tbuckley/cabot-search huggingface dataset:
Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study
Authors: Sahaja Acharya, Shengjie Wu, Jason M Ashford, Christopher L Tinkle, John T Lucas, Ibrahim Qaddoumi, Amar Gajjar, Matthew J Krasin, Heather M Conklin, Thomas E Merchant
Journal: Neuro-Oncology (2019)

Abstract Background Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. Methods Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. Results Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = −0.01 standard deviation [SD]/year, P &lt; 0.001), total recall (slope = −0.09 SD/y, P = 0.005), and long-delay recall (slope = −0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = −0.001 SD/y, P = 0.019) or left hippocampus (slope = −0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = −0.002, P = 0.025). In children &lt;12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = −0.002, P = 0.013) and left (V40 Gy slope = −0.002, P = 0.014) hippocampal dosimetry. Conclusion In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.
PS-107-SGLT2 inhibition does not reduce hepatic steatosis in overweight, insulin resistant patients without type 2 diabetes
Authors: Thomas Marjot, Charlotte Green, Catriona Mcneil, Thomas Cornfield, Jonathan Hazlehurst, Ahmad Moolla, Sarah White, Jane Francis, Stefan Neubauer, Jeremy Cobbold, Leanne Hodson, Jeremy Tomlinson
Journal: Journal of Hepatology (2019)
Physicians’ Goodness and Guilt—Emotional Challenges of Practicing Medicine
Authors: Lawrence D. Blum
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
IL23-Producing Human Lung Cancer Cells Promote Tumor Growth via Conversion of Innate Lymphoid Cell 1 (ILC1) into ILC3
Authors: Jaemoon Koh, Hye Young Kim, Youngha Lee, In Kyu Park, Chang Hyun Kang, Young Tae Kim, Ji-Eun Kim, Murim Choi, Won-Woo Lee, Yoon Kyung Jeon, Doo Hyun Chung
Journal: Clinical Cancer Research (2019)

The plasticity of innate lymphoid cells (ILCs) has been reported in vitro and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In this study, we explored plasticity of ILCs in human lung cancer.We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in coculture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 patients with lung cancer.Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCC) but not adenocarcinomas (ADC). In non-small-cell lung cancers, the percentage of ILC3 was associated with IL23 expression in tumor cells but not immune cells. In cocultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL23, thus promoting IL17-mediated tumor cell proliferation. Consistently, among IL17+ immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3-RORγt+ ILC3, IL17 expression level, and IL23- or IL17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC.Conversion from ILC1 into ILC3 by IL23-producing SqCCs promotes IL17-mediated tumor progression, resulting in a poor prognosis.
CRISPR/Cas9-mediated in vivo gene targeting corrects hemostasis in newborn and adult factor IX–knockout mice
Authors: Lili Wang, Yang Yang, Camilo Ayala Breton, John White, Jia Zhang, Yan Che, Alexei Saveliev, Deirdre McMenamin, Zhenning He, Caitlin Latshaw, Mingyao Li, James M. Wilson
Journal: Blood (2019)
Clinical benefit of anti PD-1/PD-L1 plus chemotherapy versus chemotherapy alone in first-line treatment in advanced non-small cell lung cancer: A meta-analysis
Authors: T. Landre, G. Des Guetz, A. Vergnenegre, C. Chouaid
Journal: Annals of Oncology (2019)

Background: First-line therapy for advanced non–small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Combination of anti-PD-1/PD-L1 to chemotherapy (CT) offers a new therapeutic option for this population. Methods: We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. Results: The eight eligible studies included 4401 patients (3097 males, mostly smokers (81%), median age 64 years), with 3037 nonsquamous (69 %) and 1330 squamous tumours (30%). One study evaluated nivolumab + CT (CheckMate 227), four studies evaluated atezolizumab + CT (IMpower 130,131,132 and 150), and three studies pembrolizumab + CT (Keynote 021, 189 and 407). The combination PD-1/PD-L1 inhibitor + CT was significantly associated with improvement of OS (hazards ratio [HR], 0.72; 95% CI 0.61–0.85; p < 0.0001), PFS (HR, 0.63; 95% CI 0.58–0.68; p < 0.0001) and ORR (relative ratio [RR], 2.08; 95% CI 1.69–2.55; p < 0.0001), irrespective of PD-L1 expression level. For patients with low (<1%) or undetectable PD-L1 expression, OS benefit was statistically significant (HR, 0.75; 95% CI 0.63-0.89; p < 0.0008). Conclusions: The combination of PD-1/PD-L1 inhibitor to chemotherapy, compared with chemotherapy alone, is associated with significantly improved OS, PFS, and ORR in first-line therapy in NSCLC. This strategy appears as a new standard of care for patients with untreated NSCLC, including for those with low or undetectable PD-L1 expression. Legal entity responsible for the study: APHP. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Circulating miRNAs as a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers.
Authors: Zhi-Qiang Ling, Wei-Min Mao
Journal: Journal of Clinical Oncology (2015)

e18500 Background: miRNA expression is deregulated in non-small cell lung cancer (NSCLC), and some miRNAs are associated with gefitinib sensitivity. Here, we investigated if circulating miRNAs could be a useful biomarker for the prediction of EGFR mutation and the patient's prognosis. Methods: The differential miRNAs related to gefitinib sensitivity were screened and identified by microRNA array. Using Taqman-based real-time RT-PCR, we analyzed the expression of selected miRNAs in tumor tissues and plasma of 150 NSCLC patients. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to determine the association between miRNAs expression and survival. Receiver operating characteristic curve analysis was also performed. Results: Compared with PC9 cell line, 41 microRNAs detected by microarray were significantly differentially expressed in A549 and H1299 cells. The 5 selected hsa-miRNAs were all found differently expressed between wild and mutant EGFR carriers (all P< 0.01). Down-regulation of 5 selected miRNAs were independently associated with lymphatic invasion (all P< 0.01) and clinical stage (all P< 0.01), respectively. Both down-regulation of has-miR-195 (P= 0.012) and has-miR-21 (P= 0.004) were associated with poor differentiation. All up-regulation of 5 has- miRNAs were associated with smoking (All P< 0.05). 5 hsa-miRNAs were up-regulated both in plasma and tissue samples. A model including 4 hsa- miRNAs may predict EGFR mutational status and gefitinib-sensitivity (both AUC: 0.869). Plasma levels of has-miR-125b expression were associated with disease-free survival (P= 0.033) and overall survival in the patients (P= 0.028). Conclusions: Circulating 5 selected miRNAs may especially be useful in predicting EGFR mutation, and circulating hsa-miR-125b may have prognostic values in NSCLC patients.
SAT-430-Spleen stiffness measured with ElastPQ point shear wave elastography has a good performance in predicting clinically significant portal hypertension in patients with primary sclerosing cholangitis
Authors: Davide Roccarina, Francesca Saffioti, Matteo Rosselli, Anna Mantovani, Roberta Stupia, Aileen Marshall, Massimo Pinzani, Douglas Thorburn
Journal: Journal of Hepatology (2019)
FRI-389-Impact of coronary artery disease on long term mortality after liver transplantation
Authors: Samarth Patel, Viviana Rodriguez, Mohammad Bilal Siddiqui, Masoud Faridnia, Joseph Clinton, Fei-Pi Lin, John Laurenzano, Anchalia Chandrakumaran, Trevor Reichman, Chandra Bhati, Mohammad Siddiqui
Journal: Journal of Hepatology (2019)
Correction to: DNA copy number evolution in Drosophila cell lines
Authors: Hangnoh Lee, C. Joel McManus, Dong-Yeon Cho, Matthew Eaton, Fioranna Renda, Maria Patrizia Somma, Lucy Cherbas, Gemma May, Sara Powell, Dayu Zhang, Lijun Zhan, Alissa Resch, Justen Andrews, Susan E. Celniker, Peter Cherbas, Teresa M. Przytycka, Maurizio Gatti, Brian Oliver, Brenton Graveley, David MacAlpine
Journal: Genome biology (2019)

Following publication of the original article [1], the authors reported the following errors.
Soluble EMMPRIN levels discriminate aortic ectasia in Marfan syndrome patients
Authors: Erica Rurali, Gianluca L. Perrucci, Raffaella Gaetano, Alessandro Pini, Donato Moschetta, Davide Gentilini, Patrizia Nigro, Giulio Pompilio
Journal: Theranostics (2019)

Marfan syndrome (MFS) is a rare genetic disease characterized by a matrix metalloproteases (MMPs) dysregulation that leads to extracellular matrix degradation.Consequently, MFS patients are prone to develop progressive thoracic aortic enlargement and detrimental aneurysm.Since MMPs are activated by the extracellular MMP inducer (EMMPRIN) protein, we determined whether its plasmatic soluble form (sEMMPRIN) may be considered a marker of thoracic aortic ectasia (AE).Methods: We compared plasma sEMMPRIN levels of 42 adult Caucasian MFS patients not previously subjected to aortic surgery with those of matched healthy controls (HC) by ELISA.In the MFS cohort we prospectively evaluated the relationship between plasma sEMMPRIN levels and the main MFS-related manifestations.Results: MFS patients had lower plasma sEMMPRIN levels (mean±SD: 2071±637 pg/ml) than HC (2441±642 pg/ml, p=0.009).Amongst all considered MFS-related clinical features, we found that only aortic root dilatation associated with circulating sEMMPRIN levels.Specifically, plasma sEMMPRIN levels negatively correlated with aortic Z-score (r=-0.431,p=0.004), and were significantly lower in patients with AE (Z-score≥2, 1788±510 pg/ml) compared to those without AE (Z-score<2, 2355±634 pg/ml; p=0.003).ROC curve analysis revealed that plasma sEMMPRIN levels discriminated patients with AE (AUC [95%CI]: 0.763 [0.610-0.916],p=0.003) with 85.7% sensitivity, 76.2% specificity, and 81% accuracy.We defined plasma sEMMPRIN levels ≤2246 pg/ml as the best threshold discriminating the presence of AE in MFS patients with an odds ratio [95%CI] of 19.2 [3.947-93.389](p<0.001).Conclusions: MFS patients are characterized by lower sEMMPRIN levels than HC.Notably, plasma sEMMPRIN levels are strongly associated with thoracic AE.
LBO-06-Interim safety and efficacy results of the ABI-H0731 phase 2a program exploring the combination of ABI-H0731 with Nuc therapy in treatment-naive and treatment-suppressed chronic hepatitis B patients
Authors: Xiaoli Ma, Jacob Lalezari, Tuan Nguyen, Ho Bae, Eugene R. Schiff, Scott Fung, Man-Fung Yuen, Tarek Hassanein, Hie-Won Hann, Magdy Elkhashab, Douglas Dieterich, Mark Sulkowski, Paul Kwo, Ronald Nahass, Kosh Agarwal, Alnoor Ramji, James Park, Natarajan Ravendhran, Sing Chan, Frank Weilert, Steven-Huy Han, Walid Ayoub, Edward Gane, Ira Jacobson, Michael Bennett, Qi Huang, Ran Yan, Vivian Huey, Eric Ruby, Sandy Liaw, Richard Colonno, Uri Lopatin
Journal: Journal of Hepatology (2019)
THU-436-The cost-effectiveness of one-time birth cohort screening for hepatitis C as part of the National Health Service health check programme for 40 to 74 year olds in England
Authors: Jack Williams, Alec Miners, Ross Harris, Sema Mandal, Ruth Simmons, Georgina Ireland, Matthew Hickman, Charles Gore, Peter Vickerman
Journal: Journal of Hepatology (2019)
Outpatient allogeneic hematopoietic cell transplant following alemtuzumab based reduced intensity conditioning in patients with advanced mycosis fungoides/Sezary syndrome.
Authors: Enkhtsetseg Purev, Ramaprasad Srinivasan, George Aue, Dave Stroncek, Hahn Khuu, Caltalina Ramos, Lisa Cook, Elena Cho, Monica Schmitt, Richard W. Childs
Journal: Journal of Clinical Oncology (2015)

7089 Background: Advanced mycosis fungoides/Sezari syndrome (MF/SS) is associated with poor prognosis and is incurable with conventional chemotherapeutic approaches. We describe a novel transplant approach that enables outpatient administration and monitoring, provides a measure of disease control prior to engraftment, and reduces the incidence of GHVD. Methods: Subjects with advanced MF received a G-CSF mobilized PBSC allograft from an HLA identical sibling following alemtuzumab, and fludarabine conditioning regimen. CSA was used as GVHD prophylaxis to supplement alemtuzumab-induced in-vivo T-cell depletion. Donor lymphocyte infusions (DLI) were used as required to promote transition to full donor chimerism and/or promote a graft-vs-tumor effect. Conditioning and as well as stem cell infusions were carried out largely in an outpatient setting. Results: 5 subjects with stage IIb-IV MF/SS were enrolled. The conditioning was well tolerated with no serious adverse events. None of the subjects had profound and prolonged neutropenia and thrombocytopenia. Median time to calculated donor neutrophil recovery was 45 d (range 15 d to 6 mo). 4/5 subjects achieved full and sustained donor T-cell and myeloid chimerism, which occurred at a median 9 mo and 6 mo post-transplant, respectively. Among those at risk, 2/4 developed CMV reactivation. None of the subjects developed PTLD. At a median follow-up of 3 yrs, 1 subject developed aGVHD and 1 subject developed cGVHD. 3 subjects achieved complete remission at a median of 7 mo post-transplant mediated by a potent graft-versus-tumor effect. 3 subjects are alive at 10 yrs, 8 yrs, and 6 mo after transplant. 1 subject died 3 yrs post-transplant from a second malignancy while SS was in complete remission, 1 subject died 6 mo post-transplant from grade IV GI GVHD. Conclusions: The outpatient based reduced intensity transplant approach described here is well tolerated and associated with prolonged, GVT-induced complete remissions in patients with advanced stage MF/SS. The trial is ongoing and efforts are underway to permit enrollment of patients with available HLA-matched unrelated donors. Clinical trial information: NCT00047060.
THU-164-High cure rates of hepatitis C in a genotype 3 predominant Pakistani community using generic direct acting antivirals
Authors: Ammara Naveed, Amjad Khan, Asif Butt, Ahmad Karim Malik, Farooq A. Khan, Khurram Anis, Nauman Zakir, Amer Yar Khan, Saeed Akhter, Naveed Janjua, Abdul Nadir
Journal: Journal of Hepatology (2019)
THU-477-Sumoylation/acetylation drives forward oncogenic role of LKB1 in Liver
Authors: Fernando Lopitz Otsoa, Imanol Zubiete-FRanco, Juan Luis García Rodríguez, Marina Serrano-Macia, Jorge Simón, Pablo Fernández Tussy, Lucía Barbier Torres, David Fernandez-Ramos, Virginia Gutiérrez de Juan, Sergio López de Davalillo, Onintza Carlevaris, Adolfo Beguiristain Gomez, Julio arrizabalaga, Diego F Calvisi, Cesar Martin, Edurne Berra, Patricia Aspichueta, Naiara Beraza, Marta Varela-Rey, Matías A Avila, Manuel S Rodriguez, José M. Mato, Irene Diaz-Moreno, Antonio Diaz-Quintana, Teresa Cardoso Delgado, María Luz Martínez-Chantar
Journal: Journal of Hepatology (2019)
Novel Fusion Genes Involving Hnrnpc and Rarg in Acute Myeloid Leukemia Mimicking Acute Promyelocytic Leukemia
Authors: Zhan Su, Xin Liu, Yan Xu, Weiyu Hu, Chunting Zhao, Hongguo Zhao, Xianqi Feng, Shuchao Zhang, Jie Yang, Xue Shi, Lugui Qiu, Jun Peng
Journal: Blood (2018)
Abstract 17537: Acquired Long QT Syndrome in Hospitalized Patients With Cancer
Authors: Yajuan Lin, Haixu Yu, Zhao Wang, Fuquan Zou, Xintao Li, Ying Liu, Yunlong Xia
Journal: Circulation (2017)

Background: Acquired long QT syndrome (ALQTS) as one of severe cardiac complications related to oncology treatment has been overlooked in clinical practice. Objectives: To investigate the character...
Cost-effectiveness analysis of VEGF-C: A novel predictive biomarker for response to bevacizumab in the neoadjuvant therapy of early breast cancer patients.
Authors: Patricia Renee Blank, Sibylle Loibl, Barbro Kristina Linderholm, Stefano Caramuta, Valentina Nekljudova, Thomas D. Szucs, Joris van Stiphout, Zanfina Ademi, Gunter Von Minckwitz, Matthias Schwenkglenks
Journal: Journal of Clinical Oncology (2015)

e12079 Background: It has been demonstrated that VEGF-C level has predictive value for determining pathological complete response (pCR) with bevacizumab treatment in the neo-adjuvant setting. We aimed to estimate the cost-effectiveness of using VEGF-C testing and corresponding treatment strategies in patients with triple negative breast cancer (TNBC), from a German third-party payer perspective. Methods: Using a life-long Markov state transition model, we determined the costs (EUR) and effects (quality-adjusted life years, QALYs) of VEGF-C guided use of bevacizumab therapy. Information on overall and metastasis-free survival derived from the GeparQuinto (n = 830, EudraCT No: 2006-005834-19) trial. Six alternative strategies were compared: four using different VEGF-C cut-off values; two implying the use of bevacizumab in none or all the patients, regardless of VEGF-C level. Costs and effects were discounted by 3% p.a. Results: Lifetime costs per patient ranged from EUR 40,226 (reference strategy of no bevacizumab therapy) to EUR 82,047. No bevacizumab therapy yielded 8.141 QALYs per patient. In comparison with no bevacizumab therapy, the most preferable strategy (cut-off 2600 pg/mL) yielded additional costs of 10,060 EUR and 0.338 QALYs per patient (incremental cost-effectiveness ratio, 29,722 EUR/QALY) (Table 1, only undominated strategies shown). Results remained robust in sensitivity analyses. Conclusions: Our study suggests that VEGF-C could be sensibly used to guide the neo-adjuvant administration of bevacizumab in TNBC. Compared to current practice of not using bevacizumab in this setting, the use of a cut-off value of 2600 pg/mL might be cost-effective in Germany. Strategy Cost (EUR) Incremental Cost (EUR) (vs. reference) Effects (QALYs) Incremental Effects (QALYs) (vs. reference) ICER (EUR/QALY) No test, no bevacizumab 40,226 - 8.141 - - VEGF-C 2600 pg/mL 50,286 10,060 8.479 0.338 29,722 (vs. reference) VEGF-C 2282 pg/mL 56,230 5,944 8.613 0.134 44,498 (vs. VEGF-C 2600 cut-off) VEGF-C 2100 pg/mL 60,491 4,261 8.684 0.071 60,061 (vs. VEGF-C 2282 cut-off) No test, bevacizumab all 82,047 21,557 8.726 0.042 511,041 (vs. VEGF-C 2100 cut-off)
Abstract 19286: Periodic Breathing During Asleep and Exercise in Patients with Heart Failure
Authors: Yoshitaka Oda, Shuji Joho, Ryuichi Ushijima, Daisuke Harada, Tadakazu Hirai, Hiroshi Inoue
Journal: Circulation (2010)

Backgrounds: Central sleep apnea (CSA) and exercise oscillatory ventilation (EOV) might both originate from an instability in feedback peripheral and central chemoreflex control of ventilation. However, the relation between CSA and EOV in patients with heart failure is still unknown. Methods: In 70 patients with heart failure (ejection fraction<45%), cardiorespiratory polygraphy and cardiopulmonary exercise test (CPX) were performed. EOV was defined as 3 or more regular oscillatory fluctuations in ventilation. In 10 patients with EOV, CPX and cardiorespiratory polygraphy were studied twice after intensive treatment of heart failure. Results: EOV was observed in 21 of 70 patients (30%, cycle length of EOV: 83±26 sec). The cycle length of EOV was similar to that of CSA (r=0.88, p<0.001). EOV was more frequent in patients with moderate to severe sleep apnea (apnea-hypopnea index (AHI)≥15/h) than in patients with mild sleep apnea (AHI 5–15/h) or without sleep apnea (AHI<5/h) (51% vs. 7% and 5%, respectively)....