Advancing Inclusive Research (AIR) Site Alliance: Facilitating the inclusion of historically underrepresented people in oncology and ophthalmology clinical research.

BACKGROUND: The Advancing Inclusive Research (AIR) Site Alliance is composed of clinical research centers that partner with Genentech, a biotechnology company, to advance the representation of diverse patient populations in its oncology and ophthalmology clinical trials, test recruitment, and retention approaches and establish best practices to leverage across the industry to achieve health equity. METHODS: Through a data-driven selection process, Genentech identified 6 oncology and 3 ophthalmology partners that focus on reaching historically underrepresented patients in clinical trials and worked collaboratively to share knowledge and explore original ways of increasing clinical study access for every patient, including sites co-creation of a Protocol Entry Criteria Guideline with inclusion principles. RESULTS: For patients, three publicly available educational videos about clinical trials were created in multiple languages. The AIR Site Alliance has also defined invoiceable services for sites to enhance patient support; this has been built into the new study budget templates for sustainability. For healthcare professionals (HCPs), the first-of-its-kind AIR Educational Program was developed to focus on identifying and addressing bias and engaging historically underrepresented patient populations in trials. The sites also co-created videos for HCPs and patients on why advancing inclusive research matters. Over 16 regional health equity symposia have been delivered for patients, HCPs, and community leaders. CONCLUSIONS: This AIR Site Alliance is a model for other site alliances, including Kenya, South Africa, the United Kingdom, and Canada. Such alliances will build a robust and sustainable research ecosystem that includes diverse patient groups and encourages change across the healthcare system.

That was not what I was aiming at! Differentiating human intent and outcome in a physically dynamic throwing task.

Recognising intent in collaborative human robot tasks can improve team performance and human perception of robots. Intent can differ from the observed outcome in the presence of mistakes which are likely in physically dynamic tasks. We created a dataset of 1227 throws of a ball at a target from 10 participants and observed that 47% of throws were mistakes with 16% completely missing the target. Our research leverages facial images capturing the person's reaction to the outcome of a throw to predict when the resulting throw is a mistake and then we determine the actual intent of the throw. The approach we propose for outcome prediction performs 38% better than the two-stream architecture used previously for this task on front-on videos. In addition, we propose a 1D-CNN model which is used in conjunction with priors learned from the frequency of mistakes to provide an end-to-end pipeline for outcome and intent recognition in this throwing task.

Analysis of the Long-term Visual Outcomes of ForeseeHome Remote Telemonitoring: The ALOFT Study.

PURPOSE: To evaluate long-term visual acuity (VA) and performance of a monitoring strategy with a self-operated artificial-intelligence-enabled home monitoring system in conjunction with standard care for early detection of neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective review. SUBJECTS: Patients with dry-age-related macular degeneration from 5 referral clinics. METHODS: Clinical data of patients monitored with ForeseeHome (FSH) device from August 2010 to July 2020 were reviewed. MAIN OUTCOME MEASURES: Visual acuity at baseline, VA at diagnosis of nAMD for eyes that converted while monitored, and VA from the final study follow-up, weekly frequency of use, duration of monitoring, modality of conversion diagnosis (system alert vs. detection by other standard care means), and duration and number of treatments since conversion to final study follow-up were collected. RESULTS: We reviewed 3334 eyes of 2123 patients with a mean (standard deviation [SD]) age of 74(8) years, monitored for a mean (SD) duration of 3.1 (2.4) years, with a total of 1 706 433 tests in 10 474 eye-monitoring years. The mean (SD) weekly use per patient was 5.2 (3.4), and it was persistent over the usage period. Two hundred eighty-five eyes converted while monitored at an annual rate of 2.72% and were treated with a mean (SD) 17.3 (16.5) injections over a mean (SD) 2.7 (2.0) years, with 6.4 (3.1) injections per year for eyes treated for > 1 year. The median VAs at baseline and at final follow-up for eyes that did not convert were 20/27 and 20/34 with a median change of 0.0 letters. The median VAs at baseline, conversion, and final follow-up for eyes that converted during the monitoring period were 20/30, 20/39, and 20/32 with a median change from baseline to conversion, baseline to recent, and conversion to recent of -4, -4, and 0 letters, respectively. Fifty-two percent of conversions detected had a system alert before conversion. Forty-eight percent of patients were detected by symptoms or routine visit. Patients experienced a non-nAMD alert on average every 4.6 years. At conversion and at final follow-up, the proportion (95% CI) of eyes that maintained ≥ 20/40 was 84% (78% to 88%) and 82% (76% to 86%), respectively. CONCLUSIONS: Patients in the FSH monitoring program showed excellent long-term VA years after conversion to nAMD.

Robot-Guided Evacuation as a Paradigm for Human-Robot Interaction Research.

This paper conceptualizes the problem of emergency evacuation as a paradigm for investigating human-robot interaction. We argue that emergency evacuation offers unique and important perspectives on human-robot interaction while also demanding close attention to the ethical ramifications of the technologies developed. We present a series of approaches for developing emergency evacuation robots and detail several essential design considerations. This paper concludes with a discussion of the ethical implications of emergency evacuation robots and a roadmap for their development, implementation, and evaluation.

Ziv-aflibercept for Better Regulating Neovascular Age-Related Macular Degeneration (ZEBRA): A Prospective, Randomized Trial.

OBJECTIVE: The purpose of this study is to determine if ziv-aflibercept is a safe and effective maintenance drug for nAMD. STUDY DESIGN AND METHODS: This is a randomized, prospective, single-blinded trial. Inclusion criteria were active nAMD, prior anti-VEGF treatment, and BCVA ≤20/200. The treatment group received ziv-aflibercept. The control group continued their existing anti-VEGF regimen. The main outcome measures were BCVA, CFT, and safety. RESULTS: Mean baseline BCVA was 1.58 ± 0.44 logMAR and 1.71 ± 0.39 logMAR in the control (n = 27) and treatment (n = 29) groups, respectively. After 24 months, the mean change in BCVA was 0.11 in the control group (equivalent to a loss of 5 ETDRS letters) and 0.01 logMAR in the treatment group (p = .48). Baseline CFT was 257 ± 33 µm and 247 ± 30 µm in the control and treatment groups, respectively, and after 24 months mean change in CFT was 26 µm and -5 µm (p = .24). There were no ocular or systemic adverse events during the study. CONCLUSION: Ziv-aflibercept is a safe and effective as a maintenance drug for patients with nAMD. It may represent a cost-effective alternative to aflibercept and second-line therapy for eye resistant bevacizumab or ranibizumab.

Successful Clinical Outcome of Vancomycin-induced Hemorrhagic Occlusive Retinal Vasculitis.

We present a case of a patient that experienced severe hemorrhagic occlusive retinal vasculitis secondary to injection of 1.0 mg/0.1 ml of intracameral vancomycin for endophthalmitis prophylaxis after an uneventful cataract surgery. The case is especially unique in that our patient ended up maintaining 20/25 vision with an ocular disease that is typically visually threatening. This may be due to the aggressive administration of periocular and oral steroids combined with scheduled anti-VEGF injections that were later transitioned into a treat and extend regimen.

Differences in characteristics of Medicare patients treated by ophthalmologists and optometrists.

PURPOSE: To quantify differences in the age, gender, race, and clinical complexity of Medicare beneficiaries treated by ophthalmologists and optometrists in each of the United States. DESIGN: Cross-sectional study based on publicly accessible Medicare payment and utilization data from 2012 through 2017. METHODS: For each ophthalmic and optometric provider, demographic information of treated Medicare beneficiaries was obtained from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services (CMS) for the years 2012 through 2017. Clinical complexity was defined using CMS Hierarchical Condition Category (HCC) coding. RESULTS: From 2012 through 2017, ophthalmologists in every state treated statistically significantly older beneficiaries, with the greatest difference (4.99 years in 2014) between provider groups seen in Rhode Island. In most states there was no gender difference among patients treated by the providers but in 46 states ophthalmologists saw a more racially diverse group of beneficiaries. HCC risk score analysis demonstrated that ophthalmologists in all 50 states saw more medically complex beneficiaries and the differences were statistically significant in 47 states throughout all six years. CONCLUSIONS: Although there are regional variations in the characteristics of patients treated by ophthalmologists and optometrists, ophthalmologists throughout the United States manage older, more racially diverse, and more medically complex Medicare beneficiaries.

Cost-effectiveness analysis of ocriplasmin versus watchful waiting for treatment of symptomatic vitreomacular adhesion in the US.

Aim: Evaluate the cost-effectiveness of ocriplasmin in symptomatic vitreomacular adhesion (VMA) with or without full-thickness macular hole ≤400 µm versus standard of care. Methods: A state-transition model simulated a cohort through disease health states; assignment of utilities to health states reflected the distribution of visual acuity. Efficacy of ocriplasmin was derived from logistic regression models using Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole trial data. Model inputs were extracted from Phase III trials and published literature. The analysis was conducted from a US Medicare perspective. Results: Lifetime incremental cost-effectiveness ratio was US$4887 per quality-adjusted life year gained in the total population, US$4255 and US$10,167 in VMA subgroups without and with full-thickness macular hole, respectively. Conclusion: Ocriplasmin was cost effective compared with standard of care in symptomatic VMA.

Intravitreal Ziv-Aflibercept: A Comprehensive Review.

Background: Age-related macular degeneration is the leading cause of blindness in adults over the age of 50 in the United States of America. Neovascular age-related macular degeneration (nAMD) is sight-threatening, but can be treated by three currently utilized, intravitreally administered drugs: aflibercept, bevacizumab, and ranibizumab. Ziv-aflibercept is an analogue of aflibercept, containing the same active molecule in a different buffer solution, and its recent availability has prompted numerous pre-clinical and clinical trials addressing its viability for intraocular use, summarized herein. Results: Trial outcomes demonstrate that ziv-aflibercept has a similar safety profile to other indicated drugs with effective maintenance or improvement of best-corrected visual acuity (BCVA) and reduction of retinal fluid or central foveal thickness (CFT). Clinical trials of ziv-aflibercept in other neovascular disorders such as diabetic macular edema (DME) and retinal vein occlusion (RVO) have shown similar results. Conclusion: Further prospective, randomized studies of ziv-aflibercept are needed, particularly in eyes with nAMD.

Updated Cost-Effectiveness of Intravitreal Ocriplasmin for Vitreomacular Adhesion and Macular Hole.

BACKGROUND AND OBJECTIVE: The purpose of this study is to provide an updated assessment of cost-efficacy of intravitreal ocriplasmin (IVO) for vitreomacular adhesion (VMA) and macular holes (MH). PATIENTS AND METHODS: This was a single-center, multiple-physician, institutional review board-approved, retrospective, 15-month cost-effectiveness analysis study (January 2015 to April 2016). Clinical charts and billing records of 247 patients with VMA and MH were reviewed. Patients were divided into group 1 (VMA and MH treated by pars plana vitrectomy [PPV]), group 2 (VMA and MH treated by IVO), and group 3 (VMA treated by IVO). Success rates of interventions in each group were compared, including cost-effectiveness, cost per line-year, and cost per quality-adjusted life-year (QALY). RESULTS: Success rates for initial intervention were 98% in group 1, 55.6% in group 2, and 67.7% in group 3. Cost of PPV at our institution was $6,538.00 and cost of IVO (2016) was $3,480.00. Using a cohort-based computer Markov model, the treatment decision tree demonstrated group 1 was less cost-effective, with cost per line of $2,654.39, cost per line-year saved of $185.62, and cost per QALY of $6,187.00. Group 2 was cost-effective with cost per line of $2,456.25, cost per line-year saved of $171.77, and cost per QALY of $5,726.00. The difference in cost-effectiveness showed IVO was more cost-effective than PPV, with a difference in cost per line of $198.14, cost per line-year saved of $13.85, and cost per QALY of $461.00. CONCLUSIONS: IVO is a more cost-effective intervention than vitrectomy for the treatment of VMA and MH in the setting of judicious use in appropriate patients. The success rate of IVO in our patient population was greater than currently published rates and most certainly impacted probability of cost-efficacy. Further research targeting optimizing IVO success rate is needed. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e240-e248.].

Role of enterocyte stearoyl-Co-A desaturase-1 in LDLR-null mice.

After crossing floxed stearoyl-CoA desaturase-1 (Scd1fl/fl) mice with LDL receptor-null (ldlr-/-) mice, and then Villin Cre (VilCre) mice, enterocyte Scd1 expression in Scd1fl/fl/ldlr-/-/VilCre mice was reduced 70%. On Western diet (WD), Scd1fl/fl/ldlr-/- mice gained more weight than Scd1fl/fl/ldlr-/-/VilCre mice (P < 0.0023). On WD, jejunum levels of lysophosphatidylcholine (LysoPC) 18:1 and lysophosphatidic acid (LPA) 18:1 were significantly less in Scd1fl/fl/ldlr-/-/VilCre compared with Scd1fl/fl/ldlr-/- mice (P < 0.0004 and P < 0.026, respectively). On WD, Scd1fl/fl/ldlr-/-/VilCre mice compared with Scd1fl/fl/ldlr-/- mice had lower protein levels of lipopolysaccharide-binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR4), and myeloid differentiation factor-88 (MyD88) in enterocytes and plasma, and less dyslipidemia and systemic inflammation. Adding a concentrate of tomatoes transgenic for the apoA-I mimetic peptide 6F (Tg6F) to WD resulted in reduced enterocyte protein levels of LBP, CD14, TLR4, and MyD88 in Scd1fl/fl/ldlr-/- mice similar to that seen in Scd1fl/fl/ldlr-/-/VilCre mice. Adding LysoPC 18:1 to WD did not reverse the effects of enterocyte Scd1 knockdown. Adding LysoPC 18:1 (but not LysoPC 18:0) to chow induced jejunum Scd1 expression and increased dyslipidemia and plasma serum amyloid A and interleukin 6 levels in Scd1fl/fl/ldlr-/- mice, but not in Scd1fl/fl/ldlr-/-/VilCre mice. We conclude that enterocyte Scd1 is partially responsible for LysoPC 18:1- and WD-induced dyslipidemia and inflammation in ldlr-/- mice.

Access to Ophthalmologists in States Where Optometrists Have Expanded Scope of Practice.

Importance: As the United States considers how to best structure its health care services, specialty care availability is receiving increased focus. This study assesses whether patients lack reasonable access to ophthalmologists in states where optometrists have been granted expanded scope of practice. Objective: To determine the estimated travel time (ETT) to the nearest ophthalmologist office for persons residing in states that have expanded scope of practice for optometrists, and to quantify ETT to the nearest ophthalmologist for Medicare beneficiaries who received surgical care from optometrists in those states between 2008 and 2014. Design, Setting, and Participants: This study used data from the 2010 US census, a 2016 American Academy of Ophthalmology member database, and a data set of claims data for a random sample of 20% of beneficiaries enrolled in Medicare nationwide from 2008 to 2014 (n=14 063 725). Combining these sources with geographic information systems analysis, the ETT to the nearest ophthalmologist office was calculated for every resident of Kentucky, Oklahoma, and New Mexico. This study also assessed ETT to the nearest ophthalmologist for Medicare beneficiaries in those states who had received surgery from an optometrist from 2008 to 2014. Data analyses were conducted from July 2016 to July 2017. Main Outcomes and Measures: The proportion of residents of Kentucky, Oklahoma, and New Mexico who live within an ETT of 10, 30, 45, 60, or 90 minutes of the nearest ophthalmologist office. Results: The study included 4 339 367 Kentucky residents, 3 751 351 Oklahoma residents, and 2 059 179 New Mexico residents. Of these, 5 140 547 (50.6%) were female. Racial/ethnic composition included 7 154 847 people (70.5%) who were white, 640 608 (6.3%) who were black, and 1 418 246 (14.0%) who were Hispanic. The mean (SD) age was 37.8 (22.8) years. More than 75% of residents in the 3 states lived within an ETT of 30 minutes to the nearest ophthalmology office, and 94% to 99% of residents lived within an ETT of 60 minutes to the nearest ophthalmology office. Among Medicare beneficiaries who received surgery by optometrists, 58.3%, 51.1%, and 46.9% in Kentucky, Oklahoma, and New Mexico, respectively, lived within an ETT of 30 minutes from the nearest ophthalmologist office. Conclusions and Relevance: In the states where optometrists have expanded scope of practice, most residents lived within an ETT of 30 minutes of the nearest ophthalmologist office, as do half of Medicare beneficiaries who received surgical care from optometrists. These results can help inform policy makers when weighing the pros and cons of scope of practice expansion for optometrists.

Mineralocorticoid Antagonists as Adjuncts in Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The purpose of this project was to evaluate the role of MR antagonists as an adjunct in patients with neovascular age-related macular degeneration (AMD) who have chronic subretinal fluid. METHODS: Inclusion criteria were patients with a diagnosis of neovascular AMD, who had completed at least six anti-VEGF injections, and had persistent subretinal fluid (SRF) on optical coherence tomography (OCT). Treatment with oral eplerenone was initiated and dose titrated according to protocol. RESULTS: 23 patients were included in the study (mean age = 54.6, 52.2% female, 47.8% male). 13 of the 23 patients had predominantly chronic subretinal fluid without large PEDs. In this subgroup, mean initial central macular thickness (CMT) prior to starting oral eplerenone was 305.3 µm, and mean injection interval was 40.25 days. Mean final CMT after at least 3 months of adjunctive eplerenone treatment was 240.6 µm and mean injection interval with adjunctive treatment was 54.61 days. Mean extension of the injection interval after commencing oral eplerenone was 14.36 days. CONCLUSIONS: These findings suggest oral MR antagonists may have a role as an adjunctive treatment in neovascular AMD, and may be particularly useful in dehydration of the subretinal space in the setting of chronic subretinal fluid. Further research is needed in randomized controlled trials to elucidate the precise role of oral MR antagonists in neovascular AMD.

Intravitreal Daptomycin for Recalcitrant Postoperative Endophthalmitis.

PURPOSE: To report the first case to our knowledge of intravitreal daptomycin used to successfully treat culture-negative vancomycin resistant to exogenous endophthalmitis. METHODS: Case report with preoperative, intraoperative, and postoperative findings. RESULTS: A 63-year-old Caucasian male underwent routine pars plana vitrectomy with epiretinal membrane peeling. He developed acute postoperative endophthalmitis, and underwent vitreous tap and injection of intravitreal vancomycin/ceftazidime/dexamethasone. Gram stain showed Gram-positive cocci, but cultures were negative. His infection subsequently proved very recalcitrant and his treatment course involved pars plana vitrectomy with anterior chamber washout and repeat injection of antibiotics, followed by repeat intravitreal vancomycin and ceftazidime. Ultimately, a second vitrectomy with intravitreal daptomycin controlled his intraocular infection. On each occasion, cultures were negative. CONCLUSION: This case suggests that vancomycin resistance should be considered in culture-negative postoperative endophthalmitis, and intravitreal daptomycin should be considered as an important treatment alternative. Although vancomycin resistance is fairly rare in endophthalmitis, acknowledgment of its increasing occurrence rate is critical for optimal management.

Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux.

The site and mechanism of action of the apoA-I mimetic peptide 4F are incompletely understood. Transintestinal cholesterol efflux (TICE) is a process involved in the clearance of excess cholesterol from the body. While TICE is responsible for at least 30% of the clearance of neutral sterols from the circulation into the intestinal lumen, few pharmacological agents have been identified that modulate this pathway. We show first that circulating 4F selectively targets the small intestine (SI) and that it is predominantly transported into the intestinal lumen. This transport of 4F into the SI lumen is transintestinal in nature, and it is modulated by TICE. We also show that circulating 4F increases reverse cholesterol transport from macrophages and cholesterol efflux from lipoproteins via the TICE pathway. We identify the cause of this modulation of TICE either as 4F being a cholesterol acceptor with respect to enterocytes, from which 4F enhances cholesterol efflux, or as 4F being an intestinal chaperone with respect to TICE. Our results assign a novel role for 4F as a modulator of the TICE pathway and suggest that the anti-inflammatory functions of 4F may be a partial consequence of the codependent intestinal transport of both 4F and cholesterol.

Apolipoprotein E-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative Stress and Altered Macrophage Function.

OBJECTIVE: We previously reported that hemopexin (Hx), a heme scavenger, is significantly increased and associated with proinflammatory high-density lipoprotein under atherogenic conditions. Although it is established that Hx together with macrophages plays a role in mitigating oxidative damage, the role of Hx in the development of atherosclerosis is unknown. APPROACH AND RESULTS: We used Hx and apoE double-knockout mice (HxE(-/-)) to determine the role of Hx in the development of atherosclerosis. HxE(-/-) mice had significantly more free heme, reactive oxygen species, and proinflammatory high-density lipoprotein in their circulation, when compared with control apoE(-/-) mice. Atherosclerotic plaque area (apoE(-/-)=9.72±2.5×10(4) µm(2) and HxE(-/-)=27.23±3.6×10(4) µm(2)) and macrophage infiltration (apoE(-/-)=38.8±5.8×10(3) µm(2) and HxE(-/-)=103.4±17.8×10(3) µm(2)) in the aortic sinus were significantly higher in the HxE(-/-) mice. Atherosclerotic lesions in the aortas were significantly higher in the HxE(-/-) mice compared with apoE(-/-) mice. Analysis of polarization revealed that macrophages from HxE(-/-) mice were more M1-like. Ex vivo studies demonstrated that HxE(-/-) macrophage cholesterol efflux capacity was significantly reduced when compared with apoE(-/-) mice. Injection of human Hx into HxE(-/-) mice reduced circulating heme levels and human Hx pretreatment of naive bone marrow cells ex vivo resulted in a shift from M1- to M2-like macrophages. CONCLUSIONS: We conclude that Hx plays a novel protective role in alleviating heme-induced oxidative stress, improving inflammatory properties of high-density lipoprotein, macrophage phenotype and function, and inhibiting the development of atherosclerosis in apoE(-/-) mice.

Mineralocorticoid Antagonists in the Treatment of Central Serous Chorioretinopathy: A Comparative Analysis.

BACKGROUND AND OBJECTIVE: Overaction of mineralocorticoid receptor (MR) pathways has been implicated in the pathophysiology of central serous chorioretinopathy (CSCR). The purpose of this study was to evaluate MR antagonists in the treatment of CSCR. STUDY DESIGN AND METHODS: A retrospective chart review was conducted of all CSCR patients at one center treated with spironolactone or eplerenone (50 mg p.o. b.i.d.) or observation. Patients were followed at monthly intervals with examination and optical coherence tomography. RESULTS: 32 patients (12 eplerenone, 12 spironolactone, 8 observation) were enrolled in the study. Both MR antagonists demonstrated statistically significant visual acuity improvement and subretinal fluid reduction at 1, 2, and 3 months compared to baseline (p < 0.05). 58.3% of patients had complete resolution of subretinal fluid at 2 months on MR antagonists, compared to 12.5% under observation (p < 0.05). Photodynamic therapy was used to treat refractory subretinal fluid past 6 months in 1/24 (4.2%) on MR antagonists and 2/8 (25%) patients under observation. There was no difference in efficacy between eplerenone and spironolactone. Spironolactone exhibited increased side effects (8/12, 75%) compared to eplerenone (3/12, 25%; p < 0.05). CONCLUSIONS: This data supports the use of MR antagonists in CSCR and suggests an accelerated improvement compared to observation. Prospective randomized trials are needed to better elucidate the precise role of MR antagonists in the management of CSCR.

Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis.

We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR(-/-)) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here we report that supplementing chow with unsaturated (but not saturated) LPA resulted in aortic atherosclerosis, which was ameliorated by adding transgenic 6F tomatoes. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1 (but not LysoPC 18:0) resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. PF8380 (a specific inhibitor of autotaxin) significantly ameliorated the LysoPC 18:1-induced dyslipidemia. Supplementing chow with LysoPC 18:1 dramatically increased the levels of unsaturated LPA species in small intestine, liver, and plasma, and the increase was significantly ameliorated by PF8380 indicating that the conversion of LysoPC 18:1 to LPA 18:1 was autotaxin dependent. Adding LysoPC 18:0 to chow increased levels of LPA 18:0 in small intestine, liver, and plasma but was not altered by PF8380 indicating that conversion of LysoPC 18:0 to LPA 18:0 was autotaxin independent. We conclude that i) intestinally derived unsaturated (but not saturated) LPA can cause atherosclerosis in LDLR(-/-) mice, and ii) autotaxin mediates the conversion of unsaturated (but not saturated) LysoPC to LPA.