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Adjuvant Chemotherapy And Survival Among Patients 70 Years Of Age And Younger With Node-Negative Breast Cancer And The 21-Gene Recurrence Score Of 26-30, Seho Park, Yunan Han, Ying Liu, Adetunji T Toriola, Lindsay L Peterson, Graham A Colditz, Seung Il Kim, Young Up Cho, Byeong-Woo Park, Yikyung Park

Open Access Publications

BACKGROUND: The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18-30, particularly those with RS 26-30, are not known.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18-30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox's proportional hazards model.

RESULTS: Among the breast cancer patients with the RS 18-30, 21% of them had RS 26-30. …

Redefining Noradrenergic Neuromodulation Of Behavior: Impacts Of A Modular Locus Coeruleus Architecture, Dan J. Chandler, Patricia Jensen, Jordan G. Mccall, Anthony E. Pickering, Lindsay A. Schwarz, Nelson K. Totah

Open Access Publications

The locus coeruleus (LC) is a seemingly singular and compact neuromodulatory nucleus that is a prominent component of disparate theories of brain function due to its broad noradrenergic projections throughout the CNS. As a diffuse neuromodulatory system, noradrenaline affects learning and decision making, control of sleep and wakefulness, sensory salience including pain, and the physiology of correlated forebrain activity (ensembles and networks) and brain hemodynamic responses. However, our understanding of the LC is undergoing a dramatic shift due to the application of state-of-the-art methods that reveal a nucleus of many modules that provide targeted neuromodulation. Here, we review the evidence …

Pragmatic Randomised Clinical Trial Of Proton Versus Photon Therapy For Patients With Non-Metastatic Breast Cancer: The Radiotherapy Comparative Effectiveness (Radcomp) Consortium Trial Protocol, Justin E Bekelman, Walter Bosch, Et Al

Open Access Publications

INTRODUCTION: A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer.

METHODS: We are conducting a large …

Staphylococcus Aureus Infects Osteoclasts And Replicates Intracellularly, Jennifer L Krauss, Philip M Roper, Anna Ballard, Chien-Cheng Shih, James A J Fitzpatrick, James E Cassat, Pei Ying Ng, Nathan J Pavlos, Deborah J Veis

Open Access Publications

Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. OM is predominantly caused by

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C Lam, Rajendra Upadhya, Charles A Specht, Abigail E Ragsdale, Camaron R Hole, Stuart M Levitz, Jennifer K Lodge

Open Access Publications

No abstract provided.

Pathological Progression Induced By The Frontotemporal Dementia-Associated R406w Tau Mutation In Patient-Derived Ipscs, Mari Nakamura, Celeste M Karch, Et Al

Open Access Publications

Mutations in the microtubule-associated protein tau (MAPT) gene are known to cause familial frontotemporal dementia (FTD). The R406W tau mutation is a unique missense mutation whose patients have been reported to exhibit Alzheimer's disease (AD)-like phenotypes rather than the more typical FTD phenotypes. In this study, we established patient-derived induced pluripotent stem cell (iPSC) models to investigate the disease pathology induced by the R406W mutation. We generated iPSCs from patients and established isogenic lines using CRISPR/Cas9. The iPSCs were induced into cerebral organoids, which were dissociated into cortical neurons with high purity. In this neuronal culture, the mutant tau protein …

Pten Deletion Drives Acute Myeloid Leukemia Resistance To Mek Inhibitors, Amanda M. Smith, Christine R.C. Zhang, Alexandre S. Cristino, John P. Grady, J Lynn Fink, Andrew S. Moore

Open Access Publications

Kinases such as MEK are attractive targets for novel therapy in cancer, including acute myeloid leukaemia (AML). Acquired and inherent resistance to kinase inhibitors, however, is becoming an increasingly important challenge for the clinical success of such therapeutics, and often arises from mutations in the drug-binding domain of the target kinase. To identify possible causes of resistance to MEK inhibition, we generated a model of resistance by long-term treatment of AML cells with AZD6244 (selumetinib). Remarkably, resistance to MEK inhibition was due to acquired

Mutation Of The Co-Chaperone Tsc1 In Bladder Cancer Diminishes Hsp90 Acetylation And Reduces Drug Sensitivity And Selectivity, Mark R. Woodford, Michael Hughes, Rebecca A. Sager, Sarah J. Backe, Alexander J. Baker-Williams, Michael S. Bratslavsky, Joseph M. Jacob, Oleg Shapiro, Michael Wong, Gennady Bratslavsky, Dimitra Bourboulia, Mehdi Mollapour

Open Access Publications

The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers of oncogenesis. Hsp90 inhibitors are currently under clinical evaluation for cancer treatment, however their efficacy is limited by lack of biomarkers to optimize patient selection. We have recently identified the tumor suppressor tuberous sclerosis complex 1 (Tsc1) as a new co-chaperone of Hsp90 that affects Hsp90 binding to its inhibitors. Highly variable mutations of TSC1 have been previously identified in bladder cancer and correlate with sensitivity to the Hsp90 inhibitors. Here we showed loss of TSC1 leads to hypoacetylation of Hsp90-K407/K419 …

Structured Inhibitory Activity Dynamics In New Virtual Environments, Moises Arriaga, Edward B. Han

Open Access Publications

Inhibition plays a powerful role in regulating network excitation and plasticity; however, the activity of defined interneuron types during spatial exploration remain poorly understood. Using two-photon calcium imaging, we recorded hippocampal CA1 somatostatin- and parvalbumin-expressing interneurons as mice performed a goal-directed spatial navigation task in new visual virtual reality (VR) contexts. Activity in both interneuron classes was strongly suppressed but recovered as animals learned to adapt the previously learned task to the new spatial context. Surprisingly, although there was a range of activity suppression across the population, individual somatostatin-expressing interneurons showed consistent levels of activity modulation across exposure to multiple …

Stimulation Of Piezo1 By Mechanical Signals Promotes Bone Anabolism, Xuehua Li, Li Han, Intawat Nookaew, Erin Mannen, Matthew J. Silva, Maria Almeida, Jinhu Xiong

Open Access Publications

Mechanical loading, such as caused by exercise, stimulates bone formation by osteoblasts and increases bone strength, but the mechanisms are poorly understood. Osteocytes reside in bone matrix, sense changes in mechanical load, and produce signals that alter bone formation by osteoblasts. We report that the ion channel Piezo1 is required for changes in gene expression induced by fluid shear stress in cultured osteocytes and stimulation of Piezo1 by a small molecule agonist is sufficient to replicate the effects of fluid flow on osteocytes. Conditional deletion of

Ilc3s Integrate Glycolysis And Mitochondrial Production Of Reactive Oxygen Species To Fulfill Activation Demands, Blanda Di Luccia, Susan Gilfillan, Marina Cella, Marco Colonna, Stanley Ching-Cheng Huang

Open Access Publications

Group 3 innate lymphoid cells (ILC3s) are the innate counterparts of Th17 that require the transcription factor RORγt for development and contribute to the defense against pathogens through IL-22 and IL-17 secretion. Proliferation and effector functions of Th17 require a specific mTOR-dependent metabolic program that utilizes high-rate glycolysis, while mitochondrial lipid oxidation and production of reactive oxygen species (mROS) support alternative T reg cell differentiation. Whether ILC3s employ a specific metabolic program is not known. Here, we find that ILC3s rely on mTOR complex 1 (mTORC1) for proliferation and production of IL-22 and IL-17A after in vitro activation and Citrobacter …

Protocol For A Prospective, Observational Cohort Study Of Awareness In Mechanically Ventilated Patients Admitted From The Emergency Department: The Ed-Awareness Study, Ryan D Pappal, Brian W Roberts, Nicholas M Mohr, Enyo Ablordeppey, Brian T Wessman, Anne M Drewry, Yan Yan, Marin H Kollef, Michael Simon Avidan, Brian M Fuller

Open Access Publications

INTRODUCTION: Awareness with paralysis is a complication with potentially devastating psychological consequences for mechanically ventilated patients. While rigorous investigation into awareness has occurred for operating room patients, little attention has been paid outside of this domain. Mechanically ventilated patients in the emergency department (ED) have been historically managed in a way that predisposes them to awareness events: high incidence of neuromuscular blockade use, underdosing of analgesia and sedation, delayed administration of analgesia and sedation after intubation, and a lack of monitoring of sedation targets and depth. These practice patterns are discordant to recommendations for reducing the incidence of awareness, suggesting …

Association Of Histologic Disease Activity With Progression Of Nonalcoholic Fatty Liver Disease, David E. Kleiner, Elizabeth M. Brundt, Et Al

Open Access Publications

No abstract provided.

Irak4 Mediates Colitis-Induced Tumorigenesis And Chemoresistance In Colorectal Cancer, Qiong Li, Yali Chen, Daoxiang Zhang, Julie Grossman, Lin Li, Namrata Khurana, Hongmei Jiang, Patrick M Grierson, John Herndon, David G Denardo, Grant A Challen, Jingxia Liu, Marianna B Ruzinova, Ryan C Fields, Kian-Huat Lim

Open Access Publications

Aberrant activation of the NF-κB transcription factors underlies chemoresistance in various cancer types, including colorectal cancer (CRC). Targeting the activating mechanisms, particularly with inhibitors to the upstream IκB kinase (IKK) complex, is a promising strategy to augment the effect of chemotherapy. However, clinical success has been limited, largely because of low specificity and toxicities of tested compounds. In solid cancers, the IKKs are driven predominantly by the Toll-like receptor (TLR)/IL-1 receptor family members, which signal through the IL-1 receptor-associated kinases (IRAKs), with isoform 4 (IRAK4) being the most critical. The pathogenic role and therapeutic value of IRAK4 in CRC have …

Sr9009 Administered For One Day After Myocardial Ischemia-Reperfusion Prevents Heart Failure In Mice By Targeting The Cardiac Inflammasome, Cristine J Reitz, Faisal J Alibhai, Tarak N Khatua, Mina Rasouli, Byram W Bridle, Thomas P Burris, Tami A Martino

Open Access Publications

Reperfusion of patients after myocardial infarction (heart attack) triggers cardiac inflammation that leads to infarct expansion and heart failure (HF). We previously showed that the circadian mechanism is a critical regulator of reperfusion injury. However, whether pharmacological targeting using circadian medicine limits reperfusion injury and protects against HF is unknown. Here, we show that short-term targeting of the circadian driver REV-ERB with SR9009 benefits long-term cardiac repair post-myocardial ischemia reperfusion in mice. Gain and loss of function studies demonstrate specificity of targeting REV-ERB in mice. Treatment for just one day abates the cardiac NLRP3 inflammasome, decreasing immunocyte recruitment, and thereby …

Htlv-1 Viral Oncogene Hbz Drives Bone Destruction In Adult T Cell Leukemia, Jingyu Xiang, Daniel A Rauch, Devra D Huey, Amanda R Panfil, Xiaogang Cheng, Alison K Esser, Xinming Su, John C Harding, Yalin Xu, Gregory C Fox, Francesca Fontana, Takayuki Kobayashi, Junyi Su, Hemalatha Sundaramoorthi, Wing Hing Wong, Yizhen Jia, Thomas J Rosol, Deborah J Veis, Patrick L Green, Stefan Niewiesk, Lee Ratner, Katherine N Weilbaecher

Open Access Publications

Osteolytic bone lesions and hypercalcemia are common, serious complications in adult T cell leukemia/lymphoma (ATL), an aggressive T cell malignancy associated with human T cell leukemia virus type 1 (HTLV-1) infection. The HTLV-1 viral oncogene HBZ has been implicated in ATL tumorigenesis and bone loss. In this study, we evaluated the role of HBZ on ATL-associated bone destruction using HTLV-1 infection and disease progression mouse models. Humanized mice infected with HTLV-1 developed lymphoproliferative disease and continuous, progressive osteolytic bone lesions. HTLV-1 lacking HBZ displayed only modest delays to lymphoproliferative disease but significantly decreased disease-associated bone loss compared with HTLV-1-infected mice. …

Effect Of A Novel Transition Program On Disability After Stroke: A Trial Protocol, Emily Somerville, Marian Keglovits, Yan Yan, Susan Stark

Open Access Publications

Importance: A gap in care for stroke survivors exists at the point of transition from inpatient rehabilitation to home, when survivors encounter new environmental barriers because of the cognitive and sensorimotor sequelae of stroke. Resolving these barriers and improving independence in the community have the potential to significantly improve stroke survivors' long-term morbidity.

Objective: To investigate the efficacy and safety of a novel enhanced rehabilitation transition program to reduce environmental barriers and improve daily activity performance and community participation among stroke survivors.

Design, Setting, and Participants: This is a phase 2b, single-blind, parallel-group, randomized clinical trial. Participants will be randomized …

Association Of Acquired And Heritable Factors With Intergenerational Differences In Age At Symptomatic Onset Of Alzheimer Disease Between Offspring And Parents With Dementia, Gregory S. Day, Carlos Cruchaga, Thomas Wingo, Suzanne E. Schindler, Dean Coble, John C. Morris

Open Access Publications

Importance: Acquired and heritable traits are associated with dementia risk; however, how these traits are associated with age at symptomatic onset (AAO) of Alzheimer disease (AD) is unknown. Identifying the associations of acquired and heritable factors with variability in intergenerational AAO of AD could facilitate diagnosis, assessment, and counseling of the offspring of parents with AD.

Objective: To quantify the associations of acquired and heritable factors with intergenerational differences in AAO of AD.

Design, Setting, and Participants: This nested cohort study used data from the Knight Alzheimer Disease Research Center that included community-dwelling participants with symptomatic AD, parental history of …

Associations Between Social Risk Factors And Surgical Site Infections After Colectomy And Abdominal Hysterectomy, Andrew C. Qi, Kate Peacock, Alina A. Luke, Abigail Barker, Margaret A. Olsen, Karen E. Joynt Maddox

Open Access Publications

Importance: Surgical site infection (SSI) is an important patient safety outcome. Although social risk factors have been linked to many adverse health outcomes, it is unknown whether such factors are associated with higher rates of SSI.

Objectives: To determine whether social risk factors, including race/ethnicity, insurance status, and neighborhood income, are associated with higher rates of SSI after colectomy or abdominal hysterectomy, 2 surgical procedures for which SSI rates are publicly reported and included in pay-for-performance programs by Medicare and other groups.

Design, Setting, and Participants: This cross-sectional study analyzed adults undergoing colectomy or abdominal hysterectomy, as captured in State …

Astrovirus Replication In Human Intestinal Enteroids Reveals Multi-Cellular Tropism And An Intricate Host Innate Immune Landscape, Abimbola O. Kolawole, Andrew B Janowski, David Wang, Christiane E. Wobus, Et Al.

Open Access Publications

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE …

Sequence Specificity Despite Intrinsic Disorder: How A Disease-Associated Val/Met Polymorphism Rearranges Tertiary Interactions In A Long Disordered Protein, Ruchi Lohia, Reza Salari, Grace Brannigan

Open Access Publications

The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) in precursor brain-derived neurotrophic factor (BDNF) is one of the earliest SNPs to be associated with neuropsychiatric disorders, and the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica-exchange molecular dynamics (MD) simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence. The simulations were able to correctly reproduce the location of both local and …

Lipofilling After Breast Conserving Surgery: A Comprehensive Literature Review Investigating Its Oncologic Safety, Stephanie Cohen, Yurie Sekigami, Theresa Schwartz, Albert Losken, Julie Margenthaler, Abhishek Chatterjee

Open Access Publications

Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as "safe" included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years …

Optimizing Postprandial Glucose Management In Adults With Insulin-Requiring Diabetes: Report And Recommendations, John (Jack) L. Leahy, Grazia Aleppo, Vivian A. Fonseca, Satish K. Garg, Irl B. Hirsch, Anthony L. Mccall, Janet B. Mcgill, William H. Polonsky

Open Access Publications

Faster-acting insulins, new noninsulin drug classes, more flexible insulin-delivery systems, and improved continuous glucose monitoring devices offer unprecedented opportunities to improve postprandial glucose (PPG) management and overall care for adults with insulin-treated diabetes. These developments led the Endocrine Society to convene a working panel of diabetes experts in December 2018 to assess the current state of PPG management, identify innovative ways to improve self-management and quality of life, and align best practices to current and emerging treatment and monitoring options. Drawing on current research and collective clinical experience, we considered the following issues for the ∼200 million adults worldwide with …

Stub1 Suppresseses Tumorigenesis And Chemoresistance Through Antagonizing Yap1 Signaling, Dong-E Tang, Yong Dai, Lie-Wen Lin, Yong Xu, Dong-Zhou Liu, Xiao-Ping Hong, Hao-Wu Jiang, Song-Hui Xu

Open Access Publications

Yes-associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. …

A Molecularly Detailed Na V 1.5 Model Reveals A New Class I Antiarrhythmic Target, Jonathan D Moreno, Wandi Zhu, Kathryn Mangold, Woenho Chung, Jonathan R Silva

Open Access Publications

Antiarrhythmic treatment strategies remain suboptimal due to our inability to predict how drug interactions with ion channels will affect the ability of the tissues to initiate and sustain an arrhythmia. We built a multiscale molecular model of the Na

A Human Stat1 Gain-Of-Function Mutation Impairs Cd8 + T Cell Responses Against Gammaherpesvirus 68, Wei Qian, Cathrine A Miner, Harshad Ingle, Derek J Platt, Megan T Baldridge, Jonathan J Miner

Open Access Publications

Autosomal dominant STAT1 mutations in humans have been associated with chronic mucocutaneous candidiasis (CMC), as well as with increased susceptibility to herpesvirus infections. Prior studies have focused on mucosal and Th17-mediated immunity against

Phase I, Open-Label, Dose-Escalation Study Of The Safety, Pharmacokinetics, Pharmacodynamics, And Efficacy Of Gsk2879552 In Relapsed/Refractory Sclc, Todd M Bauer, Benjamin Besse, Alex Martinez-Marti, Jose Manuel Trigo, Victor Moreno, Pilar Garrido, Geraldine Ferron-Brady, Yuehui Wu, Jennifer Park, Therese Collingwood, Ryan G Kruger, Helai P Mohammad, Marc S Ballas, Arindam Dhar, Ramaswamy Govindan

Open Access Publications

INTRODUCTION: This first-time-in-humans study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of GSK2879552 in patients with relapsed or refractory SCLC.

METHODS: This phase I, multicenter, open-label study (NCT02034123) enrolled patients (≥18 years old) with relapsed or refractory SCLC (after ≥1 platinum-containing chemotherapy or refusal of standard therapy). Part 1 was a dose-escalation study; Part 2 was a dose-expansion study. Dose escalations were based on safety, PK, and PD. The primary end point (Part 1) was to determine the safety, tolerability, and recommended dose and regimen of GSK2879552. Secondary end points were to characterize PK and PD parameters …

Measuring And Reporting Of Vertebral Endplate Bone Marrow Lesions As Seen On Mri (Modic Changes): Recommendations From The Issls Degenerative Spinal Phenotypes Group, Aaron J Fields, Michele C Battié, Richard J Herzog, Jeffrey G Jarvik, Roland Krug, Thomas M Link, Jeffrey C Lotz, Conor W O'Neill, Aseem Sharma, Issls Degenerative Spinal Phenotypes Group

Open Access Publications

PURPOSE: The positive association between low back pain and MRI evidence of vertebral endplate bone marrow lesions, often called Modic changes (MC), offers the exciting prospect of diagnosing a specific phenotype of chronic low back pain (LBP). However, imprecision in the reporting of MC has introduced substantial challenges, as variations in both imaging equipment and scanning parameters can impact conspicuity of MC. This review discusses key methodological factors that impact MC classification and recommends guidelines for more consistent MC reporting that will allow for better integration of research into this LBP phenotype.

METHODS: Non-systematic literature review.

RESULTS: The high diagnostic …

The Diagnostic Yield Of Malignancy Comparing Cytology, Fish, And Molecular Analysis Of Cell Free Cytology Brush Supernatant In Patients With Biliary Strictures Undergoing Endoscopic Retrograde Cholangiography (Erc): A Prospective Study, Vladimir M Kushnir, Daniel K Mullady, Koushik Das, Gabriel Lang, Thomas G Hollander, Faris M Murad, Sara A Jackson, Nicole A Toney, Sydney D Finkelstein, Steven A Edmundowicz

Open Access Publications

BACKGROUND: Routine cytology of biliary stricture brushings obtained during endoscopic retrograde cholangiopancreatography (ERCP) has suboptimal sensitivity for malignancy. We compared the individual and combined ability of cytology, fluorescence in situ hybridization (FISH) analysis and PCR-based mutation profiling (MP) to detect malignancy in standard biliary brushings.

METHODS: We performed a prospective study of patients undergoing ERCP using histology or 1 year follow-up to determine patient outcomes. MP was performed on free-DNA from biliary brushing specimens using normally discarded supernatant fluid. MP examined KRAS point mutations and tumor suppressor gene associated loss of heterozygosity mutations at 10 genomic loci. FISH examined chromosome …

Intensity Of Lipid Lowering With Statin Therapy In Patients With Cerebrovascular Disease Versus Coronary Artery Disease: Insights From The Palm Registry, Ying Xian, Ann Marie Navar, Shuang Li, Zhuokai Li, Jennifer Robinson, Salim S Virani, Michael J Louie, Andrew Koren, Anne Goldberg, Veronique L Roger, Peter W F Wilson, Eric D Peterson, Tracy Y Wang

Open Access Publications

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients' perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease (CAD) versus cerebrovascular disease (CeVD) versus both CAD and CeVD (CAD&CeVD). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low-density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with CeVD only (n=403), CAD only (n=2202), and CeVD&CAD (n=627), no significant differences …