tbuckley/cabot-search huggingface dataset:
Abstract P228: Abdominal Lean Muscle Mass is Associated with the Density, but Not the Volume, of Coronary Arterial Calcium and Abdominal Aortic Calcium
Authors: Margaret A Crawford, Matthew A Allison, Michael H Criqui, Britta A Larsen
Journal: Circulation (2016)

Introduction: Higher volume of coronary arterial calcium (CAC) and abdominal aortic calcium (AAC) are predictive of incident CVD, while higher density of CAC and AAC are associated with lower risk. The purpose of the present study was to determine the associations of abdominal lean muscle mass (ALMM) with CAC volume, CAC density, AAC volume, and AAC density. Hypothesis: We hypothesized that abdominal muscle mass would be negatively associated with CAC and AAC volume but positively associated with CAC and AAC density. Methods: The current study analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA) in those participants who underwent abdominal computed tomography (CT) to assess for AAC, which was also analyzed for volumes of fat (visceral and subcutaneous) and ALMM (psoas, rectus abdominis, obliques, and paraspinus). CAC and AAC were scored separately, for density and for volume. Results: Analyses were restricted to participants who had non-zero CAC or AAC volumes. The sample sizes for the CAC analyses and AAC analyses were 963 and 1283 subjects, respectively. For the CAC analyses, 39.4% (379 of 963) were female and the mean age was 66.4 years. Mean ± SD CAC volume was 218.52 ± 344.19 (range 2.34- 3244.77 mm 3 ) ; Mean ± SD CAC density was 2.70 ± .72 (range 0.83- 4.0 Hu category units). Mean ± SD AAC volume was 1402.33 ± 1888 (range 4.68- 15822.2 mm 3 ); mean ± SD AAC density was 3.02 ± .63 (range 0.83- 4.0 Hu category units). In multivariable linear regression models that controlled for age, race, gender, CVD risk factors, visceral fat, and liver and kidney markers, both CAC and AAC density were found to be significantly associated with abdominal lean muscle mass. For every 100 cm 2 increase of ALMM, CAC density decreased by .35 Hu category units (p &lt; .05). For every 100 cm 2 increase of ALMM, AAC density decreased by .26 Hu category units (p &lt; .05). Conversely, CAC and AAC volume were not significantly associated with abdominal lean muscle mass in final models. Conclusion: Higher levels of ALMM were associated with lower CAC and AAC density, but not volume. Contrary to expectation, we found an inverse association of ALMM with CAC and AAC density, independent of relevant CVD risk factors.
Effect of anti-PD-1 and anti-Id-1 combo on tumor response and survival in lung cancer.
Authors: Iosune Baraibar, Marta Roman, Ines Lopez, Daniel Ajona, Alfonso Calvo, Elisabeth Guruceaga, Jesús Corral, Juan José Lasarte, Silvestre Vicent, Ignacio Gil-Bazo
Journal: Journal of Clinical Oncology (2018)

12085 Background: PD-1/PDL-1 inhibitors are approved in advanced non-small cell lung cancer (NSCLC). Long-term survivals associated to PD-1/PDL-1 blockade have changed treatment paradigm. However, many patients do not benefit from PD-1/PDL-1 blockade. New therapeutic combinations are under investigation. Id1 is involved in proliferation, angiogenesis and immunosuppression. We described Id1 as a prognostic factor in NSCLC (Ponz-Sarvise, Clin Cancer Res 2011) and more recently showed Id1’s role in lung cancer metastasis (Castanon, Cancer Letters 2017). Here we test a combined therapeutic strategy targeting PD-1 and Id1 in a murine lung cancer model. Methods: Three in vivo studies evaluated the impact of Id1 inhibition in tumor cells, tumor microenvironment and in both, on tumor volumes and mice survival. A syngeneic tumor model using C57BL/6 and Id1-/- Id3+/- mice was created by subcutaneous injection of Lewis Lung Carcinoma (3LL) cells and Id1 silenced 3LL (Id1Sh) cells. After injection, mice were treated with an anti-PD-1 (RMP-1-14) monoclonal antibody or PBS. Tumor volumes according to mice strain, Id1 status in tumor cells and treatment were quatified. Mice's survival was calculated in those groups.Tumors PD-L1 expression and CD8+ and CD3+ TILs and CD68+ cells were quatified by specific immunostainings. Results: Id1 inhibition in the tumor environment and the injected tumor cells, combined with anti-PD-1 treatment, induced a significant tumor growth impairment (p < 0.0001) and increased survival (p = 0.0051). CD3+ and CD8+ TILs and tumor CD68 + cells were significantly higher in tumors from mice with the combined Id1-PD-1 blockade treated with the anti-PD-1 inhibitor compared to control animals suggesting that tumor increased immune-related cells infiltration exerts the effector phase of the antitumor immune response. Additionally, PD-L1 expression seemed to be higher when Id1 expression was absent in the immune microenvironment (p = 0.04). Conclusions: Id1 and PD-1 combined blockade in our syngeneic murine lung cancer model significantly impaired tumor growth and increased survival. Increased tumor PD-L1 expression and CD3+ and CD8+ TILs and CD68+ cells may explain these findings.
FDA Risk Assessment of Seafood Contamination after the BP Oil Spill: The Correspondence Section Is a Public Forum and, as Such, Is Not Peer-Reviewed. EHP Is Not Responsible for the Accuracy, Currency, or Reliability of Personal Opinion Expressed Herein; It Is the Sole Responsibility of the Authors. EHP Neither Endorses nor Disputes Their Published Commentary
Authors: Robert W. Dickey
Journal: Environmental Health Perspectives (2012)
Laser Treatment Performed More Than 4 Decades After Napalm Burns
Authors: Jill S. Waibel, Kim Phuc Phan Thi, Leonard J. Hoenig
Journal: JAMA Dermatology (2018)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Theranostic nanoparticles with tumor-specific enzyme-triggered size reduction and drug release to perform photothermal therapy for breast cancer treatment
Authors: Rui Liu, Chuan Hu, Yuanyuan Yang, Jingqing Zhang, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2018)

Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency, nanoparticles need to change size so as to fully utilize the enhanced permeability and retention (EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin (BSA) protected gold nanocluster (AuNC@CBSA, 21.06 nm) to both load indocyanine green (ICG) and act as imaging probe to realize theranostic. Then AuNC@CBSA-ICG was fabricated with negatively charged hyaluronic acid (HA) to form AuNC@CBSA-ICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed AuNC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter in vitro or in vivo, AuNC@CBSA-ICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated AuNC@CBSA-ICG@HA was potential for breast cancer therapy.
Oncological outcomes in extended intervals time betweeen preoperative chemoradiation with capecitabine and surgery in operable rectal adenocarcinoma: Experience at the National Cancer Institute of Peru.
Authors: Miguel Angel Muñoz, Manuel Giancarlo Palacios, Jenny Malca, Paola Catherine Montenegro, Iván Chávez, Raúl Mantilla
Journal: Journal of Clinical Oncology (2017)

e15158 Background: The literature reports that longer interval between the end of neoadjuvantchemoradiotherapy (CRT) and surgery is associated with a better rate of pathologic complete response (pCR) in rectal cáncer. Optimal interval remains to be defined. The effects of the extended time intervals on the prognosis are not clear. The objective was to assess whether extended time intervals ( &lt; 8, 8-12, &gt; 12-20 and &gt; 20 weeks) between the end of neoadjuvant CRT and surgery improve overall survival (OS), disease-free survival (DFS) and pathological outcomes Methods: Aretrospective study was conducted for 124 patients with rectal adenocarcinoma without evidence of metástasis (T1-4/N0-2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant CRT with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at National Cancer Institute of Peru. Patients undergoing emergency surgery and R2 resection have been excluded. Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test Results: Of the 124 patients, 72 were women (58.1%). The average age was 59.5 years. All received neoadjuvant CRT. Rates of pCR in the four groups were 25.0%, 10.3%, 7.7% and 17.2%, respectively. No significant difference was found between the association of the radial (P = 0.418) and distal edge (P = 0.487), with time interval groups and similarly with resected (P = 0.308) and compromised nodules (p = 0.783). The median OS follow-up time was 39.5 months and for DFS was 34 months. No significant differences were observed in OS (p = 0.739) and DFS (p = 0.902) according to the four groups studied. Conclusions: We found that amplifying the time interval at 31.9 weeks did not change the mean radial and distal edge. It does not affect the mean of resected and compromised nodules and does not improve overall survival and disease-free survival. The present study is the only one that reports these results at these time intervals. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery.
Survival of resected and overall pancreatic cancer patients in Europe and USA in 2003-2014: An international large-scale population-based investigation.
Authors: Lei Huang, Lina Jansen, Yesilda Balavarca, Masoud Babaei, Lydia van der Geest, Valery Lemmens, Liesbet Van Eycken, Harlinde De Schutter, Tom Børge Johannesen, Maja Primic-Žakelj, Vesna Zadnik, Petra Schrotz-King, Hermann Brenner
Journal: Journal of Clinical Oncology (2018)

e16251 Background: Literature-recorded survival for overall pancreatic cancer (PaC) patients is dismal. This is the first international large-scale population-based study aiming at providing detailed TNM stage- and age-specific survival of overall and resected PaC patients and at exploring survival changes over time in Europe and USA. Methods: Using population-based data from the US Surveillance, Epidemiology, and End Results (SEER)-18 Program and multiple European national cancer registries, survival by TNM stage and age for overall PaC patients diagnosed in 2003-2014 and those undergoing resection were computed. Temporal trends in survival were further investigated. Results: A total of 125,183 patients were analyzed. Overall, 3-year survival for patients with stage I-II PaC across countries was 20.4%-33.8% ( < 60 years), 13.6%-25.1% (60-69 years), and 8.9%-12.6% (≥70 years). Stage III-IV PaC patients had lower 3-year survival ( < 60 years, 1.8%-5.0%; 60-69 years, 1.0%-2.1%; ≥70 years, 0.5%-1.4%). Resection rates varied strongly across countries (stage I-II, 34.0%-62.7%; stage III-IV, 1.7%-6.8%). Resected patients had higher survival rates in each stage and age group in all countries (e.g., operated stage I-II patients had 3-year survival rates of 23.2%-39.0% ( < 60 years), 16.4%-30.7% (60-69 years), and 16.6%-29.7% (≥70 years)). Between 2003-2005 and 2009-2011, within overall patients, both significant short-term and long-term survival improvements were observed in USA, the Netherlands, Norway, and Slovenia; for resected patients, short-term improvements were present only in USA and Slovenia, and long-term improvements in USA, the Netherlands, Belgium, and Norway, with variations according to stage. Conclusions: Our study provides detailed survival estimates by stage and age in overall and resected PaC patients that will facilitate clinical counseling. While conclusions on potential benefit of resection should not be drawn from this study, the higher survival estimates may be helpful to better inform resected patients and clinicians specifically. Limited but inspiring improvement in survival is observed.
Repurposing ciclopirox as a pharmacological chaperone in a model of congenital erythropoietic porphyria
Authors: Pedro Urquiza, Ana Laín, Arantza Sanz-Parra, Jorge Moreno, Ganeko Bernardo-Seisdedos, Pierre Dubus, Esperanza González, Virginia Gutiérrez-de-Juan, Sandra García, Hasier Eraña, Itxaso San Juan, Iratxe Macías, Fredj Ben Bdira, Paula Pluta, Gabriel Ortega, Julen Oyarzábal, Rosario González-Muñiz, Juan Rodríguez-Cuesta, Juan Anguita, Emilio Díez, Jean-Marc Blouin, Hubert de Verneuil, José M. Mato, Emmanuel Richard, Juan M. Falcón-Pérez, Joaquín Castilla, Oscar Millet
Journal: Science Translational Medicine (2018)

The off-patent marketed antifungal ciclopirox improves symptoms in a mouse model of congenital erythropoietic porphyria.
Impact of room pooling and electronic health record on patient (pt) wait time, clinic work flow, and pts’/providers’ satisfaction.
Authors: Saroj Vadhan-Raj, Xiao Zhou, Meyyammai Narayanan, Shawn J Janarthanan, Mary Daniel, Colleen Jernigan, Shreyaskumar Patel
Journal: Journal of Clinical Oncology (2017)

e18191 Background: Excessive pt wait time can have negative effect on clinic work flow and on pts/ providers satisfaction. Increasing pt volume and limited clinic capacity can lead to long wait times for pts. The purpose of this two-part study was to evaluate the impact of Room Pooling Model (RPM) instead of Room Allocation Model (Part 1) and Electronic Health Record (EHR) on pt wait times in clinic and pts’/providers’ satisfaction (Part 2). Methods: The time studies and pts’/providers’ wait time satisfaction surveys were carried out over 2 weeks before (baseline) and 8 weeks after the implementation of RPM (Part 1), prior to the new EHR system, and 6 months after the implementation of EHR (part 2). All times of when pts, mid-level providers (MLP), and doctors (MDs) entered and exited the exam rooms were collected for 887 pts seen during the clinic. Data was analyzed using JMP and SAS. Results: As described earlier (ASCO 2016, abst 6595), the RPM was associated with increase in the proportion of pts seen by MDs within 30 min from the time roomed in the exam room and improvement in pts’/provider’s satisfaction. Post EHR, there were delays with decrease in the proportion of pts seen within 30 min from the time roomed in. Although the pt satisfaction did not change significantly, the number of times MDs had to wait for an open exam room increased from 8% (5/65) to 24% (14/59, p=0.01). The impact of RPM and EHR on pt times are shown below. The delays to see MDs after EHR were associated with longer time spent with the nurse (from median 4 to 7 min) and delays in seeing MLPs (from 11 to 18 min). Conclusions: These findings indicate that RPM can improve pt wait times. During initial stages of EHR implementation, the increase in pt wait time and reduced clinical efficiencies can be related to learning, and adapting to the new system. These data can be useful to design interventions that can target the areas of delays such as training and redesigning workflow to improve the clinical efficiency. [Table: see text]
Comprehensive genomic sequencing (CGS) of 90 patient samples of anaplastic thyroid cancer (ATC).
Authors: Saad A. Khan, Bo Ci, David E. Gerber, David G McFadden, Muhammad Shaalan Beg, Yang Xie, Pamela Kurian, Maria E. Cabanillas, Naifa Lamki Busaidy, Steven I. Sherman, Andreas Heilmann, Jeffrey S. Ross, Mark Bailey, Barbara Burtness, Siraj Mahamed Ali
Journal: Journal of Clinical Oncology (2016)

6014 Background: ATC is the most aggressive type of thyroid cancer with a median survival of 5 months from diagnosis. ATC patients with genomic alterations (GA) in TSC2, ALK, BRAF show occasional, limited benefit with targeted therapies. Methods: 90 ATC were studied by CGP to define the frequency of GA and opportunities for targeted therapy approaches in this devastating disease. DNA was extracted from 40 microns of FFPE sections, and CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 579X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. GA included base substitutions, indels, amplifications, copy number alterations and fusions/rearrangements. R software used for all statistical analyses. Fisher's exact test used for mutation frequency comparisons among age groups. Results: Median patient age was 65 (range 33-86), 50 patients were male. There was a mean of 4.2 Known Likely Variant (KLV) genomic alterations per case, range 1-11. Adding Variants of Undetermined Significance (VUS) mean was 12.9, range 5-27. The most common KLV-GA were p53 (66%), BRAF (34%), TERT (32%), CDKN2A (32%), NRAS (26%), CDKN2B (20%), NF2 (14.4%), PTEN (13.3%), PIK3CA (12.2%). There were 2 EGFR; 5 JAK2 and 29 GAin the promoter region of TERT. BRAF V600E and NRAS/HRAS alteration were entirely mutually exclusive, and one case demonstrated both BRAF V600E and KRAS. Co-occuring mutations were CDKN2A with p53 (p=0.04). Some GA were more frequent in patients greater than ≥70 yrs of age such as BRAF, CDKN2A, PIK3CA, JAK2; while others were more common in ≤50 yrs patients like PTEN, NRAS. VUS of possible interest were MLL2 (n=15), ARID1A (11), TSC2 (5), ALK(2). Conclusions: A number of identified alterations in ATC patients may be amenable to molecularly targeted therapies, guiding future clinical trial development. Further assessment will be performed to the relationship of GA in ATC with patient demographics and disease evolution from differentiated thyroid carcinoma. SELECT KLV-GA (%) ≤50 yrs n=15 >50 to ≤70 yrs n=49 >70 yrs n=25 p53 66.7 67.3 60 BRAF 20 34.7 44 CDKN2A 13.3 32.7 44 TERT 26.7 32.7 36 CDKN2B 0 20.4 32 NRAS 33.3 28.6 16 PIK3CA 0 14.3 16 RET 6.7 2 8 PTEN 20 16.3 4
Overall survival in advanced GIST over time and correlation with access to post-imatinib tyrosine kinase inhibitors: Results from the Life Raft Group Registry.
Authors: Michael C. Heinrich, Jerry Call
Journal: Journal of Clinical Oncology (2018)

e23511 Background: The use of imatinib (IM), sunitinib (SU), and regorafenib (RE) has transformed the treatment of advanced GIST. SU and RE improve progression free-survival in the second (2L) and third (3L) line, respectively, compared with placebo. However, the impact of these 2L and 3L agents on overall survival (OS) is unclear. Methods: The Life Raft Group (LRG) patient registry contains records from 1709 GIST pts; 526 of these have advanced to at least 2L treatment. Patient (pt) reported treatment and outcome data were examined to determine treatment patterns and their impact on OS. Results: In 2L, we compared SU (n = 436) to outcomes for patients taking any other drug (n = 74) and to patients that never received SU at any time (n = 42). Median OS was 32.4 months (mo.) for SU and 27.1 mo. for the any other drug group (p = 0.0232, HR 1.374). Median OS for 2L SU was 32.4 mo. and 16.8 mo. for the never received SU in any treatment line group (p = 0.0277, HR 1.507). For pts starting 3L treatment in the following time periods, the median OS from start of 3L treatment was: 2002 – 2006, 12.8 mo. (n = 73 pts); for 2007-2012, 22.4 M (n = 198 pts); and for 2013 and later, 29.3 mo. (n = 73 pts) (p = 0.0013). The 2002-2006 time period correlated with IM as the dominant drug ≥ 3L; the 2007-2012 time period correlated with nilotinib and sorafenib as the dominant drugs ≥ 3L , in the 2013+ time period RE was the dominant drug for ≥ 3L. In agreement with this data, pts receiving 3L RE (n = 53) had a longer OS than 3L pts who never received RE in any line of therapy, 26.2 vs 14.3 mo. (p = 0.0002, HR 2.224), respectively. Median OS for patients receiving 3L RE was 26.2 mo. compared with 18.6 mo. for patients who received any other 3L treatment (p = 0.0093 HR 1.74). Conclusions: OS for advanced GIST pts in the LRG registry has improved over time. In our analysis, SU and RE significantly improved OS compared with control pts in our registry. Our data also support the hypothesis that the use of KIT/PDGFRA inhibitors, including non-approved agents, has improved OS for pts with IM- and SU-resistant GIST.
Tumor mutational burden assessed by a targeted NGS assay to predict clinical benefit from immune checkpoint inhibitors in non-small cell lung cancer.
Authors: Sacha Rothschild, Ilaria Alborelli, Katharina Leonards, Laura P Leuenberger, Spasenija Savic Prince, Kirsten D Mertz, Severin Poechtrager, Alfred Zippelius, Heinz Philipp Laubli, Jasmin Haegele, Markus Tolnay, Lukas Bubendorf, Luca Quagliata, Philip Jermann
Journal: Journal of Clinical Oncology (2019)

e14266 Background: In non-small cell lung cancer (NSCLC) immune checkpoint inhibitors (ICIs) significantly improve overall survival (OS). Tumor mutational burden (TMB) has emerged as a predictive biomarker for patients treated with ICIs. Here we evaluated the predictive power of TMB measured through / by the Oncomine Tumor Mutational Load (TML - Thermo Fisher Scientific) targeted sequencing assay in 71 NSCLC patients treated with ICIs. Methods: TMB was assessed retrospectively in 71 metastatic NSCLC patients receiving ICI therapy. Clinical data (RECIST 1.1) were collected and patients were characterized as either having durable clinical benefit (DCB) or no durable benefit (NDB). Additionally, genetic alterations and PD-L1 expression were assessed and compared with TMB and response rate. Results: TMB was significantly higher in patients with DCB compared to patients with NDB (median TMB = 9.2 versus 5.3 mutations/Mb, Mann-Whitney p = 0.014). 70% of patients with high TMB (cutoff = 3rd tertile, TMB ≥ 9.2) were responders (DCB) compared to 29% of patients with low TMB (cutoff = 1st tertile, TMB ≤ 4.5). TMB-high patients showed significantly longer progression-free survival (PFS) and OS (log rank test, p = .0030 for PFS and 0 .0375 for OS, respectively). Combining PD-L1 expression and TMB value increased the predictive power of TMB. Conclusions: Our results show that the TML panel is an effective tool to stratify patients for ICI treatment. We believe that a combination of biomarkers will maximize the precision of patient selection.