Optometric Practice Patterns for Acute Central and Branch Retinal Artery Occlusion.

BACKGROUND: Optometrists are often the first providers to evaluate patients with acute vision loss and are often the first to diagnose a central retinal artery occlusion (CRAO). How quickly these patients present to the optometrist, are diagnosed, and referred for evaluation are major factors influencing the possibility of acute therapeutic intervention. Our aim was to survey the U.S. optometric community to determine current optometric practice patterns for management of CRAO. METHODS: An anonymous seven-question survey was emailed in 2020 to the 5,101 members of the American Academy of Optometry and the 26,502 members of the American Optometric Association. RESULTS: Of 31,603 optometrists who were sent the survey, 1,926 responded (6.1%). Most respondents (1,392/1,919, 72.5%) worked in an optometry-predominant outpatient clinic and were less than 30 minutes from a certified stroke center (1,481/1,923, 77.0%). Ninety-eight percent (1,884/1,922) of respondents had diagnosed less than 5 CRAOs in the previous year, and 1,000/1,922 (52.0%) had not diagnosed a CRAO in the prior year. Of the optometrists who diagnosed at least one CRAO in the previous year, 661/922 (71.7%) evaluated these patients more than 4 hours after the onset of vision loss. Optometrists who diagnosed a CRAO or branch retinal artery occlusion referred patients to an emergency department (ED) affiliated with a certified stroke center (844/1,917, 44.0%), an outpatient ophthalmology clinic (764/1,917, 39.9%), an ED without a stroke center (250/1,917, 13.0%), an outpatient neurology clinic (20/1,917, 1.0%), or other (39/1,917, 2.0%); most (22/39, 56.4%) who responded "other" would refer to a primary care physician. CONCLUSIONS: Optometrists are likely the first providers to evaluate patients with acute vision loss, including from a retinal artery occlusion. However, only 6.1% of optometrists responded to our survey despite 2 reminder emails, likely reflecting the lack of exposure to acute retinal artery occlusions, and a potential lack of interest of optometrists in participating in research. Of the optometrists who reported evaluating a CRAO in the previous year, less than 29% saw the patient within 4 hours of vision loss. In addition, a large portion of optometrists are referring acute CRAO patients to outpatient ophthalmology clinics, delaying appropriate acute management. Therefore, it is imperative that optometrists and ophthalmologists are educated to view acute retinal arterial ischemia as an acute stroke and urgently refer these patients to an ED affiliated with a stroke center. The delay in patient presentation and these referral patterns make future clinical trials for acute CRAO challenging.

AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study.

In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.

Sf3b4 regulates chromatin remodeler splicing and Hox expression.

SF3B proteins form a heptameric complex in the U2 small nuclear ribonucleoprotein, essential for pre-mRNA splicing. Heterozygous pathogenic variants in human SF3B4 are associated with head, face, limb, and vertebrae defects. Using the CRISPR/Cas9 system, we generated mice with constitutive heterozygous deletion of Sf3b4 and showed that mutant embryos have abnormal vertebral development. Vertebrae abnormalities were accompanied by changes in levels and expression pattern of Hox genes in the somites. RNA sequencing analysis of whole embryos and somites of Sf3b4 mutant and control litter mates revealed increased expression of other Sf3b4 genes. However, the mutants exhibited few differentially expressed genes and a large number of transcripts with differential splicing events (DSE), predominantly increased exon skipping and intron retention. Transcripts with increased DSE included several genes involved in chromatin remodeling that are known to regulate Hox expression. Our study confirms that Sf3b4 is required for normal vertebrae development and shows, for the first time, that like Sf3b1, Sf3b4 also regulates Hox expression. We propose that abnormal splicing of chromatin remodelers is primarily responsible for vertebral defects found in Sf3b4 heterozygous mutant embryos.

Development of effective human factors interventions for aviation safety management.

Introduction: In the aviation industry, safety management has moved away from capturing frontline failures toward the management of systemic conditions through organizational safety management systems (SMS). However, subjective differences can influence the classification of active failures and their associated systemic precursors. With levels of professional experience known to influence safety attitudes, the present research examines whether experience levels among airline pilots had an impact on the classification of causal factors using the Human Factors Analysis and Classification System (HFACS). Differences in the paths of association between categories were evaluated in an open-system context. Method: Pilots working in a large, international airline were categorized into high (≥10,000 total flight hours) and low (<10,000 h) experience groups and asked to classify aircraft accident causal factors using the HFACS framework. One-way ANOVA tests were carried out to determine experience effects on the utilization of the HFACS categories, and chi-squared analyses were used to assess the strength of association between different categories within the framework. Results: Results from 144 valid responses revealed differences in the attribution of human factors conditions. The high experience group was more inclined to attribute deficiencies to high-level precursors and found fewer paths of associations between different categories. In contrast, the low experience group presented a greater number of associations and was comparatively more affected by stress and uncertainty conditions. Discussion: The results confirm that the classification of safety factors can be influenced by professional experience, with hierarchical power distance impacting the attribution of failures to higher-level organizational faults. Different paths of association between the two groups also suggest that safety interventions can be targeted through different entry points. Where multiple latent conditions are associated, the selection of safety interventions should be made with consideration of the concerns, influences, and actions across the entire system. Higher-level anthropological interventions can change the interactive interfaces affecting concerns, influences, and actions across all levels, whereas frontline-level functional interventions are more efficient for failures linked to many precursor categories.

Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma.

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion.

OBJECTIVES: Diffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers. MATERIALS AND METHODS: Retrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed. RESULTS: We included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038). CONCLUSIONS: In this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.

TMED2 binding restricts SMO to the ER and Golgi compartments.

Hedgehog (HH) signaling is important for embryonic pattering and stem cell differentiation. The G protein-coupled receptor (GPCR) Smoothened (SMO) is the key HH signal transducer modulating both transcription-dependent and transcription-independent responses. We show that SMO protects naive mouse embryonic stem cells (ESCs) from dissociation-induced cell death. We exploited this SMO dependency to perform a genetic screen in haploid ESCs where we identify the Golgi proteins TMED2 and TMED10 as factors for SMO regulation. Super-resolution microscopy shows that SMO is normally retained in the endoplasmic reticulum (ER) and Golgi compartments, and we demonstrate that TMED2 binds to SMO, preventing localization to the plasma membrane. Mutation of TMED2 allows SMO accumulation at the plasma membrane, recapitulating early events after HH stimulation. We demonstrate the physiologic relevance of this interaction in neural differentiation, where TMED2 functions to repress HH signal strength. Identification of TMED2 as a binder and upstream regulator of SMO opens the way for unraveling the events in the ER-Golgi leading to HH signaling activation.

DCP and AFP-L3 Are Complementary to AFP in Predicting High-Risk Explant Features: Results of a Prospective Study.

Among patients with hepatocellular carcinoma (HCC), elevated α-fetoprotein (AFP) has been shown to predict waitlist dropout, high-risk histopathologic features, and inferior post-liver transplant (LT) outcome.1,2 Nevertheless, many patients with HCC have a normal AFP and yet still experience waitlist dropout or post-LT recurrence.2 Because of the degree of imprecision associated with AFP, there is a quest for other biomarkers that may be complementary to or better than AFP in predicting prognosis in LT. Lectin-reactive AFP (AFP-L3) and des-gamma-carboxyprothrombin (DCP) are biomarkers that have been used in conjunction with AFP as HCC surveillance or diagnostic tools.3,4 However, the utility of these biomarkers in LT for HCC is not established.

Copper-Catalyzed Reductive Ireland-Claisen Rearrangements of Propargylic Acrylates and Allylic Allenoates.

The copper-catalyzed reductive Ireland-Claisen rearrangement of propargylic acrylates led to 3,4-allenoic acids. The use of silanes or pinacolborane as stoichiometric reducing agents and triethylphosphite as a ligand facilitated the divergent and complementary selectivity for the synthesis of diastereomeric anti- and syn-rearranged products, respectively. Copper-catalyzed reductive Ireland-Claisen rearrangement of allylic 2,3-allenoates proceeded effectively only when pinacolborane was used as a reductant to generate various 1,5-dienes in excellent yields and with good diastereoselectivities in some cases. Mechanistic studies showed that the silyl and boron enolates, rather than the copper enolate, underwent a stereospecific rearrangement via a chairlike transition state to afford the corresponding Claisen rearrangement products.

Referral Patterns of Central Retinal Artery Occlusion to an Academic Center Affiliated With a Stroke Center.

BACKGROUND: Central retinal artery occlusion (CRAO) is a medical emergency, and patients who present acutely should be immediately referred to the nearest stroke center. We evaluated practice patterns for CRAO management at one academic center over the last decade. METHODS: This was a retrospective study on all adult patients diagnosed with a CRAO seen at one tertiary hospital and outpatient clinic affiliated with a comprehensive stroke center ("our institution") from 2010 to 2020. Our electronic medical records were searched for CRAO diagnoses, and patient medical records were reviewed. The exclusion criteria were incorrect diagnosis, unclear diagnosis, historical CRAO, or satellite clinic location. Demographics, distance and time to presentation to our institution, number and type of prior providers seen, diagnostic tests performed, and treatments provided were collected. Summary statistics of median, mean, and frequency were calculated and reported with measures of variance (interquartile range [IQR], ranges). F, Tukey, and Fisher exact tests were used for comparisons. RESULTS: We included 181 patients with a diagnosis of CRAO (80 [44.2%] women; median age 69 years [range 20-101]). The median distance from patient's home to our institution was 27.8 miles (IQR 15.5-57.4; range 2.4-930). The median time from visual loss to presentation at our institution was 144 hours (IQR 23-442 hours, range 0.5-2,920) from 2010 to 2013, 72 hours (IQR 10.5-372 hours, range 0-13,140) from 2014 to 2016, and 48 hours (IQR 7-180 hours, range 0-8,030) from 2017 to 2020 (P = 0.07). 91/181 (50%) patients presented to an outpatient provider. 73/181 (40%) presented to an emergency department. Eighty-six percent presented within 1 week of visual loss onset, and rates of comprehensive inpatient evaluation for acute CRAO improved from 44% in 2010-2013 to 82% in 2017-2020 (P < 0.01). CONCLUSIONS: Patients with CRAO often present late and only after evaluation by multiple outpatient providers. Improvement has occurred over the past decade, but delays underscore the barriers to performing clinical trials evaluating very acute treatments for CRAO. Educational interventions for healthcare providers and patients are necessary.

Acute Central Retinal Artery Occlusion Seen within 24 Hours at a Tertiary Institution.

OBJECTIVE: Acute central retinal artery occlusion (CRAO) is an emergency with poor visual outcome. Intravenous thrombolysis within 4.5 h of vision loss is safe and may improve vision, but is rarely administered because of frequent delays in presentation. We describe a subgroup of CRAO patients presenting within 24 h of vision loss to a tertiary care center affiliated with a comprehensive stroke center. MATERIALS AND METHODS: Retrospective review of 181 consecutive CRAO patients seen at our institution from 2010 to 2020. RESULTS: Out of 181 CRAO patients, 62 (34%) presented within 24 h of vision loss and tended to live closer to the hospital. These patients were more likely to be admitted to the hospital and receive comprehensive stroke work-up compared to patients who presented after 24 h of vision loss. Patients presenting after 24 h did not necessarily receive prior appropriate work-up at outside institutions. Conservative treatments for CRAO were administered to 20/181 patients, and only 3 patients received intravenous thrombolysis. CONCLUSIONS: Patients with CRAO do not present to the emergency department fast enough and diagnosis of CRAO is often delayed. Despite having a protocol in place, only 3/181 patients received IV thrombolysis, emphasizing the difficulty in administering very acute treatments for CRAO. Public education regarding CRAO is necessary to improve presentation times, management, and visual outcomes. Hospitals need to develop accelerated diagnostic pathway protocols for patients with acute vision loss so that CRAO patients may be diagnosed and be considered for potential acute treatments as quickly as possible.

Downstaging Outcomes for Hepatocellular Carcinoma: Results From the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium.

BACKGROUND & AIMS: United Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown. METHODS: In this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019. RESULTS: Probability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%. CONCLUSION: In this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.

Design of Functional Chiral Cyclen-Based Radiometal Chelators for Theranostics.

A series of water-soluble chiral cyclen-based chelators with chemical handles for selective targeting have been synthesized (cyclen = 1,4,7,10-Tetraazacyclododecane). Optical studies, relaxivity measurements, and competitive titrations were performed to show the versatility of these chiral chelators. The complexations of L3, L4, and L5 with Lu3+, Y3+, Sc3+, and Cu2+ were successfully demonstrated in around 90% to 100% yields. Efficient and rapid radiolabeling of L5 with 177Lu was achieved under mild conditions with 96% yield. The chelators exhibit near quantitative labeling efficiencies with a wide range of radiometal ions, which are promising for the development of targeting specific radiopharmaceutical and molecular magnetic resonance imaging contrast agents.

Helicate-to-tetrahedron transformation of chiral lanthanide supramolecular complexes induced by ionic radii effect and linker length.

Controlled formation of desired lanthanide supramolecular complexes is challenging because of the difficulties in predicting coordination geometry, as well as a labile coordination number. Herein, we explore the effect of ionic radii and linker length on supramolecular species formation. A helicate-to-tetrahedron transformation occurred between [Ln2L13] and [Ln4L16] (Ln = La, Sm, Eu, Gd, Tb and Lu). For six lanthanide ions, the unfavored tetrahedron [La4L16] can only be observed in a concentrated mixture with the helicate [La2L13] where no pure [La4L16] species was isolated via crystallization. For Sm, Eu, Gd, Tb, the [Ln4L16] supramolecular tetrahedron can be isolated via crystallization from diisopropyl ether. A similar result was also observed for Lu, but the tetrahedral structure was found to be relatively stable and transformed back to [Lu2L13] much slower upon dissolution.  No tetrahedron formation was observed with L3 giving rise to only [Ln2L33] species, in which L3 contains a longer and more flexible linker compared with that of L1. Results show that the supramolecular transformation in these systems is governed by both the ionic radii as well as the ligand design. Special focus is on both [Eu2L13] and [Eu4L16] which form chiral entities and exhibit interesting circular polarized luminescence.

Unusual Magnetic Field Responsive Circularly Polarized Luminescence Probes with Highly Emissive Chiral Europium(III) Complexes.

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |glum | up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral EuIII complexes, promoting an exciting development to the field of magneto-optics. The |glum | of the 5 D0 → 7 F1 transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δglum and the magnetic field strength. These EuIII complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution.

Copper-catalyzed (4+1) and (3+2) cyclizations of iodonium ylides with alkynes.

The copper(ii)-catalyzed (4+1) cyclizations and copper(i)-catalyzed (3+2) cycloadditions of iodonium ylides and alkynes were successfully developed by employing efficient and safe iodonium ylides instead of traditional diazo compounds. Highly functionalized dimethyl (E)-3-benzylideneindoline-2,2-dicarboxylates and methyl 5-(2-hydroxyphenyl)-2-methoxy-4-phenylfuran-3-carboxylates were conveniently prepared in moderate to excellent yields. The possible reaction mechanisms were also discussed.

Transverse venous sinus stenosis in idiopathic intracranial hypertension: a prospective pilot study.

OBJECTIVE: Whether transverse venous sinus stenosis (TVSS) causes idiopathic intracranial hypertension (IIH) or is an effect of the increased intracranial pressures is controversial. The purpose of this study was to assess the feasibility of serial imaging in patients with IIH on medical management. DESIGN AND PARTICIPANTS: Patients found to have IIH and TVSS on contrast-enhanced magnetic resonance venography (CEMRV) were recruited in a prospective cohort study. Patients were medically managed and followed with a CEMRV immediately after lumbar puncture, 3-6 months after diagnosis with resolution of IIH symptoms, and 1 year after diagnosis. Ophthalmological data were collected at the time of diagnosis, 3-6 months after diagnosis, and 1 year after diagnosis. Feasibility data, including patient recruitment rate, barriers, and logistical issues, were recorded. RESULTS: Twenty patients with suspected IIH were screened, and 5 of 7 (71.4%; 95% confidence interval: 36.21-100) eligible patients were enrolled in 1 year, at completion. All recruited patients had clinical resolution of their IIH on medical therapy, and none of them had any obvious change in their TVSS. CONCLUSIONS: Prospective examination of TVSS with serial magnetic resonance imaging in patients with IIH is feasible. TVSS in patients with IIH did not show any change, despite clinical improvement on medical management in all participants.

Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD). METHODS: Retrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status. RESULTS: Among 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm2 , P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02). CONCLUSION: Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.