenn Le-Guennec, Stephané Muccio, Alexandra Tavernier, Marie-Claude Rouchon, Alain Roccon, Shujia Dai, Valérie Boutet, Dominique Mouret, Béatrice Pradeilles, Sébastien Hugla, Graziella Engelvin, Deborah DiNoto, Helgi van de Velde, Olivier Fedeli
Journal: Blood (2019)
GENE-04. THE ONCOGENIC FUNCTIONS OF YAP1-GENE FUSIONS CAN BE INHIBITED BY DISRUPTION OF YAP1-TEAD INTERACTION
Authors: Frank Szulzewsky, Pia Hoellerbauer, Hua-Jun Wu, P J Cimino, Franziska Michor, Patrick Paddison, Valeri Vasioukhin, Eric Holland
Journal: Neuro-Oncology (2019)

Abstract Supratentorial ependymoma can be sub-stratified into clinically relevant subtypes characterized by distinct molecular features. The subtype defined by high YAP1 activity harbored two distinct YAP1 gene fusions, YAP1-MAMLD1 and YAP1-FAM118B. In addition, YAP1 gene fusions have been detected in several other cancer types, including Epithelioid Hemangioendothelioma and Endocervical Adenocarcinoma. YAP1 is a key transcriptional co-activator and proto-oncogene that is negatively regulated by the Hippo pathway. Here, we show that both YAP1-MAMLD1 and YAP1-FAM118B, as well as additional YAP1 fusion genes found in other cancer types, are potent oncogenic drivers that cause tumor formation in the brain and the hindlimb in mice upon overexpression by somatic cell gene transfer. Using different in vitro assays, including Luciferase, RNA-, and ChIP Seq, we show that both the N-terminal YAP1 part and the C-terminal fusion partners exert activity. We can show that the YAP1 activity still relies on the binding to TEAD transcription factors, whereas the C terminal activity does not. Furthermore, the different fusion proteins have become independent from negative Hippo pathway signaling by constitutive nuclear localization and protection from degradation. In addition, by introducing point mutations and truncations to block the YAP1 and the MAMLD1 function we can show that the activity of both halves contributes to the oncogenic function of YAP1-MAMLD1. Using in vitro and in vivo assays we can show that pharmacological and genetic ablation of YAP-TEAD interaction diminishes the oncogenic potential of the fusions, indicating that this might be a potential therapeutic approach for these tumors in the future.
ATIM-15. SUSTAINED COMPLETE RADIOGRAPHIC RESPONSE AND PROLONGED SYSTEMIC IMMUNE ACTIVATION IN A PATIENT WITH MGMT UNMETHYLATED MIDLINE GLIOBLASTOMA RECEIVING CMV pp65-LAMP RNA-PULSED DENDRITIC CELL VACCINES
Authors: Maryam Rahman, Ashley Ghiaseddin, Oleg Yegorov, Changlin Yang, Anjelika Dechkovskaia, David Tran, Tara Massini, Jesse Kresak, Duane Mitchell
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND We initiated a Phase 2, randomized, placebo-controlled, clinical trial evaluating the efficacy of autologous CMV pp65-LAMP RNA pulsed dendritic cell vaccines mixed with GM-CSF and administered during cycles of adjuvant dose-intensified temozolomide (ATTAC II, NCT02465268). STUDY OBJECTIVE A patient with partially resected GBM experienced a sustained complete radiographic response after receiving five DC vaccines. Peripheral blood responses were characterized to examine possible immunologic biomarkers concordant with a sustained clinical response. METHODS Patients with newly diagnosed glioblastoma undergoing surgical resection are eligible and randomized 2:1 to DC vaccine arms vs placebo (PBMCs in saline). DC vaccines consist of CMV pp65 RNA conjugated either to the full-length lysosomal associated membrane protein (LAMP) or to the short LAMP signal sequence. Patients undergo leukapheresis for DC generation prior to standard chemoradiation and receive cycle 1 of dose-intensified temozolomide (100 mg/m^2 x 21 days) before first three biweekly intradermal DC vaccines admixed with GM-CSF. Subsequent DC vaccines (total of 10) are given monthly with each diTMZ cycle with an intradermal tetanus-diphtheria booster given 6-24hrs before the third, fifth, seventh, and ninth DC vaccines. PBMCs and serum are collected for immune monitoring. RESULTS A 58-year old white male with partially-resected, MGMT-unmethlyated, p53 mutant, H3.3 mutant, midline glioblastoma was enrolled on the ATTAC II study and experienced a complete radiographic response after the fifth DC vaccine that has been sustained &gt; 10 months. Immune monitoring by Elispot, cytokine array, and single-cell RNA sequencing have revealed significant expansion of CMV pp65-specific immune responses, increased circulating IFNg, and marked systemic expansion of cytotoxic T cells and iNKT cells during vaccination. These responses were sustained through cycles of diTMZ despite profound lymphopenia. CONCLUSIONS CMV pp65-LAMP RNA-pulsed DC vaccination was associated with profound immunologic and clinical response in a patient with MGMT unmethylated midline glioblastoma.
O.03 KEYNOTE-189: OS Update and Progression After the Next Line of Therapy (PFS2) with Pembrolizumab + Chemotherapy for Metastatic Nonsquamous NSCLC
Authors: S. Gadgeel, M.C. Garassino, E. Esteban, G. Speranza, E. Felip, M.J. Hochmair, S. Powell, S.Y.-S. Cheng, H.G. Bischoff, N. Peled, R. Hui, M. Reck, T. Kurata, E.B. Garon, M. Boyer, J. Yang, M.C. Pietanza, D. Rodríguez-Abreu
Journal: Journal of Thoracic Oncology (2019)
No Decrease in Fracture Risk Despite 15 Years of Treatment Evolution in Multiple Myeloma Patients: A Danish Nationwide Case-Control Study
Authors: Berdien Oortgiesen, Annemariek Driessen, Mels Hoogendoorn, Robby Kibbelaar, Nic Veeger, Joop van der Bergh, Peter Vestergaard, Frank de Vries, Eric van Roon
Journal: Blood (2019)
Identification of an Expanded Immature Cell Population in Human Bone Marrow during Erythroid Responses to ESA Treatment
Authors: Isabel Juliana F Hofman, Teresa Mortera-Blanco, Sigita Venckute Larsson, Sten Eirik Waelgaard Jacobsen, Petter S Woll, Marios Dimitriou, Eva Hellstrom Lindberg
Journal: Blood (2019)
Mechanisms of Tolerance Induction through T Regulatory Cells during Chemotherapy-Mediated Immunogenic Cell Death in Acute Myeloid Leukemia
Authors: Darina Ocadlikova, Serenella Casella, Ines Pintao, Elena Adinolfi, Sabina Sangaletti, Elena De Marchi, Anna Pegoraro, Elisa Orioli, Mario Paolo Colombo, Francesco Di Virgilio, Michele Cavo, Antonio Curti
Journal: Blood (2019)
Intra-Tumoral CD8+ T-Cells in Follicular Lymphoma Contain Large Clonal Expansions That Are Amenable to Dual-Checkpoint Blockade
Authors: Karthik Nath, Soi C. Law, Muhammed B. Sabdia, Lilia Merida De Long, Mohamed Shanavas, Joshua W.D. Tobin, Jay Gunawardana, Frank Vari, Sarah-Jane Halliday, Annette Hernandez, Donna Cross, Robert J. Bird, Colm Keane, Maher K. Gandhi
Journal: Blood (2019)
Open-Label, Multicenter, Phase 2/3 Study of Recombinant Crisantaspase Produced in Pseudomonas Fluorescens (RC-P) in Patients with Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) Following Hypersensitivity to Escherichia coli-Derived Asparaginases
Authors: Luke Maese, Rachel E. Rau, Elizabeth A. Raetz, Tong Lin, Jin Zhu, Pil Kim, Reddy Chandula, Sherrie McClung, Julie Gray, Mi Rim Choi, Mignon L. Loh, Peter C. Adamson
Journal: Blood (2019)
Estimating the Relative Treatment Effect and Corresponding Cost-Effectiveness Estimates of Inotuzumab Ozogamicin Vs. Blinatumomab for Adults with Philadelphia Chromosome-Negative (Ph-) Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukaemia (B-ALL) in the United Kingdom (UK)
Authors: Simone Critchlow, Miranda Cooper, Ilse van Oostrum, Verna L Welch, T. Alexander Russell-Smith
Journal: Blood (2019)
SCIDOT-23. LOW INTENSITY PULSED ULTRASOUND ENHANCES BLOOD-BRAIN BARRIER OPENING AND IMPROVES RESPONSE TO IMMUNOTHERAPY FOR GLIOBLASTOMA
Authors: Aria Sabbagh, Anantha Marisetty, Martina Ott, Xiaoyang Ling, Emily Barton, Hillary Caruso, Ling-Yuan Kong, Ganesh Rao, Michael Canney, Amy B Heimberger
Journal: Neuro-Oncology (2019)

Abstract The blood-brain barrier (BBB) is a significant obstruction to the delivery of treatments for glioblastoma. Previous studies have demonstrated the use of Low Intensity Pulsed Ultrasound (LIPU) in combination with microbubbles as a safe and therapeutic method for temporary BBB disruption to enhance chemotherapeutic delivery to the tumor and surrounding brain parenchyma. Glioblastoma has minimal T cell infiltration. In this work, we investigated if LIPU sonications (1 MHz, 0.3 MPa, 120 s duration) could enhance T cell delivery to the tumor microenvironment and enhance immunotherapy. NSG mice with established EGFRvIII+U87 tumors were treated intravenously with bioluminescent labeled epidermal growth factor receptor variant III (EGFRvIII) expressing chimeric antigen receptor (CAR) T cells with and without ultrasound BBB disruption. Combining systemic CAR T cell administration with ultrasound BBB disruption, resulted in a significant increase in CAR T cell delivery to the mouse CNS after 12 (p&lt;0.005) and 24 hours (p&lt;0.001) associated with enhanced median survival. In a second murine model of C57BL/6 mice bearing intracerebrally implanted GL261 gliomas, mice treated with anti-PD-1 and ultrasound BBB disruption survived 58 days relative to 39 days of mice treated with only anti-PD-1. Long-term survivors in the anti-PD-1 and anti-PD-1+ ultrasound treatment groups all remained alive after contralateral hemisphere rechallenge with GL261 glioma cells. LIPU-induced BBB disruption increases the delivery of immune therapeutics to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies to the clinic.
Patatin‐Like Phospholipase Domain‐Containing Protein 3 I148M and Liver Fat and Fibrosis Scores Predict Liver Disease Mortality in the U.S. Population
Authors: Aynur Unalp‐Arida, Constance E. Ruhl
Journal: Hepatology (2019)

Fatty liver causes premature death worldwide and requires long-term health care. We examined relationships of liver disease markers, including patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M, with mortality in the U.S. National Health and Nutrition Examination Survey, 1988-1994, with 27 years of linked mortality data.We studied 13,298 viral hepatitis negative adults who fasted at least 4 hours using the nonalcoholic fatty liver disease (NAFLD) liver fat score and NAFLD fibrosis score. PNPLA3 I148M was genotyped in a subgroup of participants from 1991 to 1994 (n = 5,640). Participants were passively followed for mortality, identified by death certificate underlying or contributing causes, by linkage to the National Death Index through 2015. During follow-up (median, 23.2 years), cumulative mortality was 33.2% overall and 1.1% with liver disease, including primary liver cancer. Increased liver disease mortality was associated with PNPLA3 I148M (hazard ratio [HR], 2.9; 95% confidence interval [CI], 0.9-9.8) and 148M genotypes (HR, 18.2; 95% CI, 3.5-93.8), an intermediate (HR, 3.8; 95% CI, 1.3-10.7) or high (HR, 12.6; 95% CI, 4.3-36.3) NAFLD liver fat score, and a high NAFLD fibrosis score (HR, 12.2; 95% CI, 1.9-80.6) adjusted for risk factors. Survival curves suggest that increased mortality risk with two 148M alleles was greatest beginning in the second decade of follow-up. Overall, but not cardiovascular disease, mortality was associated with the PNPLA3 148M allele, and both mortality outcomes were associated with higher fat and fibrosis scores.In the U.S. population, PNPLA3 I148M and higher NAFLD liver fat and fibrosis scores were associated with increased liver disease mortality. Genetic variant PNPLA3 I148M may complement other liver disease markers for NAFLD surveillance.