tbuckley/cabot-search huggingface dataset:
HIPAA in the Era of Data Sharing
Authors: Charles G. Kels
Journal: JAMA (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 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
Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension
Authors: Catherine E. Simpson, Jenny Y. Chen, Rachel L. Damico, Paul M. Hassoun, Lisa J. Martin, Jun Yang, Melanie Nies, Megan Griffiths, Dhananjay Vaidya, Stephanie Brandal, Michael W. Pauciulo, Katie A. Lutz, Anna W. Coleman, Eric D. Austin, Dunbar D. Ivy, William C. Nichols, Allen D. Everett
Journal: European Respiratory Journal (2020)

The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort. IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models. Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p&lt;0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08–1.38; p&lt;0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease. IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.
Abstract 15784: Impaired Myocardial Perfusion on Stress Cardiovascular Magnetic Resonance Imaging Correlates With Invasive Fractional Flow Reserve in Children With Anomalous Aortic Origin of a Coronary Artery and/or Myocardial Bridges
Authors: Hitesh Agrawal, Cory V Noel, Athar M Qureshi, Prakash Masand, Carlos M Mery, S. Kristen Sexson Tejtel, Charles D Fraser, Silvana Molossi
Journal: Circulation (2017)

Introduction: There is paucity of data on risk stratification in patients (pts) with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridge (MB). Stress cardiovascular magnet...
Metastatic Anaplastic Thyroid Carcinoma in Complete Remission: Morphological, Molecular, and Clinical Work-Up of a Rare Case
Authors: Adam Stenman, L. Samuel Hellgren, Kenbugul Jatta, Martin Hysek, Maja Zemmler, Renske Altena, Inga-Lena Nilsson, Robert Bränström, Jan Zedenius, C. Christofer Juhlin
Journal: Endocrine Pathology (2020)

Abstract Anaplastic thyroid carcinoma (ATC) exhibits an exceedingly poor prognosis, and the current treatment options are, for most cases, palliative by nature. Few reports of long-time survivors exist, although in these patients, tumors often were limited to the thyroid and/or regional lymph nodes. We describe a 64-year-old male who developed a rapidly growing mass in the left thyroid lobe. A fine-needle aspiration biopsy (FNAB) was consistent with ATC, and the patient underwent preoperative combined chemo- and radiotherapy followed by a hemithyroidectomy. The ensuing histopathological investigation was consistent with ATC adjoined by an oxyphilic well-differentiated lesion, likely a Hürthle cell carcinoma. Tumor margins were negative, and no extrathyroidal extension was noted. Focused next-generation sequencing analysis of the primary tumor tissue identified a TP53 gene mutation but could not identify any potential druggable targets. Additional Sanger sequencing detected a C228T TERT promoter mutation. The tumor was found to be microsatellite stable and displayed PDL1 expression in 80% of tumor cells. Following a CT scan 1 month postoperatively, metastatic deposits were suspected in the lung as well as in the left adrenal gland, of which FNAB verified the latter. Remarkably, upon radiological follow-up, the disease had gone into apparent complete remission. The patient is alive and well with no signs of residual disease after 12 months of follow-up. We here summarize the clinical, histological, and molecular data of this highly interesting patient case and review the literature for possible common denominators with other patients with disseminated ATC.
Epithelioid blue naevus of the genital mucosa: report of four cases
Authors: M.J. Izquierdo, M.A. Pastor, L. Carrasco, C. Moreno, H. Kutzner, O.P. Sangueza, L. Requena
Journal: British Journal of Dermatology (2008)

Epithelioid blue naevi are an unusual cytological variant of blue naevus that have been recently described mostly in patients with the Carney complex, although they may also occur in isolation. This variant of blue naevus is composed of melanin‐laden polygonal epithelioid melanocytes situated within the dermis. The neoplastic cells show no maturation with progressive depth of dermal infiltration and, in contrast with the usual stromal changes in blue naevi, epithelioid blue naevi exhibit no dermal fibrosis. We describe four cases of epithelioid blue naevus located on the genital mucosa in four patients with no evidence of the Carney complex. Three male patients showed an epithelioid blue naevus on the mucosa of the glans penis and a female patient had a lesion of the right labium minoris. Histopathologically, the lesions consisted of entirely intradermal melanocytic naevi composed mostly of heavily pigmented epithelioid melanocytes involving the dermis of the genital mucosa. Immunohistochemically, in all cases, epithelioid melanocytes expressed immunoreactivity for S‐100 protein, HMB‐45, Melan‐A and MiTF antibodies.
Real-world outcomes of first-line U.S. patients with unresectable advanced or metastatic gastroesophageal adenocarcinoma by primary tumor location.
Authors: Veena Shankaran, Hong Xiao, David Bertwistle, Ying Zhang, Pranav Abraham, Ian Chau
Journal: Journal of Clinical Oncology (2020)

304 Background: Gastric cancer clinical trials are inconsistent in their inclusion of esophageal adenocarcinoma (EAC). Thus it is uncertain if outcomes are similar among subgroups of gastroesophageal adenocarcinoma. The aim of this study was to compare baseline characteristics and clinical outcomes of US patients with EAC versus Gastroesophageal Junction Cancer (GEJC) and Gastric Cancer (GC) treated in real world clinical settings. Methods: Adult patients with unresectable, advanced or metastatic GC, GEJC, or EAC diagnosed between January 2011 and November 2018 were identified from the Flatiron Health database. Patients with a positive HER2 test, or who received trastuzumab, were excluded. Overall survival (OS) was defined as time from first-line (1L) treatment initiation to death or loss of follow-up. Survival analyses were conducted using Kaplan-Meier methods with log-rank test and Cox models. Results: A total of 3052 patients (969 EAC and 2083 GEJC/GC) met eligibility criteria. Out of all EAC patients, 90% were males and 76% were white. Within the GEJC/GC patients, 67% were males and 57% were white. Median age was 66 years for both cohorts while proportion with ECOG PS of 0 or 1 was 78% for EAC and 84% for GEJC/GC among patients with ECOG scores. The proportion of patients receiving 1L treatment was comparable (78% for EAC, 76% for GEJC/GC) across groups with FOLFOX being the most frequent treatment (25% for EAC and 29% for GEJC/GC). There was no significant difference in OS between the two groups, with median OS of 9.1 and 9.6 months for EAC and GEJC/GC, respectively (HR 0.957, 95% CI: 0.863 - 1.062, p = 0.41). Conclusions: In this US real-world analysis, OS did not differ significantly between patients with EAC and patients with GEJC/GC who received 1L treatment, suggesting that these two populations may have comparable survival benefit from systemic therapy.
Randomised Phase II Study of Axitinib or Bevacizumab Combined with Paclitaxel/Carboplatin (PAC/CARB) as First-Line Therapy for Patients (PTS) with Advanced Non–Small Cell Lung Cancer (NSCLC)
Authors: C. Twelves, E. Chmielowska, L. Havel, S. Popat, A. Swieboda-Sadlej, P. Sawrycki, P. Bycott, A. Niethammer, P. De Besi, J.H. Schiller
Journal: Annals of Oncology (2012)
Long-term survival in patients with peritoneal metastasized gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI.
Authors: Andreas Brandl, Yutaka Yonemura, Olivier Glehen, Paul H. Sugarbaker, Beate Rau
Journal: Journal of Clinical Oncology (2020)

390 Background: Peritoneal metastasis of gastric cancer is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in median survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyze a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven peritoneal metastasis of gastric cancer, treated with CRS and HIPEC, and overall survival &gt; 5 years. Patient, tumor, and therapeutic details were collected and analyzed. Results: A total of 29 patients with a mean age of 52.5 years and a mean PCI of 3.2 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and low PCI (PCI &lt; 6) were present in 23/29 patients. 13/29 patients developed at a median of 82.2 months tumor recurrence. Tumor recurrence was associated with inferior median overall survival compared to patients without tumor recurrence (8.8 years vs. not reached; p = 0.002). Conclusions: Long-term survival and even cure are possible in patients with peritoneal metastasis of gastric cancer treated with CRS and HIPEC. Completeness of cytoreduction (CC-0) and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.
Analysis of OX40 agonist antibody (PF-04518600) in patients with hepatocellular carcinoma.
Authors: Anthony B. El-Khoueiry, Jean-Philippe Spano, ERIC ANGEVIN, Toshihiko Doi, Andrea J. Bullock, William Proctor Harris, Omid Hamid, Paul Gougis, Alison Forgie, Wenjing Yang, Ken Liao, Ruifeng Li, Carrie T. Taylor, Jeffrey Chou, Ferry Eskens
Journal: Journal of Clinical Oncology (2020)

523 Background: PF-04518600 (PF-8600) is a humanized agonist IgG2 monoclonal antibody to the tumor necrosis factor superfamily receptor OX40. PF-8600 was given to patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC) in dose expansion of a phase 1 study (NCT02315066). Safety and tolerability were primary endpoints and exploratory endpoints included biomarker analyses. Methods: Pts received either 30 mg (Arm 1) or 250 mg (Arm 2) of PF-8600 intravenously Q2W. Pts had pathologic diagnosis of advanced HCC, a Child-Pugh score of A or B7, and had ≤2 prior lines of therapy, or if treatment naïve, had declined standard of care. Radiological tumor assessments were conducted Q8W. Biopsy samples collected at baseline and wk 6 were analyzed by immunohistochemistry and RNA sequencing for pharmacodynamic (PD) analyses. Whole blood samples were collected longitudinally for DNA extraction for high-throughput sequencing of the T cell receptor β-chain. Results: Arm 1 enrolled 16 pts (mean age 65.6 yrs; range 54-81 yrs; prior PD-1/PD-L1: 5 pts) and Arm 2 enrolled 19 pts (mean age 61.7 yrs; range 26-79 yrs; prior PD-1/PD-L1: 3 pts). All grade treatment related adverse events (TRAEs) occurred in 69% of pts in Arm 1 and 58% of pts in Arm 2. The rate of ≥Grade 3 TRAEs was 31% and 16% in Arms 1 and 2, respectively. For both arms combined, the most common (≥10%) TRAEs were rashes and pruritus. In Arm 1, 8 pts (50%) and in Arm 2, 10 pts (53%) achieved stable disease (SD), with a mean duration of 18.4 (range: 14.0-30.3 wks) and 17.4 wks (range: 8.0-31.9 wks), respectively. PD effects were more evident in Arm 1 than Arm 2, including increased OX40 tumor expression and positive changes in gene signatures, reflecting an active anti-tumor immune response. Conclusions: PF-8600 was generally well tolerated and provided meaningful disease control. While safety and efficacy were not significantly different between the 2 doses, there were potential differences in the PD data. The safety and relative durability of SD in HCC pts may provide a rationale for exploration of combination therapy in this pt population. Clinical trial information: NCT02315066.
Limited role for fibroblast growth factor 23 in assessing prognosis in heart failure patients: data from the TIME‐CHF trial
Authors: Robert Stöhr, Vincent M. Brandenburg, Gunnar H. Heine, Micha T. Maeder, Gregor Leibundgut, Alexander Schuh, Urs Jeker, Matthias Pfisterer, Sandra Sanders‐van Wijk, Hans‐Peter Brunner‐la Rocca
Journal: European Journal of Heart Failure (2020)

Abstract Aim Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME‐CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C‐terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF). Methods and results In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12‐month follow‐up. In unadjusted analyses, cFGF23 significantly predicted all HF‐related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid‐range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid‐range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF. Conclusions Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation.
The adherence to The American Association for The Study of Liver Disease (AASLD) guidelines in treating patients with hepatocellular carcinoma: Institutional experience.
Authors: Ashish Manne, Daisy E. Escobar, Pranitha Prodduturvar, Phillip Henderson, Osama Abdul-Rahim, Zeiad Hussain, Spencer Liles, Annabelle Fonseca, John Harrison Howard, Wadad Mneimneh, Robert Gilbert, Sachin Gopalkrishna Pai, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2020)

496 Background: The American Association for the Study of Liver Disease (AASLD) guidelines outline an algorithm regarding the treatment modality of choice for patients with hepatocellular carcinoma (HCC) based on Barcelona Clinic Liver Cancer (BCLC) stage. The AASLD guidelines have several limitations and the adherence rate has been reported to be low. The adherence to AASLD guidelines in treating patients with HCC was explored in this study. Methods: Between 2017 and 2019, 106 patients with HCC were identified. In our cohort, 70 patients (66%) were discussed in the multidisciplinary tumor board (MDTB) and their first-line treatment modality was selected based on consensus recommendations from the MDTB team members. The adherence rate of MDTB recommendations to AASLD guidelines was calculated. Results: Median age was 65 (range 42-90). Males represented 84% while females represented 16%. Caucasians, African Americans and Asians represented 69%, 30% and 1% respectively. BCLC stage 0, A, B, C and D represented 7%, 32%, 23%, 27% and 11% respectively. First-line treatment modality of choice recommended by MDTB is summarized in Table. The overall adherence rate of MDTB recommendations to AASLD guidelines is 60%. For BCLC stage 0, A, B, C and D, the adherence rate was 60%, 86%, 44%,58% and 25% respectively. Conclusions: Our MDTB recommendations adherence rate to AASLD guidelines was 60%. The reported low adherence rate to the guidelines suggest that AASLD guidelines would benefit from further refinement and periodic update. [Table: see text]
Comparing FOLFOXIRI plus bevacizumab with doublet chemotherapy plus anti-EGFR antibody: A systemic review and network meta-analysis.
Authors: Jianwei Zhang, Jianxia Li, Xiaoyu Xie, Yue Cai, Zehua Wu, Huabin Hu, Miaomiao Ding, Yanhong Deng
Journal: Journal of Clinical Oncology (2020)

97 Background: FOLFOXIRI plus bevacizumab (Triplet+Bev) improved survival benefit when comparing with doublet chemotherapy plus Bev (doublet+Bev) as initial treatment in metastatic colorectal cancer (mCRC). Several trials also compared the efficacy of doublet plus EGFR antibody (doublet+EGFRi) with doublet+Bev. However, little is known about triplet+Bev comparing with doublet +EGFRi in mCRC. Methods: We did a systematic review and network meta-analysis with a systematic literature search on PubMed, EMbase, Web of Science, and international oncology conferences. We included phase 2 and 3 randomized controlled trials investigating FOLFOXIRI+Bev versus doublet+Bev or doublet+EGFRi versus doublet+Bev as first-line treatments in mCRC. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for PFS and OS in overall population, Ras wild type population, left or right side patients, left or right-side Ras wild-type population. And to compare relative risk (RR) for objective response rates. Results: Eight trials involving 3980 patients were included. In direct comparison, Triplet+Bev was superior to doublet+EGFRi both in OS (HR 0.83 0.72-0.97), PFS (HR 0.73, 0.65-0.83)and ORR (RR 1.5, 1.2-2.0). Doublet+EGFRi was beneficial in OS (HR 1.2, 1.1-1.5) and ORR (RR 0.74, 0.52-0.97) than doublet+Bev, but not PFS. In indirect comparison, Triplet+Bev showed no difference to doublet+EGFRi in OS (HR 1.0, 0.84-1.4) and ORR (RR 1.1, 0.73-1.6) in all population, and improved PFS (HR 0.71, 0.60-0.86). In left side RAS wild-type subgroup, Triplet+Bev showed similar efficacy in OS (HR 1.2, 0.6-2.5), PFS (HR 1.6, 0.59-4.3), and ORR (RR 0.63, 0.22-15). But in Right-side subgroup, Triplet+Bev was beneficial both in OS (HR 0.41, 0.18-0.93) and PFS (HR 0.55, 0.34-0.92). In right-side RAS wild-type subgroup, Triplet+Bev also showed trend of longer OS (HR 0.37, 0.12-1.1) and PFS (HR 0.43, 0.18-1.1) than doublet+EGFRi. Conclusions: In left-side RAS wild-type mCRC, FOLFOXIRI+Bev showed similar efficacy to doublet+EGFRi. While in right-side subgroup or right-side RAS wild-type population, Triplet+Bev is preferable as initial treatment for mCRC, in the meanwhile, in cautious of AE.
Loss of Rnf43 to accelerate KRAS-mediated neoplasia in a clinically relevant genetically engineered mouse model of pancreatic adenocarcinoma.
Authors: Abdel Nasser Hosein, Gita Dangol, Takashi Okumura, Lotfi Abou-Elkacem, Anirban Maitra
Journal: Journal of Clinical Oncology (2020)

733 Background: The genetic heterogeneity of pancreatic ductal adenocarcinoma (PDAC) demands a personalized molecular-targeted treatment approach. While activating KRAS mutations are a near ubiquitous event in PDAC pathogenesis, 5-10% of cases display deleterious driver mutations in the Wnt-signaling negative regulator, ring finger 43 (RNF43). Despite this characterization there are no personalized treatment options for this subset of patients. Methods: We have developed a genetically engineered mouse model (GEMM) of PDAC, driven by an activating mutation in Kras and deletion of Rnf43 under control of a pancreas specific promoter (KRC). Mice were followed for survival outcomes and histological changes which were compared to a Kras driven PDAC GEMM (KC). Mice underwent serial magnetic resonance imaging (MRI), with and without dynamic contrast enhanced (DCE) imaging, to evaluate cystic tumor morphology and contrast enhancement during tumor progression. Single cell RNA sequencing (scRNAseq) was also performed to assess changes in single cell populations during tumor progression. Lastly, we established ex vivo cultures from KRC and KC tumors and performed bulk RNA-sequencing (RNAseq) and in vitro pharmacology studies. Results: KRC mice displayed a decrease in overall survival and higher incidence of both high grade pre-neoplastic lesions and invasive PDAC compared to KC mice. Serial MRI revealed increased cystic morphology of KRC mice during tumor progression with increasing DCE intensity. scRNAseq of KRC tumors from moribund mice displayed two distinct populations of both macrophages and fibroblasts, similar to our previous report of Kras/Tp53 and Kras/Ink4a driven GEMMs. Lastly, primary cultures from KRC tumors demonstrated increased expression of Wnt-related genes by RNAseq and increased sensitivity to small molecule porcupine inhibition relative to KC cell lines, demonstrating functional Wnt dependence of the KRC system. Conclusions: Rnf43 is a bona fide tumor suppressor gene in PDAC. This GEMM is a novel platform for drug discovery in RNF43-mutated PDAC with the eventual goal of implementing a precision oncology approach in these patients.
Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy
Authors: Man Li, Mengmeng Li, Yiliang Yang, Yingke Liu, Hanbing Xie, Qianwen Yu, Lifeng Tian, Xian Tang, Kebai Ren, Jianping Li, Zhirong Zhang, Qin He
Journal: Journal of Controlled Release (2020)