tbuckley/cabot-search huggingface dataset:
Microscopic margins of resection in gastrointestinal stromal tumor (GIST): An analysis of 122 patients
Authors: M. Di Battista, M. Saponara, M. A. Pantaleo, F. Catena, D. Santini, C. Lolli, V. Di Scioscio, M. Astorino, A. Maleddu, M. Nannini, G. Biasco
Journal: Journal of Clinical Oncology (2009)

10554 Background: The main treatment for localized GIST is complete surgical resection. The prognosis is strongly correlated with both tumor size and mitotic index. The aim of our study was to analyze retrospectively the outcome of patients affected by GIST related to microscopic margins of resection. Methods: The outcome of 122 patients surgically managed during the past 11 years, were evaluated. We analyzed the impact of R0 and R1 resection on DFS. Results: All patients but one, had a c-Kit positive GIST, 91% had primary disease without metastasis, 9% had metastasis. There were 46% high, 31% intermediate and 28% low risk GIST. The median age was 65 years (range 29–87). The most common sites of tumor origin were the stomach (54.9%) and the small bowel (36.9%). Sites of tumor metastasis were liver (18.2%), peritoneum (36.4%) or both (19.3%). R0 resection was achieved in 102 (83.6%) patients, while 16 pts (13.1%) had positive microscopic margins (R1). With a median follow up of 24 months (range 3–119), recurrence occurred in 34 (33.3%) R0 and in 9 (56.3%) R1 patients. The median DFS was 53.7 months and 35.6 months for the R0 and R1 group, respectively. The difference tested with univariate analysis using Long rank test, was not statistically significant (p= 0.228). Conclusions: In our series, the status of microscopic margins does not appear to be important for prediction of recurrence in patients affected by GIST. No significant financial relationships to disclose.
Epidemiology of Strongyloides stercoralis in northern Italy: results of a multicentre case–control study, February 2013 to July 2014
Authors: Dora Buonfrate, Mara Baldissera, Fabrizio Abrescia, Matteo Bassetti, Giacomo Caramaschi, Mario Giobbia, Marta Mascarello, Paola Rodari, Novella Scattolo, Giuseppina Napoletano, Zeno Bisoffi
Journal: Eurosurveillance (2016)

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case–control approach was adopted and patients with a peripheral eosinophil count ≥ 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5–14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9–32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p &lt; 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count.
Failure of Exercise to Reduce Hypertension
Authors: Neil F. Gordon
Journal: JAMA (1992)

To the Editor.  —The article by Blumenthal et al 1 represents an important contribution to the existing literature on the efficacy of exercise training in controlling hypertension. However, we disagree with the authors' interpretation of some of their data.  First, the title of their article implies that resting blood pressure was not significantly reduced with exercise training, when in fact it was (by -8/-6 mm Hg). Indeed, after 4 months of aerobic exercise training, their subjects' mean blood pressure had fallen to what most clinicians would consider a normal value (133/89 mm Hg).  Second, when making a comparison with previous randomized controlled studies, Blumenthal et al failed to point out that exercise training in their study lowered resting blood pressure to a similar degree as in these previous studies. Where their study differed was the unusual finding of a significant (-9/-5 mm Hg) reduction in the blood pressure of the
Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews
Authors: M. Pollock, I. P. Sinha, L. Hartling, B. H. Rowe, S. Schreiber, R. M. Fernandes
Journal: Allergy (2016)

International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department (ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews (SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0–18 years presenting to the ED. Searching, review selection, data extraction and analysis, and quality assessments were conducted using methods recommended by The Cochrane Collaboration. Thirteen SRs containing 56 relevant trials and 5526 patients were included. Results demonstrate the efficacy of short-acting beta-agonist (SABA) delivered by metered-dose inhaler as first-line therapy for younger and older children (hospital admission decreased by 44% in younger children, and ED length of stay decreased by 33 min in older children). Short-acting anticholinergic (SAAC) should be added to SABA for older children in severe cases (hospital admission decreased by 27% and 74% when compared to SABA and SAAC alone, respectively). Continuous nebulization, addition of magnesium sulfate to SABA, and levosalbutamol compared to salbutamol cannot be recommended in routine practice.
Motesanib with or without panitumumab (pmab) plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer (mCRC).
Authors: N. C. Tebbutt, D. Kotasek, H. A. Burris, L. S. Schwartzberg, H. Hurwitz, J. Stephenson, H. Adewoye, Y. Sun, Y. Ye, D. Goldstein
Journal: Journal of Clinical Oncology (2010)

3538 Background: Motesanib is an oral inhibitor of VEGF, PDFG, and Kit receptors. Pmab, a fully human monoclonal antibody against EGFR, is approved for treatment of chemorefractory mCRC. Part 1 of this ongoing phase Ib/2 study establishes the safety of motesanib with or without pmab + chemotherapy (CT) in mCRC patients (pts). Methods: Pts had ECOG 0/1, ≤ 1 prior CT (metastatic setting), and no prior oral anti-VEGFR or anti-EGFR therapy. Cohorts (C) received, based on prior therapy, either FOLFIRI (C1) or FOLFOX-4 (C2) + pmab (6 mg/kg IV on day 1 of each 2-week cycle) and escalating doses of motesanib (50-125 mg QD or 75 mg BID) given continuously from day 3 of cycle 1; or FOLFIRI (C3) or FOLFOX-4 (C4) plus motesanib 125 mg QD. Endpoints are dose-limiting toxicities (DLTs) in the first 2 cycles (primary); adverse events (AEs), PK, and tumor response (every 6-8 wks) by RECIST (secondary). Results: 80 pts are enrolled, receiving ≥ 1 dose of motesanib (C1/2/3/4, N = 36/17/16/11), which completes part 1b of the study. 10 pts had a DLT (13 events; Table). 41 pts had motesanib-related gr 3 AEs (C1/2/3/4, n = 14/10/9/8), 1 pt had a gr 4 AE (neutropenia; C2, 75 mg QD) and no pts had gr 5 AEs. Related AEs of interest included (all worst gr ≤3) hypertension (C1/2/3/4, n=7/3/11/6); pulmonary embolism (n=2/0/0/0), and deep vein thrombosis (n=1/2/0/0). Motesanib exposure at 50 mg QD (+FOLFOX) and 50-125 mg QD (+FOLFIRI) was not affected by coadministration of CT + pmab. Motesanib did not markedly alter the PK profiles of irinotecan or its metabolites. There was 1 confirmed CR (C2); 23 confirmed PR (motesanib + pmab + CT/motesanib + CT, n = 21/2), 31 SD (n = 15/16), and 11 PD (n = 8/3). Conclusions: No unexpected toxicities were identified in mCRC patients receiving motesanib + FOLFIRI or FOLFOX. Motesanib 125 mg QD will be used in part 2 of the study. Updated safety and efficacy data will be presented. Cohorts DLTs (all gr 3) C1 Deep vein thrombosis (75 mg QD), diarrhea (n=2: 125 mg QD, 75 mg BID); high nasogastric output (75 mg BID) C2 Fatigue (n=2; 50 mg QD), febrile neutropenia (75 mg QD), diarrhea (n=2; 75 mg QD), hypokalemia (75 mg QD) C3 None C4 Congestive cardiomyopathy, diarrhea, reversible posterior leukoencephalopathy syndrome Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Bristol-Myers Squibb, Genentech, Roche Amgen Amgen, Genentech, Roche Amgen, Bristol-Myers Squibb, Genentech, Novartis, Pfizer, Roche, sanofi-aventis
Liraglutide (Saxenda) for Weight Loss
Authors: J Suzin Whitten
Journal: JAMA (2016)

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
Genomic Imprinting in the Endosperm Is Systematically Perturbed in Abortive Hybrid Tomato Seeds
Authors: Ana M. Florez-Rueda, Margot Paris, Anja Schmidt, Alex Widmer, Ueli Grossniklaus, Thomas Städler
Journal: Molecular Biology and Evolution (2016)

Hybrid seed failure represents an important postzygotic barrier to interbreeding among species of wild tomatoes (Solanum section Lycopersicon) and other flowering plants. We studied genome-wide changes associated with hybrid seed abortion in the closely related Solanum peruvianum and S. chilense where hybrid crosses yield high proportions of inviable seeds due to endosperm failure and arrested embryo development. Based on differences of seed size in reciprocal hybrid crosses and developmental evidence implicating endosperm failure, we hypothesized that perturbed genomic imprinting is involved in this strong postzygotic barrier. Consequently, we surveyed the transcriptomes of developing endosperms from intra- and inter-specific crosses using tissues isolated by laser-assisted microdissection. We implemented a novel approach to estimate parent-of-origin–specific expression using both homozygous and heterozygous nucleotide differences between parental individuals and identified candidate imprinted genes. Importantly, we uncovered systematic shifts of "normal" (intraspecific) maternal:paternal transcript proportions in hybrid endosperms; the average maternal proportion of gene expression increased in both crossing directions but was stronger with S. peruvianum in the maternal role. These genome-wide shifts almost entirely eliminated paternally expressed imprinted genes in S. peruvianum hybrid endosperm but also affected maternally expressed imprinted genes and all other assessed genes. These profound, systematic changes in parental expression proportions suggest that core processes of transcriptional regulation are functionally compromised in hybrid endosperm and contribute to hybrid seed failure.
MMP2-1306 CT/TT genotype in PSC patients is a risk factor for orthotopic liver transplantation
Authors: Kerem Sebib Korkmaz, Bert-Jan de Rooij, Minneke J. Coenraad, Robert J. Porte, Marcel Janse, Rinse K. Weersma, Bart van Hoek, Hein W. Verspaget
Journal: Hepatology (2012)
In adults ≥ 75 years of age with hypertension, intensive vs standard BP-lowering treatment reduced CV events
Authors: Paul Shekelle
Journal: Annals of Internal Medicine (2016)

Source Citation Williamson JD, Supiano MA, Applegate WB, et al; SPRINT Research Group. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥ 75 years: a randomized clinical trial. JAMA. 2016;315:2673-82. 27195814
Prostate cancer–specific mortality and competing causes of mortality among elderly men after local therapy for prostate cancer.
Authors: Maria Carmen Mir, Joseph C. Klink, Brandon Isariyawongse, Adam Stuart Kibel, Eric A. Klein, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2012)

103 Background: The benefit of definitive local therapy among elderly patients (&gt; 65 years) with localized prostate cancer (PC) is uncertain, particularly for those with comorbid illness. Despite this uncertainty, the majority of these men currently receive local therapy. We analyzed the risk of prostate cancer-specific mortality (PCSM) relative to competing causes of mortality (CCM), stratified by disease severity and comorbidity, among contemporary men treated at two high-volume hospitals Methods: Between 1995-2005, 4237 consecutive men aged 65 years or older were managed by radical prostatectomy (N = 1634), external-beam radiotherapy (N = 1570), or brachytherapy (N = 1033) at Cleveland Clinic or Barnes-Jewish Hospital. Clinical information was obtained from prospective data bases. Comorbidity was assessed using ACE-27 and Charlson Comorbidity indices. PC risk was classified according to D’Amico criteria. Fine and Gray competing risk analysis was used to assess PCSM and CCM at 10 years. Results: Over a median follow-up of 72 months (IQR: 46-97), 88 and 748 PCSM and CCM events were observed. Among healthy men with low risk PC, 10 year PCSM was 2% and CCM was 19%. Among healthy men with high risk PC, PCSM was 11% and CCM was 27%. In the group with moderate-to-severe comorbidities, CCM was 49, 59%, and 58% and PCSM was 1%, 3%, and 21% among those with low-, intermediate- and high-risk PC, respectively. Among these unhealthy men, 26% were treated by radical prostatectomy, of whom 45% had low-risk PC and 16% had high-risk PC. Among healthy men, 41% were treated by radical prostatectomy, of whom 54% and 9% had low- and high-risk PC, respectively. Conclusions: The risk of PCSM vs. CCM for older men is low, particularly for those with moderate-to-severe comorbidity; 49-59% had died from CCM within 10 years. Current evidence suggests that local therapy for PC is associated with a 25% reduction in PCSM, at best. Thus, with active surveillance, it is unlikely that PCSM would exceed 5-7% in those with low- and intermediate-risk PC. These results should inform elderly men and physicians about the risk of PCSM and CCM when deciding upon treatment for localized PC.
Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training
Authors: Lily Riggs, Janine Piscione, Suzanne Laughlin, Todd Cunningham, Brian W. Timmons, Kerry S. Courneya, Ute Bartels, Jovanka Skocic, Cynthia de Medeiros, Fang Liu, Nicholas Persadie, Katrin Scheinemann, Nadia Scantlebury, Kamila U. Szulc, Eric Bouffet, Donald J. Mabbott
Journal: Neuro-Oncology (2016)

Exercise promotes repair processes in the mouse brain and improves cognition in both mice and humans. It is not known whether these benefits translate to human brain injury, particularly the significant injury observed in children treated for brain tumors. We conducted a clinical trial with crossover of exercise training versus no training in a restricted sample of children treated with radiation for brain tumors. The primary outcome was change in brain structure using MRI measures of white matter (ie, fractional anisotropy [FA]) and hippocampal volume [mm3]). The secondary outcome was change in reaction time (RT)/accuracy across tests of attention, processing speed, and short-term memory. Linear mixed modeling was used to test the effects of time, training, training setting, and carryover. Twenty-eight participants completed training in either a group (n=16) or a combined group/home (n=12) setting. Training resulted in increased white matter FA (Δ=0.05, P<.001). A carryover effect was observed for participants ~12 weeks after training (Δ=0.05, P<.001). Training effects were observed for hippocampal volume (Δ=130.98mm3; P=.001) and mean RT (Δ=-457.04ms, P=0.36) but only in the group setting. Related carryover effects for hippocampal volume (Δ=222.81mm3, P=.001), and RT (Δ=-814.90ms, P=.005) were also observed. Decreased RT was predicted by increased FA (R=-0.62, P=.01). There were no changes in accuracy. Exercise training is an effective means for promoting white matter and hippocampal recovery and improving reaction time in children treated with cranial radiation for brain tumors.
Heterogeneity in Simvastatin-Induced Cytotoxicity in AML Is Related to Differential Ras-Isoprenylation, Rather Than to Blockade of Cholesterol Synthesis.
Authors: Karen van der Weide, Patrick M. Korthuis, Folkert Kuipers, Elisabeth G.E. de Vries, Edo Vellenga
Journal: Blood (2009)
Microrna Expression Profiling In Pediatric Acute Myeloid Leukemia Reveals a Tumor-Suppressive Role Of Mir-9 Associated With Translocation (8;21)
Authors: Stephan Emmrich, Jenny Katsman-Kuipers, Kerstin Henke, Razan Jammal, Felix Engeland, Ferhat Dasci, Michel Zwaan, Monique L. Den Boer, Lonneke Verboon, Jan Stary, Andre Baruchel, Valerie de Haas, Astrid Danen- van Oorschot, Rob Pieters, Dirk Reinhardt, Jan-Henning Klusmann, Marry M. Van Den Heuvel
Journal: Blood (2013)
The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation
Authors: Xiang Qi, Kevin Tak-Pan Ng, Yan Shao, Chang Xian Li, Wei Geng, Chang Chun Ling, Yuen Yuen Ma, Xiao Bing Liu, Hui Liu, Jiang Liu, Wai Ho Yeung, Chung Mau Lo, Kwan Man
Journal: Theranostics (2016)

Background and Aims: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth.GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study.Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation.Methods: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established.To investigate the clinical relevance of GPx3, 105 HCC patients who underwent liver transplantation were recruited.The suppressive role of GPx3 in HCC cells was studied using wound healing, Matrigel invasion assay and lung metastasis model.The real-time intravital imaging system was applied to directly visualize the tumor cells invasion in a living animal.The underlying mechanism was further explored.Results: GPx3 was identified as a down-regulated protein in small-for-size liver graft and significantly associated with invasive phenotype of tumor growth in a rat model.Plasma GPx3 was significantly lower in small-for-size graft group post-transplantation (day1: 33 vs 1147; day3: 3209 vs 4459; day7: 303 vs 2506; mU/mL, P<0.05) in rat model.Clinically, the plasma GPx3 was significantly lower in the recipients with HCC recurrence post-transplantation (day1: 4.16 vs 8.99 µg/mL, P<0.001; day7: 3.86 vs 9.99 µg/mL, P<0.001).Furthermore, lower plasma GPx3 was identified as an independent predictor (HR=4.528,P=0.046) for poor overall survival post-transplantation. Over-expression of GPx3 significantly suppressed migration, invasiveness and metastasis of HCC cells.Real-time intravital imaging showed that GPx3 significantly suppressed HCC invasiveness in a live animal.GPx3 suppressed the tumor invasiveness through inhibition of JNK-cJun-MMP2 pathway.Conclusion: GPx3 may possess prognostic and therapeutic value for HCC patients after liver transplantation.
Thymic renewal and antileukemic effect in adults after haploidentical transplantation and suicide gene therapy.
Authors: C. Bordignon, L. Vago, G. Oliveira, D. Ghio, M. Lupo Stanghellini, J. Peccatori, A. Bondanza, A. Lambiase, F. Ciceri, C. Bonini
Journal: Journal of Clinical Oncology (2010)

6534 Background: Hematopoietic Cell Transplantation from partially-HLA matched family donors (haplo-HCT) represents a promising therapy for high-risk leukemia. The infusion of donor lymphocytes transduced with the HSV-Tk suicide gene provides a rapid immune reconstitution while controlling GVHD (Ciceri and Bonini et al., Lancet Oncology, 2009). Here we investigated the contribution of gene-modified cells to post-transplantation thymic renewal and Graft-versus-Leukemia effect. Methods: In a phase II trial of haplo-HSCT for high-risk leukemia, 28 patients received Tk+ donor T-cells. In a selected subset of patients, thymic function was assessed quantitation of CD31+ recent thymic emigrants (RTEs) in CD4+ naïve T cells and was correlated with thymic volume, assessed by CT scans. Alloreactivity against leukemic blasts was studied by MLC. Results: Posttransplant recovery of Tk- Naïve T cells occurred, reaching values comparable to controls in approximately one year. After Tk+ cells infusion, CD4+ naïve T cells became almost entirely CD31+ RTEs, suggesting a direct role of the infused Tk+ cells in promoting thymopoiesis. Accordingly, CT scans documented an increase in thymic volume following Tk+ cell infusion. Tk+ cells displayed also a direct antileukemic effect, as demonstrated by their selective enrichment and functional activity against leukemic blasts. Consistent with their ex vivo alloreactivity, in two of the treated patients Tk+ cells drove in vivo selection of immunoresistant leukemic variants with genomic loss of the mismatched HLA haplotype. Conclusions: The infusion of gene-modified T cells prompts renewal of thymic activity which contributes to recovery of a polyclonal T cell repertoire. Contextually, transduced cells also mediate a direct antitumor effect. TK+ cell activity in the context of haplo-HSCT for leukemia is assessed in a phase III trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MolMed
Frontline Hyper-CVAD with Ponatinib for Patients (pts) with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Results of a Phase II Study
Authors: Koji Sasaki, Susan O'Brien, Farhad Ravandi, Deborah A Thomas, Haim G Moore, Jorge E. Cortes, Naveen Pemmaraju, Musa Yilmaz, Tapan Kadia, Rebecca Garris, Guillermo Garcia-Manero, Twilla Victoria Jeanis, Jad Chahoud, Gautam Borthakur, William Wierda, Alessandra Ferrajoli, Hagop M. Kantarjian, Elias Jabbour
Journal: Blood (2015)