tbuckley/cabot-search huggingface dataset:
Outcomes of advanced gastrointestinal (GI) cancer patients in relationship to opioid use: An individual patient data pooled analysis from eight clinical trials.
Authors: Omar Abdel-Rahman, Hatim Karachiwala, Jacob C. Easaw
Journal: Journal of Clinical Oncology (2020)

687 Background: The current study aims at assessing the patterns of opioid use, and evaluating the impact of opioid use on survival outcomes among patients with advanced GI cancers who were included in eight clinical trials. Methods: De-identified datasets of eight clinical trials evaluating first-line systemic treatment for advanced GI cancers (NCT01124786; NCT00844649; NCT00290966; NCT00678535; NCT00699374; NCT00272051; NCT00305188; NCT00384176) were accessed from the Project Data Sphere platform. These trials evaluated patients with pancreatic, gastric, hepatocellular and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was used to assess the impact of opioid use on survival outcomes in each disease entity. Results: A total of 3441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age (P = 0.004), non-white race (P = 0.010), higher ECOG score (P &lt; 0.001) and pancreatic primary site (P &lt; 0.001). Use of opioids was consistently associated with worse overall survival in Kaplan-Meier survival estimates of each disease entity (for pancreatic cancer: P = 0.008; for gastric cancer: P &lt; 0.001; for hepatocellular carcinoma: P &lt; 0.001 and for colorectal cancer: P &lt; 0.001). Within multivariable Cox regression analysis, opioid use was associated with worse overall survival among patients with pancreatic cancer (HR = 1.245; 95% CI: 1.063-1.459; P = 0.007), gastric cancer (HR = 1.725; 95% CI: 1.403-2.122; P &lt; 0.001), hepatocellular carcinoma (HR = 1.841; 95 CI: 1.480-2.290; P &lt; 0.001) and colorectal cancer (HR = 1.651; 95% CI: 1.380-1.975; P &lt; 0.001). Conclusions: Opioid use is consistently associated with worse overall survival among patients with different GI cancers. Further studies are needed to evaluate the underlying mechanisms of this observation.
Box of Chocolates
Authors: Lealani Mae Y. Acosta
Journal: JAMA Neurology (2020)

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 Neurology 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 Neurology journal
Stoma closure reinforcement with biological mesh and incisional hernia
Authors: Arturo J Rios-Diaz, John P Fischer
Journal: The Lancet (2020)

Incisional hernia is a prevalent complication after abdominal surgery, with an incidence as high as 39% at 2 years. 1 Bosanquet DC Ansell J Abdelrahman T et al. Systematic review and meta-regression of factors affecting midline incisional hernia rates: analysis of 14,618 patients. PLoS One. 2015; 10e0138745 Crossref PubMed Scopus (167) Google Scholar Incisional hernia adversely affects health-related quality of life, particularly in regards to pain, physical function, ability to work, and feelings about appearance. 2 van Ramshorst GH Eker HH Hop WCJ Jeekel J Lange JF Impact of incisional hernia on health-related quality of life and body image: a prospective cohort study. Am J Surg. 2012; 204: 144-150 Summary Full Text Full Text PDF PubMed Scopus (210) Google Scholar The condition can lead to serious complications due to bowel obstruction with incarceration or strangulation 3 Read RC Yoder G Recent trends in the management of incisional herniation. Arch Surg. 1989; 124: 485-488 Crossref PubMed Scopus (273) Google Scholar and can recur after surgical repair, necessitating additional procedures. 4 Flum DR Horvath K Koepsell T Have outcomes of incisional hernia repair improved with time? A population-based analysis. Ann Surg. 2003; 237: 129-135 Crossref PubMed Scopus (432) Google Scholar Incisional hernia represents a true global public health issue with a substantial burden to health-care systems around the world. 5 Gillion JF Sanders D Miserez M Muysoms F The economic burden of incisional ventral hernia repair: a multicentric cost analysis. Hernia. 2016; 20: 819-830 Crossref PubMed Scopus (69) Google Scholar , 6 Poulose BK Shelton J Phillips S et al. Epidemiology and cost of ventral hernia repair: making the case for hernia research. Hernia. 2012; 16: 179-183 Crossref PubMed Scopus (566) Google Scholar However, the condition is potentially preventable, with estimated savings of $32 million in the USA for each 1% reduction and €4 million in France for each 5% reduction. 5 Gillion JF Sanders D Miserez M Muysoms F The economic burden of incisional ventral hernia repair: a multicentric cost analysis. Hernia. 2016; 20: 819-830 Crossref PubMed Scopus (69) Google Scholar , 6 Poulose BK Shelton J Phillips S et al. Epidemiology and cost of ventral hernia repair: making the case for hernia research. Hernia. 2012; 16: 179-183 Crossref PubMed Scopus (566) Google Scholar
Prognostic utility of inflammation biomarkers in a PDAC trial involving the human anti-CTGF antibody pamrevlumab.
Authors: Mark D. Sternlicht, Dongxia Li, Viet-Tam Nguyen, Mairead Carney, Duo Zhou, Kenneth E. Lipson, Elias Kouchakji, Vincent J. Picozzi, Ewa Carrier, Todd W. Seeley
Journal: Journal of Clinical Oncology (2020)

752 Background: Pancreatic ductal adenocarcinomas (PDAC) often exhibit desmoplasia, elevated CTGF (connective tissue growth factor) expression and inflammation. The influence of inflammation on patient outcomes was examined in a dose-ranging trial of the anti-CTGF antibody pamrevlumab in combination with a fixed regimen of gemcitabine and erlotinib in locally advanced or metastatic PDAC patients (NCT01181245; Picozzi et al. J Cancer Clin Trials 2017 2:123; n = 75). Methods: The prognostic utility of pre-treatment plasma levels of C-reactive protein (CRP), transforming growth factor β1 (TGFβ1), albumin, CTGF and CA 19-9 were assessed by univariate and multivariate Cox analysis. Demographic parameters, treatment cohort, and pamrevlumab exposure determined on treatment day 15 were also evaluated, as were changes in biomarker levels over the first four weeks of treatment. Results: Elevated baseline CTGF and CRP were prognostic for shorter overall survival (OS) by univariate analysis (HR = 3.2 for CRP &gt; 10 mg/L, p= 0.00002 and HR = 1.6 for CTGF &gt; 10 ng/mL, p= 0.045). In a five-factor multivariate Cox model that included CRP and TGFβ1 as continuous Ln-transformed variables, performance status, age, and pamrevlumab treatment cohort, cohort assignments associated with increasing pamrevlumab exposure predicted improved OS (HR = 0.87, p= 0.03). Removing CRP from this model reduced the prognostic utility of pamrevlumab cohort assignment and exposure, indicating an important contribution of inflammation to interpretation of treatment outcome. Changes in inflammation biomarkers over the course of treatment were also evaluated, but were not prognostic in this study. Conclusions: In multivariate Cox models, assessment of pre-treatment CRP levels improved ability to detect significant differences in PDAC patient survival outcomes associated with pamrevlumab treatment. Our results emphasize the utility of accounting for pre-treatment CRP levels as an independent prognostic factor in PDAC treatment effect models.
Response to : ‘Interleukin-4 as a emerging target for IgG4-related disease’ by Akiyama et al
Authors: Rachel S Simpson, Jason K Lee
Journal: Annals of the Rheumatic Diseases (2020)

We thank Akiyama et al , for their kind words regarding our manuscript.1 We agree that IgG4-related disease (IgG4-RD) relapse frequently occurs in patients tapering glucocorticoids, and we wanted to offer a novel solution to our patient to potentially mitigate or all together avoid this. As communicated in our previous correspondence response2 it has actually come to our attention post-publication (December 29th, 2019) that the patient noted in our report never took a dose of prednisone that was prescribed to him due to undisclosed non-compliance. Therefore, the remission of IgG4-RD can be completely attributed to dupilumab treatment. We are happy to report our findings and hope that our report will propel this treatment to be studied further for the treatment of this disease which otherwise, as you mentioned, is poorly controlled by glucocorticoids especially when tapering,3 and when other agents such as chemotherapeutic immunosuppressants come with profound adverse effects.4 Although this disease has a low prevalence, so low that it is actually unknown due to being underrecognized …
A meta-analysis of the accuracy of a neuroendocrine tumor mRNA biomarker (NETest) in the blood.
Authors: Kjell E. Oberg, Andrea Califano, Jonathan R. Strosberg, Steven M. Ma, Ulrich-Frank Pape, Lisa Bodei, Gregory Kaltsas, Christos Toumpanakis, James Goldenring, Andreja Frilling, Andrew Scott Paulson, Irvin Mark Modlin
Journal: Journal of Clinical Oncology (2020)

606 Background: There is no accurate blood biomarker of neuroendocrine tumor (NET) disease. The inability to effectively assess disease in real-time has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy – liquid biopsy – to facilitate management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD) to assess clinical utility. Methods: A systematic review of the literature using PRISMA guidelines was undertaken. The methodological quality was evaluated using the QUADAS-2 tool. We identified 10 original scientific papers, which met inclusion criteria. These were assessed by qualitative analysis, and thereafter meta-analysis. Data were pooled and median (95% CI) diagnostic odds ratio (DOR), positive likelihood ratio (+LR) and negative likelihood ratio (–LR) calculated. For the meta-analysis, a generic inverse variance method was undertaken using the accuracy and AUC data. Results: The ten studies exhibited moderate to high methodological quality. They evaluated NETest usage both as a diagnostic and as a monitoring tool. Meta-analysis identified the diagnostic accuracy of the NETest to be 94.9-96% with a median DOR of 400, +LR of 164 and–LR of 0.05. The NETest was 85.5-86% accurate in differentiating stable from progressive disease. As a marker of natural history, the accuracy was 90-94%. As an interventional/ response biomarker, the accuracy was 94-97%. The pooled AUC for the NETest was 0.954±0.005, with a z-statistic of 175.06 ( p&lt; 0.001). Conclusions: The NETest is an accurate biomarker suitable for clinical use in NET disease management. The meta-analysis supports the utility of the NETest as an IVD to establish a diagnosis and monitor therapeutic efficacy. The use of a multianalyte genomic test as a biomarker provides information relevant to NET management consistent with observations regarding the utility of liquid biopsy in other oncological disciplines.
Phenotypic Convergence Is Not Mirrored at the Protein Level in a Lizard Adaptive Radiation
Authors: Russell B Corbett-Detig, Shelbi L Russell, Rasmus Nielsen, Jonathan Losos
Journal: Molecular Biology and Evolution (2020)

Abstract There are many compelling examples of molecular convergence at individual genes. However, the prevalence and the relative importance of adaptive genome-wide convergence remain largely unknown. Many recent works have reported striking examples of excess genome-wide convergence, but some of these studies have been called into question because of the use of inappropriate null models. Here, we sequenced and compared the genomes of 12 species of anole lizards that have independently converged on suites of adaptive behavioral and morphological traits. Despite extensive searches for a genome-wide signature of molecular convergence, we found no evidence supporting molecular convergence at specific amino acids either at individual genes or at genome-wide comparisons; we also uncovered no evidence supporting an excess of adaptive convergence in the rates of amino acid substitutions within genes. Our findings indicate that comprehensive phenotypic convergence is not mirrored at genome-wide protein-coding levels in anoles, and therefore, that adaptive phenotypic convergence is likely not constrained by the evolution of many specific protein sequences or structures.
Smartphones vs Wearable Devices for Remotely Monitoring Physical Activity After Hospital Discharge
Authors: Mitesh S. Patel, Daniel Polsky, Edward H. Kennedy, Dylan S. Small, Chalanda N. Evans, Charles A. L. Rareshide, Kevin G. Volpp
Journal: JAMA Network Open (2020)

This secondary analysis of a randomized clinical trial compares smartphones with wearable devices for remotely monitoring the duration of physical activity of patients after hospital discharge to home.
Exploring online access of an immuno-oncology wallet card among oncology providers.
Authors: Janelle Schrag, Latha Shivakumar, Monique Dawkins, Leigh Boehmer, Lorna Lucas
Journal: Journal of Clinical Oncology (2020)

93 Background: In 2019, the Association of Community Cancer Centers (ACCC) developed an immuno-oncology (IO) wallet card to address the continuous need for immune-related adverse event education and resources, particularly for IO patients and the non-oncology providers from whom they receive care. The wallet card was distributed to ACCC’s membership of cancer programs via mailings and online, which included a short survey for users to complete at time of download. Methods: To better understand the demographics and motivations of individuals who access the IO wallet card, an exploratory analysis was performed on data collected through the download survey. Data included the survey responses from all downloads between March and September 2019 (n = 141), which was then cleaned to remove duplicates, incomplete responses, and responses from ACCC staff, international users, pharmaceutical representatives, consultants, and patients. Analysis was then performed on the resulting data set of downloads from US-based health care providers (n = 86). Results: Cancer program administrators and nurses accounted for the majority of downloads (30% and 20%, respectively), as well as individuals from comprehensive community cancer programs (44%) and NCI-designated comprehensive cancer programs (16%). Fewer downloads came from other oncology disciplines (2-9%) and small practices (2-6%). Survey responses indicated that the majority of downloads were due to the cancer program not already having the resource (47%), or for comparison with a wallet card developed by the cancer program (15%) or another organization (10%). Patient education materials provided by these institutions included wallet cards (45%), as well as print materials developed by the cancer program (16%), another professional organization (7%), or distributed by drug companies (5%). Conclusions: These finding shed light on the primary audiences accessing the IO wallet card, how this resource may complement other IO patient education materials, and areas where additional education may be needed. Specifically, IO wallet card dissemination or related education may need to be tailored to better reach specific oncology disciplines as well as those practicing in smaller clinics.
Initial lenvatinib therapy with no prior TACE in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept study.
Authors: Masatoshi Kudo, Kazuomi Ueshima, Stephen Lam Chan, Tomoko Aoki, Satoru Hagiwara, Yasunori Minami, Hiroshi Ida, Mamoru Takenaka, Tomohiro Watanabe, Masahiro Morita, Chikara Ogawa, Yoshiyuki Wada, Masafumi Ikeda, Hiroshi Ishii, Namiki Izumi, Atsushi Hiraoka, Hiroshi Aikata, Naoshi Nishida
Journal: Journal of Clinical Oncology (2020)

522 Background: Intermediate-stage HCC is a heterogenous population with subgroups of patients that do not benefit from TACE. Hence, we conducted a matched cohort study to compare the efficacy of lenvatinib to TACE in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-7 criteria. Methods: This study first identified 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-7 criteria, without prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected. Propensity score matching was used to adjust for patients’ demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials [1 Phase II and 13 Phase III REFLECT trial], 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The lenvatinib group showed a higher objective response rate (73.3% vs. 33.3%; p &lt; 0.001) and longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p &lt; 0.001). Median overall survival was also significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p &lt; 0.01). The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p &lt; 0.01), respectively. Conclusions: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-7 criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib is associated with better outcome than TACE. In particular, leventinib is associated with preservation of hepatic function during treatment while TACE is associated with deterioration of hepatic function.
Tissue Regeneration: Reactive Oxygen Species‐Scavenging Scaffold with Rapamycin for Treatment of Intervertebral Disk Degeneration (Adv. Healthcare Mater. 3/2020)
Authors: Jinyu Bai, Yingzi Zhang, Qin Fan, Jialu Xu, Huajian Shan, Xiang Gao, Qingle Ma, Lei Sheng, Xin Zheng, Weinan Cheng, Dazhuang Li, Mingchao Zhang, Yu Hao, Liangzhu Feng, Qian Chen, Xiaozhong Zhou, Chao Wang
Journal: Advanced Healthcare Materials (2020)

In article number 1901186 by Xiaozhong Zhou, Chao Wang, and co-workers, a reactive oxygen species-scavenging scaffold loaded with rapamycin (Rapa@Gel) offers a new strategy for modulating the local inflammatory microenvironment to improve intervertebral disk tissue regeneration.
Comprehensive genomic profiling for chemotherapy-naïve advanced gastrointestinal malignancies.
Authors: Tomohiro Kondo, Quy Pham Nguyen, Junichi Matsubara, Keita Fukuyama, Motoo Nomura, Taro Funakoshi, Mari Funakoshi, Hitomi Sakamoto, Kanami Ashida, Kumi Mukai, Shinji Uemoto, Yoshiharu Sakai, Hiroshi Seno, Sachiko Minamiguchi, Hironori Haga, Shinji Kosugi, Masashi Kanai, Shigemi Matsumoto, Manabu Muto
Journal: Journal of Clinical Oncology (2020)

832 Background: From June, 2019, two comprehensive genomic profiling (CGP) assays, "FoundationOne CDx" and “OncoGuide NCC Oncopanel”, were reimbursed by the national insurance system in Japan for patients who were refractory to standard chemotherapy. However, their clinical utility for chemotherapy-naïve cancer patients is unknown. Methods: We conducted a single institutional prospective observational study to evaluate the clinical utility of FoundationOne CDx assay (Cambridge, MA, USA) for the patients with chemotherapy-naïve advanced gastrointestinal malignancies. Patients with adequate H.E. sample were registered in this study. Primary outcome was the detection rate of at least one actionable/druggable cancer genomic alterations. The evidence levels were classified according to clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 1.0) (Sunami K. Cancer Sci. 2018). Results: From October 2018 to June 2019, a total of 238 patients were screened and the following 158 patients were registered: colorectal cancer (n = 60), gastric cancer (n = 19), esophageal cancer (n = 23), pancreatic cancer (n = 30), biliary tract cancer (n = 11), rare gastrointestinal malignancies (n = 15). The CGP data were obtained for 113 patients . Median turn-around time was 14 days (range 10-247 days). Actionable/druggable cancer genomic alterations were observed in 113 patients (100%)/ 65 patients (57.5%), respectively. Clinically relevant biomarkers and genomic alterations were identified in 22 patients (19.5%); BRCA2 (n = 4), ERBB2 (n = 4) , BRAF (n = 3) , EGFR (n = 3), FGFR2 (n = 2), MET (n = 2), NTRK (n = 2) , MSI-H (n = 2 ), TMB-high (n = 2), ALK (n = 1) , KIT (n = 1) and ROS1 (n = 1). Of note, novel biomarkers such as ROS1- GOPC fusion and PALB2 rearrangement were obtained in the patients with esophageal squamous cell carcinoma. Conclusions: This is the first study to evaluate the clinical utility of CGP in patient with chemotherapy-naïve advanced gastrointestinal malignancies. Our result indicated that CGP might provide a chance of potentially effective drugs as a novel approach in precision cancer medicine. Clinical trial information: UMIN000034830.
20(S)-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network via multiomic analysis
Authors: Zhihua Wang, Wenbo Wu, Xiangchen Guan, Shuang Guo, Chaowen Li, Ruixue Niu, Jie Gao, Min Jiang, Liping Bai, Elaine Laihan Leung, Yuanyuan Hou, Zhihong Jiang, Gang Bai
Journal: Acta Pharmaceutica Sinica B (2020)

Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20(S)-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.