tbuckley/cabot-search huggingface dataset:
Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.
Authors: A R Ablin, M D Krailo, N K Ramsay, M H Malogolowkin, H Isaacs, R B Raney, J Adkins, D M Hays, D R Benjamin, J L Grosfeld
Journal: Journal of Clinical Oncology (1991)

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.
Letter by Guazzi Regarding Article, “Right Ventricular Function in Heart Failure With Preserved Ejection Fraction: A Community-Based Study”
Authors: Marco Guazzi
Journal: Circulation (2015)

I read with interest the article by Mohammed and coworkers 1 on the prevalence and prognostic significance of right ventricular (RV) dysfunction in a large set of patients with heart failure with preserved ejection fraction.RV function was assessed by tricuspid annular systolic peak excursion (TAPSE) in 500 of 562 patients and by semiquantitative assessment in the whole population.Interestingly, patients with either mild or moderate to severe RV dysfunction by semiquantitative assessment compared with no RV dysfunction were more likely to present with atrial fibrillation, permanent pacing, and diuretic treatment.On the contrary, just a lower TAPSE tertile was reflective of a worse clinical condition.The analysis is strengthened by an 8-year outcome follow-up.Findings are new and stimulating, addressing a topic of growing attention in the heart failure with preserved ejection fraction syndrome that has been clearly underestimated in the past. 2-4I would like to extend the discussion a little as follows.TAPSE is an endurance index of RV systolic function that, although feasible, easy to obtain, and clinically meaningful, does not reflect the contractile state of the RV but just its motion and is afterload dependent.In a previous study by our group 3 performed in a group of patients with either systolic or heart failure with preserved ejection fraction, we obviated this potential disadvantage by examining the TAPSE versus pulmonary artery systolic pressure relationship, looking at the first as a variation in length and the second as a developed pressure or force.This in vivo length-toforce relationship provided robust clinical and prognostic insights that were stronger than those provided by TAPSE alone.It should be interesting to know how this approach may work in the present population and whether it may help to differentiate disease severity and prognosis at a further step.
Numbers needed to treat to prevent tuberculosis
Authors: Martina Sester, Reinout van Crevel, Frank van Leth, Christoph Lange
Journal: European Respiratory Journal (2015)

A new action framework advocacy document for tuberculosis elimination in low-incidence countries has recently been published in this journal [1]. We completely agree with the importance of addressing the goal of elimination of tuberculosis, which may be achievable in regions such as Western Europe and North America, but we are concerned that this goal may be overly ambitious at this point in time. As protective immunity can, unfortunately, not be achieved by a vaccine or other immune-based intervention, tuberculosis control still relies on early identification and treatment of active tuberculosis, and preventive chemotherapy of individuals with latent Mycobacterium tuberculosis infection (LTBI). However, both the tuberculin skin test (TST) and interferon-γ release assays (IGRAs) (the ELISA-based QuantiFERON-TB Gold In-Tube assay (QIAGEN, Venlo, the Netherlands) or the ELISPOT-based T-SPOT. TB assay (Oxford Immunotec, Oxford, UK)) that are recommended to diagnose LTBI have a low positive predictive value for the future development of tuberculosis, and are therefore insufficient as biomarkers to identify individuals developing active disease. With tuberculosis being a rare event, the vast majority of individuals with positive test results will never develop disease [2]. Moreover, in immunocompromised individuals, especially in patients with HIV infection, the negative predictive value of an immunodiagnostic test is insufficient to rule out the future development of tuberculosis, as was recently demonstrated in a large study in Europe [3]. Thus, systematic testing and treatment of LTBI of risk groups [1] is considered difficult to implement. Comparing the NNT to prevent one case can help define groups at highest TB risk and prioritise prevention strategies <http://ow.ly/TITzR>
MRI with hyperpolarised [1-<sup>13</sup>C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model
Authors: Eva M Serrao, Mikko I Kettunen, Tiago B Rodrigues, Piotr Dzien, Alan J Wright, Aarthi Gopinathan, Ferdia A Gallagher, David Y Lewis, Kristopher K Frese, Jaime Almeida, William J Howat, David A Tuveson, Kevin M Brindle
Journal: Gut (2015)

<h3>Objectives</h3> Pancreatic cancer (PCa) is treatable by surgery when detected at an early stage. Non-invasive imaging methods able to detect both established tumours and their precursor lesions are needed to select patients for surgery. We investigated here whether pancreatic preneoplasia could be detected prior to the development of invasive cancers in genetically engineered mouse models of PCa using metabolic imaging. <h3>Design</h3> The concentrations of alanine and lactate and the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were measured in extracts prepared from the pancreas of animals at different stages of disease progression; from pancreatitis, through tissue with predominantly low-grade and then high-grade pancreatic intraepithelial neoplasia and then tumour. <sup>13</sup>C magnetic resonance spectroscopic imaging (<sup>13</sup>C-MRSI) was used to measure non-invasively changes in <sup>13</sup>C labelling of alanine and lactate with disease progression, following injection of hyperpolarised [1-<sup>13</sup>C]pyruvate. <h3>Results</h3> Progressive decreases in the alanine/lactate concentration ratio and ALT/LDH activity ratio with disease progression were accompanied by a corresponding decrease in the [1-<sup>13</sup>C]alanine/[1-<sup>13</sup>C]lactate signal ratio observed in <sup>13</sup>C-MRSI images of the pancreas. <h3>Conclusions</h3> Metabolic imaging with hyperpolarised [1-<sup>13</sup>C]pyruvate enables detection and monitoring of the progression of PCa precursor lesions. Translation of this MRI technique to the clinic has the potential to improve the management of patients at high risk of developing PCa.
Safety and Tolerability of ACP-501, a Recombinant Human Lecithin:Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study
Authors: Robert D. Shamburek, Rebecca Bakker-Arkema, Alexandra M. Shamburek, Lita A. Freeman, Marcelo J. Amar, Bruce Auerbach, Brian R. Krause, Reynold Homan, Steve J. Adelman, Heidi L. Collins, Maureen Sampson, Anna Wolska, Alan T. Remaley
Journal: Circulation Research (2015)

Low high-density lipoprotein-cholesterol (HDL-C) in patients with coronary heart disease (CHD) may be caused by rate-limiting amounts of lecithin:cholesterol acyltransferase (LCAT). Raising LCAT may be beneficial for CHD, as well as for familial LCAT deficiency, a rare disorder of low HDL-C.To determine safety and tolerability of recombinant human LCAT infusion in subjects with stable CHD and low HDL-C and its effect on plasma lipoproteins.A phase 1b, open-label, single-dose escalation study was conducted to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of recombinant human LCAT (ACP-501). Four cohorts with stable CHD and low HDL-C were dosed (0.9, 3.0, 9.0, and 13.5 mg/kg, single 1-hour infusions) and followed up for 28 days. ACP-501 was well tolerated, and there were no serious adverse events. Plasma LCAT concentrations were dose-proportional, increased rapidly, and declined with an apparent terminal half-life of 42 hours. The 0.9-mg/kg dose did not significantly change HDL-C; however, 6 hours after doses of 3.0, 9.0, and 13.5 mg/kg, HDL-C was elevated by 6%, 36%, and 42%, respectively, and remained above baseline ≤4 days. Plasma cholesteryl esters followed a similar time course as HDL-C. ACP-501 infusion rapidly decreased small- and intermediate-sized HDL, whereas large HDL increased. Pre-β-HDL also rapidly decreased and was undetectable ≤12 hours post ACP-501 infusion.ACP-501 has an acceptable safety profile after a single intravenous infusion. Lipid and lipoprotein changes indicate that recombinant human LCAT favorably alters HDL metabolism and support recombinant human LCAT use in future clinical trials in CHD and familial LCAT deficiency patients.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01554800.
Shedding of tumor necrosis factor receptors by activated human neutrophils.
Authors: F Porteu, C Nathan
Journal: The Journal of Experimental Medicine (1990)

The capacity of human neutrophils (PMN) to bind tumor necrosis factor (TNF) was rapidly lost when the cells were incubated in suspension with agents that can stimulate their migratory and secretory responses. Both physiological (poly)peptides (FMLP, C5a, CSF-GM) and pharmacologic agonists (PMN, calcium ionophore A23187) induced the loss of TNF receptors (TNF-R) from the cell surface. Half-maximal loss in TNF-R ensued after only approximately 2 min with 10(-7) M FMLP at 37 degrees C, and required only 10(-9) M FMLP during a 30-min exposure. However, there were no such changes even with prolonged exposure of PMN to FMLP at 4 degrees or 16 degrees C. Scatchard analysis revealed loss of TNF-binding sites without change in their affinity (Kd approximately 0.4 nM) as measured at incompletely modulating concentrations of FMLP, C5a, PMA, or A23187. The binding of anti-TNF-R mAbs to PMN decreased in parallel, providing independent evidence for the loss of TNF-R from the cell surface. At the same time, soluble TNF-R appeared in the medium of stimulated PMN. This inference was based on the PMN- and FMLP-dependent generation of a nonsedimentable activity that could inhibit the binding of TNF to fresh human PMN or to mouse macrophages, and the ability of mAbs specific for human TNF-R to abolish inhibition by PMN-conditioned medium of binding of TNF to mouse macrophages. Soluble TNF-R activity was associated with a protein of Mr approximately 28,000 by ligand blot analysis of cell-free supernatants of FMLP-treated PMN. Thus, some portion of the FMLP-induced loss of TNF-R from human PMN is due to shedding of TNF-R. Shedding was unaffected by inhibitors of serine and thiol proteases and could not be induced with phosphatidylinositol-specific phospholipase C. Loss of TNF-R from PMN first stimulated by other agents may decrease their responsiveness to TNF. TNF-R shed by PMN may be one source of the TNF-binding proteins found in body fluids, and may blunt the actions of the cytokine on other cells.
Induction of Prosurvival Molecules During Treatment: Rethinking Therapy Options for Photodynamic Therapy
Authors: Charles J. Gomer
Journal: Journal of the National Comprehensive Cancer Network (2012)

Photodynamic therapy (PDT) not only causes direct cytotoxicity to malignant cells within a tumor but also appears to have both direct and indirect effects on nonmalignant components of the tumor microenvironment. A host of preclinical studies have been performed to document how PDT modulates the tumor microenvironment. This article explores the role of cellular components such as the hypoxia-inducible factor 1α, vascular endothelial growth factor, cyclooxygenase-2, matrix metalloproteinases, the antiapoptotic protein survivin, and 17-AAG (an inhibitor of heat shock proteins), with the hope that combined modality regimens targeting these processes may improve PDT tumor responsiveness.
Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)
Authors: Tomoya Mita, Naoto Katakami, Hidenori Yoshii, Tomio Onuma, Hideaki Kaneto, Takeshi Osonoi, Toshihiko Shiraiwa, Keisuke Kosugi, Yutaka Umayahara, Tsunehiko Yamamoto, Hiroki Yokoyama, Nobuichi Kuribayashi, Hideaki Jinnouchi, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
Journal: Diabetes Care (2015)

OBJECTIVE Recent experimental studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1–dependent and –independent manners. The current study investigated the effects of alogliptin, a DPP-4 inhibitor, on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS This prospective, randomized, open-label, blinded-end point, multicenter, parallel-group, comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and randomly allocated to treatment with alogliptin (n = 172) or conventional treatment (n = 169). Primary outcomes were changes in mean common and maximum intima-media thickness (IMT) of the carotid artery measured by carotid arterial echography during a 24-month treatment period. RESULTS Alogliptin treatment had a more potent glucose-lowering effect than the conventional treatment (−0.3 ± 0.7% vs. −0.1 ± 0.8%, P = 0.004) without an increase of hypoglycemia. Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment (−0.026 mm [SE 0.009] vs. 0.005 mm [SE 0.009], P = 0.022; −0.045 mm [SE 0.018] vs. 0.011 mm [SE 0.017], P = 0.025, and −0.079 mm [SE 0.018] vs. −0.015 mm [SE 0.018], P = 0.013, respectively). CONCLUSIONS Alogliptin treatment attenuated the progression of carotid IMT in patients with T2DM free of apparent cardiovascular disease compared with the conventional treatment.
Final results of a phase Ib study of gemcitabine plus PEGPH20 in patients with stage IV previously untreated pancreatic cancer.
Authors: Sunil R. Hingorani, William Proctor Harris, Joseph Thaddeus Beck, Boris A. Berdov, Stephanie Ann Wagner, Eduard M. Pshevlotsky, Sergei Tjulandin, Oleg Gladkov, Randall F. Holcombe, Ping Jiang, Craig E. Devoe
Journal: Journal of Clinical Oncology (2015)

359 Background: Poor outcome in pancreatic cancer (PDA) has been associated with tumor stroma limiting access of chemotherapy drugs. PEGPH20 (PEG), PEGylated recombinant human hyaluronidase, which depletes hyaluronan (HA) in tumors, has demonstrated anti-tumor activity in preclinical PDA models. In a KPC model of PDA, PEG + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Phase 1 PEG monotherapy studies, the MTD was 3µg/kg. The most common adverse events (AEs) were musculoskeletal events. Methods: This was a phase 1b study to determine the recommended phase 2 dose of PEG + Gem in patients (pts) with previously untreated Stage IV pancreatic cancer. PEG was given at 1, 1.6, or 3µg/kg IV twice weekly Wks 1–4 and weekly Wks 5–7, followed by 1 wk rest. Gem was given at 1000mg/m 2 IV once weekly for Wks 1–7, then 1 wk rest. Thereafter, PEG + Gem were given once weekly for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEG doses. Due to evolving SOC, the study was discontinued before initiation of the phase 2 randomization. Results: Twenty-eight pts were enrolled in the study. The majority of the patients (89%) had metastatic sites in the liver. Four, 4 and 20 pts received PEG at 1, 1.6 and 3µg/kg, respectively. The most common AEs related to PEG were muscle spasm (54%), myalgia (39%), arthralgia (29%), peripheral edema (29%), fatigue (25%), and extremity pain (18%). Median progression free survival (PFS) and overall survival (OS) were assessed and were 154 and 200 days, respectively. In an exploratory analysis, tumor biopsies from 17 pts were evaluated for HA levels (HA high or HA low ). 6 pts were determined to have HA high tumors and 11 pts had HA low tumors. The median PFS and OS for HA high pts were 219 days (95% CI: 159-276) and 395 days (95% CI: 210-578). For HA low pts median PFS and OS were 108 (95% CI: 14-163) and 174 days (95% CI: 34-293). Conclusions: PEG + Gem is generally well tolerated in advanced pancreatic cancer and shows promising clinical activity, especially in pts with HA high tumors. ClinicalTrials.gov Identifier: NCT01453153.
Biomarkers in reproductive medicine: the quest for new answers
Authors: Carlos Simon, Denny Sakkas, David K. Gardner, Hilary O.D. Critchley
Journal: Human Reproduction Update (2015)

Personalized medicine in assisted reproductive technologies (ART) is still in its infancy. Precision medicine, based on objective molecular tools added, to clinical medicine is well-accepted and developed in oncology and other potent medical disciplines. The impact of personalized medicine in cancer is broad, from screening to diagnosis, with the stratification of patients into cancer subgroup categories, facilitating individualized therapies that impact treatment effectiveness and disease recurrence (Diamandis et al., 2010; Hamburg and Collins, 2010). In reproductive medicine many ‘unknown black boxes’ still exist. These will only be unraveled with the timely application of novel technologies and knowledge from modern medicine, complementing classical clinical protocols. Albert Einstein wrote: ‘If you want different results, do not do the same’. This quotation is applicable to the current status of our field. In addition to classic single molecular markers, high-throughput approaches may be used for personalized diagnosis, including next generation sequencing (NGS), single-nucleotide polymorphisms (SNP), microarray analysis or mass spectrometry. A common trend among these tools is their ability to analyze a myriad of targets simultaneously. Consequently with the addition of bioinformatics and systems biology to the equation, the sensitivity, specificity, and accuracy, as well as the complexity of new biomarkers discovered, is increasing. The complication of applying personalized medicine in reproduction is that it is not ‘personalized’ to one individual but in fact three; the
Improving Health Care Transition Services
Authors: Peter Scal
Journal: JAMA Pediatrics (2015)

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 Pediatrics 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 Pediatrics journal
Phase III, randomized, open-label study of durvalumab (MEDI4736) in combination with tremelimumab or durvalumab alone versus platinum-based chemotherapy in first-line treatment of patients with advanced/metastatic NSCLC: MYSTIC
Authors: Naiyer Rizvi, Fabrice Barlesi, Julie Brahmer, Enriqueta Felip, Patrick Forde, Marina Garassino, Sarah Goldberg, Johan Vansteenkiste, Anthony Jarkowski, Stuart McIntosh, Luping Zhao, Scott Antonia
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Platinum-based doublets are standard of care (SoC) first-line treatment for advanced NSCLC, but durable benefit is observed infrequently, with resistance to chemotherapy invariably developing. The blockade of immune checkpoints is a promising novel approach in cancer treatment.
Autoantibodies from patients with primary biliary cirrhosis preferentially react with the amino-terminal domain of nuclear pore complex glycoprotein gp210.
Authors: J Wesierska-Gadek, H Hohenauer, E Hitchman, E Penner
Journal: The Journal of Experimental Medicine (1995)

Patients with primary biliary cirrhosis frequently develop autoantibodies directed to gp210, a major glycoprotein of the nuclear pore complex. This protein contains a large glycosylated cisternal domain, a single transmembrane segment, and a short cytoplasmic tail. It has been previously shown that autoantibodies from primary biliary cirrhosis patients exclusively react with the cytoplasmic tail. We demonstrate that autoantibodies against gp210 recognize at least two different epitopes. 4 out of 12 anti-gp210 positive sera reacted with the fragment consisting of the cytoplasmic tail, and 8 sera targeted a novel epitope located within the large glycosylated lumenal domain. Moreover, our data prove that carbohydrate moieties are an essential part of this novel epitope. We propose, therefore, that future screening assays should be performed with antigens possessing both epitopes to detect all sera with anti-gp210 specificity.
Recurrence rate of lentigo maligna after micrographically controlled staged surgical excision
Authors: K. de Vries, K. Greveling, L.M. Prens, K. Munte, S. Koljenović, M.B.A. van Doorn, E.P. Prens
Journal: British Journal of Dermatology (2015)

Lentigo maligna is a slowly growing melanoma in situ. Current guidelines advise wide local excision with a margin of 5 mm as the treatment of first choice, which has recurrence rates ranging from 6% to 20%.To determine retrospectively the recurrence rate of lentigo maligna after staged surgical excision.Records of all patients with lentigo maligna treated with our method of staged surgical excision between 2002 and 2011 were retrieved. To identify recurrences we used the computer program Sympathy, which is linked to PALGA, a nationwide network and registry of histo- and cytopathology in the Netherlands.We identified 100 patients, who were treated with staged surgical excision with 100% immunohistopathological control of lateral margins. Digital pictures were used to facilitate orientation during the several stages of surgery. After a mean follow-up of 60 months, four patients had a recurrence, after 37, 58, 74 and 77 months of follow-up.Staged surgical excision is superior in clearance and recurrence rates to wide local excision for lentigo maligna and should be considered as the treatment of first choice in national and international guidelines.