tbuckley/cabot-search huggingface dataset:
Leucovorin shortage: Impact on leucovorin/levoleucovorin usage and tx choices in colon cancer patients treated in the United States.
Authors: Ann Katler, Zhaohui Wang, Kimberly A. Bergstrom
Journal: Journal of Clinical Oncology (2013)

e14668 Background: 5FU + leucovorin (LV) containing regimens are the most commonly used regimens for colorectal cancer (CRC). A LV shortage in the U.S. beginning Apr 2010 became critical by fall 2011. In May ’11, levoleucovorin (LLV) was approved to treat CRC in the U.S. LV replacement by LLV incurs a 34 fold cost increase. This study examines if the LV shortage impacted colon cancer (CC) regimen selection and LV/LLV usage in the adjuvant and 1st line tx. Methods: Data obtained via web-based, drug dispensing technology was used to identify 3 groups of adult CC patients starting adjuvant or first-line tx within a 6 month period: Group 1 (Q2,Q3 2009), Group 2 (Q2,Q3 2010) and Group 3 (Q4, 2011 – Q1, 2012). Regimen selection and LV usage were examined from tx onset through completion. Results: Adjuvant and first- line tx administered by 545 practices across 47 states was examined and including 2,502 pts, 2,551 pts, and 2,689 pts in Groups 1, 2, and 3 respectively. The median pt age was 66. 77% of pts in each group received FOLFOX for adjuvant tx. Approx 7% of pts in Groups 1 and 2 received capecitabine-containing regimens compared to 9.9% in Group 3. 58% of pts in Group 1, 51% in Group 2 and 56% in Group 3 received mFOLFOX6 or mFOLFIRI + bevacizumab for first-line tx. Use of 5FU + LV or LLV-containing regimens remained constant in all 3 groups. The Table summarizes LV/LLV usage in LV-containing regimens planned for ’09 - Q1 of ‘12. Lower LV dosing and relative dose intensity (RDI), fewer LV administrations and increased LLV usage are seen for the time period reviewed. Conclusions: Based on data examined from 2009-Q1 2012, while no significant impact on regimen selection was observed, the LV shortage significantly decreased LV and raised LLV usage (and cost) in the adjuvant and first-line tx for colon cancer. [Table: see text]
Wake Up and Smell the Fusions: Single-Modality Molecular Testing Misses Drivers
Authors: Kurtis D. Davies, Dara L. Aisner
Journal: Clinical Cancer Research (2019)

Multitarget assays have become common in clinical molecular diagnostic laboratories. However, all assays, no matter how well designed, have inherent gaps due to technical and biological limitations. In some clinical cases, testing by multiple methodologies is needed to address these gaps and ensure the most accurate molecular diagnoses.See related article by Benayed et al., p. 4712.
Alternatives to Intention-to-Treat Analyses
Authors: Pascal Geldsetzer, Till Bärnighausen, Nikkil Sudharsanan
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract MP08: Higher Diet Quality is Associated with Lower Odds of Inflammation and Peripheral Artery Disease in the Hispanic Community Health Study/Study of Latinos
Authors: Josiemer Mattei, Daniela Sotres-Alvarez, Marc Gellman, Sheila F Castaneda, Frank B Hu, Katherine L Tucker, Anna-Maria Siega-Riz, Robert C Kaplan
Journal: Circulation (2016)

Introduction: C-reactive protein (CRP; a marker of inflammation) and the ankle-brachial index (ABI; a marker of peripheral artery disease (PAD)) are considered emerging risk factors for cardiovascular disease (CVD) in addition to traditional cardiometabolic markers. Results on the association of a healthy diet and these emerging risk factors have been inconsistent, and few studies have been conducted on Hispanics/Latinos, who present high prevalence of cardiometabolic risk factors. Hypothesis: We hypothesized that higher diet quality as measured with the Alternate Healthy Eating Index (AHEI; range 0-110: lowest to highest quality) would be associated with lower odds of having high-risk levels of CRP and of ABI, independently from cardiometabolic risk factors. Methods: Baseline data were analyzed from US-Hispanics/Latinos aged 18-74y without previously-diagnosed CVD participating in the population-based Hispanic Community Health Study/Study of Latinos cohort. There were 14,623 participants with complete CRP data, and 7,892 with ABI data (measured only for those aged ≥45y). Food and nutrients components of AHEI were assessed from two 24-hour recalls. High-risk CRP was defined as &gt;3.0 mg/L, and high-risk ABI was defined as &lt;0.90 or &gt;1.40, with further categorization into PAD (&lt;0.90) and arterial stiffness (&gt;1.40). Results: Nearly 35% of Hispanics/Latinos had high-risk CRP levels and 6.3% had high-risk ABI (4.2% had PAD and 2.1% had arterial stiffness). After adjusting for demographic, socioeconomic, and lifestyle factors, as well as cardiometabolic risk factors (diabetes, hypertension, obesity, or dyslipidemia), the odds (95% confidence interval) of having high-risk ABI were 36% (5, 43%) lower for each 10-unit increase in AHEI (p=0.020). The association remained significant for PAD alone, albeit attenuated (p=0.046), but not for arterial stiffness (p=0.210). Each 10-unit increase in AHEI was associated with 21% (10, 31%) lower odds of high-risk CRP(p=0.0003) after similar adjustments. There were no significant interactions between AHEI and sex, background, smoking, or cardiometabolic risk factors for the associations with ABI. The association of AHEI with high-risk CRP was stronger for those with diabetes (0.68 (0.52, 0.89) vs. 0.82 (0.71, 0.94) without diabetes; p-interaction=0.0002) and with obesity (0.70 (0.58, 0.85) vs. 0.86 (0.73, 1.01) without obesity; p-interaction=0.0001). Conclusions: A higher diet quality is associated with lower inflammation and PAD among Hispanics/Latinos, independently from traditional cardiometabolic risk factors. Promoting a healthy overall diet may benefit with further lowering CVD-risk related to emerging factors in a population that already presents high prevalence of cardiometabolic markers.
Ten ways to improve information technology in the NHS
Authors: S. Ford
Journal: BMJ (2003)

# Users, not geeks, should design interface {#article-title-2} EDITOR—With reference to the article by Majeed et al,1 the consultation is central to medicine, and information technology must facilitate it. With the constant changes in information technology it remains nascent, disjointed, and user hostile. It is no surprise that implementation remains problematic. Paper records will be superseded, but successors must emulate their familiarity and simplicity. The authors do not mention the main weakness—what users see and what they can do with it. Background issues (coding, networks, intranets, security, maintenance, data transfer, etc) are the province of geeks. Even the brand leader (EMIS) is difficult to operate in consultation, and its presentation of data, especially lab results, is dire. Interfaces operated by hand via large colour liquid crystal display touch screens are the technologies that can transform health computing by rendering the consultation process “natural.” Healthcare computing will be wonderful when the user can use it easily. Get users, not geeks, to design the interface, and the project will take wing. 1. 1.↵1. Majeed A, 2. de Lusignan S . Ten ways to improve information technology in the NHS [with commentary by S Teasdale]. BMJ 2003; 326: 202–206 [OpenUrl][1][FREE Full Text][2] # Any change in information technology in general practice requires extensive piloting {#article-title-4} EDITOR—I disagree with Majeed et al's contention that better information technology support for practices requires locating patients' records on central servers.1 Good support for practice based servers may be a better choice. Running a primary care trust's records on a single server is a high risk … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DMajeed%26rft.auinit1%253DA.%26rft.volume%253D326%26rft.issue%253D7382%26rft.spage%253D202%26rft.epage%253D206%26rft.atitle%253DTen%2Bways%2Bto%2Bimprove%2Binformation%2Btechnology%2Bin%2Bthe%2BNHS%2B%2A%2BCommentary%253A%2Bimprove%2Bthe%2Bquality%2Bof%2Bthe%2Bconsultation%2B%2A%2BCommentary%253A%2BClinical%2Bfocus%2Bmight%2Bmake%2Bit%2Bwork%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.326.7382.202%26rft_id%253Dinfo%253Apmid%252F12543838%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=326/7382/202&atom=%2Fbmj%2F326%2F7397%2F1034.atom
Impact of Acquired Del(17p) in Patients with Multiple Myeloma
Authors: Arjun Lakshman, Utkarsh Painuly, S. Vincent Rajkumar, Rhett P. Ketterling, Prashant Kapoor, Patricia Greipp, Morie A. Gertz, Francis K. Buadi, Martha Q. Lacy, David Dingli, Angela Dispenzieri, Amie Fonder, Suzanne R. Hayman, Miriam Hobbs, Wilson I Gonsalves, Yi Hwa, Nelson Leung, Ronald S. Go, Yi Lin, Taxiarchis Kourelis, Rahma Warsame, John A. Lust, Stephen J. Russell, Steven Zeldenrust, Robert A. Kyle, Shaji K. Kumar
Journal: Blood (2018)
Effective Delivery of a Microtubule Polymerization Inhibitor Synergizes with Standard Regimens in Models of Pancreatic Ductal Adenocarcinoma
Authors: Jaime A. Eberle-Singh, Irina Sagalovskiy, H. Carlo Maurer, Stephen A. Sastra, Carmine F. Palermo, Amanda R. Decker, Min Jung Kim, Josephine Sheedy, Anna Mollin, Liangxian Cao, Jianhua Hu, Arthur Branstrom, Marla Weetall, Kenneth P. Olive
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that is broadly chemoresistant, due in part to biophysical properties of tumor stroma, which serves as a barrier to drug delivery for most classical chemotherapeutic drugs. The goal of this work is to evaluate the preclinical efficacy and mechanisms of PTC596, a novel agent with potent anticancer properties in vitro and desirable pharmacologic properties in vivo. Experimental Design: We assessed the pharmacology, mechanism, and preclinical efficacy of PTC596 in combination with standards of care, using multiple preclinical models of PDA. Results: We found that PTC596 has pharmacologic properties that overcome the barrier to drug delivery in PDA, including a long circulating half-life, lack of P-glycoprotein substrate activity, and high systemic tolerability. We also found that PTC596 combined synergistically with standard clinical regimens to improve efficacy in multiple model systems, including the chemoresistant genetically engineered “KPC” model of PDA. Through mechanistic studies, we learned that PTC596 functions as a direct microtubule polymerization inhibitor, yet a prior clinical trial found that it lacks peripheral neurotoxicity, in contrast to other such agents. Strikingly, we found that PTC596 synergized with the standard clinical backbone regimen gemcitabine/nab-paclitaxel, yielding potent, durable regressions in a PDX model. Moreover, similar efficacy was achieved in combination with nab-paclitaxel alone, highlighting a specific synergistic interaction between two different microtubule-targeted agents in the setting of pancreatic ductal adenocarcinoma. Conclusions: These data demonstrate clear rationale for the development of PTC596 in combination with standard-of-care chemotherapy for PDA.
Oral idasanutlin in patients with polycythemia vera
Authors: John Mascarenhas, Min Lu, Heidi Kosiorek, Elizabeth Virtgaym, Lijuan Xia, Lonette Sandy, Ruben Mesa, Bruce Petersen, Noushin Farnoud, Vesna Najfeld, Raajit Rampal, Amylou Dueck, Ronald Hoffman
Journal: Blood (2019)
Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas
Authors: Xuan Zhang, Chengfeng Bi, Ting Lu, Weiwei Zhang, Ting Yue, Cheng Wang, Tian Tian, Xiaoyan Zhang, Yuhua Huang, Matthew Lunning, Xinbao Hao, Lauren E. Brown, William G. Devine, Julie Vose, John A. Porco, Kai Fu
Journal: Leukemia (2019)
AQP4 and the Fate of Gliomas
Authors: Mahmood Amiry-Moghaddam
Journal: Cancer Research (2019)

Abstract High-grade glioma is the most common primary brain cancer type and is characterized by invasive and fast growth. In a previous issue of Cancer Research, Simone and colleagues show that the two isoforms of the aquaporin-4 (AQP4) water channel may determine the fate of gliomas. Glioma cell lines expressing the M23-AQP4 isoform, which forms large aggregates of orthogonal arrays of particles, shrink and undergo apoptosis, whereas cell lines expressing the tetramer-forming M1-AQP4 isoform display higher activity of matrix metalloproteinases, making them more invasive. This study provides new insight on the role of AQP4 isoforms in the biology of gliomas. See related article by Simone and colleagues; Cancer Res 79(9):2182–94.
Abstract 409: LRRC10 Associates With and Regulates Cardiac Ca <sub>V</sub> 1.2 L-type Ca <sup>2+</sup> Channels, and I195T LRRC10 Variant is Linked to Dilated Cardiomyopathy
Authors: Marites T Woon, Pamela A Long, Louise Reilly, Jared M Evans, Alexis M Keefe, Martin R Lea, Carl J Beglinger, Ravi C Balijepalli, Youngsook Lee, Timothy M Olson, Timothy J Kamp
Journal: Circulation Research (2017)

Leucine-rich repeat containing (LRR) proteins facilitate protein-protein interactions critical in a number of cellular functions including ion channel regulation. Leucine-rich repeat containing protein 10 (LRRC10), a cardiac-specific protein expressed in zebrafish, mice and humans, is essential for normal cardiac physiology with loss of Lrrc10 in Lrrc10 -/- mice resulting in dilated cardiomyopathy (DCM). However, the mechanism by which LRRC10 contributes to DCM is unknown. Further, the functional role of LRRC10 in the regulation of ion channels in the heart has not been explored. Here we recorded L-type Ca 2+ channel currents (I Ca,L ) from isolated ventricular myocytes of WT and Lrrc10 -/- mice, demonstrating a significant reduction in I Ca,L in Lrrc10 -/- myocytes (-4.9 ± 0.19 pA/pF, n=10) compared to WT (-6.5 ± 0.24 pA/pF, n=8). Co-immunoprecipitation (co-IP) experiments showed an association between LRRC10 and Ca v 1.2 in WT, but not Lrrc10 -/- mouse lysates, with immunocytochemistry studies further demonstrating colocalization of LRRC10 and Ca v 1.2 in isolated ventricular myocytes from wild-type (WT) mice. Additionally, whole exome sequencing revealed a novel homozygous recessive missense variant in LRRC10 , I195T, found in a pediatric DCM patient. To determine whether the I195T variant impacts Ca v 1.2 L-type Ca 2+ channels, whole-cell patch clamp experiments were performed using HEK293 cells transiently expressing the L-type Ca 2+ channel complex (LTCC) alone or with WT or I195T LRRC10. These electrophysiology experiments demonstrated a significant increase in I Ca,L with WT LRRC10 coexpression (-81 ± 5.3 pA/pF, n=12), but a decrease in I Ca,L when I195T (-18.2 ± 3.3 pA/pF, n=9) was coexpressed compared to the LTCC alone (-34.1 ± 2.2 pA/pF, n=17). Parallel surface biotinylation experiments demonstrated that WT and I195T LRRC10 did not alter L-type Ca 2+ channel expression on the plasma membrane, while co-IP experiments using lysates prepared from the transiently transfected HEK293 cells showed the association between Ca v 1.2 and I195T LRRC10 variant. Overall, these findings newly identify LRRC10 as a cardiac-specific component of the Ca v 1.2 macromolecular complex and demonstrate dysregulation of I Ca,L by the DCM associated I195T LRRC10 variant.
Abstract 16973: Children With Pulmonary Hypertension and Electrical Dyssynchrony Have Worse Left Ventricular Function
Authors: Michal Schäfer, Kathryn K Collins, Lorna Browne, Dunbar Ivy, Steven Abman, Richard Friesen, Benjamin Frank, Brian Fonseca, Michael DiMaria, Kendall S Hunter, Uyen Truong, Johannes von Alvensleben
Journal: Circulation (2017)

Introduction: Electrical and right ventricular (RV) mechanical dyssynchrony has been previously described in pediatric pulmonary arterial hypertension (PAH). However, less is known about the relati...
Fatty Liver Among Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)
Authors: Sine Knorr, Birgitte Bytoft, Zuzana Lohse, Anne B. Boisen, Tine D. Clausen, Rikke B. Jensen, Peter Damm, Henning Beck-Nielsen, Jens J. Holst, Bolette Hartmann, Holger J. Møller, Kurt Højlund, Claus H. Gravholt, Dorte M. Jensen
Journal: Diabetes Care (2019)

Intrauterine exposure to maternal type 1 diabetes is associated with a less favorable metabolic profile later in life. Nonalcoholic fatty liver disease is the hepatic manifestation of a cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational type 1 diabetes on the presence of fatty liver in offspring and the association between maternal BMI, glycemic control during pregnancy, offspring metabolic risk factors, and offspring level of soluble CD163 (sCD163) (a marker of macrophage activation) and risk of fatty liver.
Retraction: The E3-ligase E6AP Represses Breast Cancer Metastasis via Regulation of ECT2-Rho Signaling
Authors: Mariam Mansour, Sue Haupt, Ai-Leen Chan, Nathan Godde, Alexandra Rizzitelli, Sherene Loi, Franco Caramia, Siddhartha Deb, Elena A. Takano, Mark Bishton, Cameron Johnstone, Brendon Monahan, Yarra Levav-Cohen, Yong-Hui Jiang, Alpha S. Yap, Stephen Fox, Ora Bernard, Robin Anderson, Ygal Haupt
Journal: Cancer Research (2019)

[This article][1] ([1][2]) has been retracted at the request of the editors. Following an institutional review by Peter MacCallum Cancer Center (Victoria, Australia), the primary affiliation for several of the authors, it was not possible to confidently identify and assign the primary datasets to
Rapidly Lethal Ruptured Hepatocellular Carcinoma With Disseminated Peritoneal Carcinomatosis on FDG PET/CT
Authors: Zulqar Islam, Brett Hausauer, Jayanth Keshavamurthy, Darko Pucar
Journal: Clinical Nuclear Medicine (2019)

Abstract Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Hepatocellular carcinoma commonly metastasizes to lungs, lymph nodes, and bone. Although HCC usually occurs in setting of chronic liver disease due to alcoholism or HBV/HCV infection, the incidence of HCC arising from nonalcoholic steatohepatitis is increasing. We present a very unusual initial presentation of occult HCC with peritoneal carcinomatosis secondary to liver rupture in a 70-year-old man with known nonalcoholic steatohepatitis–cirrhosis, best appreciated on FDG PET/CT. Our patient died a few days later. Tumor rupture is a rare but usually rapidly lethal complication of HCC.
Long-Term PM10 Exposure and Cause-Specific Mortality in the Latium Region (Italy): A Difference-in-Differences Approach
Authors: Matteo Renzi, Francesco Forastiere, Joel Schwartz, Marina Davoli, Paola Michelozzi, Massimo Stafoggia
Journal: Environmental Health Perspectives (2019)

Background: The link between particulate matter (PM) exposure and adverse health outcomes has been widely evaluated using large cohort studies. However, the possibility of residual confounding and lack of information about the health effects of PM in rural and suburban areas are unsolved issues. Objective: Our aim was to estimate the effect of annual PM≤10 μm (PM10) exposure on cause-specific mortality in the Latium region (central Italy, of which Rome is the main city) during 2006–2012 using a difference-in-differences approach. Methods: We estimated daily PM10 concentrations for each 1 km2 of the region from 2006 to 2012 by use of satellite data, land-use predictors, and meteorological parameters. For each of the 378 regional municipalities and each year, we averaged daily PM10 values to obtain annual mean PM10 exposures. We applied a variant of the difference-in-differences approach to estimate the association between PM10 and cause-specific mortality by focusing on within-municipality fluctuations of mortality rates and annual PM exposures around municipality means, therefore controlling by design for confounding from all spatial and temporal potential confounders. Analyses were also stratified by population size of the municipalities to obtain effect estimates in rural and suburban areas of the region. Results: In the period 2006–2012, we observed deaths due to three causes: 347,699 nonaccidental; 92,787 cardiovascular; and 16,509 respiratory causes. The annual average (standard deviation, SD) PM10 concentration was 21.9 (±4.9) μg/m3 in Latium. For each 1-μg/m3 increase in annual PM10 we estimated increases of 0.8% (95% confidence intervals (CIs): 0.2%, 1.3%), 0.9% (0.0%, 1.8%), and 1.4% (−0.4%, 3.3%) in nonaccidental, cardiovascular, and respiratory mortality, respectively. Similar results were found when we excluded the metropolitan area of Rome from the analysis. Higher effects were estimated in the smaller municipalities, e.g., those with population <5,000 inhabitants. Conclusion: Our study suggests a significant association of annual PM10 exposure with nonaccidental and cardiorespiratory mortality in the Latium region, even outside Rome and in suburban and rural areas. https://doi.org/10.1289/EHP3759