tbuckley/cabot-search huggingface dataset:
Annals Graphic Medicine - An Apple a Day
Authors: Caroline Shooner, Tracy Morton
Journal: Annals of Internal Medicine (2020)

Web Exclusives3 March 2020Annals Graphic Medicine - An Apple a DayFREECaroline Shooner, MD and Tracy Morton, MDCaroline Shooner, MDUniversity of British Columbia, Queen Charlotte, British Columbia, Canada (C.S., T.M.)Search for more papers by this author and Tracy Morton, MDUniversity of British Columbia, Queen Charlotte, British Columbia, Canada (C.S., T.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0026 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of British Columbia, Queen Charlotte, British Columbia, Canada (C.S., T.M.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0026.Author/Illustrator Information: Caroline Shooner, MD (e-mail, caroline.[email protected]ca), and Tracy Morton, MD (e-mail, tracy.[email protected]ca), are rural family physicians affiliated with the University of British Columbia. They share a practice on Haida Gwaii, the traditional territory of the Haida. Caroline's cartoons (www.theboondocs.org) explore the comic side of small town medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 March 2020Volume 172, Issue 5Page: W71-W72KeywordsConflicts of interestDisclosureHealth care ePublished: 3 March 2020 Issue Published: 3 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract P140: Linear Versus Volumetric Measures Of Left Ventricular Sphericity: Concordance And Normal Reference Values
Authors: Philimon N Gona, Carol J Salton, Saadia Qazi, Connie W Tsao, Christopher J O'Donnell, Warren J Manning, Michael L Chuang
Journal: Circulation (2020)

Introduction: Greater left ventricular (LV) sphericity, a more globular shape, is associated with poor outcomes. Two measures of sphericity are commonly used: Linear sphericity (LinS) is the ratio of LV end-diastolic diameter (EDD) to 4-chamber length (4cL); volumetric sphericity (VolS) is the ratio of end-diastolic volume (EDV) to the volume of a sphere with diameter=4cL. We sought to compare LinS to VolS and to determine: 1) whether LinS and VolS differ with sex and age group; 2) normal values for LinS and VolS, 3) whether LinS and VolS are concordant in how they stratify individuals. Methods: 1794 adults (age 65±9y, 47.1% men) in the Framingham Offspring cohort underwent CMR imaging; LV EDD, EDV and 4cL were measured. A referent group (340M, 512W) free of clinical cardiovascular disease, hypertension, diabetes and smoking was identified. Among these, we compared LinS and VolS between sexes and across age groups (&lt;55, 55-64, ≥65y). Referent-group upper 90 th percentile (P90) cutpoints for LinS and VolS were determined and applied to the entire cohort (N=1794) to stratify each individual as having or not having high sphericity. Concordance between LinS and VolS was assessed using kappa coefficient and McNemar’s test. Methods: LinS was greater than VolS for each sex, but there was robust, positive linear (Pearson) correlation between LinS and VolS for men (r=0.864) and women (r=0.855), p&lt;0.0001 both. The Table shows women had minimally greater sphericity than men. Sphericity did not vary with age group in either sex. LinS and VolS were concordant in classifying individuals as having high (≥P90) sphericity with kappa=0.63 (men) and 0.62 (women), p&lt;0.0001 for both. McNemar’s test for difference was not significant (p&gt;0.27) for either sex. Conclusion: Linear and volumetric measures of LV sphericity are concordant in how they rank and stratify adults in a community dwelling cohort, but the measures are not directly comparable, as mean LinS is markedly greater than VolS. Neither measure of sphericity varies with age among healthy adults.
Abstract MP72: Using Non-HDL-C/Triglyceride Ratio To Screen For Direct LDL-C Testing: Improving LDL-C Estimates At A Cost
Authors: Nestor Vasquez, Renato Quispe, Steven R Jones, Seth S Martin, Parag H Joshi, Alagarraju Muthukumar
Journal: Circulation (2020)

Introduction: Despite more accurate low-density lipoprotein cholesterol (LDL-C) estimates by the Martin (mLDL-C) method, most laboratories still use the Friedewald (fLDL-C) equation. Low non-high density lipoprotein (non-HDL-C) and high triglycerides (TG) drive inaccuracy in LDL-C estimation. We compared a strategy of identifying errors in fLDL-C using non-HDL-C/TG ratios with subsequent reflex direct LDL-C testing to a strategy of using mLDL-C. Methods: We included 4,939,542 individuals (2/3 derivation, 1/3 validation dataset) with TG &lt;400 mg/dL with lipid profiles directly measured via Vertical Auto Profile from the Very Large Database of Lipids. We compared directly measured LDL-C with estimated fLDL-C and mLDL-C. The direct LDL-C assay has an allowable error of 12% which was used as the threshold for accuracy assessment. LDL-C estimates above and below non-HDL-C/TG cutpoints (range 0-2.0) were evaluated for accuracy from the derivation dataset and the 4 best performing ratios were tested in the validation set. Individuals with non-HDL-C/TG ratios below the cutpoints were assumed to require direct LDL-C measurement. Medicare costs ($17 lipid panel; $12 direct LDL-C) were used to estimate added costs of direct LDL-C measurement. Results: Nearly 8% of fLDL-C results deviated &gt;12% from direct LDL-C compared with only 2.5% of mLDL-C results in the entire population. Non-HDL-C/TG ratios of 0.6-0.9 performed best in the derivation dataset. In the validation dataset, a non-HDL-C/TG ratio of 0.7 had the highest area under the curve for identifying &gt;12% error in fLDL-C estimates (Table). At this ratio, 14.5% of fLDL-C samples would need direct LDL-C measurement at an increase in costs of lipid testing by 10%. Conclusions: Use of non-HDL-C/TG ratio &lt;0.7 as screening for direct LDL-C measurement can improve the accuracy of LDL-C estimates in labs using the Friedewald equation. However, such an approach is significantly costlier than using mLDL-C.
Independent information deserves more attention
Authors: Bruno Toussaint
Journal: BMJ (2020)

Moynihan and colleagues are investigating pathways for the production and use of trustworthy evidence that are free from financial conflicts of interest, in medical research, education, and practice.1 Independent sources of information do exist, and many are members of the International Society of Drug Bulletins.23

Since 1981, Prescrire has been proof that the provision of …
Theranostic MRI liposomes for magnetic targeting and ultrasound triggered release of the antivascular CA4P
Authors: Caroline J. Thébault, Grégory Ramniceanu, Sarah Boumati, Aude Michel, Johanne Seguin, Benoit Larrat, Nathalie Mignet, Christine Ménager, Bich-Thuy Doan
Journal: Journal of Controlled Release (2020)
Abstract P427: Coronary Artery Calcium Assessed Years Before Was Positively Associated With Subtle White-matter Injury in Asymptomatic Middle-aged Men: The Framingham Heart Study
Authors: Harumitsu Suzuki, Kendra Davis-Plourde, Alexa Beiser, Katsuyuki Miura, Charles DeCarli, Pauline Maillard, Gary F Mitchell, Sudha Seshadri, Akira Fujiyoshi
Journal: Circulation (2020)

Introduction: Using magnetic resonance (MR) diffusion tensor imaging (DTI), we previously showed a cross-sectional association between carotid-femoral pulse wave velocity (CFPWV), a measure of aortic stiffness, and subtle white-matter injury in clinically asymptomatic middle-age adults. Although coronary artery calcification (CAC) predicted cerebral small vessel diseases evident in conventional MR technique in some studies, it remains unclear whether CAC predicts DTI-based subtle white matter injuries. Hypothesis: CAC and CFPWV are associated with global measures of subtle white-matter injury in middle-aged adults free of clinical brain diseases. Methods: We studied third-generation participants of the Framingham Heart Study who were assessed for CAC (2002-2005), CFPWV, and brain DTI (2009-2013). After excluding prevalent stroke, dementia, other neurological conditions, or those with missing data, 1052 participants (women, 45.4%, mean age: 45.4 years) were analyzed. Two DTI-based outcomes were examined (average within voxels from the white matter mask): free water (FW) and FW-corrected fractional anisotropy (FA). Using linear regression, we calculated slopes of the outcomes per 20-80 th percentiles higher CAC (log-transformed Agatston score) or CFPWV (negative inverse) after adjustment for age and age squared at CAC or CFPWV, time between at CAC/CFPWV and DTI exam, systolic blood pressure, diabetes, total cholesterol, medication(s) for hypertension or dyslipidemia, smoking, and total cranial volume. Results: After multivariable adjustment, in men, CAC was associated only with FA (p=0.033), whereas CFPWV was associated only with FW (p=0.030) ( Figure ). No associations were observed in women. Conclusions: In men, CAC assessed at &gt;7.5 years earlier was associated with worse FA, while CFPWV assessed at 1.7 years earlier was associated with worse FW. CAC may be a sensitive maker to predict subtle white-matter injury in asymptomatic middle-aged men.
Prediction of response to temozolomide (TMZ)-based therapy by loss of MGMT expression in patients with advanced neuroendocrine tumors (NET)
Authors: M. H. Kulke, C. S. Frauenhoffer, S. M. Hooshmand, D. P. Ryan, P. C. Enzinger, J. A. Meyerhardt, J. W. Clark, J. Hornick, C. S. Fuchs, M. S. Redston
Journal: Journal of Clinical Oncology (2007)

4505 Background: TMZ, an oral alkylating agent, has recently been shown to be active in a subset of patients with NETs. In other tumor types, methyl-guanine methyl transferase (MGMT) expression is associated with TMZ resistance through its ability to remove methyl/alkyl groups from the O 6 -position of guanine, thereby preventing TMZ-induced DNA damage. Methods: To better define NET pts who benefit from TMZ, we performed a retrospective analysis of 76 NET pts treated with TMZ-based regimens at 3 institutions, identified using IRB-approved observational and clinical trial databases. Immunohistochemical MGMT expression was measured in a subset of pts with available paraffin-embedded archival tissue specimens in a blinded fashion, utilizing mouse monoclonal antibodies to MGMT. Nuclear MGMT expression was scored as either present or absent in tumor cells and correlated with tumor type and treatment outcome. Results: Of 76 pts, 30 received TMZ/thalidomide and 46 received TMZ/bevacizumab. Both regimens incorporate oral TMZ, administered at a dose of 150 mg/m2 qd for 7d, every other week. 63 pts were enrolled on phase II studies, and 13 pts were treated outside a formal study protocol. Pt characteristics were: M:F=42:34; median age 57.5 (20–75); tumor type carcinoid (38), pancreatic NET (35), paraganglioma/pheochromocytoma (3). PR or CR (as measured by RECIST) was observed in 11/35 (31%) pancreatic NETs and 0/38 carcinoid pts (P&lt;0.001), as well as 1/3 pts with paraganglioma/pheo. In 21 pts with available specimens, complete absence of MGMT expression was observed in 5/8 pancreatic NET and 0/13 carcinoid tumors (P&lt;0.01). In this pt subset, absence of MGMT expression was associated with response to TMZ ( Table 1 ). Conclusions: Treatment with TMZ is associated with radiologic response in approximately one third of pts with pancreatic NET, but not in pts with carcinoid tumors. Absence of MGMT expression appears to define pts with pancreatic NET who achieve significant benefit from TMZ. [Table: see text] No significant financial relationships to disclose.
Integration of Immunotherapy Into the Treatment of Advanced Urothelial Carcinoma
Authors: Pooja Ghatalia, Elizabeth R. Plimack
Journal: Journal of the National Comprehensive Cancer Network (2020)

Five new PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma (UC): pembrolizumab, atezolizumab, durvalumab, nivolumab, and avelumab. Although cisplatin-based chemotherapy remains the recommended frontline option for cisplatin-eligible patients with metastatic UC, immunotherapy is now an available option in the second-line setting as well as the frontline setting for selected cisplatin-ineligible patients who are either unable to tolerate chemotherapy or PD-L1-positive. This review describes the updated clinical efficacy of these checkpoint inhibitors in the treatment of advanced UC and suggests how they can be sequenced in the context of available chemotherapeutic options.
Preventing a covid-19 pandemic
Authors: John Watkins
Journal: BMJ (2020)

In the aftermath of the 2009 H1N1 global threat, the Department of Health's pandemic preparedness planning team paid particular attention to the value, or otherwise, of containment as a strategy to prevent spread.In 2009 considerable time and effort were spent on a catch, isolate, and treat approach in the early stages of the emerging pandemic, and public health teams were expending considerable energy with, as it turned out, little effect.The resulting UK Influenza Pandemic Preparedness Strategy 2011 1 emphasised the need to maintain the continuity of essential services and continue everyday activities as far as possible. Catch and isolateIn a recent speech in the House of Commons, Matt Hancock, the UK secretary of state for health and social care, highlighted the mainstay of the government's approach, as set out in the plan: contain, delay, research, and mitigate. 2 In relation to influenza, the plan sees these phases as detection, assessment, treatment, escalation, and recovery, and during the assessment phase it emphasises the need to actively find, test, isolate, and treat cases-our current approach to covid-19.Unlike for influenza, no vaccine or antiviral agents are available for covid-19, and the mainstay of treatment is supportive care, in high dependency units if necessary, for the most critically ill patients.
Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology
Authors: B. A. Burtness, M. Powell, J. Berlin, D. Liles, A. Chapman, E. Mitchell, A. B. Benson
Journal: Journal of Clinical Oncology (2007)

4519 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). Second cytotoxic or biologic agents do not substantially advance survival. EGFR is expressed on PC and a phase II trial of G plus cetuximab (C) resulted in favorable 1 year survival. A phase II trial of irinotecan/docetaxel (I/D) chemotherapy reported a median survival for metastatic patients (pts) of 9 m. We conducted this randomized phase II trial to confirm the activity of this non-G regimen, and determine whether combining it with C was feasible and active. The primary endpoint was response. Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, evidence of distant metastases, ECOG PS 0–1, normal bilirubin, written informed consent, and were randomly assigned to Arm A (N=47) or B (N=45). Imaging with CT or MR within 4 weeks (wk) was used for tumor measurement. Dexamethasone was given 12 hours (h), 1 h before and 12 h after chemotherapy. Pts on Arm A received D 35 mg/m 2 over 1 h and I 35 mg/m 2 over 30 minutes weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, but C (loading dose 400 mg/m 2 wk 1, 250 mg/m 2 weekly thereafter) was given before D. Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles. Results: Median age Arm A: 59.9, Arm B: 60.2 years. Arm A 55% male, 32% PS 0, 97% EGFR immuno+. Arm B 84% male, 42% PS 0, 97% EGFR +. Median number of cycles for each arm 2 (1 -10). &gt;4 cycles were delivered to 10.5% of pts Arm A, 20.9% Arm B. Grade ¾ neutropenia 26% Arm A, 33% Arm B. Grade 3 nausea 28% Arm A, 18% Arm B; Grade ¾ diarrhea 33% Arm A, 44.4% Arm B. 1 treatment-related death per arm. Median overall survival (OS), with 70.2% of pts known to have died, 6.5m [(95% CI (4.8, 8.6)] in Arm A. With 86.7% of pts known to have died in Arm B, OS 7.4 m [95% CI (4.4, 10.7)]. Response/progression data will be available at time of presentation. Conclusions: Weekly I/D ± C is associated with high rates of grade ¾ neutropenia/diarrhea. Median survival is 6.5m for I/D and 7.4m for I/D/C. Non-G containing therapy is active in metastatic PC. [Table: see text]
Abstract 16298: Change in Salusin-α is Related to Aerobic Exercise Training-Induced Blood Pressure Reduction in Middle-Aged and Older Adults
Authors: Shumpei Fujie, Natsuki Hasegawa, Kiyoshi Sanada, Takafumi Hamaoka, Motoyuki Iemitsu
Journal: Circulation (2017)

Introduction: Aging-induced elevation of blood pressure is reduced by aerobic exercise training. Administration of salusin-α to rats induces a decrease in arterial mean blood pressure, and circulat...
Abstract 14033: The Impact of Anxiety Disorders on In-Hospital Outcomes in Patients With Myocardial Infarction
Authors: Pengyang Li, Fangcheng Wu, Lingling Wu, Ying Ning, Kristina Duan, Qi Liu
Journal: Circulation (2019)

Introduction: Anxiety disorders are prevalent in patients with myocardial infarction (MI), but the risks associated with anxiety disorders in MI patients have not been well studied. Aim: To examine...
Abstract P249: Association Between Cardiovascular Event Type And Smoking Cessation Rates Among Outpatients With Atherosclerotic Cardiovascular Disease: Insights From The Ncdr Pinnacle Registry
Authors: Vittal Hejjaji, Yuanyuan Tang, Philip Jones, Edward Ellerbeck, Christina Pacheco, Ali O Malik, Paul S Chan, John Spertus, Suzanne V Arnold
Journal: Circulation (2020)

Introduction: Understanding the factors that drive cessation may help inform patient counseling and improve quit rates. We aimed to determine if the type of atherosclerotic cardiovascular disease (ASCVD) event impacts the patient’s likelihood of quitting, independent of patient factors. Hypothesis: We assessed the hypothesis that more impactful ASCVD events would be associated with a greater likelihood of smoking cessation (e.g., more likely to quit after CABG vs PCI). Methods: Using 2013-2016 data from the NCDR PINNACLE outpatient cardiac registry, we identified patients who were current smokers and had an eventual diagnosis of ASCVD. Self-reported smoking status was assessed at each consecutive visit and rates of smoking cessation after each interim ASCVD event (MI, PCI, CABG, stroke/TIA, and PAD diagnosis) were examined. We then constructed separate Cox models with non-proportional hazards for interim ASCVD events (time-dependent covariates), adjusting for age, sex, race, dyslipidemia, diabetes, hypertension, and heart failure; and compared models using AIC. Results: Across 358 cardiology practices, 378478 patients were smokers who eventually had ASCVD (mean age 65.8±11.9, male 63.6%). Cessation rates after each ASCVD event were: MI 30.5%, PCI 30.7%, CABG 28.5%, stroke/TIA 24.7%, and PAD 24.6% (Table). After multivariable adjustment, patients were more likely to quit smoking after a stroke/TIA (HR 2.46, 95% CI 2.40-2.52) followed by CABG (HR 2.45, 95% CI 2.37-2.53), PCI (HR 1.85, 95% CI 1.79-1.91), MI (HR 1.79, 95% CI 1.72-1.86), and a new diagnosis of PAD (HR 1.47, 95% CI 1.42-1.51); p&lt;0.0001 for all events. Conclusion: In a large US registry, we found that only ~25-30% of patients reported quitting smoking after an ASCVD event, but the type of ASCVD event significantly impacts the likelihood of smoking cessation. Using these data to inform patient counseling—targeting cessation efforts to those most likely to quit—may help improve outcomes.
First clinical experience with <sup>90</sup>Y-radiolabeled humanized anti-MUC1 antibody (hPAM4) in patients with advanced pancreatic cancer: A phase I study
Authors: S. A. Gulec, S. J. Cohen, L. S. Zuckier, H. Horne, N. Teoh, W. A. Wegener, D. V. Gold, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2007)

15034 Background: The humanized antibody, hPAM4, specifically targets an epitope in the mucin glycoprotein MUC1 expressed in most pancreatic cancers, but not normal pancreas or most other normal tissues. This study evaluated the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics (PK), dosimetry and preliminary efficacy of 90 Y-DOTA-hPAM4 administered as a single dose to patients (pts) with pancreatic adenocarcinoma. Methods: Pts with locally advanced disease and progression on 1 prior therapy (TX) or metastatic disease with 0–1 prior TX’s were eligible if they were ≥ 4 wks beyond prior TX, had adequate hematology/chemistries, with measurable disease, but no lesion &gt;10 cm. Pts initially received 111 In-hPAM4 followed by 7 days of serum samples and imaging for PK, biodistribution and organ radiation dose analysis. Pts then received a single infusion of 90 Y-hPAM4 with the 90 Y dose escalated in cohorts of 3–6 pts (5-mCi/m 2 increments) until 2 evaluable pts/cohort encountered DLT. Treatment toxicity was evaluated by NCI CTC v. 3 criteria and tumor response by CT-based RECIST criteria. Results: Fifteen pts (8F/7M; median age 60; 11 metastatic/4 locally advanced;13 with, 2 without prior TX) received 90 Y-hPAM4 at a dose level of 15 mCi/m 2 (n=4), 20 mCi/m 2 (n=7), and 25 mCi/m 2 (n=4). Pre-therapy 111 In-hPAM imaging showed acceptable biodistribution and organ radiation dosimetry in all pts. Four wks after treatment, 1 pt at 15 mCi/m 2 and 2 pts at 20 mCi/m 2 had CT responses, with 32–51% shrinkage of their pancreatic mass, while 3 other pts at various dose levels had stable target lesions by CT. All pts showed disease progression at or after wk 8. The only significant drug-related toxicity was hematologic, with &gt;1 DLT (&gt;7 day grade 4 thrombocytopenia and/or neutropenia) encountered at the 25 mCi/m 2 level. Conclusions: For 90 Y-hPAM administered once as a single agent, hematologic toxicity was dose-limiting, the MTD was established at 20 mCi/m 2 , and CT demonstrated several transient reductions or stabilization of index lesions. Based on this Phase I experience, combined/sequential treatment with chemotherapy and fractionated radioimmunotherapy is being considered for future trials. No significant financial relationships to disclose.